Coronary Artery Calcium Predicts Coronary Heart Disease Events Even at the Extremes of - PowerPoint Presentation

Slide1

Coronary Artery Calcium Predicts Coronary Heart Disease Events Even at the Extremes of Age: The Multi-Ethnic Study of Atherosclerosis.

Rajesh

Tota-Maharaj

, Michael J

Blaha

,

Ron

Blankstein

,

Leslee

J Shaw,

Roger

S Blumenthal,

Matthew

J

Budoff

,

Khurram

Nasir

.

No disclosures for this presentation.

Slide2

Incidence of MI in USA: 935,000 (ARIC +CHS from NHLBI)

Annual cost: $177 billion in 2007.

Significance of refining CHD risk stratification.

Background

Slide3

AHA/ACC 2010: Intermediate-risk patients (Class IIA).Superior to high-sensitivity C-reactive protein in risk stratification.

? Expanded utility of coronary calcium scoring in the future.

Coronary Calcium in risk-stratification

- Greenland, et al: 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults. JACC 2010;56(25):e50-103.

-

Blaha

, et al: Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet 2011; 378: 684–92.

Slide4

Background

Tota-Maharaj

R,

Blaha

MJ, Muse ED, Blumenthal RS,

Budoff

MJ, Shaw LJ, Berman DS,

Rana

JS,

Nasir

K.

The Utility of Coronary Artery Calcium in Predicting Mortality at Extremes of Age. Presented at ACC 2011.

Slide5

Coronary artery calcium will be an independent predictor of CHD events even at the extremes of age, after adjusting for conventional cardiovascular risk factors.

Hypothesis

Slide6

MESA study design: 6809 patients, 4 ethnic groups, who had coronary artery calcium scoring performed for risk stratification.Median followup

of 5.8 years.

Primary endpoint: cardiovascular death, non-fatal MI, angina and coronary revascularization.

Methodology

Bild

, et al: Multi-Ethnic Study of Atherosclerosis: Objectives and Design. Am J

Epidemiol

2002;156:871–881.

Slide7

Age groups: 45-54, 55-64, 65-74, 75-84. Coronary artery calcium was stratified as: CAC=0, CAC 1-100, CAC >100. Population characteristics: baseline and examination and followup

phone calls.

CHD events: confirmed with clinical documentation, deaths reviewed by MESA’s M+M committee.

Methodology

Slide8

% patients with CAC across increasing age groups was calculated. CHD events (%) within age groups, CAC groups, and combined.CHD events calculated per 1000 person/years, and stratified across age groups and CAC.

Kaplan-Meier curves.

Methodology

Slide9

Cox regression analyses: within age groups and for increasing CAC.Hazard ratios: 4 models with increasing multi-variable adjustment.Hazard ratios calculated for each CAC category within each age group.

Methodology

Slide10

Characteristic

Age

45-54

N= 1947

Age

55-64

N= 1882

Age

65-74

N= 2015

Age

75-84

N=965

P value

Male (no., %)

909/47

881/47

962/48

458/48

0.90

Caucasian

723/37711/38795/40390/400.14Chinese224/12222/12236/12121/13African-American536/28519/28584/29253/26Hispanic464/24430/23400/20201/21Tobacco: Never Former Current1001/52916/49964/48535/56< 0.0001575/30672/36858/43379/39367/19289/15184/947/5Family History705/38797/45843/45385/44< 0.0001

Baseline Characteristics

Slide11

Baseline Characteristics

Characteristic

Age 45-54

Age 55-64

Age 65-74

Age 75-84

P value

Hypertension

479/25

790/42

1156/57

631/65

< 0.0001

SBP

117

(

17)

125 (20)

132

(22)

138 (23)< 0.0001DM149/8248/13307/15152/16< 0.0001LDL118 (31)119 (33)116 (31)114 (31)0.0003HDL50 (14)51 (15)52 (15)52 (15)< 0.0001BMI29 (6)29 (6)28 (5)27 (5)< 0.0001Heart rate63 (9)63 (10)63 (10)63 (10)0.09Lipid meds144/7294/16456/23202/21< 0.0001BP meds

394/20

653/35

977/49

509/53

< 0.0001

Slide12

Coronary Calcium Distribution across Age groups

Indices of Coronary Calcium increase with aging.

Slide13

CHD Event Rate per 1000 person-years

CHD events increase with increasing age group

Events increase with increasing coronary calcium as expected, but exhibit a much higher event rate with CAC>100.

Slide14

CHD Event Rate per 1000 person-years: Stratified by CAC within Age groups

In all age groups, CHD event rate increases with CAC 1-100, and CAC >100.

CAC > 100 imparts a poorer prognosis in terms of incident CHD events throughout all age groups.

Slide15

Survival analyses for CAC as a function of each age group

Slide16

Survival analyses for CAC as a function of each age group

Slide17

Hazard Ratio for CHD Events across Age Groups: Multi-variable Adjustment

Age Group (compared to age 45-54)

Hazard Ratio (95% Confidence Interval)

Model 1

Model 2

Model 3

Model 4

P values

(Model 4)

Age 55-64

2.9 (1.8-4.5)

2.9 (1.8-4.5)

2.2 (1.4-3.5)

1.7 (1.1-2.7)

0.03

Age 65-74

4.3 (2.8-6.6)

4.2 (2.8-6.5)

3.1 (2.0-5.0)

1.7 (1.1-2.8)

0.02

Age 75-846.3 (4.0-9.8)6.3 (4.0-9.9)4.4 (2.7-7.2)1.9 (1.2-3.3)0.01 Model 1: unadjusted Model 2: adjusted for gender, ethnicity and MESA site Model 3: Model 2 + hypertension, diabetes mellitus, LDL, HDL, smoking, family history, BMI, mean heart rate, hypertensive + lipid-lowering meds. Model 4: Model 3 adjusted for coronary artery calcium. All p-values except those shown are ≤ 0.0001.

Slide18

CAC Group (compared to CAC=0)

Model 1

Model 2

Model 3

CAC 1-100

4.6 (3.0-7.1)

4.4 (2.9-6.7)

2.94 (1.9-4.6)

CAC >100

13.8 (9.4-20.3)

12.4 (8.4-18.5)

8.0 (5.3-12.0)

Hazard Ratio for CHD Events across CAC groups

For both CAC 1-100 and CAC >100, the risk for CHD events remains elevated compared to CAC=0 even after multi-variable adjustment.

Slide19

Age Group

Coronary Calcium Score

Hazard Ratio (95%

CI)

Model 1

Model 2

45-54

CAC 1-100

3.5 (1.3-9.8)

1.8 (0.6-5.4)

CAC >100

18.5 (7.4-45.9)

8.3 (2.8-24.1)

55-64

CAC 1-100

4.0 (1.9-8.5)

2.1 (0.9-4.7)

CAC >100

14.5 (7.2-28.9)

7.9 (3.8-16.7)

65-74

CAC 1-1004.0 (1.9-8.0)

2.9 (1.4-6.0)

CAC >100

7.6 (3.9-14.7)

4.7 (2.3-9.5)

75-84

CAC 1-100

3.8 (0.8-16.8)

3.0 (0.6-14.1)

CAC >100

11.61 (2.83-47.6)

8.8 (2.1-36.9)

HAZARD RATIOS FOR CHD EVENTS IN DIFFERENT AGE GROUPS STRATIFIED BY CAC

Within each age group, increasing CAC is independently predictive of events.

After adjusting for risk factors, CAC is still a powerful tool in the

youngest

and

oldest

age groups to predict events.

Slide20

Discussion

Guidelines have changed drastically over the last 10 years.

While coronary calcium screening has been endorsed for intermediate risk patients, its use in specific populations remains unclear.

Slide21

Most contemporary risk-scoring algorithms are heavily weighted in favor of increasing age. Many older individuals are classified as intermediate and high-risk, primarily on the basis of age. Rotterdam study

Raggi

et al

The Elderly

-

Vliegenthart

et al: Coronary Calcium Score Improves Classification of Coronary Heart Disease Risk in the Elderly: The Rotterdam Study. J Am

Coll

Cardiol

2010;56:1407–14.

-

Raggi

et al: Coronary Artery Calcium to Predict All-Cause Mortality in Elderly Men and Women. J Am

Coll

Cardiol

2008;52:17–23.

Slide22

1795 patients, mean age 71.1 ± 5.7.Median followup 3.3 years.

The Elderly- Rotterdam

Vliegenthart

, et al: Coronary Calcification Improves Cardiovascular Risk

Prediction in the Elderly. Circulation 2005;112: 572-577.

Slide23

35,388 patients, mean age 70.Median followup of 5.8 years.

Similar to Rotterdam, there remains the potential

to reclassify patients into a more appropriate group.

The Elderly-

Raggi

et al

Raggi

, et al: Coronary Artery Calcium to Predict All-Cause Mortality in Elderly Men and Women. J Am

Coll

Cardiol

2008;52:17–23.

Slide24

When compared to other studies, MESA also demonstrates that increasing CAC is independently associated with CHD events in the 75-84 age group.Most, but not all of the excess risk may be accounted for by CAC and not chronological age.

↑ CAC represents an increased burden of atherosclerosis, including unstable mixed calcified plaque which may account for the increased incidence of CHD events.

The Elderly- MESA

Slide25

MESA: Risk Factors vs CAC

Silverman et al: Impact of Coronary Artery Calcium on Coronary Heart Disease Events

In Individuals at the Extremes of Traditional Risk Factor Burden: The Multi-Ethnic Study of Atherosclerosis.

Slide26

19% of patients in the 75-84 age group had NO coronary artery calcium. Event rate of 2.1/1000 person-years (1.1%).Hazard ratio compared to CAC=0 in the 45-54 age group: 2.1 (0.4-10.63).

Raggi

, et al: Annual mortality rate of 2.2% for CAC=0 in patients ≥ 70 years old.44,000 cohort: Annual mortality rate of 2.8/1000 person-years for CAC=0 in patients ≥ 75 years old.

Zero CAC in the Elderly

Slide27

Young Persons

Framingham Offspring

CAC >100 in 45-55 age group: 12%.

CARDIA

Any CAC in 33-45 age group: 1.5%.

PACC

N=1983, mean age 43.

CAC ≥45: 6.7%.

7/364 with CAC had an event.

HR

for CHD event for CAC ≥45: 4.8.

44,000

cohort

Prevalence

of CAC >100 in <45 age group: 4%.

HR for CAC 100-400: 6.6

HR for CAC >400: 10.8.

MESA

Prevalence of CAC

>100 in 45-55 age group: 7.3%. HR of CHD events in this group: 8.3 (2.8-24.1).

Slide28

Accurate means of improving cardiovascular risk stratification in elderly patients.Beneficial in discriminating CHD risk in young persons, who may be asymptomatic yet have a significant atherosclerotic burden.

Conclusion