Dataset Information

Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.

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.

SUBMITTER: Talbot D

PROVIDER: S-EPMC5937846 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.

Talbot Denis D Delaney Joseph A Chris JAC Sandfort Veit V Herrington David M DM McClelland Robyn L RL

Pharmacoepidemiology and drug safety 20180206 4

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 29405501

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Project description:BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.

Project description:AimWe assess the improvement in discrimination afforded by the addition of the computed tomography risk markers thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT), and liver attenuation (LA) to the Framingham risk score (FRS) + coronary artery calcium (CAC) for incident coronary heart disease (CHD) and incident cerebrovascular disease (CVD) in a multiethnic cohort.Methods and resultsA total of 5745 participants were enrolled, with 2710 at intermediate Framingham risk, 210 CVD events, and 155 CHD events). Over 9 years of follow up, 251 had adjudicated CHD, 346 had CVD events, and 321 died. The data were analysed using Cox proportional hazard, receiver operator curve (ROC), and net reclassification improvement (NRI) analyses. In the whole cohort and also when the analysis was restricted to only the intermediate-risk participants, CAC, TAC, AVC, and MAC were all significantly associated with incident CVD, incident CHD, and mortality, and CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CVD and incident CHD; LA had the least. The addition of TAC, AVC, MAC, PAT, and LA to FRS + CAC all resulted in a significant reduction in AUC for incident CHD (0.712 vs. 0.646, 0.655, 0.652, 0.648, and 0.569; all p < 0.01, respectively) in participants with intermediate FRS. The addition of CAC to FRS resulted in an NRI of 0.547 for incident CHD in the intermediate-risk group. The NRI when TAC, AVC, MAC, PAT, and LA were added to FRS + CAC were 0.024, 0.026, 0.019, 0.012, and 0.012, respectively, for incident CHD in the intermediate-risk group. Similar results were obtained for incident CVD in the intermediate-risk group and also when the whole cohort was used instead of the intermediate FRS group.ConclusionsThe addition of CAC to the FRS provides superior discrimination especially in intermediate-risk individuals compared with the addition of TAC, AVC, MAC, PAT, or LA for incident CVD and incident CHD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT, or LA individually to FRS + CAC worsens the discrimination for incident CVD and incident CHD. These risk markers are unlikely to be useful for improving cardiovascular risk prediction.

Dataset Information

Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.

Publications

Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.

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