Association of LDL cholesterol levels and all cause mortality in a real world analysis using data from an international network

Abstract

Abstract Background Current cholesterol guidelines have recommended low low-density lipoprotein cholesterol (LDL-C) treatment targets for secondary prevention of cardiovascular disease. However, recent studies have suggested that very low or very high levels of LDL-C may be associated with increased mortality and other adverse outcomes. The association between LDL-C levels and mortality remains to be determined. Methods and Results This cohort study included data from a large multinational electronic health record network (TriNetX) of patients aged 18 years or older with coronary artery disease. LDL-C levels were divided into 4 categories: <30 (cohort 1), 30-50 (cohort 2), 50-70 (cohort 3), and 70-100 (cohort 4). Deaths were ascertained by linkage to death records in the last 10 years before the analysis. Five-year Kaplan-Meier curves and hazard ratios were calculated. We identified 1,136,600 patients, of whom 36,060 had LDL-C <30 mg/dL, 282,500 had LDL-C <50 mg/dL, 255,964 had LDL-C 50-70 mg/dL and 596,136 had LDL-C 70-100 mg/dL. Comparative analyzes were performed on the cohorts (cohort 1 vs. cohort 2, cohort 2 vs. cohort 3, and cohort 3 vs. cohort 4) after propensity score matching. After adjustment, individuals of cohort 2 (n = 36,004), compared with those of cohort 1 (n = 36,004), had higher all-cause mortality (HR 1.086; CI 95% 1.064-1.109, p <0.0001), individuals of cohort 3 (n = 244,908), compared to those of cohort 2 (n = 270,359), had higher risk of all-cause mortality (HR 1.063; 95% CI 1.055-1.1071, p <0.0001), and induviduals of cohort 4 (n = 254,465), compared with those of cohort 3 (n = 254,465), had lower risk of all-cause mortality (HR 0.937; CI 95% 0.929-0.944, p <0.0001). Conclusions Lower LDL-C levels are associated with a reduced risk of all-cause mortality in patients with coronary artery disease.