Combining Biomarkers and Imaging for Short-Term Assessment of Cardiovascular Disease Risk in Apparently Healthy Adults

Abstract

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5- and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

Keywords: N‐terminal pro B‐type natriuretic peptide; carotid intima‐media thickness; coronary artery calcium; high‐sensitivity C‐reactive protein; high‐sensitivity cardiac troponin T; plaque.

Figure 1. Cumulative incidence rates of global cardiovascular disease (CVD) and atherosclerotic cardiovascular disease composite outcomes stratified by the number of abnormal test results.

We pooled data from participants in 3 large population‐based cohorts, free from CVD at baseline (N=16 581), with measurements including N‐terminal pro‐B‐type natriuretic peptide; high‐sensitivity cardiac troponin T; high‐sensitivity C‐reactive protein; and a composite imaging measure of subclinical atherosclerosis (coronary artery calcium or carotid intima‐media thickness or plaque). Using an integer score to count the number of abnormal tests in each study participant, higher integer scores were associated with higher incidence of global CVD events (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation) and atherosclerotic CVD events (fatal or non‐fatal myocardial infarction or stroke) during 3 years of follow‐up. ASVCD indicates atherosclerotic cardiovascular disease; and CVD, cardiovascular disease.

Figure 2. Association between the number of abnormal test results and global cardiovascular disease outcomes in study subgroups.

Higher integer scores (representing the number of abnormal test results) were associated with global cardiovascular disease after multivariable adjustment regardless of the type of subclinical atherosclerosis imaging test used (carotid intima‐media thickness or plaque in ARIC; coronary artery calcium in DHS and MESA), and across categories of sex, race, age, and 10‐year cardiovascular risk estimated using pooled cohort equations. There were no significant interactions across subgroups (P interaction >0.05 across each subgroup). ARIC indicates Atherosclerosis Risk in Communities study; DHS, Dallas Heart Study, MESA, Multi‐Ethnic Study of Atherosclerosis; and PCE, pooled cohort equations.

Figure 3. Absolute 3‐year global cardiovascular disease event rates in the combined cohorts stratified by pooled cohort equation‐estimated risk and the number of abnormal test results.

Higher integer scores (representing the number of abnormal test results) were associated with higher 3‐year global cardiovascular disease risk across pooled cohort equation categories, and, conversely, a low integer score (0 or 1) was associated with lower global cardiovascular disease risk even among individuals with borderline or elevated 10‐year risk by pooled cohort equations. PCE indicates pooled cohort equations.