Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk

Brian A. Ference, John J.P. Kastelein, Henry N. Ginsberg, M. John Chapman, Stephen J. Nicholls, Kausik K. Ray, Chris J. Packard, Ulrich Laufs, Robert D. Brook, Clare Oliver‐Williams, Adam S. Butterworth, John Danesh, George Davey Smith, Alberico L. Catapano, Marc S. Sabatine

JAMA · 2017

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Summary

This Mendelian randomisation study examined whether the cardiovascular benefit of lowering LDL cholesterol depends on the biological mechanism by which it is lowered, using genetic variants in CETP and HMGCR genes as natural experiments. In a cohort of over 102,000 participants with external validation in nearly 190,000 more, CETP variants associated with raised HDL-C and lower LDL-C (and apoB) showed cardiovascular protection comparable to statin-induced LDL reduction, suggesting that different pathways to LDL reduction may confer similar clinical benefit.

Regional applicability

The study includes cohort and case-control data from the United Kingdom, and the findings are therefore directly applicable to UK population genetics and cardiovascular risk assessment. The genetic variants studied are common across European ancestry populations, making the results broadly transferable to UK clinical and public health contexts.

Key measures

Odds ratios for major cardiovascular events; HDL-C, LDL-C, and apoB levels; CETP and HMGCR genetic scores

Outcomes reported

The study measured the association between genetic variants in CETP and HMGCR genes, changes in lipoprotein levels (HDL-C, LDL-C, apoB), and risk of major cardiovascular events. Findings were validated across multiple cohort and case-control studies in North America and the United Kingdom.

Theme
Nutrition & health
Subject
Dietary fats & fatty acids
Study type
Research
Study design
Mendelian randomization analyses with external validation
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1001/jama.2017.11467
Catalogue ID
BFmowc2by2-4ec1j3

Topic tags

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