Can cholesterol be too low? A retrospective correlation of cholesterol lab values to other markers of cardiovascular disease risk

Abstract

Abstract Introduction/Objective Most recommendations for lipid panel reference ranges are one-sided (desirable total cholesterol is <200 mg/dL, optimal LDL cholesterol [LDL-C] is <100 mg/dL). However, recent studies suggest risks for cardiovascular diseases or mortality at very low cholesterol values. In this retrospective study, we investigated the association between lipid panel results and surrogate markers of cardiovascular disease to test the hypothesis that very low cholesterol levels are associated with increases in cardiovascular risk. Methods/Case Report Patients with lipid panels reported from April 2020-March 2021 at LAC+USC Medical Center were included. Lipid panels (total cholesterol, LDL-C, HDL-C, triglycerides) and laboratory results representing risk factors for cardiovascular disease (troponin T (TnT), NT-pro brain natriuretic peptide (BNP), hemoglobin A1c (HbA1c), high sensitivity C-reactive protein (CRP)) were collated. Lipid panel values were compared against the percentage of patients with non-optimal laboratory results for the cardiovascular risk markers. Results (if a Case Study enter NA) Decreasing total cholesterol levels vs. the percentage of patients with high TnT or BNP showed a U-curve with a nadir at 200-240 mg/dL (elevated TnT: 15%, BNP: 49%) and further increased with lower cholesterol levels <60 mg/dL (TnT: 56%, BNP: 92%); HbA1c (U-curve, nadir: 160-180 mg/dL); and CRP (90% at cholesterol <60 mg/dL; 43% at 220-240 mg/dL). Decreasing HDL-C against all markers of cardiovascular disease demonstrated a continued downtrend below optimal HDL-C levels. Decreasing LDL-C vs. the percentage of high TnT showed a U-curve with a nadir at 120-140 mg/dL; BNP (uptrends in the optimal range of LDL-C); HbA1c (U-curve, nadir: 90-100 mg/dL); and CRP (uptrends with decreasing LDL-C). TnT and BNP decreased with increasing triglycerides, while HbA1c increased with increasing triglycerides. Data points (TnT: n > 5,000; BNP: n > 3,000; HbA1c: n > 29,000; CRP: n > 4,500). Conclusion Very low concentrations of total cholesterol and LDL-cholesterol are associated with elevated markers of cardiovascular risk. Laboratories may wish to consider incorporating low ends to total cholesterol and LDL-cholesterol reference ranges.