Abstract 60: Remnant Lipoprotein Cholesterol and Mortality after Acute Myocardial Infarction: The TRIUMPH Prospective Multi-Center Registry

Abstract

Background: Prior studies suggest a hypercholesterolemia paradox in which acute myocardial infarction (AMI) patients with higher low-density lipoprotein cholesterol have better outcomes, seemingly explained by confounding due to pre-existing statin use and other factors. We sought to examine whether remnant lipoprotein cholesterol (RLP-C) also fits this paradox, and if so, whether the association is explained by potential confounders, including pre-existing statin use. Methods: We examined the 2,465 patients participating in lipid testing in TRIUMPH; a prospective, 24-center U.S. study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured during AMI hospitalization by density gradient ultracentrifugation (Atherotech, Birmingham, AL). RLP-C was defined as the sum of very low-density lipoprotein fraction 3 cholesterol (VLDL 3 -C) and intermediate-density lipoprotein cholesterol (IDL-C). We assessed the association with 2-year mortality by Cox regression models adjusting for GRACE score, site, age, sex, race, insurance, education, tobacco use, diabetes mellitus, hypertension, alcohol use, physical activity, body mass index, statin use, and high-density lipoprotein cholesterol. Results: Patients were 58±12 years old (mean±SD) and 68% were men. After 2 years of follow-up, 226 (9%) patients died. The mortality rate was 12.4% in the lowest tertile of RLP-C (0 to <16 mg/dl), 8.5% in the middle tertile (16 to <24 mg/dl), and 6.9% in the highest tertile (24 to 120 mg/dl) (P=0.0003). In multivariable Cox regression, a one SD increase in RLP-C (11 mg/dl) was associated with a 23% lower risk of 2-year mortality (HR, 0.77; 95% CI, 0.65 to 0.90). Similar results were found for the individual components of RLP-C: for a one SD increase in VLDL 3 -C (4 mg/dl), HR, 0.72; 95% CI, 0.60 to 0.86; for a one SD increase in IDL-C (8 mg/dl), HR, 0.78; 95% CI, 0.66 to 0.91. Conclusion: Compatible with a hypercholesterolemia paradox, higher RLP-C levels were associated with lower mortality 2 years after AMI. This observation remained consistent after adjustment for statin use, as well as demographic, socio-economic, and clinical risk factors, suggesting that unknown protective factors may explain these paradoxically better outcomes with higher RLP-C levels.