Blood lipids and the incidence of atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis and the Framingham Heart Study

Abstract

Background: Dyslipidemia is a major contributor to the development of atherosclerosis and coronary disease. Its role in the etiology of atrial fibrillation (AF) is uncertain.

Methods and results: We studied 7142 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Framingham Heart Study who did not have prevalent AF at baseline and were not on lipid-lowering medications. Total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standard procedures. Incident AF during follow-up was identified from hospital discharge codes; review of medical charts; study electrocardiograms; and, in MESA only, Medicare claims. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of AF by clinical categories of blood lipids in each cohort. Study-specific results were meta-analyzed using inverse of variance weighting. During 9.6 years of mean follow-up, 480 AF cases were identified. In a combined analysis of multivariable-adjusted results from both cohorts, high levels of high-density lipoprotein cholesterol were associated with lower AF risk (hazard ratio 0.64, 95% CI 0.48 to 0.87 in those with levels ≥60 mg/dL versus <40 mg/dL), whereas high triglycerides were associated with higher risk of AF (hazard ratio 1.60, 95% CI 1.25 to 2.05 in those with levels ≥200 mg/dL versus <150 mg/dL). Total cholesterol and low-density lipoprotein cholesterol were not associated with the risk of AF.

Conclusion: In these 2 community-based cohorts, high-density lipoprotein cholesterol and triglycerides but not low-density lipoprotein cholesterol or total cholesterol were associated with the risk of AF, accounting for other cardiometabolic risk factors.

Keywords: atrial fibrillation; cholesterol; epidemiology; lipids; risk factors.

Figure 1.

Flowchart of study participants: MESA, 2000–2002, and the FHS, 1995–1998. AF indicates atrial fibrillation; CVD, cardiovascular disease; FHS, Framingham Heart Study; HF, heart failure; MESA, Multi‐Ethnic Study of Atherosclerosis; MI, myocardial infarction; NT‐proBNP, N‐terminal prohormone of B‐type natriuretic peptide.

Figure 2.

Association of blood lipids with AF. Cohort‐specific and combined HRs and 95% CIs associated with a 1SD increment in blood lipids (total cholesterol: 35 mg/dL; HDLc: 15 mg/dL; LDLc: 35 mg/dL; triglycerides: 65 mg/dL). P values are from heterogeneity tests. Cohort‐specific estimates are combined using fixed‐effects meta‐analysis. Results from Cox proportional hazards models adjusted for age, sex, race or ethnicity (only in MESA), study site (only in MESA), education, height, body mass index, smoking status, alcohol drinking, physical activity, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes, C‐reactive protein, and log_e(N‐terminal prohormone of B‐type natriuretic peptide) (in MESA) or log_e(B‐type natriuretic peptide) (in the FHS). FHS indicates Framingham Heart Study; HDLc, high‐density lipoprotein cholesterol; HR, hazard ratio; LDLc, low‐density lipoprotein cholesterol; MESA, Multi‐Ethnic Study of Atherosclerosis.

Figure 3.

Kaplan–Meier curves presenting AF‐free survival probabilities by categories of HDLc and triglycerides in the MESA and FHS studies. A, HDLc in MESA. B, HDLc in FHS. C, triglycerides in MESA. D, triglycerides in FHS. AF indicates atrial fibrillation; FHS, Framingham Heart Study; HDLc, high‐density lipoprotein cholesterol; MESA, Multi‐Ethnic Study of Atherosclerosis.