Association of Serum Lipids and Coronary Heart Disease in Contemporary Observational Studies

Abstract

Background: The use of statins increased among US adults with high coronary heart disease (CHD) risk after publication of the 2001 cholesterol treatment guidelines.

Methods and results: We analyzed the association between lipids and CHD among 9578 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and 346,595 Kaiser Permanente Southern California (KPSC) members with baseline lipid measurements in 2003 to 2007. We performed the same analyses among 14,590 Atherosclerosis Risk In Communities (ARIC) study participants with lipid measurements in 1987 to 1989. Analyses were restricted to blacks and whites 45 to 64 years of age without CHD who were not taking statins at baseline. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline. Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and ratios of total to high-density lipoprotein cholesterol and triglycerides to high-density lipoprotein cholesterol were calculated. The prevalence of diabetes mellitus, history of stroke, and antihypertensive medication use increased at higher low-density lipoprotein cholesterol in ARIC but not in REGARDS or KPSC. Over 8.9 years of follow-up, 225 CHD events occurred in REGARDS, 6547 events in KPSC, and 583 events in ARIC. After multivariable adjustment, less favorable lipid levels were associated with higher hazard ratios for CHD in ARIC. These associations were attenuated in REGARDS and KPSC. For example, the hazard ratio associated with the highest versus lowest quartile of low-density lipoprotein cholesterol (≥ 146 versus ≤ 102 mg/dL) was 1.89 (95% confidence interval, 1.42-2.51) in ARIC, 1.25 (95% confidence interval, 0.81-1.92) in REGARDS, and 1.49 (95% confidence interval, 1.38-1.61) in KPSC.

Conclusion: The association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals.

Keywords: coronary disease; epidemiology; follow-up studies; lipids.

Figure 1

Flowchart of individuals from REGARDS, KPSC and ARIC included in the analysis. ARIC: Atherosclerosis Risk In Communities; CHD: coronary heart disease; KPSC: Kaiser Permanente Southern California; LDL-C: low-density lipoprotein cholesterol; REGARDS: REasons for Geographic And Racial Differences in Stroke; TG: triglycerides.

Figure 2

Forest-plot of hazard ratios for coronary heart disease by lipid categories in REGARDS, KPSC and ARIC. * 6,163 events from 336,851 members for the analysis of LDL-C. All analyses include adjustment by age, race, sex, education and income levels, alcohol consumption, current smoking, diabetes, reduced eGFR, stroke and use of antihypertensive medications. Analyses from REGARDS also include adjustments for region of residence. CHD definition from REGARDS and ARIC includes definite or probable MI or CHD death. CHD definition for KPSC includes non-fatal MI (defined by an inpatient stay with a discharge ICD-9 diagnosis code of 410.× in any position) or CHD death (defined by an underlying cause of death ICD-10 code I20–I25). Analyses in KPSC and ARIC are limited to 8.9 years of follow-up. Categories of serum lipids were defined based on quartiles from REGARDS study participants. ARIC: Atherosclerosis Risk In Communities; CHD: coronary heart disease; eGFR: estimated glomerular filtration rate; HDL-C: high-density lipoprotein cholesterol; KPSC: Kaiser Permanente Southern California; LDL-C: low-density lipoprotein cholesterol; MI: myocardial infarction; REGARDS: REasons for Geographic And Racial Differences in Stroke; TG: triglycerides.