The grey zone: What to do for the “intermediate risk” patient? - PowerPoint Presentation

Slide1

The grey zone: What to do for the “intermediate risk” patient?

Slide2

Lifestyle-Heart Hypothesis

Mozaffarian

et al.

Circulation

2008;117;3031-3038

Slide3

Atherosclerosis: Traditional and novel risk factors

Interheart: Developed and developing countries (N = approx 30,000) IHD Risk Factor Odds Ratio Population attributable risk ApoB/ApoAI 3.25 49%Smoking 2.87 36%Hypertension 1.91 18%Diabetes 2.37 10%Abdominal obesity 1.12 – 1.62 20%Psychosocial 2.67 33%Diet (fruit & veg) 0.70 14%Activity 0.86 12%Alcohol (not binge) 0.91 7%

Slide4

Atheroma: Stages and timeframe

Slide5

Atheroma is proportional to the number and severity of classic risk factors

Where is my

patient?

Slide6

Novel risk factors and atheroma

Slide7

Development of an atheroma

ß-VLDL = beta-very low-density lipoprotein; Lp(a) = lipoprotein (a); VCAM-1 = vascular cell adhesion molecule-1; ICAM-1 = intercellular adhesion molecule-1; MCP-1 = monocyte chemoattractant protein-1; CCR-2 = specific receptor present on the surface of monocytes; oxLDL = oxidized low-density lipoprotein; MMP = matrix metalloproteinases; GM-CSF = granulocyte macrophage-colony stimulating factor; SR-A = macrophage scavenger receptor class A

Monocyte

Induction of adhesion

molecules and chemotaxis

Adhesion

VCAM-1

ICAM-1P-selectinE-selectin

MigrationMCP-1CCR-2oxLDL

oxidation

CytokinesMMPsEndothelin-1

Endothelial

cells

Smooth muscle cells

Intima

Internal elastic lamina

Lumen

CD36

SR-A

Differentiation

(GM-CSF)

Macrophage

Foam cell

T lymphocyte

CD40

IFN-gamma

LDL-C,

β

-VLDL, Lp(a)

Adapted with permission from Fan et al, J

Atheroscler

Thromb

2003; 10: 63

Slide8

Integration of risk factors: Risk calculators

Slide9

Limitations of CVD Risk Assessment

Underlying data (

eg

FRS) is historical, geographical

Suitable for non-western populations in 21

st

century?

Some data components are infrequently available

Left ventricular hypertrophy

No mechanism to take advantage of risk predictors

High sensitivity C-reactive protein etc

Predominant effect of age

Assigns low 10-year risk to some patients with moderate to high lifetime risk who might benefit from more aggressive management, particularly in women & younger men

Omits or fails to quantify several major risk factors

Family history, smoking, diabetes.

Slide10

High sensitivity C-reactive protein as a discriminator in intermediate risk?

US Preventive Services Task Force (2009) “CRP is associated with CHD events....Adding CRP to risk prediction models among initially intermediate risk persons improved risk stratification. However.. evidence that reducing CRP levels prevents CHD is lacking” “ the current evidence is insufficient to assess the balance of benefits and harms of using the non-traditional risk factors studied to screen asymptomatic men and women with no history of CHD to prevent CHD events.”

American Heart Assoc and CDC (2008) “the entire adult population should not be screened for hs-CRP for the purposes of CVD risk assessment.”Additional analytes, improved assays or evidence of benefits of combinations of assays may in future be found to have advantages, but further research is needed”

Canadian Cardiovascular Society (2009)

“men older than 50 years and women older than 60 years of age, of intermediate risk whose LDL-C does not already suggest treatment, hs-CRP can be used for risk stratification”

Slide11

Clinical risks: Microalbuminuria, renal impairment and inflammatory disorders

Slide12

Markers of end-organ damage

BNP

Hs-

TnT

Slide13

Genetic evidence for additional risks factors

Slide14

Non-invasive imaging detects sub-clinical atheroma

Shaw et al.

Radiology

2003; 228:826-833

Raggi

P et al.

Arterioscler

Thromb

Vasc

Biol

. 2004;24:1272-77

Slide15

Primary Author

Study Type

N

o

of Patients

Mean Follow-up (years)

Type of Events

N

o

of events

Incremental Prognostic Value of Coronary Calcium

Shaw L

2

Observational

10,377

5

All-cause death

249

Yes

Kondos

G

1

Observational

5,635

3

Myocardial Infarction, Death and Revascularizations

224

Not Assessed

Greenland P

5

Prospective

1,029

7.0 (median)

Myocardial Infarction and Death

84

Yes

LaMonte

M

6

Prospective

10,746

3.5

Myocardial Infarction and Cardiovascular Death

81

Yes

Arad Y

4

Prospective

4,613

4.3

Atherosclerotic Cardiovascular Events

119

Yes

Taylor A

7

Prospective

1,983

3

Acute Coronary Syndrome and Sudden Cardiac Death

9

Yes

Detrano

R

8

Prospective

6,722

3.8

Myocardial Infarction and Cardiovascular Death

89

Yes

Becker A

9

Prospective

1,726

3.4

Myocardial Infarction and Cardiovascular Death

179

Yes

Slide16

Reclassification of intermediate risk patients

Slide17

Where to set the risk threshold? Benefit versus risk or benefit versus cost?

“If

statins

cost $4/month, treatment thresholds of low-density lipoprotein cholesterol > 4

mmol

/l

for low-risk persons (0 to 1 risk factor), >3.3

mmol

/l for moderate-risk persons (≥2 risk factors

and 10-year risk <10%), and >2.6 mg/

dL

for moderately high-risk persons (≥2 risk factors and

10-year risk >10%) would reduce annual healthcare costs by $430 million compared with

Adult Treatment Panel III guidelines”. Lazar LD. Circ 124:146-53

Slide18

Strategies that compete with the absolute risk approach.

Slide19

Epidemiological methods identify risk factors The more independent risk factors for a outcome / disease, the worse each is likely to perform on its own as a predictorWhat matters is the amount of the total risk attributable to the risk factor

Establishing a risk factor

Slide20

Establishing a risk factor

Lowest

fifth

Highest

fifth

Slide21

Establishing a risk factor

Rate of disease = 5 / 1000

Rate of disease = 50 / 1000

Incidence ratio = (50/1000) / (5/1000) = 10

Odds ratio = (50/950) / (5/995)



10

Slide22

60% of the

population!

Establishing a risk factor

Slide23

1. Law MR, Watt HC, Wald NJ

,.

Slide24

1. Law MR, Watt HC, Wald NJ

,.

Slide25

Threshold risk factor

Threshold

Slide26

Continuous risk factor

No threshold

Slide27

O.R.

What happens when you treat?

Slide28

Cholesterol

x

x?

Slide29

Summary and transition to cases

deCODE

MI re class, 2 cases

Complex cases 1

Slide30

O.R.

Slide31

Cholesterol reduction

Reduction in risk in treatment group

TrialNet change in TCIncidence of major coronary events in placebo group (%/yr)Relative (%)Absolute (%/yr)WOSCOPS1.7 mmol/L1.439 (20 – 52)0.5 (0.3 – 0.7)*4S1.4 mmol/L5.235 (27 – 42)1.8 (1.4 – 2.2)*

1. Shepherd J, Cobbe S, et al.,

Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group

.

New England Journal of Medicine

, 1995.

333

(20):1301.

Slide32

Cholesterol reduction

Reduction in risk in treatment groupTrialNet change in TCIncidence of major coronary events in placebo group (%/yr)Relative (%)Absolute (%/yr)WOSCOPS1.7 mmol/L1.439 (20 – 52)0.5 (0.3 – 0.7)*4S1.4 mmol/L5.235 (27 – 42)1.8 (1.4 – 2.2)*

1. Scandinavian Simvastatin Survival Study Group,

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).

Lancet

, 1994.

344

(8934):1383.

Slide33

Cholesterol reduction

Reduction in risk in treatment group

Trial

Net change in TC

Incidence of major coronary events in placebo group (%/yr)

Relative (%)

Absolute (%/yr)

WOSCOPS

1.7

mmol

/L

1.4

39 (20 – 52)

0.5 (0.3 – 0.7)*

4S

1.4 mmol/L

5.2

35 (27 – 42)

1.8 (1.4 – 2.2)*

Slide34

Systolic blood pressure

Usual SBP (mmHg)

Floating Absolute Risk & 95% CI

110

120

130

140

150

160

170

0.25

0.50

1.00

2.00

4.00

8.00

1.

Asia-Pacific Cohort Studies Collaboration

,

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).

Lancet

, 1994.

344

(8934):1383.

Slide35

Odds ratio for CHD

Coronary disease

Odds ratio for CHD

Coronary disease

O.R.

Usual diastolic blood pressure (mmHg)

Diastolic blood pressure

Stroke

MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J,

et al

.

Blood pressure, stroke and coronary heart disease. 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias

.

Lancet

1990;

335

:765­74.

Slide36

Diastolic blood pressure

Odds ratio for CHD

Coronary disease

O.R.

Usual diastolic blood pressure (mmHg)

Stroke

MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J,

et al

.

Blood pressure, stroke and coronary heart disease. 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias

.

Lancet

1990;335:765­74.

Slide37

Smoking

Yusuf S, Hawken S, et al. 2004:

Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study

.

Lancet

,

364

(9438): p. 937.

Slide38

Yusuf S, Hawken S

, et al.

2004:

Effect of potentially modifiable risk factors

associated with myocardial infarction in 52 countries (the INTERHEART study):

case-control study.

Lancet

, 364(9438): p. 937.

Slide39

Attributable risk

1. Law MR, Watt HC, Wald NJ

,.

Slide40

Framingham equation



=



0 +

1 x female + 2 x log(age) + 3 x log(age) x female + 4 x [log(age)]2 x female + 5 x log(SBP) + 6 x cigarettes + 7 x log(TC/HDL) + 8 x diabetes + 9 x diabetes x female + 10 LVH

 = exp(0 + 1 )

u = [log(10)] - ] / 

10 y predicted

P

for CHD = 1 – exp(-exp(u))

Slide41

Framingham equation



=



0 +

1 x female + 2 x

log

(age) + 3 x

log

(age) x female + 4 x [

log

(age)]2 x female + 5 x

log

(SBP) + 6 x cigarettes + 7 x

log

(TC/HDL) + 8 x diabetes + 9 x diabetes x female + 10 LVH

 =

exp

(0 + 1 )

u = [

log

(10)] - ] / 

10 y predicted

P

for CHD = 1 –

exp

(-

exp

(u))

Slide42

Framingham equation mismatches

Slide43

Framingham equation recalibration

Slide44

Slide45

Slide46

Slide47

Limitations

Underestimates for extremes of risk factors

Younger people have lower risk

But more life years lost

Consider projecting risk forward in time

Normalising for age

New/novel risk factors

Continuous HbA1c

hsCRP

Lp(a)

Apo E4/E4

Obesity

CKD

Slide48

Implications of global risk approach

Treat anyone at high risk

1. Law MR, Watt HC, Wald NJ,

The Underlying Risk of Death After Myocardial Infarction in the Absence of Treatment

.

Archives of Internal Medicine

, 2002;

162

(21):2405.

Slide49

The major determinant of risk is existing disease

Untreated MI: Death rates for first event: 36%Before hospital 23%During admission 16% (of those admitted)Subsequent events: 53%Before hospital 33%During admission 30%

Treat anyone at high risk

1. Law MR, Watt HC, Wald NJ,

The Underlying Risk of Death After Myocardial Infarction in the Absence of Treatment

.

Archives of Internal Medicine

, 2002;

162

(21):2405.

Slide50

The major determinant of risk is existing disease

Untreated MI: First eventDeath rates for first year: 10.3%Stroke & heart disease 9.6%Annual death rate 5.3% (for life)Stroke & heart disease 4.6%Subsequent events:First year 21% (19% CVD)Annual death rate 12% (10% CVD)

Treat anyone at high risk

1. Law MR, Watt HC, Wald NJ,

The Underlying Risk of Death After Myocardial Infarction in the Absence of Treatment

.

Archives of Internal Medicine

, 2002;

162

(21):2405.

Slide51

Implications of global risk approach

Not just the “abnormal” ones

Change all the risk factors together

25%

25%

>50%

Slide52

The major determinant of risk is existing disease

Treat anyone at high risk

1. Australian Institute of Health and Welfare.

Heart, stroke and vascular diseases: Australian Facts

2004.

AIHW

.

Slide53

fixrhubarbzumab

fixrhubarbzumab

Slide54

Don

’

t do unnecessary trials

Slide55

?

Don

’

t do unnecessary trials

Slide56

Adapted from:

Law MR, Wald NJ,

Risk factor thresholds: their existence under scrutiny

.

BMJ

, 2002;

324

:1570.

Don

’

t do unnecessary trials

Slide57

Cost efficacy

Slide58

Mr J.S.

Mr J.S. has a history consistent with Familial Combined

Hyperlipidaemia

. He is 49 years old, BP 150/90 and his lipids include: TC = 7.8

mmol

/l, TG = 2.7

mmol

/l, HDL = 1.1

mmol

/l, LDL = 5.6

mmol

/l. His older brother, who, like J.S, was a non smoker, suffered onset of CVD at this age. J.S.’s total CVD risk is 14%

Slide59

Questions concerning Mr J.S.

Does he warrant lipid-lowering treatment according to NHF guidelines? Yes / No

A colleague suggests that his

ankle:brachial

index should be measured. Is this non invasive test for CVD risk A) Specific B) Sensitive C) Both

Could his risk assessment be improved by Genome Wide Association Studies? Yes / No

Slide60

Mr J.S. has a history consistent with Familial Combined

Hyperlipidaemia

. He is 49 years old, BP 150/90 and his lipids include: TC = 7.8

mmol

/l, TG = 2.7

mmol

/l, HDL = 1.1

mmol

/l, LDL = 5.6

mmol

/l. His older brother, who, like J.S, was a non smoker, suffered onset of CVD at this age. J.S.’s total CVD risk is 14%

Does he warrant lipid-lowering treatment according to NHF guidelines? Yes / No

A colleague suggests that his

ankle:brachial

index should be measured. Is this non invasive test for CVD risk A) Specific B) Sensitive C) Both

Could his risk assessment be improved by Genome Wide Association Studies? Yes / No

Slide61

Does he warrant lipid-lowering treatment according to NHF guidelines?

Yes

No

Slide62

Does he warrant lipid-lowering treatment according to NHF guidelines?The case for “Yes”

Others with elevated absolute risk of CVD

Lipid-modifying therapy is indicated for those with: C

◦ absolute risk ≥15% of a CVD event in the next 5 years or

◦ absolute risk 10–15% of a CVD event in the next 5 years when either of the following is present:

- family history of premature CHD (first degree relative who developed CHD before age 60)

the metabolic syndrome

2005 Update of NHF Lipid Management Guidelines

Slide63

A colleague suggests that his ankle:brachial index should be measured. Is this non- invasive test for CVD risk...

: A) Specific

B) Sensitive

C) Both

Slide64

A colleague suggests that his ankle:brachial index should be measured. Is this non- invasive test for CVD risk...The case for “A”

Arteriosclerosis, Thrombosis, and Vascular Biology.

2005; 25: 1463-146

 

Sensitivity and Specificity of the Ankle–Brachial Index to Predict Future Cardiovascular Outcomes A Systematic Review

Anand

V.

Doobay

, 

Sonia S.

Anand

The sensitivity and specificity of a low ankle–brachial index to predict incident coronary heart diseases were 16.5% and 92.7%, for incident stroke were 16.0% and 92.2%, and for cardiovascular mortality were 41.0% and 87.9%, respectively. The corresponding positive likelihood ratios were 2.53 (95% CI, 1.45 to 4.40) for coronary heart disease, 2.45 (95% CI, 1.76 to 3.41) for stroke, and 5.61 (95% CI, 3.45 to 9.13) for cardiovascular death.

Slide65

Could his risk assessment be improved by Genome Wide Association Studies?

Yes

No

Slide66

Could his risk assessment be improved by Genome Wide Association Studies?The case for “No”?

C

N (%)GN (%)2 (1df)P-value Cases2,132 (55.4)1,716 (44.6)55.11.2 x 10-13Controls2,783 (47.4)3,089 (52.6)Allelic Odds Ratio = 1.38CC N (%)CG N (%)GGN (%)2 (2df) P-valueCases586 (30.5) 960 (49.9) 378 (19.6)59.71.1 x 10-14Controls676 (23.0)1,431 (48.7)829 (28.2)Heterozygote Odds Ratio = 1.47Homozygote Odds Ratio = 1.90

Samani N et al, N Engl J Med 2007; 357:443-453.

 Number of Variants MeasuredEuropean ancestry16East Asian ancestry3

The deCODEme Complete Scan identifies validated MI risk variants and uses them to provide a personalized interpretation of the associated genetic risk for having a heart attack. The number of variants included in the deCODEme Complete Scan for each ethnic group are listed in the table below.

Slide67

Mr J.S (continued).

Mr J.S does not have chest pain or any exertional symptoms, but he had an anaphylactic reaction, which may have been related to the introduction of statins.

He remained off statin, but then developed atypical chest pain.

Slide68

More questions regarding Mr J.S.

Which non-invasive test would you favour to weigh up risks versus benefits of re-attempting

statin

therapy? A) CT coronary angiogram B)

Sestamibi

perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

Which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? (more than 1 possible)

A) CT coronary angiogram B)

Sestamibi

perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

He underwent CT coronary angiogram which suggested 70%

stenosis

in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?

Underestimate / Overestimate / Neither

Slide69

Mr J.S does not have chest pain or any exertional symptoms, but he had an anaphylactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh up risks versus benefits of re-attempting

statin

therapy? A) CT coronary angiogram B)

Sestamibi

perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

If he remained off

statin

, which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? (more than 1 possible)

A) CT coronary angiogram B)

Sestamibi

perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

Mr J.S. Developed atypical chest pain and underwent CT coronary angiogram which suggested 70%

stenosis

in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?

Underestimate / Overestimate / Neither

Slide70

Mr J.S does not have chest pain or any exertional symptoms, but he had an anaphylactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh up risks versus benefits of re-attempting statin therapy?

A) CT coronary angiogram

B)

Sestamibi

perfusion scan

C) Stress Echo

D) Coronary Calcium Score

E) Exercise ECG

Slide71

Mr J.S does not have chest pain or any exertional symptoms, but he had an anaphyllactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh up risks versus benefits of re-attempting statin therapy? The case for “D”, but “C” and “E” reasonable

Slide72

If he remained off statin, which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? (more than 1 possible)

CT coronary angiogram

B)

Sestamibi

perfusion scan

C) Stress Echo

D) Coronary Calcium Score

E) Exercise ECG

Slide73

If he remained off statin, which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? The case for “D” (“C” and “E” reasonable)

Slide74

Mr J.S. developed atypical chest pain and underwent CT coronary angiogram which suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?

Underestimate

Overestimate.

Neither

Slide75

Mr J.S. developed atypical chest pain and underwent CT coronary angiogram which suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?The case for “B”

Heart 

2011;

97

:1363-1364 

CT coronary angiography: a new unique prognosticator?

Lisan

A

Neefjes

,

Pim

J de

Feyter

.

CTCA tends to overestimate the severity of the coronary

stenosis

, resulting in a number of patients with false-positive outcomes that is too high. This is mainly caused by the blooming effect of calcified lesions in combination with the still too limited spatial resolution of CTCA as compared with invasive coronary angiography. CTCA provides, additional to

luminography

, comprehensive assessment of the anatomical manifestations of coronary atherosclerosis, including the distribution (proximal, mid and distal) and extent (one-, two-, three-vessel disease, left main disease) of CAD, the presence of ‘positive remodelling’ of the vessel and a, rather crude, assessment of the coronary plaque components (calcified, non-calcified and mixed) 

Slide76

Ms A.Y.

Ms A.Y is a 53 year-old woman with a 20 year history of severe rheumatoid arthritis. She is suffering a flare-up despite systemic steroid therapy and steroid sparing agents. Central chest pain is consistent with

pericarditis

, but cardiovascular risk assessment is thought to be justified. BP (115/75) is normal but

creatinine

is mildly elevated (112

umol

/l). TC = 5.7, TG = 2.6, HDL = 0.9

mmol

/l, LDL = 3.6

mmol

/l. Family history is unremarkable but uncertainty concerning her risk prompts measurement of

hs

-CRP (5 mg/l), lipoprotein (a), (678 mg/l) and total

homocysteine

, (23

umol

/l) all of which are elevated.

Slide77

Questions concerning Ms A.Y.

Calculated 5 year risk is 2%. Do you agree with this estimation? Yes / No

Which of the following is unlikely to be affected by the inflammatory state? A) Lipid profile B)

hs

-CRP C) Lipoprotein (a) D)

homocysteine

Which of the following is less likely to be affected by the renal impairment? A) Lipid profile B)

hs

-CRP C) Lipoprotein (a) D)

homocysteine

How much is Ms A.Y’s RELATIVE risk of CVD increased? A) 20% B) 50% C) 100% D) 200% E) More than 200%

Slide78

Ms A.Y is a 53 year-old woman with a 20 year history of severe rheumatoid arthritis. She is suffering a flare-up despite systemic steroid therapy and steroid sparing agents. Central chest pain is consistent with

pericarditis

, but cardiovascular risk assessment is thought to be justified. BP (115/75) is normal but

creatinine

is mildly elevated (112

umol

/l). TC = 5.7, TG = 2.6, HDL = 0.9

mmol

/l, LDL = 3.6

mmol

/l. Family history is unremarkable but uncertainty concerning her risk prompts measurement of

hs

-CRP (5 mg/l), lipoprotein (a), (678 mg/l) and total

homocysteine

, (23

umol

/l) all of which are elevated.

Calculated 5 year risk is 2%. Do you agree with this estimation? Yes / No

Which of the following is less likely to be affected by the inflammatory state? A) Lipid profile B)

hs

-CRP C) Lipoprotein (a) D)

homocysteine

Which of the following is unlikely to be affected by the renal impairment? A) Lipid profile B)

hs

-CRP C) Lipoprotein (a) D)

homocysteine

How much is Ms A.Y’s RELATIVE risk of CVD increased? A) 20% B) 50% C) 100% D) 200% E) More than 200%

Slide79

Calculated 5 year risk is 2%. Do you agree with this estimation?

Yes

No

Slide80

Calculated 5 year risk is 2%. Do you agree with this estimation? The case for “No”

StudynOR (SMR)ORALE12363.17 (adj)Rochester Cohort2603 2.12 (MI)Nurses Health Study35272.0Stockport Inception cohort410101.93Van Doornum et al.5-1.70 overall mortality

Maradit-Kremers H, et al. Arthritis Rheum 2005; 52:722–732;

3. Solomon DH,

et al.

Circulation

2003; 107:1303–1307;

4. Goodson N,

et al.

Ann Rheum Dis

2005; 64:1595–601; 5. Van Doornum S,

et al. Arthritis Rheum

2002; 46: 862–73

Slide81

Which of the following is less likely to be affected by the inflammatory state?

A) Lipid profile

B)

hs

-CRP

C) Lipoprotein (a)

D)

homocysteine

E) None of the above

Slide82

Which of the following is less likely to be affected by the inflammatory state?The case for “E”

Circulating

Homocysteine

Is An Inflammation Marker

And A Risk Factor of Life-Threatening Inflammatory Diseases

J Biomed Lab

Sci

2007 James T. Wu

Deficiency in vitamin B6, B12 or

folate

is the major cause of

hyperhomocysteinemia

. Since inflammation promotes cell proliferation at the expense of excess amount of vitamins, therefore,

hyperhomocysteinemia

may indicate the presence of inflammation. Moreover, inflammation enhances the synthesis of nitric oxide, which again produces

hyperhomocysteinemia

through binding with

vitamin B12. Consequently, varying degrees of

hyperhomocysteinemia

are detectable in all inflammatory diseases

Slide83

Which of the following is unlikely to be affected by the renal impairment?

A) Lipid profile

B)

hs

-CRP

C) Lipoprotein (a)

D)

homocysteine

E) None of the above

Slide84

Which of the following is unlikely to be affected by the renal impairment? The case for “E”

C-reactive protein, cardiovascular risk, and renal disease in a remote Australian

Aboriginal community. Clinical Science 106, 121–128

Stephen

McDONALD

, Graeme MAGUIRE, Natalia DUARTE, Xing Li WANG and Wendy HOY

Higher CRP concentrations were associated with the following:

45–54-year age group, female subjects, the presence of skin sores, higher body mass index, waist circumference, BP,

glycated

haemoglobin and greater

albuminuria

. CRP concentrations increased with the number of cardiovascular risk factors, carotid IMT and

albuminuria

independently of other risk factors. These CRP concentrations were markedly higher than described in other community settings and are probably related, in a large part, to chronic and repeated infections.

Their association with markers of cardiovascular risk and renal disease are compatible with the high rates of cardiovascular and renal disease in this community, and provide more evidence of strong links between these conditions, through a shared background of infection/

inflammation

Slide85

How much is Ms A.Y’s RELATIVE risk of CVD increased?

A) 20%

B) 50%

C) 100%

D) 200%

E) More than 200%

Slide86

How much is Ms A.Y’s RELATIVE risk of CVD increased? The case for “D-E”

Del Rincon (n=236)CV events (95% CI)Age- and sex-adjusted 3.96 (1.86–8.43)After adjusting for CV risk factors using Poisson regression3.17 (1.33–6.36)

Del

Rinc

ón

I,

et al.

Arthritis Rheum

2001; 44:2737–2745;

2.

Slide87

Ms A.Y.

Ms A.Y is commenced on anti-TNF alpha therapy for her

rheumatological

condition.

Slide88

More questions concerning Ms A.Y.

Ms A.Y is commenced on anti-TNF alpha therapy for her

rheumatological

condition.

Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF therapy (

Adalimumab

(

Humira

))? A) LDL particle number B) HDL-C C) TG D) LDL-C E)

Lp

(a)

Evidence suggests this treatment improves A) Vascular reactivity B) CVD morbidity C) Both A and B D) All aspects of the lipid profile

Is folic acid therapy warranted in order to reduce

homocysteine

? Yes / No

Do

statins

and

Humira

have identical effects on lipids and CVD risk? Yes / No

Slide89

Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF therapy (Adalimumab (Humira))? (2 correct answers)

A) LDL particle size

B) HDL-C

C) TG

D) LDL-C

E)

Lp

(a)

Slide90

Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF therapy (Adalimumab (Humira))? The case for “E”

Lipids and Cardiovascular Risk in Rheumatoid Arthritis

Increases from baseline in mean total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and

apolipoprotein

A

1

 and B levels -- unlike typical

dyslipidemia

(increased LDL and decreased HDL) -- were observed within 6 weeks of treatment initiation. These levels persisted to week 24 in patients treated with TCZ. Concurrent substantial reductions from baseline in mean levels of several inflammatory biomarkers, including C-reactive protein (CRP), serum

amyloid

A (SAA),

haptoglobin

, and lipoprotein(a), were also observed in patients treated with TCZ.

Slide91

Evidence suggests this treatment improves

A) Vascular reactivity

B) CVD morbidity

C) Both A and B

D) All aspects of the lipid profile

Slide92

Evidence suggests this treatment improvesThe case for “B”. No data on “A”

Anti-TNF Use Linked to Cardiovascular-Disease Drop in RA

MITCHEL L. ZOLER

In both studies, treatment with an anti-TNF agent was linked to a statistically significant cut in cardiovascular (CV) events of about 50%.

These results support another recent, similar finding reported in June at the Annual European Congress of Rheumatology in London. In that study, analysis of medical records from more than 109,000 U.S. patients with RA showed that every 6 months of treatment with an anti-TNF drug 

reduced the rate

 of CV events by 13%, compared with RA patients who did not receive a TNF blocker.

Slide93

Is folic acid therapy warranted in order to reduce homocysteine?

Yes

No

Slide94

Is folic acid therapy warranted in order to reduce homocysteine?The “State of Play” favours “No”

Slide95

Do statins and Humira have identical effects on lipids and CVD risk?

Yes

No

Slide96

Do statins and Humira have identical effects on lipids and CVD risk?The case for “No”

Ann Rheum

Dis

 

2007;

66

:1503-1507 

Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis

Popa

C

et al

During therapy, the changes in disease activity and inflammatory status were inversely correlated with changes in plasma total and HDL cholesterol levels and positively correlated with the variation of

atherogenic

index.