Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation
2020/10/12 by Ron C Hoogeveen, Ron C. Hoogeveen, Christie M. Ballantyne +1 · 318 citations
Immunology and Microbiology · Medicine · #Atherosclerosis and Cardiovascular Diseases #Atherosclerotic cardiovascular disease #Cardiology #Cholesterol #Computer science #Diabetes, Cardiovascular Risks, and Lipoproteins #Disease #Inflammation #Internal medicine #Ldl cholesterol #Lipoprotein #Lipoproteins and Cardiovascular Health #Low-density lipoprotein #Medicine #Residual #Residual risk
paper · pdf · doi:10.1093/clinchem/hvaa252
published in Clinical Chemistry 67(1), 143-153 (American Association for Clinical Chemistry)
openalex publication_date 2020/10/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract
BACKGROUND: Current guidelines target low-density lipoprotein cholesterol (LDL-C) concentrations to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and yet clinical trials demonstrate persistent residual ASCVD risk despite aggressive LDL-C lowering. CONTENT: Non-LDL-C lipid parameters, most notably triglycerides, triglyceride-rich lipoproteins (TGRLs), and lipoprotein(a), and C-reactive protein as a measure of inflammation are increasingly recognized as associated with residual risk after LDL-C lowering. Eicosapentaenoic acid in statin-treated patients with high triglycerides reduced both triglycerides and ASCVD events. Reducing TGRLs is believed to have beneficial effects on inflammation and atherosclerosis. High lipoprotein(a) concentrations increase ASCVD risk even in individuals with LDL-C < 70 mg/dL. Although statins do not generally lower lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitors reduce lipoprotein(a) and cardiovascular outcomes, and newer approaches are in development. Persistent increases in C-reactive protein after intensive lipid therapy have been consistently associated with increased risk for ASCVD events. SUMMARY: We review the evidence that biochemical assays to measure TGRLs, lipoprotein(a), and C-reactive protein are associated with residual risk in patients treated to low concentrations of LDL-C. Growing evidence supports a causal role for TGRLs, lipoprotein(a), and inflammation in ASCVD; novel therapies that target TGRLs, lipoprotein(a), and inflammation are in development to reduce residual ASCVD risk.
Citations
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