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

Study Questions:

What is the impact of coronary artery calcium (CAC) in individuals at the extremes of risk factor (RF) burden?


A total of 6,698 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for coronary heart disease (CHD) events over a mean of 7.1 ± 1 years. Annualized CHD event rates were compared among each RF category (0, 1, 2, or ≥3) after stratification by CAC score (0, 1–100, 101–300, and >300). The following traditional modifiable RFs were considered: cigarette smoking, low-density lipoprotein cholesterol ≥3.4 mmol/L, low high-density lipoprotein cholesterol, hypertension, and diabetes.


There were 1,067 subjects (16%) with 0 RFs, whereas 1,205 (18%) had ≥3 RFs. Among individuals with 0 RFs, 68% had CAC 0, whereas 12% and 5% had CAC >100 and >300, respectively. Among individuals with ≥3 RFs, 35% had CAC 0, whereas 34% and 19% had CAC >100 and >300, respectively. Overall, 339 (5.1%) CHD events occurred. Individuals with 0 RFs and CAC >300 had an event rate 3.5 times higher than individuals with ≥3 RFs and CAC 0 (10.9/1,000 vs. 3.1/1,000 person-years). Similar results were seen across categories of Framingham risk score.


The authors concluded that among individuals at the extremes of RF burden, the distribution of CAC is heterogeneous.


This study reported that although individuals with increasing RFs are more likely to have CAC as well as have a higher burden of CAC, large heterogeneity exists. Furthermore, the data suggest that the presence of CAC is associated with increased CHD events (all and hard) across all levels of RF burden, even among individuals with no RFs. It appears that CAC testing may offer important prognostic information across a wider spectrum of individuals, and questions the need for a paradigm shift from RFs to detection of subclinical atherosclerosis. However, whether this new paradigm improves outcomes and is cost-effective will need to be evaluated in rigorous prospective trials.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension, Smoking

Keywords: Ethnic Groups, Cost-Benefit Analysis, Coronary Artery Disease, Atherosclerosis, Coronary Disease, Calcinosis, Smoking, Cholesterol, Dyslipidemias, Coronary Angiography, Cardiology, Hypertension, Diabetes Mellitus

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