The Association Between Low-Density Lipoprotein Cholesterol and Incident Atherosclerotic Cardiovascular Disease in Older Adults: Results From the National Institutes of Health Pooled Cohorts

Abstract

Background/objectives: Elevated low-density lipoprotein cholesterol (LDL-C) in early adulthood is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). The strength of the association between LDL-C and ASCVD among older adults, however, is less understood.

Design: We examined individual-level cohort data from the National Institutes of Health Pooled Cohorts (Framingham Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study), which prospectively measured CVD risk factors and incident disease.

Setting: Prospective cohort study.

Participants: Adults, aged 75 years or older, free of ASCVD.

Measurements: We evaluated the associations between LDL-C and incident ASCVD (stroke, myocardial infarction, and cardiovascular death) in unadjusted analysis and in multivariable-adjusted Cox proportional hazards models. We assessed 5-year Kaplan-Meier ASCVD event rates in patients with and without hyperlipidemia (LDL-C ≥130 mg/dL or on lipid-lowering medications), stratified by the number of other risk factors, including smoking, diabetes, and hypertension.

Results: We included 2667 adults, aged 75 years or older (59% female), free of ASCVD; median age was 78 years, with median LDL-C of 117 mg/dL. In both unadjusted and adjusted analyses, there was no association between LDL-C and ASCVD (adjusted hazard ratio = 1.022; 95% confidence interval = 0.998-1.046; P = .07). Among adults without other risk factors (free of smoking, diabetes, and hypertension), event rates were similar between those with and without hyperlipidemia (Kaplan-Meier rates = 5.8% and 7.0%, respectively). Among adults with one or two or more other risk factors, the presence of hyperlipidemia was also not associated with 5-year CVD event rates (Kaplan-Meier rates = 12.8% vs 15.0% [P = .44] for one other risk factor and 21.9% vs 24.0% [P = .59] for two or more other risk factors).

Conclusion: Among a well-characterized cohort, LDL-C was not associated with CVD risk among adults aged 75 years or older, even in the presence of other risk factors. J Am Geriatr Soc 67:2560-2567, 2019.

Keywords: cardiovascular disease risk; low-density lipoprotein cholesterol; older adults.

Figure 1.. LDL-C and ASCVD risk among untreated older adults (≥75 years).

This figure demonstrates the results from the univariable evaluation of association between LDL-C and ASCVD risk with LDL-C modeled as a linear variable (HR per 10 unit increase was 1.009 [0.986–1.032], p=0.46) and using restricted cubic splines. In multivariable modeling the HR was 1.022 (95% CI 0.998–1.046, p=0.07), with a p-value for non-linearity=0.40. The model for non-linear LDL does not significantly improve the fit and there was no significant evidence of a non-linear relationship between LDL-C and ASCVD in the unadjusted model (p=0.15); 306 observations on lipid-lowering medications were excluded from this analysis. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol

Figure 2.. Association between hyperlipidemia and ASCVD risk in the presence or absence of other risk factors

This figure demonstrates the observed ASCVD risk of older adults (≥75 years old) with: A) no traditional risk factors (no current smoking, diabetes, hypertension, or hyperlipidemia) vs. individuals with no risk factors other than hyperlipidemia (defined as LDL-C ≥130 mg/dL or on lipid-lowering therapy); B) 1 traditional risk factor (from current smoking, diabetes, or hypertension) vs. individuals with 1 risk factor plus hyperlipidemia (defined as LDL-C ≥130 mg/dL or on lipid-lowering therapy); and C) 2 or more traditional risk factors (from current smoking, diabetes, or hypertension) vs. individuals with 2 or more risk factors plus hyperlipidemia (defined as LDL-C ≥130 mg/dL or on lipid-lowering therapy). Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; HLD, hyperlipidemia