Is LDL cholesterol associated with long-term mortality among primary prevention adults? A retrospective cohort study from a large healthcare system

Abstract

ObjectivesAmong primary prevention-type adults not on lipid-lowering therapy, conflicting results exist on the relationship between low-density lipoprotein cholesterol (LDL-C) and long-term mortality. We evaluated this relationship in a real-world evidence population of adults.DesignRetrospective cohort study.SettingElectronic medical record data for adults, from 4 January 2000 through 31 December 2022, were extracted from the University of Pittsburgh Medical Center healthcare system.ParticipantsAdults without diabetes aged 50–89 years not on statin therapy at baseline or within 1 year and classified as primary prevention-type patients. To mitigate potential reverse causation, patients who died within 1 year or had baseline total cholesterol (T-C) ≤120 mg/dL or LDL-C <30 mg/dL were excluded.Main exposure measureBaseline LDL-C categories of 30–79, 80–99, 100–129, 130–159, 160–189 or ≥190 mg/dL.Main outcome measureAll-cause mortality with follow-up starting 365 days after baseline cholesterol measurement.Results177 860 patients with a mean (SD) age of 61.1 (8.8) years and mean (SD) LDL-C of 119 (31) mg/dL were evaluated over a mean of 6.1 years of follow-up. A U-shaped relationship was observed between the six LDL-C categories and mortality with crude 10-year mortality rates of 19.8%, 14.7%, 11.7%, 10.7%, 10.1% and 14.0%, respectively. Adjusted mortality HRs as compared with the referent group of LDL-C 80–99 mg/dL were: 30–79 mg/dL (HR 1.23, 95% CI 1.17 to 1.30), 100–129 mg/dL (0.87, 0.83–0.91), 130–159 mg/dL (0.88, 0.84–0.93), 160–189 mg/dL (0.91, 0.84–0.98) and ≥190 mg/dL (1.19, 1.06–1.34), respectively. Unlike LDL-C, both T-C/HDL cholesterol (high-density lipoprotein cholesterol) and triglycerides/HDL cholesterol ratios were independently associated with long-term mortality.ConclusionsAmong primary prevention-type patients aged 50–89 years without diabetes and not on statin therapy, the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100–189 mg/dL, which is much higher than current recommendations. For counselling these patients, minimal consideration should be given to LDL-C concentration.