Abstract P595: Low Serum Cholesterol and Coronary Heart Disease Mortality in Veterans

Abstract

Background: The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by recent studies that observed a U-shaped relation between cholesterol and mortality. The effect of low cholesterol and CHD risk among Veterans is unclear. Methods: This prospective cohort study included Veterans greater than 18 years of age with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018 in the Veterans Health Administration electronic health record system. Veterans were followed to assess CHD mortality risk in relation to outpatient blood cholesterol levels. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CHD mortality associated with total cholesterol (TC). Results: Among 4,467,942 Veterans, 381,871 CHD deaths were recorded. We observed a V-shaped relation between TC and age-, sex, race and smoking-adjusted risk of CHD mortality. The association became U-shaped after adjustment for statin use, body mass index, hypertension, and diabetes. When further adjusted for high-density lipoprotein level, 11 baseline diseases, and applying a 2-year lag analysis, the relation to CHD mortality was J-shaped--flat for TC<180 mg/dL and greater risk was present at higher cholesterol levels. Compared to Veterans with TC between 180-199 mg/dL, risk for CHD mortality (HR (95%CI)) was 1.03 (1.02-1.04), 1.07 (1.06-1.09), 1.15 (1.13-1.18), 1.25 (1.22-1.28) and 1.45 (1.42-1.49) times greater among Veterans with TC (mg/dL) of 200-219, 220-239, 140-259, 260-279 and ≥280, respectively. Transition of the TC- CHD mortality patterns were J-J-J, V-U-J and L-U-J among young, middle, and older veterans (P for interaction between TC and age group < 0.001). Similar J-shaped but weaker relations were observed in statin users at baseline. Conclusions: Based on prospective data for almost 4.5 million adult Veterans, CHD mortality risk steadily increased for TC ≥200mg/dL after adjustment for a range of health conditions. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD risk and lower prevalence of multimorbidity, mental health disorders, nutritional deficits, and other risk factors for CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication. The changes in risk for CHD mortality by TC groups observed in our study (L- to U- to J-shape) highlights the importance of fully adjusting for the presence of multimorbidity and HDL-C to avoid misleading conclusions.