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CLINICAL PRACTICE GUIDELINESHypertensionMOH Clinical Practice Guidelin CLINICAL PRACTICE GUIDELINESHypertensionMOH Clinical Practice Guidelin

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CLINICAL PRACTICE GUIDELINESHypertensionMOH Clinical Practice Guidelin - PPT Presentation

Published by Ministry of Health Singapore16 College RoadCollege of Medicine BuildingSingapore 169854Printed by Chung Printing Pte LtdCopyright by Ministry of Health SingaporeISBN Available on the M ID: 960940

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CLINICAL PRACTICE GUIDELINESHypertensionMOH Clinical Practice Guidelines /201 Published by Ministry of Health, Singapore16 College Road,College of Medicine BuildingSingapore 169854Printed by Chung Printing Pte LtdCopyright by Ministry of Health, SingaporeISBN Available on the MOH website: http://www.moh.gov.sg/cpg Statement of IntentThese guidelines are not intended to serve as a standard of medical care. Such standards are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge advances and patterns of care evolve. The contents of this publication are guidelines for clinical practice, based on the best available evidence at the time of development. Adherence to these guidelines ightnot ensure a successful outcome in every case. These guidelines should neither be construed as including all proper methods of care, nor exclude other acceptable methods of care. Contents Page List of recommendations 1 1 Introduction 1 4 2 Epidemiology 1 5 3 Definition and classification of hypertension 1 8 4 Measuring blood pressure 19 5 Evaluating high blood pressure 2 4 6 Stratifying risk and approach to hypertension management 2 6 7 Treating high blood pressure 30 8 Treatment goals and follow - up 4 1 9 Treating high blood pressure in special conditions 4 4 10 Treat ment of associated risk factors 5 7 11 Clinical Quality Improvement 5 8 References 59 Self - assessment (MCQs) 7 2 Workgroup members 7 4 ForewordIn the Global Burden of Disease 2010 study, hypertension is the leadingassociated risk factorfor cardiovascular disease. High blood pressure accounts for 9.4 million deathand 7.0% of global disabilityadjusted life years (DALYs) worldwide.These adverse outcomes exceed those

due toelevated BMI, fasting plasma glucose, and total cholesterol combined. Hypertension is prevalent and increasing in many developing and developed countries. In Singapore, the 2010 National Health Survey showed decreasing trend in the crude prevalence of hypertension among Singapore residents aged between 30 and 69years, from 27.3% in 1998 to 24.9% in 2004, and down to 23.5% in 2010.However, the agespecific prevalence for hypertension rises markedly from age 40 years onwards andwith our ageing population, we continue to face challenges in the prevention and control ofhypertension.The last hypertension guidelines were published in 2005. Many important studies have since been publishedand it is timely to update the hypertension guidelines to include new findings and evidencebased recommendations. The new guidelines continue to adhere to the fundamental principles diagnosing, evaluating and treating high blood pressures. It is hoped that this set of guidelines will assist doctors in managing patients with hypertension costeffectively, with maximal benefits and minimal risks, to further reduce the prevalence of hypertension in Singapore.ASSOCIATE PROFESSOR BENJAMIN ONGDIRECTOR OF MEDICAL SERVICES Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, AdairRohaniH et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 19902010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2013; 380:22242260.Epidemiology and Disease Control Division Ministry of Health Singapore. National Health Survey 2010 Report. Commonly used abbreviationsThe following is a list of abbreviations commonly used in this set of guidelines (arranged in alphabetical order), and a description of what they represent:ABPMambulatory blood pressure monitoringACEangiotensin

converting enzymeACRalbuminreatinine ratioARBangiotensin receptorblockBMIody mass indexlood pressureCADoronary artery diseaseECGelectrocardiographyestimated glomerular filtration rateHBPMhome blood pressure monitoringLVHleft ventricular hypertrophyNational Health SurveyPCRproteinreatinine ratioRAASreninangiotensinaldosterone systemrandomised controlled trial 1 List of recommendationsDetails of recommendations appearin the main text at the pages indicatedThe key recommendations are highlighted in brownlassification of hypertension No. Recommendation Grade, Level of Evidence CPG page no. 1 Classify hypertension according to systolic BP and diastolic BP levels. When the systolic BP and the diastolic BP fall into different categories, the higher category appliesGrade D, Level 4 Measuring blood pressure No. Recommendation Grade, Level of Evidence CPG page no. 2 Use the following procedures when recording BP: Allow the patient to sit or lie down for at least 3 minutes before measuring the BP. The patient should refrain from smoking or taking caffeinated drinks during the 30 minutes before measurement.Use a cuff with a bladder 12 13 cm x 35 cm in size. A cuff with a larger bladder should be used for large upper arms; where a thigh cuff should be used for extremely large arms. When using the auscultatory method, use the disappearance of phase V Korotkoff sounds to measure the diastolic BP.Measure the BP in both arms at the first visit; subsequently remeasure BP on the arm with the higher reading, if applicable Take 2 or more readings separated by 2 minutes. Average these two values. If the first two readings differ by 5 mmHg or more, further readings should be obtained and averaged.Grade D, Lev 2 No. Recommendation Grade, Level of Evidence CPG page no. 7. In elderly subjects and diabetic patients, m

easure the BP in the supine (or sitting) position, and within 2 minutes after standing, to record any postural fall in BP. Place the manometer cuff at the level of the heart, regardless of the position of the patient. 3 Wherever practicable, HBPM or ABPM (in that order) should be offered to younger patients, and to those whom target organ damage is found without a raised clinic BPGrade D, Level 4 4 The preferred manometer is an automated oscillometricdevice, with or without memoryGrade C, Level 2 5 To ensure reliable values, the patient or carer needs training in device use, and a BP logbook (for basic devices without memory)Grade D, Level 4 6 ABPM is recommended whenever in doubt about the diagnosis, e.g. to confirm borderline hypertension or abnormal results from HBPM GPP 21 7 ABPM is also indicated for older, cognitively impaired, anxious or obsessive patients, in whom HBPM might be unreliable or inappropriate.GPP 8 Patient s with an average BP ≥135/85 mmHg measured repeatedly at rest at home may be regarded as hypertensiveGrade D, Level 3 9 Patient s with a 24 - hour ABPM average BP ≥130/80 mmHg, or a daytime average BP ≥135/85 mmHg, or a nighttime average BP ≥120/70 mmHg,are regarded as hypertensive Grade D, Level 4 22 Evaluating high blood pressure No. Recommendation Grade, Level of Evidence CPG page no. 10 Routine clinical evaluation of a patient with elevated BP includes the followingClinical and family historyFull standard physical examinationLaboratory investigations, including:Urine analysis: Dipstick for hematuria/albumin, microscopic examinationand test for albuminuria Measurement of serum concentrations of electrolytes, creatinine, urea, fasting glucose and fasting lipids Computation of estimated glomerular filtration rate (eGFR) lead electrocardiography (ECG)Grade D,

Level 4 Stratifying risk and approach to hypertension management No. Recommendation Grade, Level of Evidence CPG page no. 11 Assess the overall cardiovascular risk and the patient’s BP to guide the management of high BP GPP 26 12 Refer to the locally adapted Framingham Risk Score to estimate cardiovascular risk.Grade D, Level 4 13 Offer to start drug treatment immediately in patients with hypertension and existing high cardiovascular riskGPP 14 Take the BP and other prognostic factors into account when deciding on the management of hypertensipatientsGrade D, Level 4 4 No. Recommendation Grade, Level of Evidence CPG page no. 15 For high or very high risk individuals, begin immediate drug treatment for hypertension when other risk factors or conditions are presentGrade A, Level 1++ 16 For medium risk individuals, monitor the BP and other risk factors for several weeks, and obtain further information, before deciding whether to begin drug treatmentGrade B, Level 1 17 For low risk individuals, observe the patient over a significant period of time before deciding whether or not to begin drug treatmentGrade B, Level 1 Treating high blood pressure No. Recommendation Grade, Level of Evidence CPG page no. 18 Wherever possible, use a team - based approach to managa patient with hypertension, involving trained nurses and pharmacists with medical practitioners.Grade A, Level 1 Lifestyle modification 19 Recommend lifestyle changes to all hypertensive patients, and in patients with high normal BP. However, drug treatment should not be delayed without reason beyond 3 to 6 monthsif indicated Grade A, Level 1 31 20 Advise patient to restrict salt intake to 5 to 6 g per day. Grade A, Level 1 31 21 Moderat e alcohol consumption to no more than 2 standard drinks per day

formen, and to no more than standarddrinkper day forwomen. Grade A, Level 1 31 5 No. Recommendation Grade, Level of Evidence CPG page no. 22 Increase the consumption of vegetables, fruits, low - fat dairy products, and decreasetheintake of saturated and total fats. Grade A, Level 1 31 23 Unless contraindicated, advise patients to reduce weightto a body mass index (BMI) below23 kg/m and to a waist circumference below90cm in men, and below80cm in women (for Asians). Grade B, Level 2 31 24 Advise patients to do at least 30 minutes of moderate dynamic exercise 5 to 7 days per week. Any physical exerciseabove the basal level, up to 150 minutes/week,confers incremental cardiovascular and metabolic benefits, including BP reduction. Grade A, Level 1 32 25 A dvi s e and offer assistance to all smokers to quit smoking Grade A, Level 1 32 Pharmacological treatment 26 Begin appropriate combination treatment in patients whose pretreatment is raised (i.e.mmHg), and specifically in patients whose BP is severely raised (180/110 mmHg),as they will require two or moredrugs for adequate control.Grade B, Level 2 27 Initiate treatment at low doses of drugs, either singly or as a two drug combination, to minimise side effects.Grade D, Level 4 28 If an adequate dose of the first drug used demonstrated limited response or was poorlytolerated, change to a different drug class instead of inceasing thedose of the first drug.Grade A, Level 1 29 Add a second drug when a single drug fails to achieve target BP. Grade B, Level 1 + 34 6 No. Recommendation Grade, Level of Evidence CPG page no. 30 Use long - acting drugs which provid e 24 - hour efficacy daily. Grade B, Level 2 3 1 In hypertensive patients without compelling indications or contraindications for any particular

drug, consider any one, or an appropriate combination, of the five major classes of drugs as the initial treatment. Grade B, Level 2 32 Take compelling indications and contraindications into account when prescribing an antihypertensive drug (Table ). Grade A, Level 1 3 3 Be aware of the cost of treatment in selecting antihypertensive drugs. Grade D, Level 4 37 3 4 Generic formulations which usually cost less than newer non generic (i.e. proprietary) drugs are acceptable for useGrade D, Level 4 3 5 Do not offer aldosterone (mineralocorticoid) antagonists (e.g. spironolactone) to patients with chronic kidney disease(eGFR 45 ml/min) , in particular when combined with an ACE inhibitoror ARB. This is because of the risks of further renal functionimpairment,and of hyperkalaemia.An aldosterone antagonist might be considered in patients with resistant hypertension after a full work up has excluded secondary hypertension (Table 4). Grade C, Level 2 3 6 Prescribe a diuretic with caution as initial treatment in patients with uncomplicated hypertension, who are at risk for diabetes, because it might causehyperglycaemiaGrade B, Level 2 3 7 U s e beta - blockers with caution in patients at risk of developing diabetes , as it raises blood glucose concentrations . Grade A, Level 1 7 No. Recommendation Grade, Level of Evidence CPG page no. 3 8 Use the following drug combinations to treat hypertension:Calciumchannel blocker (dihydropyridine type) plusACE inhibitor or ARBCalciumchannel blocker plus diuretic Diuretic plus ACE inhibitor or ARB Betablocker plus calciumchannel blocker(see caveat in Figure 2) 5. Beta - blocker plus diuretic (see caveat in Figure 2) . Grade Level 3 9 Avoid treating patients with an ACE inhibitor plus ARB combination, particularly patient s who

have chronic kidney disease . Grade B, Level 1 40 Beware of an increased risk of diabetes mellitus when offering a beta blocker plus diuretic combination to patients with risk factors such as obesity or metabolic syndrome . Grade B, Level 2++ 41 Do not offer renal sympathetic denervation for routine treatment resistant hypertension. Grade A, Level 1 40 4 2 Do not offer carotid - sinus baro receptor reflex activationfor routine treatment of resistant hypertension. Grade B, Level 2++ reatment goals and follow up No. Recommendation Grade, Level of Evidence CPG page no. 43 The recommended target BP treatment levels are: BP 140/90 mmHg in patients aged under 80 years BP 150/90 mmHg in patients aged 80 years or olderIn fragile elderly individualsthe systolic BP goals should be adapted to individual tolerability. Grade A, Level 1 8 No. Recommendation Grade, Level of Evidence CPG page no. 44 Patients with the following problems should be referred to a hypertension specialist or clinic:Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heart failure, or other impending complicationsHypertension that is difficult to manage, e.g. unusually labile BP, or hypertension refractory to multiple drugs in different pharmacological classesSecondary hypertension, i.e. hypertension due to an underlying c ause, such as hyperaldosteronismHypertension in special circumstances, e.g. pregnancy, and young children. Grade D, Level 4 Treating high blood pressure in special conditions No. Recommendation Grade, Level of Evidence CPG page no. Type 2 diabetes mellitus 4 5 For patients with type 2 diabetes mellitus who have hypertension, an acceptable treatment target BPis below140/80 mmHg. Grade B, Level 2 44 4 6 Use ACE inhibitor, ARB, or calcium

- channel blockerfirstline treatment in patients with diabetes without chronic kidney disease or proteinuria. Grade A, Level 1 44 4 7 Optimised BP control is recommended to reduce the riskor slow the progression, of diabetic nephropathy Grade A, Level 1 46 9 No. Recommendation Grade, Level of Evidence CPG page no. 4 8 Treat patients with diabetic nephropathy to a target below140 mmHg systolic BP Grade A, Level 1 46 4 9 If a diabetic nephropathy patient has severe albuminuria (equivalent to urinary albumin:creatinine ratio (ACR)more than 30 mg/mmol, or urinary PCR more than 50 mg/mmol), consider target below130 mmHg systolic BP provided GFR changes are monitored carefully Grade B, Level 2 47 50 Treat diabetic chronic kidney disease patients with moderate albuminuria (urinary ACR 330 mg/mmol, or PCR between 150 mg/mmol) to a target BP equal to orbelow0 mmHgGrade D, Level 4 5 1 Use an ACE inhibitor or ARB as first - line treatment,whenevertreatment with lowering drugs is indicatedin diabetic nephropathy. Grade A, Level 1 48 5 2 In diabetic nephropathy , if one class of RAAS blocker(either ACEinhibitoror ARB) is not tolerated, replace it withthe other Grade D, Level 4 48 5 3 Combination treatment with both an ACE inhibitor and an ARBshould not be routinein diabetic nephropathy. Grade A, Level 1 48 5 4 When ACE inhibitors , ARBs, or diuretics are used in diabetic nephropathy, it is recommended to monitor the serum creatinine and potassium levels for thepossibledevelopment of acute kidney injury and hyperkalemia. Grade D, Level 4 48 5 5 Beta - blockers, calcium - channel blockers , and thiazides are all appropriate secondline therapyin diabetic nephropathy.Grade A, Level 1 10 No. Recommendation Grade, Level of Evidence CPG page no. Non -

diabetic chronic kidney disease 5 6 Treat non - diabetic , non - proteinuric chronic kidney disease patients toa target below140/90 mmHg.Grade A, Level 1 5 7 Treat non - diabetic chronic kidney disease patient with severe albuminuria to a target equal to or below 130/80 mmHg. Grade A, Level 50 5 8 Treat non - diabetic chronic kidney disease patients with moderate albuminuria to a target BP equal to below0 mmHg.Grade D, Level 4 5 9 Use either an ACE inhibitor or an ARB as the first - line drugwhenever treatment with lowering drugs is indicated in nondiabetic chronic kidney disease patients. Grade A, Level 1 50 60 Combination treatment with both an ACE inhibitor and an ARB should not be routinely prescribedin nondiabetic chronic kidney disease patients.Grade A, Level 1 Stroke 6 1 Where systolic BP is above 140 mmHg but below 220 mmHg within the first two weekof onset of acute ischaemic stroke, lowering of high should be based on individual clinical judgment after careful consideration of all the contraindications Grade A, Level 1++ 51 6 2 It is reasonable to lower, with care, a markedly elevated (systolic above20 mmHg or diastolic above20 mmHg, or both) by 10% to 15% during the first 24 hours after the onset of acuteischaemicstroke. Grade D, Level 52 11 No. Recommendation Grade, Level of Evidence CPG page no. 6 3 A fter the acute phase of stroke, begin a ntihypertensive treatment in hypertensive patients if the systolic is more than 140 mmHg and diastolic is more than 90 mmHg. Grade D, Level 4 52 6 4 Use any of the five major pharmacological classes of antihypertensive drugsfor stroke prevention in patients during theacute phasestroke, provided that the is effectively lowered. Grade A, Level 1++ 53 6 5 The target BP level in patients after a tra

nsient ischemic attack and after acute phasestroke should be individualised, with careful consideration of medical comorbidities. A lower systolic target might benefit a patient who has small vessel disease, but might harm a patient with severe cerebrovascular stenosis.GPP Pregnancy 6 6 Even though the classification of mild, moderate and severe hypertensionby levelis different in pregnancy, pharmacologicaltreatmentis recommended pregnant women with chronic hypertensionwho havepersistently elevated systolic of 10 mmHg or greateror diastolic of 10mmHg or greaterGrade D, Level 4 6 7 Avoid a ggressive rates of lowering of BP in pregnant women with chronic hypertension because of the potential risk ofcompromising theuteroplacental blood flow.GPP 6 8 I n pregnant women w ith no target organ damage , anduncomplicated chronic hypertensionaim to keep the BPbelow150/100mmHg.Grade D, Level 4 12 No. Recommendation Grade, Level of Evidence CPG page no. 6 9 In pregnant women with target organ damage secondary to chronic hypertension, aim to keep the below 140/90mmHgGrade D, Level 4 70 In pregnant women with uncomplicated chronic hypertensiondo not use drug treatment to decrease thediastolic belowmmHg.Grade D, Level 4 7 1 T reat pregnant women with chronic hypertension usingmethyldopa, labetalolnifedipine, or a combination thereofGrade D, Level 4 7 2 Methyldopa, labetolol, and nifedipine are also considered safe for use during breastfeeding postpartum.GPP 7 3 ACE inhibitors, ARB s , direct renin inhibitors (e.g. aliskiren),and aldosterone antagonists should be avoided during pregnancy.Grade D, Level 4 Elderly patient s 7 4 I n elderly hypertensive patients whose systolic BP is 160 mmHg or higher, the BP should be reduced to below150/90 mmHg. Grade A, Level 1 55 7 5 I n patients

under the age of 80 years with good physical and mental status, systolic BP can be lowered to below140 mmHg if treatment is well tolerated.Grade B, Level 2 7 6 The management of hypertension in the elderly followthe same general guidelines, but begin drug treatment gradually, especially in the frail elderly. On starting drug treatment, carefully consider the patients’ associated clinical conditions. Grade A, Level 1 56 13 No. Recommendation Grade, Level of Evidence CPG page no. 7 7 In elderly patients with isolated systolic hypertension, consider using calciumchannel blockers and diuretics Grade B, Level 2 56 7 8 I n the elderly , measure the BP often in the supine (or sitting) position and standingposition to detect postural dropin the BPTake care to avoid fluid depletion and electrolyte imbalance in the elderly. GPP 56 reatment ofassociated risk factors Recommendation Grade, Level of evidence CPG Page No. 7 9 Take into account the use of other drugs that decreasecardiovascular risk, such as lipid regulating drugs and antiplatelet drugs, in hypertensive patients with concomitant risk factors and increased cardiovascular risk. Grade A, Level 1++ 57 Clinical quality improvement(Page The recommended target BP levels in antihypertensive treatmentare:Below 140/90 mmHg in patients aged under 80 yearsBelow 150/90 mmHg in patients aged 80 years or more*In elderly patients aged under 80 years with good physical and mental status if treatment is well tolerated.The schedules shown in Table (Page are recommended to allow patients and healthcare providersto optimise the quality of care. 14 IntroductionObjectives and scope of guidelineThe second edition of the MOH clinical practice guidelines on hypertension for Singapore was published in 2005. Since then, more facts about this impo

rtant condition have emergedparticularly those recommending home blood pressure monitoring (HBPM) andhour ambulatory blood pressure monitoring (ABPM) as key procedures in diagnosing suspected hypertension. Target groupThe main aim of these guidelines is to help physicians make sound clinical decisions about hypertension by presenting update informationabout diagnosis, classification, treatment, outcomes, and followup. These guidelines are developed for all healthcare professionals in Singapore.Guideline developmentThese guidelines have been produced by a MOHappointed committee of cardiologists, internists, general medicine practitioners, renal physicians, family physicians and a neurologist. They were developed by the adaptation of existing guidelines, critical review of relevant literature and expert clinical consensus taking local practice into consideration. The guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or his guardian or carer. Review of guidelinesEvidencebased clinical practice guidelines are onlyas current as the evidence that supports them. Users must keep in mind that new evidence could supersede recommendations in these guidelines. The workgroup advises that these guidelines be scheduled for review five years after publication, or earlier if new evidence appears that requires substantive changes to the recommendations. 15 Epidemiology lood pressure (BP)levels are continuously related to the risk of cardiovascular disease as shown in Figure 1 below. The definition of hypertension or raised is therefore arbitrary. Figure 1 Relative risk of cardiovascular disease in relat

ion to patients’ usual diastolic (square sizes proportional to numbers of events) rom MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke, and coronary heart disease. The Lancet. 1990; 335:7651 2.1 Epidemiology The Singapore National Health Survey (NHS)2010 showed that the crude prevalence of hypertension (defined as of 140/90 mmHg) among Singapore residents aged 30 to 69 years was 23.5%, compared 24.9% in 2004 and 27.3% in 1998. Of those aged between 18 to 69 years,close to1 in 5 residents (18.9%) had hypertension in 2010. In the NHS 2010, it was found that Malays (28.0%) had the highest prevalence of hypertension, followed by Chinese (23.4%) and Indians (19.3%). This result is in contrast to the NHS 2004, in whichChines (25.6%) persons had the highest prevalence of hypertension, followed by Malays(22.7%)and Indians(21.6%)Hypertension was more common among men(26.4%) than women(20.7%). The highest prevalence of hypertension among Singapore residents aged 30 to 69 years was in Malay women(29.8%), followed by Chinese men (27.2%) and Malay men(26.0%).The crude prevalence of hypertension by gender and ethnic group is shown in Figure 2 below.The agespecific prevalence for hypertension rises markedly from age 40 years onwards. The agespecific prevalence of hypertension amongst those aged 60 to 69 years was 53.4% as compared to 7.6% in those aged 30 to 39 years. Although infrequent, hypertension also occurs in younger individuals and children, many of whom have secondary hypertensionThe NHS found that 3.3% of Singapore residents aged 18 to 29 years had hypertension, compared with4.2% in n contrastmajority of adult hypertensipatients have primary hypertension (i.e. without any definedcauses). The NHS 2010 also found that the proportion of known hypertensive patientswith good control (i.e. 140/90 mmHg

) was67.4%, compared with49.5% in 2004as shown in Figure 3, while the proportion with good control among those receivingtreatment was 69.1%, compared with52.9% in 2004. In addition, 26.3% of those found to have hypertension in the NHS had not been previously diagnosedcompared with38.5% in 2004. Figure 2Crude revalence (%) of hypertension among Singapore residents aged 30 to 69 years old, by gender and ethnic group, 2010 Figure 3Proportion (%) of patients with under control (140/90 mmHg) in 2004 and 2010 Year 2004 Year 2010 27.2 19.7 23.4 26.0 29.8 28.0 21.2 17.1 19.3 0 5 10 15 20 25 30 35 Males Females Total Chinese Malay Indian % Good BP control 49.5% Poor BP control 50.5% Good BP controlPoor BP control 32.6% 18 Definition and classification of hypertensioncharacterisedby large spontaneous variationsthe diagnosis of hypertension should be based on multiple measurements taken on several separate occasions.Definitions are given in Table 1for subjects who are not taking antihypertensive medication and not acutely ill.Table Definitions and lassification of evels for dults ged 18 ears and lder Category Systolic BP Diastolic BP Normal 130 mmHg 85 mmHg Highnormal 130 to 139 mmHg 85 to 89 mmHg Grade 1 hypertension 140 to 159 mmHg * 90 to 99 mmHg Grade 2 hypertension 160 to179 mmHg * 100 to 109 mmHg Grade 3 hypertension 180 mmHg * 110 mmHg Isolated systolic hypertension 140 mmHg * 90 mmHg Isolated systolic hypertension is graded according to the same level of systolic Classifyhypertension according to systolic and diastolic levelsWhen the systolic BP and the diastolic fall into different categories, the higher categoryapplies.Grade D, Level 4For example, a of 162/92 mmHg is regarded as Grade 2 hypertension. 19 Measuring blood pressureClinicor officemeasurementThe measured at rest sev

eral times on several occasionswith the patient in a supine or sitting positionusing a noninvasive manometer, preferably an automated oscillometric device, validated according to standardised protocols and used in large studies across different populationsTo ensure accuracy,mercury devices are periodiccalibrated againstvalues obtained simultaneously from a mercury sphygmomanometer, which itself has been calibrated and regularly serviced. When mercury devices become obsolete, periodic calibration will be done by the manufacturers of ocillometric devices.Automated oscillometric devices remove the manual effort of cuff inflation, which can raise the to a misleading value,and avoid missing the true systolic because a ‘silent interval’ sometimes occurs within the auscultatory method. Automation also promotes consistency and ease in HBPM; and produces greater accuracy if values are storedelectronically Use the following procedures when recording llow the patient to sit or lie down for at least 3minutes before measuring the he patient should refrain from smoking or takingcaffeindrinksduring the 30 minutes beforemeasurementse a cuff with a bladder 1213 cm x 35 cm in size. A cuff with a larger bladder should be used for large upperarms; where a thigh cuff should be used for extremely large arms.When using the auscultatory method, use the disappearance of phase V Korotkoff sounds to measure the diastolic easure the in both arms at the first visit; subsequently measureon the arm with the higher reading, if applicableake 2 or more readings separated by 2 minutes. Average these twovalues. If the first tworeadings differ by 5 mmHgor morefurtherreadings should be obtained and averaged 20 elderly subjects and diabetic patientsmeasure the in the supine (or sitting) position, and within 2 minutes after standing, to record any postural fall in lac

e the manometer cuff at the level of the heart, regardlessthe position of the patientGrade D, Level 4Out of office measurementHome and ambulatory values obtained by HBPM, or by 24hour ABPM are usually several mmHg lower than those obtained by clinic or office measurement3,7BothHBPM and ABPM methods are validand moreover, the 24hour average from ABPM independently and reliably predicts cardiovascular mortality.3,8When measured in clinic oroffice, the alerting response in about 1 in 4 patientscan result in exaggerated Bleadingto overdiagnosis of the disorder, or to the diagnosis of isolated clinic (‘whitecoat’) hypertension.3,9Conversely, when a patient’s clinic is normalthe outclinic is raised, the condition is called isolated ambulatory or outclinic hypertension (‘masked’ hypertension). Wherever practicable, HBPMor ABPM(in that order) should be offered to younger patients, and to those whom target organ damage is found without raised clinic Grade D, Level 4HBPM is cheaper, more widely available, easily repeatable, and shows dayday variability. Where affordable, HBPM can be offered to committed patients to boost treatment adherence via positive data feedback.With HBPM, the BP should preferably be measured twice daily, in the morning and eveningadjusting for patients in longterm nightshift work. For each value inHBPM, at least two consecutive measurements are taken, 2 minutes apart and with the patientseated.3,9Additionally, BPshould be measured over 4to (minimum 4) consecutive days. The HBPM mean is the average of BP valuescounting from the monitoring day3,11 21 The preferred manometer is an automated oscillometric devicewith or without memory.Grade C, Level 2+HBPM yields many values over several days in the subject’s usual environment. To ensure reliable values, the patient or carer needs training in device use, and a

logbook (for basic deviceswithout memoryGrade D, Level 4hour ambulatory monitoring (ABPM) is the reference or ‘gold standard’ investigation, which records the during routine, dayday activities and during sleep, providing a measure of hour variability. This is because alarge body of information has been obtained previously using ABPM, across different subsets of patientsacross differentcountries. ABPMis recommended whenever in doubt about the diagnosise.g. to confirm borderline hypertension or abnormal results from HBPM ABPMis also indicated for older, cognitively impaired, anxious or obsessive patients, in whom HBPMmight be unreliable or inappropriate.In borderline hypertension, ABPM can be repeated at intervals tosupporta definite diagnosis.3,9,11It is also used to optimise BP treatment to ensure BP levels are keptto the targetrangelevels. Moreover, ABPM identifies patients with ‘masked hypertension’ (‘isolated outclinic hypertension’) in whom average is normal in the clinic but elevated at home and elsewhere.Masked hypertension, often occurring in young obese men who smoke and drink excessively, is linked to a higher risk KEY RECOMMENDATION 22 of diabetes and chronic kidney disease.3,11The definitionof hypertension basedon HBPM and ABPM are listed in Table 2. Table Definitions of hypertension in HBPM and ABPM Systolic BP Diastolic BP HBPM ≥ 135 mmHg ≥ 85 mmHg ABPM Daytime ≥ 135 mmHg ≥ 85 mmHg 24 - hour ≥ 130 mmHg ≥ 80 mmHg Nighttime ≥ 120 mmHg ≥ 70 mmHg Patients with an average 135/85 mmHg measured repeatedly at rest at home may be regarded ashypertensive.3,9Grade D, Level 3 Patients with a 24hourABPM average ≥130/80 mmHg, or a daytime average ≥135/85 mmHg, or a nighttime average ≥120/70 mmHg, areregarded ashypertensive.3,9,10Grade D, Level KEY RECOMME

NDATION Table Clinical indications for HBPM or 24hour ABPM Clinical indications for HBPM or 24 - hour ABPM 1. Diagnosis of hypertension Borderline clinic b)Unusual variability of clinic 2. Suspicion of isolated clinic (‘white coat’) hypertension in subjects with low cardiovascular risk a) High clinic BP (grade s 1& 2) in individuals without target organ damage 3. Suspicion of isolated am bulatory (isolated out - of - clinic, or ‘masked’) hypertension Normal/highnormal clinic in individuals with target organ damage or at high total cardiovascularrisk 4. Monitoring of the BP in treated hypertensive patients Identification of the excitatory (alerting) response (white coat effect) to aid the monitoring of treated b)Patients with wide variability of clinic Suspicion of nonadherence to treatment d)Clinic not at target values after appropriate antihypertensive therapy Hypotensive symptoms after appropriate clinicand tailored antihypertensive treatment 5.Autonomic, postural, postprandial, siestaand druginduced symptoms ymptoms suggesting hypotension from any likely cause, such as postural, autonomic, postprandial, afternoon naprelatand druginduced fall 6. Elevated clinic BP or suspected pre - eclampsi a in pregnant women 7. Identification of true and false resistant hypertension 8. Other indications for 24 - hour ABPM are Extreme discordance between clinic and home b)Assessment of withinday variability c) Evaluation of nocturnal BP dipping status 9. Suspicion of nocturnal hypertension, or absence of night - dipping, such as in patients with diabetes, chronic kidney disease, and obstructive sleep apnea syndrome, and in lonterm nightshift workers dapted from the 2013 ESH/ESC Guidelines for the management of arterial hypertensionCentral (aortic) BPCentralBP, measured

by applanation tonometry and pulsewave analysis, represents thehaemodynamicload imposed on the heart, large arteries, and other target organs. The arterial pressure waveform includes the forward pulse wavepeak and a reflected wavepeak. Relating the pressure difference between these peaks to the pulse pressure yields an augmentation index, which predicts mortality from chronic kidney disease. Measuring central BP might reassureyoung patients with isolated systolic hypertension based on the brachial However, central BP only adds slight prognostic value beyond brachial BP, and is unhelpful in most patients. The routine measurement of central BP is therefore premature. 24 Evaluating high blood pressureAims of evaluationThe objectives of the clinical and laboratory evaluation of the hypertensive patient s to:Determine the true level, and provide a definitive diagnosis of hypertensionExclude or identify secondary causes of hypertensionLook for targetorgan damage, and quantify its extent if presentandIdentify other cardiovascular risk factors and clinical conditions that might influence the patient’s treatment and prognosisClinical evaluation Routine clinical evaluation of a patient with elevated BP includes the following4,5,12linical and family historyull standard physical examinationaboratory investigations, including:rine analysis: Dipstick for hematuria/albumin, microscopic examinationand test for albuminuria easurement of serum concentrations of electrolytes, creatinine, urea, fasting glucose and fasting lipidsomputation of estimated glomerular filtration rate (eGFR)lead electrocardiography (ECG)Grade D, Level 4Further s should be guided by the history, physical examination and results of routine investigations. Thes aim to identifysecondarycauses of hypertensionin particular endocrine causes in younger subjects in the 2to 4decades

of life, andto obtain results which mightsignificantly affectthe patient’s management. Such investigations include creatinine clearance, 24hour urinecontent ofproteincatecholaminesand metanaphrinesserumuric acidand calciumlevelsthyroid function indices, and the ratio of plasmalevels ofaldosteroneto renin imited echocardiography could be conductedto confirmleft ventricular hypertrop(LVH)in patients whom examination or ECG, or both, suggest LVH3,9,10ascular ultrasonography used to detect aortic, carotid and peripheral arterial diseasemight also be necessary if clinically indicated.In older patients, an unexpected or rapid reduction (0 mmHg systolic or 0 mmHg diastolic 3,9after taking low doses of an angiotensinconverting enzyme (ACE) inhibitor or angiotensinreceptor blocker (ARB) suggests high circulating levels of renin and angiotensin II. In this situation, look out forbilateral renal artery stenosis.3,9,10The identifiable secondary causes of hypertension are listed in Table 4.Table Identifiable secondary causes of hypertension Identifiable secondary causes of hypertension Drugrelated and substancerelated* causes Chronic kidney disease Renal artery stenosis Primary hyperaldosteronism Hypercortisolism (Cushing’s syndrome Phaeochromocytoma Thyroid or parathyroid disease Coarctation of the aorta Obstructive sleep apnoea syndrome Nephropathy from Type 1 diabetes mellitus Rare monogenic ion transport disorders * Several nonprescribed and illicit substances causes hypertension, e.g. liquorice, cocaine, amphetamine, crystal methamphetamine, and 3,4methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) 26 Stratifying risk and approach to hypertension managementRisk assessment ssess the overall cardiovascular risk and the patient’s to guide the management of high Manymethodsof assessing overall cardiovascular risk existinvolvingrisk tab

les, charts or formulasof whichthe Framingham Risk Scoreis the prototype risk scoring system.The Framingham Risk Scorehas been modified locally, taking into account the Singapore cardiovascular epidemiological datain Singapore Refer to the locally adaptedFramingham Risk Scoreto estimate cardiovascularrisk.13,14Grade D, Level 4In individuals such as those with known or established coronary arterydisease (CD), other atheroscleroticvesseldisease, diabetes mellitus, familial hypercholesterolemiaor malignant hypertension, the overall cardiovascular risk assessment is often unnecessaryas the risk is already high Offer to start drug treatment immediately in patients with hypertension and existing high cardiovascular risk.Prognostic factorsPrognostic factorsconsist of risk factors for cardiovascular disease, target organ damage, concomitant diseases such as renal disease, and other aspects of the patient’s individual and medical circumstances (Table 5). Take the and other prognostic factors into account when deciding on the management of hypertensipatients15,16Grade D, Level 4 KEY RECOMMENDATION Table Prognostic factors5,17* Commensurate Asian body mass index (BMI) cutpointfor action Risk factors for cardiovascular disease 1. Levels of systolic and diastolic (Grades 1&2) Age (men ≥ 55 years; women ≥ 65 years) Smoking Family history of premature cardiovascular disease (men ≤ 55 years; women ≤ 65 years) 5. Dyslipidaemia Total cholesterol �6.2 mmol/L (240 mg/ Triglyceride�s 1.7mmol/L (150 mg/dL) HDL cholesterol 1.0 mmol/L (40 mg/ LDL cholesterol � 4.1 mmol/L (160 mg/ Diabetes mellitus Obesity (BMI ≥ 30 kg/m (BMI ≥ 27.5 kg/m Target organ damage (TOD) / associated clinical condition (ACC) Cerebrovascular disease Stroke (ischaemic or haemorrhagic) Transi

ent ischaemic attack Renal disease Albuminuria, at least moderately increased (A�CR 30 mg/mmol; P�CR mg/mmol or proteinu�ria ( 500g/24 hrs) Chronic kidney disease, at least stage 3 (eGFR0ml/min) Heart disease Left ventricular hypertrophy (ECG, echocardiogram or chest ray) Angina pectoris Myocardial infarction Coronary revascularisation Congestive heart failure Vascular disease Aortic aneurysm Peripheral arterial disease Hypertensive retinopathy Atherosclerosis Ultrasound or radiological evidence of artherosclerotic plaque (carotid, iliac, femoralperipheral arteriesandaorta) 28 Overall strategyatients’ risk levelfor cardiovascular disease depends on BP and prognostic factors (seeTable5,17Table Risk stratificationHT: Hypertension For high or very high risk individuals, begin immediate drug treatment for hypertension when other risk factors or conditions are presentGrade A, Level 1++ For medium risk individuals, monitortheand other risk factors for several weeksand obtain further information, before deciding whether to begin drug treatment.Grade B, Level 1+ For low risk individuals, observe the patient over a significant period of time before deciding whether or not to begin drug treatmentGrade B, Level 1+ Benefits of treating hypertensionEvidence from a number of randomised controlledtrials(RCTs)and metaanalyses show that the administration of lowering drugs in hypertensive individuals decreasthe risk of major clinical cardiovascular outcomes (i.e. fatal and nonfatal stroke, myocardial infarction, heart failureand other cardiovascular deaths).Based on metaanalyses of RCTsantihypertensivetreatmentloweringdiastolic 6 mmHg reduced stroke incidence by more than andCADby more than 14%sustained reduction of 12 mmHg in systolic over 10 years prevents1 death per 11 patients with stage 1 hypertension an

d other cardiovascular risk factorsand1 death per 9 patients in whomcardiovascular disease or target organ damage is present4,2 30 Treating high blood pressureGood communication between the physician and the patient is core to the successful management of hypertension. Since the treatment of hypertension is for life, it is essential that the physician establishes a good professional relationship with the patientprovides the patient with information (both verbal and written)and answers any questions the patient mighthave. Adequate information on the following is essential for satisfactory lifelong control of hypertension:BP monitoringisks assessmentand prognosisarget levelifestyle modificationandExpected benefits as well as the risks and side effects of treatment Wherever possible, use a teambased approach to managa patient with hypertension, involving trained nurses and pharmacists with medical practitioners.Grade A, Level 1Hypertension, like many other chronic diseases, often requires a multidisciplinary approach involving clinicians who manage the majority of hypertensive patientstrained nurses (nurse clinicians)and pharmacists. A teambased approach with a disease management programme s associated with significantly improved control.89,90Case management by nurseled teams and interventions by pharmacists have been shown to improve medication adherence and to achieve higher proportions of targets reached. However, the delivery of the teamcare service will depend on the local setups, availability of trainednurses and pharmacists, and costeffectiveness 31 pharmacological therapy (Lifestyle modifications Recommend lifestyle changesto all hypertensive patients, and in patients with high normal However, drug treatment should not be delayed without reason beyond 3to monthsif indicated Grade A, Level 1 Adv

ise patient to restrict salt intake to 5 to 6 g per day.29 Grade A, Level 1+ Moderatalcohol consumption to no more than 2standard drinks per day formen, and to no more than 1 standard drinkper day forwomen.25,30,31 Grade A, Level 1+ Increase the consumption of vegetables, fruits, lowfat dairy products, and decreasetheintake of saturated and total fats.25,32Grade , Level Unless contraindicated, advise patients to reduceweight to a body mass index (BMI) below23 kg/mand to a waist circumference below 90cm in men, and below 80cm in women (for Asians).38,39Grade , Level KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION 32 Advise patients to doat least 30 minutes of moderate dynamic exercise 5 to 7 days per week.25,40Any physical exerciseabove the basal level, up to about 150 minutes a week,confers incremental cardiovascular and metabolic benefits, including BP reductionGrade A, Level 1 dvie and offer assistanceto all smokers to quit smokingGrade , Level Pharmacological treatmentPrinciples of drug treatmentAchieving target levels as rapidly as practicable isthe most important principlehypertension treatment.Figure 4 Flowchart for drug treatmentStart with the lowest effective dosedrug combinations may be either 2 separate drugs, or a fixed twodrug combination tablet. KEY RECOMMENDATION KEY RECOMMENDATION 33 Begin appropriate combination treatment in patients whose pretreatment is raised (i.e.0 mmHg), and specifically in patientswhose BP is severely raised (180/110 mmHg),as they will require two or moredrugs for adequate control.3,9,47Grade B, Level 2 Initiate treatment at low doses, either singly or as a twodrug combination, to minimise side effects3,9 Grade D, Level 4 If an adequate dos

e of the first drugused demonstrated limited response or was poorlytolerated, change to a different drug class instead of increasing the dose of the first drug.Grade A, Level 1+ The following principles may be applied when usingantihypertensive drugs to lower regardless of the drug class:Firstly, useow doses of drugs to initiate treatment, either singly or as a twodrug combination, starting with the lowest effective dose of a particular drug, to minimie side effects. drug combination works faster in more severe hypertension, which might require 2 or even three drugs to attain target 3,9If there is a significant response to a low dose of a single drug, but the is still above target , a low dose of a second drug from a different classshould be addedAlternatively, the doctor may also increase the dose of the same drug if it is tolerated by the patientAdding a low dose of a second drug, rather than increasing the dose of the original drug, confers advantages. This action allows both components to act at low doses, which are more likely to be free of side effects. he 2drug combination also promotes the quicker attainment of targets. In this context, fixed lowdose combinations that are cheap should firstbe considered. If taking a particular 2drug combination does not reach target at full doses, then either switch to another 2drug combination, starting with the lowest effective doses of the component drugs, or add a third drug from a different class.Doctors should be aware that, in patients receiving longterm treatment, any change in drug dose or regimen takes full effect only 34 after 25 weeks, unlike the quicker changes in treatmentnaïve patientTherefore, at least 2 weeks should pass before measuring the at the new steadystate, when t

itrating drug dosage or changing regimens, particularly in older patient Add a seconddrug when a single drug fails to achieve target 47,48 Grade B, Level 1 Use of appropriate drug combinations maximises thelowering efficacy while minimiing side effects. In most patients, appropriate combination treatmentdoubles thereduction compared to usingsingle drugse.g. in patients with an initial of 160/100mmHgcombination treatment reduces the to about 138/86mmHg, compared to about 148/93mmHg with single drug47,48 Use longacting drugs which providhour efficacy daily.Grade B, Level 2The advantages of longacting drugs include betteradherence todaily treatment,and smoother and more consistent control of the i.e. reducedvariability. Threduction in variability mightconfergreater protection against both the risk of major cardiovascular eventsandthe development of target organ damage.Choice of antihypertensive drugs In hypertensive patients withoutcompelling indications or contraindications for any particular drug, consider any one, or any appropriate combination, of the five majorpharmacological classes of antihypertensive drugsas the initialtreatment3,9,10,73 Grade B, Level 2++ Takecompelling indications and contraindications into account when prescribingan antihypertensive drug(Table Grade A, Level 1+ 35 Table Guidelines for selecting drug(s) for antihypertensive treatment Concomitant conditions Status Drugs Grade and level Heart failure Recommended Diuretic , 3,10,11 ACE inhibitor , 52,53 ARB , 54 a ldosterone antagonist spironolactoneeplerenone)3,9,10or eta blocker(bisoprolol, carvedilol) Grade A, Level 1 ++ Supplementary treatment D ihydropyridine calcium - channel blocker (amlodipine,55,56felodipine Grade

C, Level 2 + Contraindicated Non - dihydropyridine calcium - channel blocker (verapamil, diltiazem) Grade D, Level 4 Angina pectoris Recommended Beta - blocker 5 9 or d ihydropyridine calcium - channel blocker Grade A, Level 1 + Previous myocardial nfarction Recommended BetablockerACE inhibitorARB Grade A, Level 1 Atrial fibrillation, prevention Recommended Beta - blocker , 3,10,11 ACE inhibitor , 3 or ARB 3 Grade B, Level 1 + Atrial fibrillation, ventricular rate control Recommended Betablocker3,11 Grade A, Level 1 Recommended Non - d ihydropyridine calcium - channel blocker 3,11 Grade B, Level 2 ++ Heart block Contraindicated Beta - blocker , 3,11 or n on - d ihydropyridine calcium - channel blocker3,11 Grade B, Level 2 ++ Peripheral artery disease Recommended ACE inhibitor 3 or d ihydropyridine calcium - channel blocker Grade C, Level 2 + Aortic aneurysm Recommended Beta - blocker 3 Grade C, Level 2 + Isolated systolic hypertension Recommended D iuretic , 3,6 4 or d ihydropyridine calcium - channel blocker57,6 Grade A, Level 1 + Diabetes mellitus Recommended ACE inhibitor 6 6 or ARB 6 7 Grade A, Level 1 + Recommended D ihydropyridine calcium - channel blocker 3,6 8 Grade B, Level 2 ++ Supplementary treatment D iuretic 3,6 8 or b eta - blocker 3,11 Grade B, Level 1 + Table Guidelines for selecting drug(s) for antihypertensive treatment Concomitant conditions Status Drugs Grade and level Heart failure Recommended Diuretic , 3,10,11 ACE inhibitor , 52,53 ARB , 54 a ldosterone antagonist ( spironolactone , eplerenone) , 3,9,10 or b eta - blocker (bisoprolol, carvedilol) Grade A, Level 1 ++ Supplementary treatment D ihydropyridine calcium - channel blocker (amlodipine, 55,56 fe

lodipine 57 ) Grade C, Level 2 + Contraindicated Non - dihydropyridine calcium - channel blocker (verapamil, diltiazem) 58 Grade D, Level 4 Angina pectoris Recommended Beta - blocker 5 9 or d ihydropyridine calcium - channel blocker 60 Grade A, Level 1 + Previous myocardial i nfarction Recommended Beta - blocker , 6 1 ACE inhibitor , 6 2 or ARB 6 3 Grade A, Level 1 ++ Atrial fibrillation, prevention Recommended Beta - blocker , 3,10,11 ACE inhibitor , 3 or ARB 3 Grade B, Level 1 + Atrial fibrillation, ventricular rate control Recommended Beta - blocker 3,11 Grade A, Level 1 + Recommended Non - d ihydropyridine calcium - channel blocker 3,11 Grade B, Level 2 ++ Heart block Contraindicated Beta - blocker , 3,11 or n on - d ihydropyridine calcium - channel blocker 3,11 Grade B, Level 2 ++ Peripheral artery disease Recommended ACE inhibitor 3 or d ihydropyridine calcium - channel blocker 3 Grade C, Level 2 + Aortic aneurysm Recommended Beta - blocker 3 Grade C, Level 2 + Isolated systolic hypertension Recommended D iuretic , 3,6 4 or d ihydropyridine calcium - channel blocker 5 5 - 57,6 5 Grade A, Level 1 + Diabetes mellitus Recommended ACE inhibitor 6 6 or ARB 6 7 Grade A, Level 1 + Recommended D ihydropyridine calcium - channel blocker 3,6 8 Grade B, Level 2 ++ Supplementary treatment D iuretic 3,6 8 or b eta - blocker 3,11 Grade B, Level 1 + 36 Table Guidelines for selecting drug(s) for antihypertensive treatment(continue) Concomitant conditions Status Drugs Grade and level Diabetes mellitus with albuminuriamoderatelyor severelyincreased albuminuria) Recommended ACE inhibitoror ARB Grade A, Level 1 Contraindicated Any combination of ACE inhibitor with ARB

Grade A, Level 1 + Previous stroke Recommended Any drug which effectively lowers the BP 3,11 Grade A, Level 1 ++ Asthma & chronic obstructive pulmonary disease Contraindicated Beta - blocker 3,11 Grade B, Level 2 ++ Gout Contraindicated D iuretic 3 Grade C, Level 2 + Bilateral renal artery stenosis Contraindicated ACE inhibitor 3 or ARB 3 Grade B, Level 2 ++ Chronic kidney disease stage 5 (endstage renal failure) Recommended ACE inhibitor 3 or ARB * 3 Grade A, Level 1 + Contraindicated Aldosterone antagonist 10 Grade C, Level 2 + * An ACE inhibitor should not be combined with an ARB in chronic kidney disease 3 (see page 51 ) Consider use of other firstline antihypertensive drug classes onpage 38. 36 Table Guidelines for selecting drug(s) for antihypertensive treatment(continue) Concomitant conditions Status Drugs Grade and level Diabetes mellitus with albuminuria ( moderately - or severely - increased albuminuria) Recommended ACE inhibitor 69 or ARB 70 - 72 Grade A, Level 1 + Contraindicated Any combination of ACE inhibitor with ARB Grade A, Level 1 + Previous stroke Recommended Any drug which effectively lowers the BP 3,11 Grade A, Level 1 ++ Asthma & chronic obstructive pulmonary disease Contraindicated Beta - blocker 3,11 Grade B, Level 2 ++ Gout Contraindicated D iuretic 3 Grade C, Level 2 + Bilateral renal artery stenosis Contraindicated ACE inhibitor 3 or ARB 3 Grade B, Level 2 ++ Chronic kidney disease stage 5 (end - stage renal failure) Recommended ACE inhibitor 3 or ARB * 3 Grade A, Level 1 + Contraindicated Aldosterone antagonist 10 Grade C, Level 2 + * An ACE inhibitor should not be combined with an ARB in chronic kidney disease 3 (see page 51 ) Cons

ider use of other first - line antihypertensive drug classes on page 38. 37 Some combination productsightalso cost less than the total cost of their separate components.Selection of antihypertensive drug within the same class also depends on differences in cost and dosing frequencThe choice of antihypertensive drug should be tailored to the individual patient, taking into account the following factors, in addition to risk profile and cost:ide effectsrugdruginteractions atient preferenceBegin firstline antihypertensive treatment with any one, or an appropriate combination, of the five major drug classes available in Singapore, namely:Angiotensinconverting enzyme inhibitor (ACE inhibitor)Angiotensin II receptor blocker (ARB)Calciumchannel blocker (CCDiuretic (thiazide, thiazidelike, or loop)Betablockerther classes of antihypertensive drugs, such as methyldopa, hydralazine, and alphaadrenergic receptor blockers(peripheral alpha1 blockers such as terazosin; central alpha2 blockers like clonidine) may be used in combination treatment as third or fourthline agents Be aware of the cost of treatmentin selecting antihypertensive drugs.77,78Grade D, Level Generic formulationswhich usually cost less than newer nongeneric (i.e. proprietary) drugsare acceptable for useGrade D, Level 4 38 Do not offer aldosterone (mineralocorticoid) antagonists (e.g. spironolactone) to patients with chronic kidney disease, in particular when combined with an ACE inhibitoror ARB. This isbecause of the risks of further renal functionimpairment, and of hyperkalaemia.3,9An aldosterone antagonist might be considered in patients with resistant hypertension after a full workup has excluded secondary hypertension (Table 4).Grade C, Level 2Recent RCT data indicate that the diuretic and beta-blocker combination drug produces metabolic changes which in

crease the risk of developing diabetes mellitus. Prescribe a diuretic with caution initial treatment in patients with uncomplicated hypertension, who are at risk for diabetes, because it might cause hyperglycaemia.3,9,78 Grade B, Level 2+ beta-blockers with caution in patients at risk of developing diabetes, as it raises blood glucose concentrations79 Grade A, Level 1+Combination therapy Figure 5 below summarises the pairing of the major drug classes.Figure 5Pairing the major drug classes 39 Use the followingdrug combinations to treat hypertensionCalciumchannel blocker (dihydropyridine type) plusACE inhibitoror ARBCalciumchannel blocker plus diureticDiuretic plusACEinhibitoror ARBBetablocker plus calciumchannel blocker (see caveat in Figure 5 aboveblockerplusiuretic(see caveat in Figure 5 above)Grade B, Level 2++There is insufficient evidence thatcalciumchannel blocker plus ACEinhibitor or ARBcombinations produce better cardiovascular outcomethandiuretic plus ACEinhibitor or ARBcombinationsThebetablocker and ACEinhibitor or ARBcombinationsdo not produce synergistic reductions in the . The ACEinhibitor and ARB combination decreases glomerular filtration rate in patients with chronic kidney disease.3,9 Avoid treating patients with ACE inhibitor plusARBcombination, particularly patients who have chronic kidney disease3,9Grade B, Level 1Although effective for lowering , the betablocker and diuretic combination increasethe risk of developing diabetes mellitus. wareincreased risk of diabetes mellitus when offering betablocker plus diuretic combination to patients with riskfactorssuch obesity or metabolic syndromeGrade B, Level 2++ 40 Novel treatments in resistant hypertensionResistant hypertension is defined as an average sustained at 40/90 mmHg despite taking 3 antihypertensive agents at optimal tolerated doses, including a diure

tic. When an aldosterone antagonist is used, it should be in patients with eGFR 45 ml/min,and closer monitoring of the renal function and serum electrolytes is needed if used in combination with an ACE inhibitor or ARB. Before diagnosing ‘resistant hypertension’, it is vital to exclude secondary causes of a raised BP (see Table 4, page 2Despite evidence of effectiveness based on an observational study (Symplicity HTN1) and a randomised, nonshamcontrolled study (Symplicity HTN2), renal sympathetic denervation did not show effectiveness in a randomised, singleblind, shamcontrolled trial (Symplicity HTN. Boththe denervation groupandcontrol groupshowed a significant reductionin 6 months after the procedure 14.1 ±23.9 mmHg in the denervation group, versus.7 ±25.9 mmHg in the shamprocedure group) but there were no additional benefit of renal denervation Do not offer renal sympathetic denervation for routine treatment resistant hypertension.Grade A, Level 1Prolongedbilateralactivation of the carotidsinus baroreceptor reflex baroreflex) inhibits the adrenergic nervous system, thereby lowering the . Electrical stimulation of the baroreceptor reflex effectively decreases the for up to one year in patients with resistant hypertension.However, thelongterm efficacy and safety of carotidsinus baroreceptor flex activationis unknown.Thetechnique is expensive and presently restricted to investigational use Do not offer carotidsinusbaroreceptor reflex activationfor routine treatment of resistant hypertension.Grade B, Level 2++ KEY RECOMMENDATION 41 Treatment goals and follow upTreatment goalsThe primary treatment goal of a patient with hypertension is to achieve the maximum reduction in the total risk of cardiovascular diseaseApart from treating the raised , this goalrequirestheidentification and treatment of all reversible risk factors, suc

h as smoking, raisedserumcholesteroldiabetes, and the management of associated clinical conditionsThe greater the risk profile,the more rigorous the control should be. For most patientsthe goal of antihypertensive treatmentshould be to reduce the to 140/90 mmHg. The recommended target treatment levels are140/90 mmHg in patients aged under 80 years150/90 mmHg inpatients aged 80 years or olderfragileelderlyindividualsthesystolic goalsshouldadaptedindividualtolerability.Grade A, Level 1he el attainable with treatment is influenced by medication side effects and other comorbidities, such as cerebrovascular disease. Good clinicaljudgmentshould therefore be exercised for every patientFigure 6 below summarises the clinic BP targets for different conditions Figure 6Flowchart for clinic blood pressure targePresence of condition*Target blood pressure*If 2 conditions exist in the same patient, the condition that is mentioned first will determine the level. Clinic BPcontrol should be optimised for individual patients to achieve the targets without worsening the eGFR and cardiovascular outcomes. Well patients above 80 years tolerating treated BP 150/90 do not necessarily require treatment alteration. Home target will be the lower of either 135/85 mmHg, or the clinic BP target as determined above.FollowFollowup during evaluation and stabiliation of treatment should be sufficiently frequent to monitortheand othercardiovascularrisk factors (Table , page 43 Table Frequency of recommended tests/actions4,5,12,7Grade C, Level 2* Goal achieved. Patients with the following problems should be referred to a hypertension specialist or clinic:Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heartfailureor other impending complicationsHypertension that is difficult to managee.g. unusually labile or hypertension re

fractory to multiple drugs in different pharmacologicalclasseSecondary hypertensioni.e. hypertension due to an underlying cause, such as hyperaldosteronismHypertension in special circumstancese.g. pregnancy, and young childrenGrade D, Level 4 Recommended test/action Recommended frequency BP monitoring Risk level* Low added risk Medium to very high risk monthly to annually to 6monthly BMI Fasting glucose Fasting lipid profile Serum electrolytes, urea, creatinine Urine - albumin measurement Annually or more frequently , as per individual risk profile ECG As per individual risk and cardiac profile Patient education Lifestyle modification and Medication adherence At each visit 44 Treating high blood pressure in special conditionsType 2 diabetes mellitustreatment targets For patients with type 2 diabetes mellituswho have hypertensionan acceptable treatment target is below140/80 mmHg.Grade B, Level 2 ACE inhibitor, ARB, or calciumchannel blockerfirstline treatment in patientwith diabetes without chronic kidney disease or proteinuria.Grade A, Level 1The new recommendation of range140/80 mmHg for patients with type 2 diabetes mellitusdiffers from the previous CPGtarget of 130/80 mmHg. While lowering treatment is strongly recommended in patients with diabetes when systolic BP is 40 mmHg, the results from a 2011 metaanalysis of RCTsof targets in subjects with type 2 diabetes and impaired fasting glucosesuggest that most of the beneficial reductionin allcause mortality in the intensivetreatmentgroup(systolic 140 mmHg)occurred in trials in whichthe intensive grouphad achieved a systolic BPbetween 130 and 135 mmHg. For the outcomes of cardiovascular mortality, myocardial infarctionand heart failure, although there was no statistical difference between the two groups, the point estimatefavouredthe intensivegroup,

again mainly driven by trials which achieved systolic BP between 130 and 135 mmHg. Neither the INVEST study nor thACCORD study showany improvement in cardiovascular outcomes in the intensive contro KEY RECOMMENDATION KEY RECOMMENDATION group(systolic 130 mmHgin INVEST and 120 mmHg in ACCORDcompared tothe usualcontrol group(systolic between 130 and 139 mmHg).In the ACCORD trial, targetingsystolic mmHgdid not improve cardiovascular benefitbutthere were significantly more adverse eventsincluding hypotension and renal impairment.The metaanalysis results showed thatnlyforthe outcome ofstroke, the intensive treatment group with systolic BP ≤130 mmHg obtained greater benefitcompared to standard control groupandthe group treated to systolic between 130 and 135 mmHg.Results from ACCORD and ONTARGET studies also showed improvement in stroke outcomes where the systolic BP was 130 mmHg.Weighingthe above evidence, it is reasonable to recommendfor mostpatienwith type 2 diabetestarget systolic between 130 andmmHg.Lower systolic targets might be appropriate in younger patients who are at low risk from the adverse consequences of achieving these targets. If a particular patient is atgreater riskforischaemicstroke than forother cardiovascular outcomes,a lower systolic target of 130 mmHg can be consideredHowever, the risk of more adverse events with a lower target needs to be discussed with the patient.In contrast, the existence of a Jcurve has been investigated for diastolic becausea critical zoneof diastolic is believed to be particularly important for maintaining coronary artery blood flow. The INVEST study showed that the hazardratio nadir in diastolic for both primary and secondary outcomes across age groups was between 70 and 80 mmHg.Furthermore, an analysis of both the baseline and onstudy the VADTstudy subjects showed a higherrisk for the pr

imary composite cardiovascular endpoint in patients with a diastolic lower than mmHg.Thus, based on current evidence, an acceptable target diastolic is 0 mm Hg. 46 Prioritising specific classes of antihypertensive drugsIn diabetic patients with severelyincreased albuminuria (formerly ‘macroalbuminuria’), hypertension is treated with an ACE inhibitor11,6or an ARB.10,11,The two classes of reninangiotensinaldosterone (RAAS) blockerare also useful in patients with moderatelyincreased albuminuria (formerly ‘microalbuminuria’), although the benefit of RAASblockade on kidney disease progression in suchpatients is unproven.In patients without increased albuminuria,3,10,11monotherapy can start withan ACE inhibitor, ARB,calciumchannel blocker(e.g. amlodipine), or a thiazide diuretic. Many experts, however, would select an ACE inhibitor or an ARB in these patients because theseRAASblockers can prvent albuminuria, whilethiazidediuretics increase blood glucose levels(Table If 2 drugs are needed, combine acalciumchannel blocker with an ACE inhibitor. an ACE inhibitor is not tolerated, thencombinthe calciumchannel blocker with an ARB.Diabetic nephropathy Optimised control is recommended to reduce the riskor slow the progression, ofdiabetic nephropathy100,101Grade A, Level 1 Treat patients with diabetic nephropathy to a target belowmmHg systolic ,10,10Grade A, Level 1 KEY RECOMMENDATION KEY RECOMMENDATION 47 If diabetic nephropathy patient has severe albuminuria (equivalent to urinary albumin:creatinine ratio (ACRmore than 30mg/mmol, or urinary PCR more than 50mg/mmol), consider target below130 mmHg systolic BP provided GFR changes are monitored carefully,10,10Grade B, Level 2 Treat diabetic chronic kidney disease patients with moderate albuminuria (urinary ACR 330 mg/mmol, or urinary PCR between 1550 mg/mmol) to a target BP equ

al to orbelow0 mmHg.Grade D, Level 4In patients with diabetes, largescale randomised clinical trials have consistently shownthe benefits of loweringincident nephropathydefined as the progression of albuminuria or worsening of serum creatinine, or bothThere is sufficient evidence folowering thebelow 140/90 mmHin most patients with diabetic nephropathy. Recent evidence shows that lowering to 130/80 mmHg in patients with diabeticnephropathy and preexisting CADpotentially harmful,10,10However, the recommendation to aim for a lower BP of 130/80 mmHg in diabetic nephropathy patientswith severealbuminuria (equivalent to urinary ACR more than 3mg/mmol, or urinary PCR more than mg/mmol) was supported by a To decrease the risk or slow the progression of nephropathy, a target130/80 mmHg appears reasonable. When moderate to severealbuminuriais present, systolic values Hg can be pursued, aimingto slow the progression of kidney disease, provided that changes in eGFR are monitored. The evidence for this recommendation is extrapolated from RCTs and from systematic review of patients with nondiabetic nephropathy.,10,10There are insufficientdata to specify a diastolic target. KEY RECOMMENDATION 48 However, the extent of reductionintending toretard the progression of diabetic nephropathy, needsto be weighed against potential cardiovascular harms in highrisk patients. an ACE inhibitor or ARBas firstline treatment,whenevertreatment with lowering drugs is indicatedin diabetic nephropathy.Grade A, Level 1 In diabetic nephropathy, if one classof RAASblocker(either ACEinhibitoror ARB) is not tolerated, replace it with the other classGrade D, Level 4 Combination treatmentwith both an ACE inhibitor and an ARBshould not be routinein diabetic nephropathy.10,10Grade A, Level 1 When ACE inhibitors, ARBs, or diuretics are usedin diabetic nephropathy, it is reco

mmended to monitor the serum creatinine and potassium levels for thepossibledevelopment of acute kidney injuryand hyperkalemia.Grade D, Level KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION 49 Betablockers, calciumchannel blockersand thiazides are all appropriate secondline therapyin diabetic nephropathy., 50Grade A, Level 1control in diabetic nephropathyoften requires combination therapy. Due to the greater effect of RAASblockers on urinary protein excretioncombination is recommended to include either an ACE inhibitors or an ARB. Althoughconcurrentadministration of an ACEinhibitorand an ARB can further decreaseproteinuria, prescribingtwo RAASblockerstogethercannot be routinely recommended in highrisk patients because of the increased risks of hyperkalemia and renal dysfunction, asreported in ONTARGET.,10Thiazide and thiazidelike diuretics are often used together with RAASblockerto control the and to attenuate hyperkalemia. Calciumchannel blockershave been shown to be useful, especially when combined with RAASblocker. The ndihydropyridine lcium blockererapamil anddiltiazemhave consistently greaterantiproteinuric effects in proteinleaking patientscompared to dihydropyridine CCBs, according to metaanalysis of 2randomisedtrials.The likely explanation liein the differentefficaciesof the nondihydropyridineand dihydropyridine blockers inaltering theautoregulation of renal blood flow. However, in practice, so long as the calciumchannelblocker is used together with either an ACE inhibitoror an ARB, the differencein protein excretionbetween calciumchannel blocker subclasses vanishesdiabetic chronic kidney diseaseHypertension is a risk factor for the development and progression of chronic kidney disease.Conversely, chronic kidney diseases a majorisk factor for cardiovascular disease. Treatinghypertensioncan

slow the progression of proteinuric chronic kidney diseasemoderate to severealbuminuriaequivalent to urinary ACR more than mg/mmol, or urinary PCR more than mg/mmoland reduce the rate of cardiovascular complications.s suggest that maintained ator below 130/80 mmHg retards theprogression of proteinuric chronic kidney disease 50 BothACE inhibitorsand ARBs have been shown to decreaseurinaryalbumin levels.In RCTspatients with severelyincreased albuminuria,both ARBs and ACE inhibitors significantly lowerthe risks of adverse renal outcomes. Treat nondiabeticnonproteinuric chronic kidney disease patients a target below140/90 mmHg.Grade , Level 1 Treat nondiabetic chronic kidney disease patient with severe albuminuria to a target equal to or below 130/80 mmHg.Grade A, Level 1+ Treat nondiabetic chronic kidney disease patients with moderate albuminuria to a target BP equal to orbelow0 mmHg.106Grade D, Level 4 either an ACE inhibitor or an ARB as the firstline drug whenever treatment with lowering drugs is indicated in nondiabetic chronic kidney disease patients.Grade A, Level 1+ Combination treatmentwith both an ACE inhibitor and an ARB should not be routinely prescribedin nondiabetic chronic kidney disease patients.Grade A, Level 1+ KEY RECOMMENDATION KEY RECOMMENDATION 51 Heart failureHeart failure with reduced ejection fractionBetablockers are useful for control in combination therapy, in particularin patients with CADand heart failure.In patients with systolic heart failure(also known as heart failure with reduced ejection raction), the appropriate BP lowering drug classes are ACE inhibitorARBbetablocker,3,11and aldosterone antagonist0,1or appropriacombinationthereofwhich improve survival(Table ). Diuretics, including loop diuretics (e.g. furosemide, bumetanide) or thiazide/thiazidelike drugs are given torelieve heartfailure symp

toms and fluid retention.10An ACE inhibitoror ARB, or a betablocker is particularly useful in hypertensive patients ith atrial fibrillation.betablocker is also helpful in those with exertional angina.Of the dihydropyridine calciumchannel blockersamlodipine5,5and felodipineare well tolerated in systolic heart failure, but should probably constitute supplementary treatment, because they do not increase survival, effort tolerance, or the quality of life5,57,5Nondihydropyridine calciumchannel blockers increase the risk of worsening HF and of hospital care therefrom.StrokeLowering ofin acute strokeBoth extremely high andextremelylow areassociated with poor outcomeduring the earlyphase of acuteischaemicstroke.A high BP decreasesspontaneously byabout20/10 mmHg in patients with acuteischaemicstroke within the first ten days of hospital stay Where systolic BP is above 140 mmHg but below 220 mmHg within the first two weekof onset of acute ischaemic stroke, lowering of high should be based on individual clinical judgmentafter careful consideration of all the contraindicationsGrade A, Level 1++ KEY RECOMMENDATION 52 According to randomised trials, the owering of high with antihypertensive drugswithin the first two weekafter theonset of acute stroke does not significantly improve thefunctional outcome.Generally, the patients who were enrolled in thesetrials had mild stroke, and patientwith severe cerebrovascular stenosis and impaired consciousness were usually excluded. It is reasonable to lower, with care, a markedly elevated (systolic above20 mmHg or diastolic above20 mmHg, or both) by 10% to15% during the first 24 hours after the onset of acuteischaemicstroke.Grade D, Level 4During the first 24 hours after stroke onset, atargeted reduction in BP by 10%15% from baseline pressure is inadequate for a stroke patient who has receivedfibrinolytic

(thrombolyticagent, or who has hypertensive encephalopathy, aortic dissection, acute renal failure, acute myocardial infarction, acute pulmonary edema, or any combination thereofstroke patientwith these comorbiditiesthelowered more rapidlybelow 180/110 mmHgif their initial systolic BP� 220 mmHg or diastolic BP� 120 mmHg, before specific treatment begins.The rate of reduction would depend on the specific comorbiditiesLowering ofafter transient ischemic attackand after acute phaseof stroke fter the acute phaseof stroke, begin antihypertensive treatment in hypertensive patients if the systolic is more than 140 mmHg and diastolic is more than 90 mmHg.,12Grade D, Level 4 KEY RECOMMENDATION KEY RECOMMENDATION 53 Use any of the fivemajor pharmacological classes of antihypertensive drugfor stroke prevention in patients aftertheacute phasestroke, provided that the is effectively lowered.21,7Grade A,Level 1 The target level in patients after transient ischemic attack and after acute phasestroke should be individualised,with careful consideration of medical comorbidities. A lower systolic target might benefit a patient who has small vessel disease, but might harm a patient with severe cerebrovascular stenosis.The lowering of the with antihypertensive drugs after the acute phaseof stroke in both normotensive and hypertensive patients decreases recurrent stroke and other vascular events.Some internationalguidelines recommendbeginningtreatment for patients withischaemicstroke, in whom the systolic is 40 mmHg and diastolic is 0 mmHg.A reduction of 10/5 mmHg from baseline BP has been shown to preventvascular events in stroke patientsThe absolute target level is uncertain. There is preliminary evidence showing that a lowsystolic benefits patients with strokewhich is dueto small vessel disease,but harmsthose with stroke associat

ed with severe cerebrovascular stenosis.,12Metaanalyses of RCTsuggest that all five majorpharmacologicalclasses of antihypertensive drugs are appropriatefor stroke prevention, provided thattheeffectively decreas21,7(see 7.2.2above)PregnancyHypertension in pregnancy is defined by a systolic BP of 140 mmHg or greater, diastolic BP of 90 mmHg or greater, or both. High before pregnancy or that which occurs in the first half of pregnancy is called chronic (primary) hypertension. Primary care physicians should refer to specialist for treatment in pregnancy if hypertension is classified as chronic hypertension with superimposed preeclampsia, preeclampsia/eclampsia and gestational hypertension. KEY RECOMMENDATION 54 Even though the classification of mild, moderate and severe hypertensionby levelis different in pregnancy, pharmacological treatmentis recommended pregnant women with chronic hypertensionwho havepersistently elevated systolic of 1mmHg or greateror diastolic of 10mmHg or greaterGrade D, Level 4 Avoid aggressiverates oflowering of in pregnant women with chronic hypertensionbecause of the potential risk ofcompromisingthe uteroplacental blood flow. n pregnant women ith no target organ damageanduncomplicated chronic hypertensionaim to keep the BPbelow150/100mmHg.Grade D, Level 4 In pregnant women with target organ damage secondary to chronic hypertension, aim to keep the BPbelow 140/90mmHgGrade D, Level 4 In pregnant women with uncomplicated chronic hypertensiondo not use drug treatment to decrease thediastolic BP tobelowmmHg.Grade D, Level 4 reat pregnant women with chronic hypertension usingmethyldopa, labetalolnifedipine, or a combination thereofGrade D, Level 4 Methyldopa, labetolol, and nifedipineare also considered safe for use during breastfeeding postpartum. 55 Diuretics of all types are less often used during pregn

ancybecause of possibleconcerns about depletion of the intravascular volume; they mightalso reduce the quantity of milk production postpartum.In particular, for hydrochlorothiazide, there mightbe an increased risk of congenital abnormality and neonatal complications if taken during pregnancy ACEinhibitors, ARBdirect renin inhibitors(e.g. aliskiren),and aldosterone antagonists should be avoided during pregnancy.Grade D, Level 4Elderly patient elderly hypertensive patients whose systolic is 160 mmHg or higher, the should be reduced to below150/90 mmHg.3,10,11,37,1Grade A, Level 1 patientsunder the age of 80 years with good physical and mental status, systolic can be lowered to below140 mmHg if treatment is well tolerated.3,10,11Grade B, Level 2++An elevated systolic is common in the elderlyand is termed isolated systolic hypertension. Arterial compliance decreaseswith advancing age,and thischangeproducesa gradual rise in the systolic and a fall in the diastolicA wide pulse pressure is strongly associatedwith an increase incardiovascularand cerebrovascular eventsand withheart failure.RCTshave shown the benefits of treating isolated systolic hypertension across a wide age range.In patients over the age of 80 years, a recent metaanalysis of antihypertensive drug treatment concluded that combined fatal and nonfatal cardiovascular events decreasedsignificantlybut allcause mortality didnot. KEY RECOMMENDATION 56 Themanagement of hypertension in the elderly followthe same general guidelines, but begin drug treatment gradually, especially in the frail elderly. On starting drug treatment, carefully consider the patients’ associated clinical conditions.Grade A, Level 1Various classes of drugs (ACE inhibitors, ARB, betablockers, calciumchannel blockers and diuretics) have been shown in s to be effectiveand beneficial in elderlypatient In

elderly patients with isolated systolic hypertension, consider using calciumchannel blockers and diureticsGrade B, Level 2+Similar toother patients, many elderly patients require two or more antihypertensive drugs to achieve good control. Consistent control of the diastolic is difficultand the optimum range of the treated diastolic needs further clarification. The current impression is that the diastolic pressure should not be allowed to fall below 60 mmHgparticularlythose with known CAD, becauseimpaired coronary artery filling at extremely low BP levels mightincrease the risk of coronary events. n the elderlymeasure BP often in the supine (or sitting) position and standing position to detect postural dropin the Take care to avoid fluid depletion and electrolyte imbalance in the elderly. KEY RECOMMENDATION KEY RECOMMENDATION KEY RECOMMENDATION 57 Treatment of associated risk factorsCholesterol lowering and antiplatelet therapy Take into accountthe use of other drugs that decreascardiovascular risk, such as lipid regulating drugs and antiplatelet drugs, in hypertensive patients with concomitant risk factors and increased cardiovascular risk.Grade A, Level 1++In patients with high serum cholesterol level, there arebenefitsfor cholesterol lowering treatment regardless of the level. Therefore, the use of lipid regulating drugsis recommended for hypertensive patients who have elevated serum cholesterol levels, aiming in particular to decrease serum lowdensity lipoprotein cholesterolIn patients with a history of CADor cerebrovascular disease, there is evidence that aspirin and some other antiplatelet agents (e.g. clopidogrel, prasugrel, and cagrelor) can decrease cardiovascular risks.4,19,1Antiplatelet drug treatmentshould also be considered in some patients in the high risk categories (Table , page ) who already have satisfactory

control. 58 Clinical quality improvementThe recommended target evels in antihypertensive treatment areBelow 140/90 mmHg in patients aged under 80 yearsBelow 150/90 mmHg in patients aged 80 years or more10,11In elderly patients aged under 80 years with good physical and mental statusif treatment is well toleratedhe ultimate objective of managinghypertension is not to lowertheper sebut to decrease the patientsoverallrisks of morbidity and mortality. These risks are also influenced by other coexisting cardiovascular disease risk factors. The greater thetotal cardiovascular diseaserisk, the more rigorousthe should be controlHowever, the level attainable with antihypertensive treatment influenced by medication side effects and other comorbidities, such as diabetes, chronic kidney diseaseCADand cerebrovascular disease. Good clinical judgmentshouldthereforebe exercised in every patientThe schedules shown in Table (page arerecommended to allow patients and healthcare providers to optimise thequality of care.ach patient should be managedappropriateaccording to theassessed risk level. 59 ReferencesMacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, etal. Blood pressure, stroke, and coronary heart disease. The Lancet. 1990; 335:765Epidemiology and Disease Control Division Ministry of Health Singapore. National Health Survey 2010 Report.Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of Hypertension. 2013; 31:1281obanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood ressure. Hypertension. 2003; 42:1206Guidelines S

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in hypertensive chronic kidney disease. New EnglandJournal of Medicine. 363:918Peterson JC, Adler S, Burkart JM, et al. Blood pressure control, proteinuria, and the progression of renal disease: The modification of diet in renal disease study. Annals of Internal Medicine. 1995;123:754Lv J, Ehteshami P, Sarnak MJ, et al. Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and metaanalysis. Canadian Medical Association Journal. 2013;185:949CooperDeHoff RM, Gong Y, Handberg EM, et al. Tightblood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. The Journal of the American Medical Association. 2010;304:61The ACCORD Study Group. Effects of intensive bloodpressure control in type 2 diabetes mellitus. New England Journal of Medicine. 2010;362:1575Redon J, Mancia G, Sleight P, et al. Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the TARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). Journal of the American College of Cardiology. 2012;59:74UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. British Medical Journal. 1998;317:703Patel A. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. The Lancet. 370:829 Berl T, Hunsicker LG, Lewis JB, et al. Impact of achieved blood pressure on cardiovascular outcomes in the irbesartan diabetic nephropathy trial. Journal of the American Society of Nephrology. 2005;16:2170Haller H, Ito S, Izzo JL, et al. Olmesartan for the delay or prevention of microalbum

inuria in type 2 diabetes. New England Journal of Medicine. 364:907Sarnak MJ, Greene T, Wang X, et al. The effect of a lower target blood pressure on the progression of kidney disease: Longterm followup of the modification of diet in renal disease study. Annals of Internal Medicine. 142:342Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review: Blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Annals of Internal Medicine. 2011;154:541Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements. 2013; 3The ONTARGET Investigators. Telmisartan, Ramipril, or both in patients at high risk for vascular events. New England Journal of Medicine. 2008;358:1547Krause MW, Fonseca VA, Shah SV. Combination inhibition of the reninangiotensin system: is more better? Kidney International. 2011;80:245Bakris GL, Weir MR, Secic M, Campbell B, WeisMcNulty A. Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney International. 2004;65:1991OliveiraFilho J, Silva SCS, Trabuco CC, Pedreira BB, Sousa EU, Bacellar A. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology. 2003;61:1047Castillo J, Leira R, García MM, Serena J, Blanco M, Dávalos A. Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke. 2004;35:520Ahmed N, Wahlgren G. High initial blood pressure after acute stroke is associated with poor functional outcome. Journal of Internal Medicine. 249:467Wallace JD, Levy LL. Blood pressure after stroke. The Journal of the American MedicalAssociation. 1981;246:2177He J, Zhang Y, Xu T, et al. Effects of immediate blood p

ressure reduction on death and major disability in patients with acute ischemic stroke: The CATIS randomized clinical trial. The Journal of the American Medical sociation. 2014;311:47989. Sandset EC, Bath PMW, Boysen G, Jatuzis D, Kõrv J, Lüders S, et al. The angiotensinreceptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebocontrolled, doubleblind trial. The Lancet. 2011;377:741Robinson TG, Potter JF, Ford GA, et al. Effects of antihypertensive treatment after acute stroke in the Continue Or Stop postStroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blindedendpoint trial. The Lancet Neurology. 2010;9:767Potter JF, Robinson TG, Ford GA, Mistri A, James M, Chernova J, et al. Controlling hypertension and hypotension immediately poststroke (CHHIPS): a randomised, placebocontrolled, doubleblind pilot trial. The Lancet Neurology. 2009;8:48Schrader J, Lüders S, Kulschewski A, Berger J, Zidek W, Treib J, et al. The ACCESS Study: Evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke. 2003; 34:1699Bath PM, Krishnan KInterventions for deliberately altering blood pressure in acute stroke. Cochrane Database of Systematic Reviews. :CD000039.Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke: A guidelinefor healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:870Katz JN, Gore JM, Amin A, et al. Practice patterns, outcomes, and endorgan dysfunction for patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension (STAT) Registry. American heart journal. 2009;158:599606.e1.Go AS, Bauman MA, Coleman King SM, et al. An effective approach to high blood pressure control: A science advisory from the American HeartAssociat

ion, the American College of Cardiology, and the Centers for Disease Control and Prevention. Journal of the American College of Cardiology. 2014;63:1230Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014; 45:2160236.Rashid P, LeonardiBee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: A systematic review. Stroke. 2003; 34:2741 The SPS3 Study Group. Bloodpressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. The Lancet. 2013;382:507YamauchiH, Higashi T, Kagawa S, Kishibe Y, Takahashi M. Impaired perfusion modifies the relationship between blood pressure and stroke risk in major cerebral artery disease. Journal of Neurology, Neurosurgery & Psychiatry. 2013;84:1226Rothwell PM, Howard SC, Spence JD, Carotid Endarterectomy Trialists’ Collaboration. Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease. Stroke. 2003;34:2583NICE. The management of hypertensive disorders during pregnancy. NICE clinical guideline 107: National Institute for Health and Clinical Excellence 2010.MacMahon S. The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Clinical and Experimental Hypertension. 1993;15:967Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: metaanalysis of outcome trials. The Lancet. 2000;355:865Chae CU, Pfeffer MA, Glynn RJ, Mitchell GF, Taylor JO, Hennekens CH. Increased pulse pressure and risk of heart failure in the elderly. The Journal of the American Medical Assoc

iation. 1999;281:634Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup metaanalysis of randomised controlled trials. The Lancet. 1999;353:793Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension2 study. The Lancet. 1999;354:1751Gong L, Zhang W, Zhu Y, et al. Shanghai trial of nifedipine in the elderly. Journal of Hypertension. 1996;14:1237Liu L, Wang JG, Gong L, Liu G, Staessen JA, Systolic Hypertension in China Collaborative Group. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Journal of Hypertension. 1998;16:1823Sever PS, Dahlöf B, PoulterNR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lowerthanaverage cholesterol concentrations, in the AngloScandinavian Cardiac Outcomes TrialLipid Lowering Arm (ASCOTLLA): a multicentre randomised controlled trial. The Lancet. 2003;361:1149 Roberts JM, August PA, Bakris GL, et al. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstetrics & Gynecology. 2013;122:1122 72 Selfassessment (MCQs)After reading the Clinical Practice Guidelines, you can claim one CME point under Category 3A (SelfStudy) of the SMC Online CME System. Alternatively, you can claim one CME point under Category 3B (Distance Learning Verificable SelfAssessment) if you answer at least 60% of the following MCQs correctly. You can submit your answers through the SMJ website at this link: http://sma.org.sg/publications/index.aspx?ID=26(the link will only be available once the January issue of the SMJ becomes available). The answ

ers will be published in the SMJ March 2018issue and at the MOH webpage for these guidelines after the period for submitting the answers is over.Instruction: Choose True or False for each statement. True False 1 . With regards to diagnosis of hypertension A. Patient s with a 24 - hour ABPM are regarded as hypertensive if the average is ≥135/85 mmHg.It has been estimated that antihypertensive treatment, on average, reduces stroke by 35If 165/95mmHg we should grade the hypertension as Grade 2.The cardiovascular risks rise exponentially for BP between 140/90 and 220/120 mmHg; the urgency of treatment is therefore guided by the grade of measured BP 2. With regards to evaluation and prognostic factors of hypertension, A. One of the objectives of the clinical and laboratory evaluation of the hypertensive patient is to look for target organ damage.Urine analysis should be part of routine clinical evaluation.Central aortic pressure should be part of routine evaluation in a hypertensive patient.Chronic sleep deprivation syndrome is a common secondary cause of hypertension 73 3 . With regards to lifestyle modifications and non - p harmacotherapy, A. Salt (sodium chloride) restriction up to 5 - 6 g a day is strongly recommended in those with ypertension.Regular dynamic (ie aerobic) exercise on at least 5 days a week, whether as single or interrupted pisodes of 30 minutes or longer, confers both cardiovascular and overall health benefits, beyond a reduction in the Lifestyle modifications are not required inpatients whose average is in the high normal range of 130139 / 8589 mmHg.Cessation of tobacco smoking confers major benefit in terms of reduction, as well as

avoiding coronary arterydisease and other serious systemic disorders. 4 . The following two - drug antihypertensive combinations decrease the BP (BP) beyond the amount obtained by adding together the individual drugeffects on the A. Atenolol plus lisinopril. Amlodipine plus valsartan.Carvedilol plus indapamide.Enalapril plus losartan. 5. With regards to treatment in various conditions: A. In treatment of Type 2 diabetes mellitus, an acceptable treatmentinitiation and target is 40/80 mmHg.In lowering of for secondary prevention of stroke, the threshold for starting antihypertensive therapy is 40/90 mmHg. In treatment during pregnancy, initiation of pharmacological treatment is recommended for pregnant women with chronic hypertension if the is more than 140/90 mm Hg. Elderly patients above age 80years with isolated systolic hypertension should have their systolic reduce d to 40mmHg. 74 Workgroup membersThe members of the workgroup, who were appointed in their personal professional capacity, are:ChairmanA/Prof Tay Jam ChinSenior ConsultantDepartmentof General Medicine IITan Tock Seng HospitalMembers (in alphabetical order) Dr Ashish Anil Sule Senior ConsultantDepartment of General MedicineSubVascular Medicine and HypertensionTan Tock Seng Hospital Dr Daniel Chew Senior Consultant and Head Department of EndocrinologyTan Tock Seng HospitalDr Jeannie TeyDeputyDirector (NonCommunicable Diseases) Epidemiology & Disease ControlDivision, Ministry of Health Dr Titus LauSenior Consultant Department of MedicineDivision of NephrologyNational University Hospital Dr Simon Lee Family Physician, ConsultantChief Operating Officer and

Chief Medical Informatics OfficerNational Healthcare Group PolyclinicsDr Lee Sze Haur Senior Consultant Department of Neurology National Neuroscience Institute Dr Leong Choon KitFamily PhysicianMission Medical Clinic A/Prof Lim Soo TeikDeputy Medical Director,Senior Consultantmentof Cardiology;Director of the Cardiac Catherisation LaboratoryNational Heart CentreDr Low Lip Ping Low Cardiology ClinicMount Elizabeth Medical Centre Members (in alphabetical order) Prof Vernon Oh Min Sen Senior Consultant PhysicianDepartment of Medicine Yong Loo Lin School of MedicineNational University HospitalDr Ian PhoonFamily PhysicianSingHealth PolyclinicsDr Kenneth Tan Kian WeeMedical OfficerPrimary and CommunityCare Ministry of Health Dr Akira Wu Renal PhysicianWu Nephrology & Medical ClinicMt Elizabeth Medical CentreMs Yeo Loo SeeDeputy DirectorNursing ServicesNational Healthcare Group PolyclinicsSubsidiary editors:Ms Elaine TeoDeputy Director(Health Technology Assessment/ Utilisation Management ReviewClinical Quality, Performance & Technology DivisionMinistry of HealthDr Pwee Keng HoConsultant(Health Technology Assessment)Clinical Quality, Performance & Technology DivisionMinistry of HealthMr Muhammad FaridSenior Manager (Utilisation Management ReviewClinical Quality, Performance & Technology Division Ministry of Health 8 No. Recommendation Grade, Level of Evidence CPG page no. 44 Patients with the following problems should be referred to a hyp ertension specialist or clinic: 1. Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heart failure, or other impending complications 2. Hypertension that is difficult to manage, e.g. unusually labile BP, or hypertension refractory to multiple drugs in different pharmacological classes 3. Secondary hypertension, i.e. hy

pertension due to an underlying c ause, such as hyperaldosteronism 4. Hypertension in special circumstances, e.g. pregnancy, and young children. Grade D, Level 4 43 Treating high blood pressure in special conditions No. Recommendation Grade, Level of Evidence CPG page no. Type 2 diabetes mellitus 4 5 For patients with type 2 diabetes mellitus who have hypertension , an acceptable treatment target BP is below 140/80 mm Hg. Grade B, Level 2 + 4 4 4 6 Use ACE inhibitor, ARB, or calcium - channel blocker as first - line treatment in patients with diabetes without chronic kidney disease or proteinuria. Grade A, Level 1 + 4 4 4 7 Optimised BP control is recommended to reduce the risk , or slow the progression , of diabetic nephropathy . Grade A, Level 1 + 4 6 1 List of recommendations Details of recommendations appear in the main text at the pages indicated . The key recommendations are highlighted in brown . C lassification of hypertension No. Recommendation Grade, Level of Evidence CPG page no. 1 Classify hypertension according to systolic BP and diastolic BP levels. When the systolic BP and the diastolic BP fall into different categories, the higher category applies . Grade D, Level 4 1 8 Measuring blood pressure No. Recommendation Grade, Level of Evidence CPG page no. 2 Use the following procedures when recording BP: 1. Allow the patient to sit or lie down for at least 3 minutes before measuring the BP. 2. The patient should refrain from smoking or taking caffeinated drinks during the 30 minutes before measurement. 3. Use a cuff with a bladder 12 - 13 cm x 35 cm in size. A cuff with a larger bladder should be used for larg e upper arms; where a thigh cuff should be

used for extremely large arms. 4. When using the auscultatory method, use the disappearance of phase V Korotkoff sounds to measure the diastolic BP. 5. Measure the BP in both arms at the first visit; subsequently re - mea sure BP on the arm with the higher reading, if applicable . 6. Take 2 or more readings separated by 2 minutes. Average these two values. If the first two readings differ by 5 mmHg or more, further readings should be obtained and averaged. Grade D, Lev el 4 19 5 No. Recommendation Grade, Level of Evidence CPG page no. 22 Increase the consumption of vegetables, fruits, low - fat dairy products, and decrease the intake of saturated and total fats. Grade A, Level 1 + 3 1 23 Unless contraindicated, advise patients to reduce weight to a body mass index (BMI) below 23 kg/m 2 and to a waist circumference below 90cm in men, and below 80cm in women (for Asians). Grade B, Level 2 + 3 1 24 Advise patients to do at least 30 minutes of moderate dynamic exercise 5 to 7 days per week. Any physical exercise above the basal level , up to 150 minutes/week, confers incremental cardiovascular and metabolic benefits, including BP reduction. Grade A, Level 1 + 3 2 25 A dvi s e and offer assistance to all smokers to quit smoking . Grade A, Level 1 + 3 2 Pharmacological treatment 26 Begin appropriate combination treatment in patients whose pretreatment BP is rais ed ( i.e. �t 1 4 0/ 9 0 mmHg) , and specifically in patients whose BP is severely raised ( �t 180/110 mmHg), as they will require two or more drugs for adequate BP control. Grade B, Level 2 + 3 3 27 Initiate treatment at low doses of drugs, either singly or as a two - drug combination, to minimise side effects.

Grade D, Level 4 3 3 28 If an adequate dose of the first drug used demonstrated limited response or was poorly - tolerated , change to a different drug class instead of increasing the dose of the first drug. Grade A, Level 1 + 3 3 29 Add a second drug when a single drug fails to achieve target BP. Grade B, Level 1 + 3 4 6 No. Recommendation Grade, Level of Evidence CPG page no. 30 Use long - acting drugs which provid e 24 - hour efficacy daily. Grade B, Level 2 + 3 4 3 1 In hypertensive patients without compelling indications or contraindications for any particular drug, consider any one, or an appropriate combination, of the five major classes of drugs as the initial treatment. Grade B, Level 2 + 3 4 32 Take compelling indications and contraindications into account when prescribing an antihypertensive drug (Table 7 ). Grade A, Level 1 + 3 4 3 3 Be aware of the cost of treatment in selecting antihypertensive drugs. Grade D, Level 4 3 7 3 4 Generic formulations which usually cost less than newer non - generic (i.e. proprietary) drugs are acceptable for use . Grade D, Level 4 3 7 3 5 Do not offer aldosterone (mineralocorticoid) antagonists (e.g. spironolactone) to patients with chronic kidney disease (eGFR 45 ml/min) , in particular when combined with an ACE inhibitor or ARB . This is because of the risks of further renal function impairment, and of hyperkalaemia. An aldosterone antagonist might be considered in patients with res istant hypertension after a full work - up has excluded secondary hypertension (Table 4). Grade C, Level 2 + 3 8 3 6 Prescribe a diuretic with caution as initial treatment in patients with uncomplicated hypertension , who are at risk for diabetes,

because it might cause hyperglycaemia . Grade B, Level 2 + 3 8 3 7 U s e beta - blockers with caution in patients at risk of developing diabetes , as it raises blood glucose concentrations . Grade A, Level 1 + 3 8 6 No. Recommendation Grade, Level of Evidence CPG page no. 30 Use long - acting drugs which provid e 24 - hour efficacy daily. Grade B, Level 2 + 3 4 3 1 In hypertensive patients without compelling indications or contraindications for any particular drug, consider any one, or an appropriate combination, of the five major classes of drugs as the initial treatment. Grade B, Level 2 + 3 4 32 Take compelling indications and contraindications into account when prescribing an antihypertensive drug (Table 7 ). Grade A, Level 1 + 3 4 3 3 Be aware of the cost of treatment in selecting antihypertensive drugs. Grade D, Level 4 3 7 3 4 Generic formulations which usually cost less than newer non - generic (i.e. proprietary) drugs are acceptable for use . Grade D, Level 4 3 7 3 5 Do not offer aldosterone (mineralocorticoid) antagonists (e.g. spironolactone) to patients with chronic kidney disease (eGFR 45 ml/min) , in particular when combined with an ACE inhibitor or ARB . This is because of the risks of further renal function impairment, and of hyperkalaemia. An aldosterone antagonist might be considered in patients with res istant hypertension after a full work - up has excluded secondary hypertension (Table 4). Grade C, Level 2 + 3 8 3 6 Prescribe a diuretic with caution as initial treatment in patients with uncomplicated hypertension , who are at risk for diabetes, because it might cause hyperglycaemia . Grade B, Level 2 + 3 8 3 7 U s e beta - blockers with caution

in patients at risk of developing diabetes , as it raises blood glucose concentrations . Grade A, Level 1 + 3 8 6 No. Recommendation Grade, Level of Evidence CPG page no. 30 Use long - acting drugs which provid e 24 - hour efficacy daily. Grade B, Level 2 + 3 4 3 1 In hypertensive patients without compelling indications or contraindications for any particular drug, consider any one, or an appropriate combination, of the five major classes of drugs as the initial treatment. Grade B, Level 2 + 3 4 32 Take compelling indications and contraindications into account when prescribing an antihypertensive drug (Table 7 ). Grade A, Level 1 + 3 4 3 3 Be aware of the cost of treatment in selecting antihypertensive drugs. Grade D, Level 4 3 7 3 4 Generic formulations which usually cost less than newer non - generic (i.e. proprietary) drugs are acceptable for use . Grade D, Level 4 3 7 3 5 Do not offer aldosterone (mineralocorticoid) antagonists (e.g. spironolactone) to patients with chronic kidney disease (eGFR 45 ml/min) , in particular when combined with an ACE inhibitor or ARB . This is because of the risks of further renal function impairment, and of hyperkalaemia. An aldosterone antagonist might be considered in patients with res istant hypertension after a full work - up has excluded secondary hypertension (Table 4). Grade C, Level 2 + 3 8 3 6 Prescribe a diuretic with caution as initial treatment in patients with uncomplicated hypertension , who are at risk for diabetes, because it might cause hyperglycaemia . Grade B, Level 2 + 3 8 3 7 U s e beta - blockers with caution in patients at risk of developing diabetes , as it raises blood glucose concentrations . Grade A, Level 1 +

3 8 9 Grade, Level of Evidence CPG page no. 4 8 Treat patients with diabetic nephropathy to a target below 140 mmHg systolic BP . Grade A, Level 1 + 4 6 4 9 If a diabetic nephropathy patient has severe albuminuria (equivalent to urinary albumin:creatinine ratio (ACR) more than 30 mg/mmol, or urinary PCR more than 50 mg/mmol ), consider target below 130 mmHg systolic BP provided GFR changes are monitored carefully . Grade B, Level 2 + 4 7 50 Treat diabetic chronic kidney disease patients with moderate albuminuria (urinary ACR 3 - 30 mg/mmol, or PCR between 15 - 5 0 mg/mmol) to a target BP equal to or below 130 / 8 0 mmHg . Grade D, Level 4 4 7 5 1 Use an ACE inhibitor or ARB as first - line treatment, whenever treatment with BP - lowering drugs is indicated in diabetic nephropathy. Grade A, Level 1 + 4 8 5 2 In diabetic nephropathy , if one class of RAAS blocker (either ACE inhibitor or ARB) is not tolerated, replace it with the other class . Grade D, Level 4 4 8 5 3 Combination treatment with both an ACE inhibitor and an ARB should not be routine in diabetic nephropathy. Grade A, Level 1 + 4 8 5 4 When ACE inhibitors , ARBs, or diuretics are used in diabetic nephropathy , it is recommended to monitor the serum creatinine and potassium levels for the possible development of acute kidney injury and hyperkalemia. Grade D, Level 4 4 8 5 5 Beta - blockers, calcium - channel blockers , and thiazides are all appr opriate second - line therapy in diabetic nephropathy. Grade A, Level 1 + 49 No. Recommendation 58 11 Clinical quality improvement The recommended target BP l evels in antihypertensive treatment are �x Below 140/90 mmHg in

patients aged under 80 years * 9-11 �x Below 150/90 mmHg in patients aged 80 years or more 10,11 * In elderly patient s aged under 80 years with good physical and mental status , if treatment is well tolerated . T he ultimate objective of managing hypertension is not to lower the BP per se , but to decrease the patients �¶ overall risks of morbidity and mortality . These risks are also influenced by other coexisting cardiovascular dis ease r isk factors. The greater the total cardiovascular disease risk, the more rigorous ly the BP should be control led . However, the BP level attainable with antihypertensive treatment is influenced by medication side effects and other comorbidities, such as diabetes, chronic kidney disease , CAD , and cerebrovascular disease. Good clinical judgment should therefore be exercised in every patient . T h e s c h e d u l e s s h o w n i n T a b l e 8 ( p a g e 4 4 ) a r e r e c o m m e n d e d t o a l l o w patients and health care providers to optimise the quality of care. E ach patient should be managed appropriate ly according to the ir assessed risk level. 58 11 Clinical quality improvement The recommended target BP l evels in antihypertensive treatment are �x Below 140/90 mmHg in patients aged under 80 years * 9-11 �x Below 150/90 mmHg in patients aged 80 years or more 10,11 * In elderly patient s aged under 80 years with good physical and mental status , if treatment is well tolerated . T he ultimate objective of managing hypertension is not to lower the BP per se , but to decrease the patients �¶ overall risks of morbidity and mortality . These risks are also influenced by other coe

xisting cardiovascular dis ease r isk factors. The greater the total cardiovascular disease risk, the more rigorous ly the BP should be control led . However, the BP level attainable with antihypertensive treatment is influenced by medication side effects and other comorbidities, such as diabetes, chronic kidney disease , CAD , and cerebrovascular disease. Good clinical judgment should therefore be exercised in every patient . The schedules shown in Table 8 (page 43 ) are recommended to allow patients and health care providers to optimise the quality of care. E ach patient should be managed appropriate ly according to the ir assessed risk level. 58 11 Clinical quality improvement The recommended target BP l evels in antihypertensive treatment are �x Below 140/90 mmHg in patients aged under 80 years * 9-11 �x Below 150/90 mmHg in patients aged 80 years or more 10,11 * In elderly patient s aged under 80 years with good physical and mental status , if treatment is well tolerated . T he ultimate objective of managing hypertension is not to lower the BP per se , but to decrease the patients �¶ overall risks of morbidity and mortality . These risks are also influenced by other coexisting cardiovascular dis ease r isk factors. The greater the total cardiovascular disease risk, the more rigorous ly the BP should be control led . However, the BP level attainable with antihypertensive treatment is influenced by medication side effects and other comorbidities, such as diabetes, chronic kidney disease , CAD , and cerebrovascular disease. Good clinical judgment should therefore be exercised in every patient . The schedules shown in Table 8 (page 43 ) are reco

mmended to allow patients and health care providers to optimise the quality of care. E ach patient should be managed appropriate ly according to the ir assessed risk level. 72 Self - assessment (MCQs) After reading the Clinical Practice Guidelines, you can claim one CME point under Category 3A (Self - Study) of the SMC Online CME System. Alternatively, you can claim one CME point under Category 3B (Distance Learning �± Verificable Self - Assessment) if you a nswer at least 60% of the following MCQs correctly. You can submit your answers through the SMJ website at this link: http://sma.org.sg/publications/index.aspx?ID=26 (the link will only be available once the January 201 8 issue of the SMJ becomes available) . The answers will be published in the SMJ March 2018 issue and at the MOH webpage for these guidelines after the period for submitting the answers is over. Instruction: Choose True or False for each statement. True False 1 . With regards to diagnosis of hypertension A. Patient s with a 24 - hour ABPM are regarded as hypertensive if the average BP �L�V��•��������P�P�+�J� B. It has been estimated that antihypertensive treatment, on average, reduces stroke by 35 - 40% C. If BP 165/95 mmHg we should grade the hypertension as Grade 2. D. The cardiovascular risks rise exponentially for BP between 140/90 and 220/120 mmHg; the urgency of treatment is therefore guided by the grade of measured BP . 2. With regards to evaluation and prognostic factors of hypertension, A. One of the objectives of the clinical and laboratory evaluation of the

hypertensive patient is to look for target organ damage. B. Urine analysis should be part of routine clinical evaluation. C. Central aortic pressure should be part of routine evaluation in a hypertensive patient. D. Chronic sleep deprivation syndrome is a common secondary cause of hypertension 73 3 . With regards to lifestyle modifications and non - p harmacotherapy, A. Salt (sodium chloride) restriction up to 5 - 6 g a day is strongly recommended in those with h ypertension. B. Regular dynamic (ie aerobic) exercise on at least 5 days a week, whether as single or interrupted e pisodes of 30 minutes or longer, confers both cardiovascular and overall health benefits, beyond a reduction in the BP . C. Lifestyle modifications are not required in patient s whose average BP is in the high normal range of 130 - 139 / 85 - 89 mmHg. D. Cessation of tobacco smoking confers major benefit in terms of BP reduction, as well as avoiding coronary artery disease and other serious systemic disorders. 4 . The following two - drug antihypertensive combinations decrease the BP (BP) beyond the amount obtained by adding together the individual drug effects on the BP : A. Atenolol plus lisinopril. B. Amlodipine plus valsartan. C. Carvedilol plus indapamide. D. Enalapril plus losartan. 5. With regards to treatment in various conditions: A. In treatment of Type 2 diabetes mellitus, an acceptable treatment - initiation and target BP is 40/80 mmHg. B. In lowering of BP for secondary prevention of stroke, the threshold for

starting anti - hypertensive therapy is � 1 40/90 mmHg. C. In treatment during pregnancy, initiation of pharmacological treatment is recommended for pregnant women wi th chronic hypertension if the BP is more than 140/90 mm Hg. D. Elderly patients above age 80years with isolated systolic hypertension should have their systolic BP reduce d to 40mmHg. 73 3 . With regards to lifestyle modifications and non - p harmacotherapy, A. Salt (sodium chloride) restriction up to 5 - 6 g a day is strongly recommended in those with h ypertension. B. Regular dynamic (ie aerobic) exercise on at least 5 days a week, whether as single or interrupted e pisodes of 30 minutes or longer, confers both cardiovascular and overall health benefits, beyond a reduction in the BP . C. Lifestyle modifications are not required in patient s whose average BP is in the high normal range of 130 - 139 / 85 - 89 mmHg. D. Cessation of tobacco smoking confers major benefit in terms of BP reduction, as well as avoiding coronary artery disease and other serious systemic disorders. 4 . The following two - drug antihypertensive combinations decrease the BP (BP) beyond the amount obtained by adding together the individual drug effects on the BP : A. Atenolol plus lisinopril. B. Amlodipine plus valsartan. C. Carvedilol plus indapamide. D. Enalapril plus losartan. 5. With regards to treatment in various conditions: A. In treatment of Type 2 diabetes mellitus, an acceptable treatment - initiation and target BP is 40/80 mmHg. B. In low

ering of BP for secondary prevention of stroke, the threshold for starting anti - hypertensive therapy is � 1 40/90 mmHg. C. In treatment during pregnancy, initiation of pharmacological treatment is recommended for pregnant women wi th chronic hypertension if the BP is more than 140/90 mm Hg. D. Elderly patients above age 80years with isolated systolic hypertension should have their systolic BP reduce d to 40mmHg. 43 C Table 8 Frequency of recommended tests/actions 4,5,12,7 7 Grade C, Level 2 + * Goal BP achieved. D Patients with the following problems should be referred to a hypertension specialist or clinic: 3 1. Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heart failure , or other impending complications 2. Hypertension that is difficult to manage , e.g. unusually labile BP , or hypertension refractory to multiple drug s in different pharmacological classe s 3. Secondary hypertension , i.e. hypertension due to an underlying cause, such as hyperaldosteronism 4. Hypertens ion in special circumstances , e.g. pregnancy, and young children . Grade D, Level 4 Recommended test/action Recommended frequency BP monitoring Risk level* - Low added risk - Medium to very high risk 6 - monthly to annually 3 - to 6 - monthly BMI Fasting glucose Fasting lipid profile Serum electrolytes, urea, creatinine Urine - albumin measurement Annually or more frequently , as per individual risk profile ECG As per individual risk and cardiac profile Patient education Lifestyle modification and Medication adherence At each visit 43 C Table 8 Freque

ncy of recommended tests/actions 4,5,12,7 7 Grade C, Level 2 + * Goal BP achieved. D Patients with the following problems should be referred to a hypertension specialist or clinic: 3 1. Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heart failure , or other impending complications 2. Hypertension that is difficult to manage , e.g. unusually labile BP , or hypertension refractory to multiple drug s in different pharmacological classe s 3. Secondary hypertension , i.e. hypertension due to an underlying cause, such as hyperaldosteronism 4. Hypertens ion in special circumstances , e.g. pregnancy, and young children . Grade D, Level 4 Recommended test/action Recommended frequency BP monitoring Risk level* - Low added risk - Medium to very high risk 6 - monthly to annually 3 - to 6 - monthly BMI Fasting glucose Fasting lipid profile Serum electrolytes, urea, creatinine Urine - albumin measurement Annually or more frequently , as per individual risk profile ECG As per individual risk and cardiac profile Patient education Lifestyle modification and Medication adherence At each visit 43 C Table 8 Frequency of recommended tests/actions 4,5,12,7 7 Grade C, Level 2 + * Goal BP achieved. D Patients with the following problems should be referred to a hypertension specialist or clinic: 3 1. Conditions needing emergency or urgent treatment, e.g. malignant hypertension, hypertensive heart failure , or other impending complications 2. Hypertension that is difficult to manage , e.g. unusually labile BP , or hypertension refractory to multiple drug s in different pharmacological classe s 3. Secondary hypertension ,

i.e. hypertension due to an underlying cause, such as hyperaldosteronism 4. Hypertens ion in special circumstances , e.g. pregnancy, and young children . Grade D, Level 4 Recommended test/action Recommended frequency BP monitoring Risk level* - Low added risk - Medium to very high risk 6 - monthly to annually 3 - to 6 - monthly BMI Fasting glucose Fasting lipid profile Serum electrolytes, urea, creatinine Urine - albumin measurement Annually or more frequently , as per individual risk profile ECG As per individual risk and cardiac profile Patient education Lifestyle modification and Medication adherence At each visit ISBN 978-981-11-5731-8Ministry of Health, SingaporeCollege of Medicine Building16 College RoadSingapore 169854Tel: (65) 6325 9220Fax: (65) 6224 1677www.moh.gov.sg Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine PhysiciansAcademy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medic

ine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine PhysiciansAcademy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians

Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Levels of evidence and grades of recommendationLevels of evidence Level Type of Evidence High quality metaanalyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias 1 + Well conducted meta - analyses, systematic reviews of RCTs, or RCTs with a low risk of bias - Meta - analyses, systematic reviews of RCTs, or RCTs with a high risk of bias 2 + + High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal 2 + Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal - Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3 Non - analytic studies, e.g. case reports, case series 4 Expert opinion Grades of recommendation Grade Recommendation A At least one metaanalysis, systematic review of RCTs, or RCT rated as and directly applicable to the target population; orA body of evidence consisting principally of studies rated as 1directly applicable to the target population, and demonstrating overall consistency of results B A body of evidence including studies rated as 2 ++ , directly applicable to the target population, and demonstrating overall consistency of results; orExtrapolated evidence from studies rated as 1or 1 C A bod

y of evidence including stu dies rated as 2 + , directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2 + + D Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2 GPP (good practice points) Recommended best practice based on the clinical experience of the guideline development group. Secretariat teamMs Chin Mien ChewSenior ManagerUtilisation Management ReviewClinical Quality, Performance & Technology Division Ministry of HealthMs Suriana TaibManager Utilisation Management ReviewClinical Quality, Performance & Technology Division Ministry of HealthDr Edwin Chan ShihYen Head, Epidemiology Singapore Clinical Research InstituteAssocProfessor, DukeNUS Graduate Medical School, SingaporeDirector, Singapore Branch, Australasian Cochrane Centre;Head (Evidencebased Medicine)Clinical Quality, Performance & Technology Division Ministry of HealthThese organisationshave commented on and endorsed the guidelines (in alphabetical order):Chapter of Family Medicine Physicians, Academy of Medicine, SingaporeChapter of Endocrinologists, College of Physicians, SingaporeCollege of Family Physicians SingaporeSingapore Hypertension Society Levels of evidence and grades of recommendationLevels of evidence Level Type of Evidence 1+ + High quality metaanalyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias 1 + Well conducted meta - analyses, systematic reviews of RCTs, or RCTs with a low risk of bias 1 - Meta - analyses, systematic reviews of RCTs, or RCTs with a high risk of bias 2 + + High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high pro

bability that the relationship is causal 2 + Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal 2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal 3 Non - analytic studies, e.g. case reports, case series 4 Expert opinion Grades of recommendation Grade Recommendation A At least one metaanalysis, systematic review of RCTs, or RCT rated as and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1 directly applicable to the target population, and demonstrating overall consistency of results B A body of evidence including studies rated as 2 ++ , directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1or 1 C A body of evidence including stu dies rated as 2 + , directly applicable to the target population and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2 + + D Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2 GPP (good practice points) Recommended best practice based on the clinical experience of the guideline development group. Secretariat teamMs Chin Mien ChewSenior ManagerUtilisation Management ReviewClinical Quality, Performance & Technology Division Ministry of HealthMs Suriana TaibManager Utilisation Management ReviewClinical Quality, Performance & Technology Division Ministry of HealthDr Edwin Chan ShihYen Head, Epidemiology Singapore Clinical Research InstituteAssocProfessor, DukeNUS Graduate Medical School, SingaporeDirector, Singapore Br

anch, Australasian Cochrane Centre;Head (Evidencebased Medicine)Clinical Quality, Performance & Technology Division Ministry of HealthThese organisationshave commented on and endorsed the guidelines (in alphabetical order):Chapter of Family Medicine Physicians, Academy of Medicine, SingaporeChapter of Endocrinologists, College of Physicians, SingaporeCollege of Family Physicians SingaporeSingapore Hypertension Society Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine PhysiciansAcademy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family P

hysicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine PhysiciansAcademy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 Chapter of Family Medicine Physicians Academy of Medicine, Singapore Chapter of EndocrinologistsCollege of Physicians, Singapore Singapore Hypertension Society College of Family Physicians Singapore MOH Clinical Practice Guidelines 1/2017 Hypertension N o v e m b e r 2 0 1 7 ISBN 978-981-11-5731-8Ministry of Health, SingaporeCollege of Medicine Building16 College RoadSingapore 169854Tel: (65) 6325 9220Fax: (65) 6224 1677www.moh.gov