Lipids and Coronary Disease in Modern Observational Studies

Study Questions:

Has the association between cholesterol levels and coronary heart disease (CHD) changed over time in relation to increased statin use?


Data from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study (n = 9,578), Kaiser Permanente Southern California members (n = 346,595) who had baseline lipid measures between 2003 and 2007, were used to examine the association between lipids and CHD. The same analysis was then performed using older data from the ARIC (Atherosclerosis Risk in Communities) study (n = 14,590) with lipid measures collected between 1987 and 1989. Adults ages 45-64 years without CHD, not on statins at baseline, and were black or white race were included in this analysis. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured at baseline and low-density lipoprotein cholesterol (LDL-C), non–HDL-C,and total-to-HDL-C and triglyceride-to-HDL-C ratios were calculated.


Comparing the older ARIC data to the more recent cohorts, the mean age of the adults included in this analysis was 56.7, 53.4, and 54.0 years in REGARDS, Kaiser Permanente Southern California members, and ARIC, respectively. The prevalence of diabetes, history of stroke, and antihypertensive medication use increased at higher LDL-C in ARIC, but not in REGARDS or Kaiser Permanente Southern California members. A total of 225 CHD events occurred in REGARDS, 6,547 events in Kaiser Permanente Southern California members, and 583 events in ARIC, over an 8.9-year follow-up period. Less favorable lipid levels were associated with higher hazard ratios (HRs) for CHD in ARIC. These associations were attenuated in REGARDS and Kaiser Permanente Southern California members. Comparing the highest versus lowest quartile of LDL-C (≥146 mg/dl vs. ≤102 mg/dl), the HR was 1.89 (95% confidence interval [CI], 1.42-2.51) in ARIC, 1.25 (95% CI, 0.81-1.92) in REGARDS, and 1.49 (95% CI, 1.38-1.61) in the Kaiser Permanente Southern California group.


The investigators concluded that the association between lipids and CHD in contemporary studies may be attenuated due to preferential use of statins by high-risk individuals.


As the authors suggest, use of statins for primary prevention may contribute to an attenuation of the association between lipids and CHD. Understanding statin utilization patterns in current obervational cohorts has important implications.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Antihypertensive Agents, Atherosclerosis, Coronary Artery Disease, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Lipoproteins, HDL, Lipoproteins, LDL, Primary Prevention, Stroke, Dyslipidemias

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