High levels of high-density lipoprotein cholesterol (HDL-C) and major adverse cardiovascular events and 10-year all-cause mortality:results from Women's Ischemia Syndrome Evaluation (WISE) study

Abstract

Abstract Background High and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with lower and higher cardiovascular risk, respectively. Emerging data in the general population and those with coronary artery disease have shown an increased risk of adverse outcomes with high (>1.8mmolL [70 mg/dL]) HDL-C levels. However, there are limited data on the risk of adverse of outcomes in women with suspected ischemic heart disease and high HDL-C levels. Purpose To investigate relationships between high (>1.8mmol/L [70 mg/dL]), average (1.3 - 1.8 mmol/L [ 50 - 70 mg/dL]), and low (<1.3 mmol/L [50 mg/dL]) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and 10-year all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods Participants (N= 935) enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) study from 1997-2001 underwent baseline testing that included fasting lipids, detailed demographic, and clinical data. A total of 607 women with available HDL-C values were included in this analysis. The adjudicated MACE outcome median follow-up was 5.9 years (range, 0 - 9.3), and the all-cause mortality median follow-up was 8.4 years (range, 0 - 11.3). Associations between HDL-C level and outcomes were obtained via multivariate cox regression and adjusted for age, race, BMI, waist circumference, menopausal status, hypertension, diabetes, family history of CAD, history of stroke, smoking history, alcohol use, statin use, and CAD status. The U-shaped curve was obtained using continuous HDL-C with the cubic spline analysis before adjusting for covariates listed above. Results The mean age of the cohort was 59±12 years, 62% had 3 or more cardiac risk factors, and 66 (10.9%) had a high HDL-C. High and low HDL-C were both associated with increased MACE risk compared to average HDL-C (HR 1.80, CI 1.03 - 3.14, p = 0.038; HR 1.63, CI 1.09 - 2.42, p = 0.016, respectively. Similarly, high and low HDL-C were associated with increased risk of all-cause mortality (HR 3.64, CI 1.84 - 7.20, p <0.001; HR 2.81, CI 1.67 - 4.71, p <0.001, respectively, Figure). Conclusions High and low HDL-C levels are associated with an increased MACE and all-cause mortality in women presenting with suspected ischemia undergoing coronary angiography. Our results highlight the need for additional prospective studies to discern the mechanisms behind high HDL-C levels and elevated risk of adverse outcomes in women.