Importance of the lipid-related pathways in the association between statins, mortality and cardiovascular disease risk : the multi-ethnic study of atherosclerosis

Authors: Talbot, Denis; Delaney, Joseph A. C.; Sandfort, Veit; Herrington, David M.; McClelland, Robyn L.
Abstract: PURPOSE: Estimating how much of the impact of statins on coronary heart diseases (CHD), cardiovascular disease (CVD), and mortality risk is attributable to their effect on low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides. METHODS: A semi-parametric g-formula estimator together with data from the Multi-Ethnic Study of Atherosclerosis (a prospective multi-center cohort study) was utilized to perform a mediation analysis. A total of 5280 participants, men and women of various race/ethnicities from multiple sites across the United States, were considered in the current study. RESULTS: The adherence adjusted total relative risk reduction (RRR) estimate (95% confidence interval) of statins on CHD was 14% (-16%, 37%), and the indirect component through LDL was 23% (-4%, 58%). For CVD, the total RRR was 23% (2%, 40%), and the indirect component through LDL was 5% (-13%, 25%). The total RRR of mortality was 18% (-1%, 35%), and the indirect component through LDL was -4% (-17%, 12%). The estimated indirect components through HDL and triglycerides were close to zero with narrow confidence intervals for all 3 outcomes. CONCLUSIONS: The estimated effect of statins on mortality, CVD, and CHD appeared to be independent of their estimated effect on HDL and triglycerides. Our study provides evidence that the preventive effect of statins on CHD could be attributed in large part to their effect on LDL. Our g-formula estimator is a promising approach to elucidate pathways, even if it is hard to make firm conclusions for the LDL pathway on mortality and CVD
Document Type: Article de recherche
Issue Date: 6 February 2018
Open Access Date: 19 March 2019
Document version: AM
This document was published in: Pharmacoepidemiology and drug safety, Vol. 27 (4), 365-372 (2018)
International Society for Pharmacoepidemiology
Alternative version: 10.1002/pds.4393
Collection:Articles publiés dans des revues avec comité de lecture

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