Denis Talbot1,2, Joseph A Chris Delaney3, Veit Sandfort4, David M Herrington5, Robyn L McClelland6. 1. Département de médecine sociale et préventive, Université Laval, Québec, Qc, Canada. 2. Unité santé des populations et pratiques optimales en santé, CHU de Québec - Université Laval research center, Québec, Qc, Canada. 3. Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA. 4. National Institutes of Health, Bethesda, MD, USA. 5. Heart and Vascular Center of Excellence, Wake Forest University School of Medicine, Winston Salem, NC, USA. 6. Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA.
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.
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.
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