Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very-Low-Density Lipoproteins.

Background: It is uncertain whether pharmacological reductions in very-low-density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low-density lipoprotein cholesterol (LDL-C) has been adequately lowered. We examined whether individuals with greater on-statin reductions in VLDL-related measures-beyond reductions in LDL-C-were at further reduced risk of ASCVD.

Methods And Results: In 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400-MHz proton nuclear magnetic resonance spectroscopy-measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin-allocated participants who achieved minimal (
Conclusions: Pharmacological reduction in small, cholesterol-enriched, triglyceride-depleted VLDL was associated with reduction in ASCVD risk. Chemically measured triglycerides may not sufficiently capture risk related to VLDL pathways. These findings also support broader profiling of lipid and lipoprotein changes in response to statins as prognostic markers of individual benefit, supporting more precision-medicine, individualized approaches to cardiovascular risk reduction.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.