John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 1/10/2020

Mediation of cardiovascular risk factor effects through subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis.

Yeboah J, Delaney JA, Nance R, McClelland RL, Polak JF, Sibley CT, Bertoni A, Burke GL, Carr JJ, Herrington DM
Arterioscler Thromb Vasc Biol. 2014 34 (8): 1778-83

PMID: 24876350 · PMCID: PMC4329880 · DOI:10.1161/ATVBAHA.114.303753

OBJECTIVE - It is unclear to what extent subclinical cardiovascular disease (CVD) such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial flow-mediated dilation (FMD) are mediators of the known associations between traditional cardiovascular risk factors and incident CVD events. We assessed the portion of the effects of risk factors on incident CVD events that are mediated through CAC, CIMT, and FMD.

APPROACH AND RESULTS - Six thousand three hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants were included. Nonlinear implementation of structural equation modeling (STATA mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of the association between traditional risk factors and incident CVD event. Mean age was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the highest mediation while FMD showed the least. Age had the highest percent of total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking had the least percent of total effect mediated via CAC (percent [95% confidence interval]: 80.2 [58.8-126.7] versus 10.6 [6.1-38.5], respectively). Body mass index showed the highest percent of total effect mediated via CIMT (17.7 [11.6-38.9]); only a negligible amount of the association between traditional risk factors and CVD was mediated via FMD.

CONCLUSIONS - Many of the risk factors for incident CVD (other than age, sex, and body mass index) showed a modest level of mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers may not be optimal intermediaries for gauging upstream risk factor modification.

© 2014 American Heart Association, Inc.

MeSH Terms (30)

Aged Aged, 80 and over Age Factors Asymptomatic Diseases Atherosclerosis Body Mass Index Brachial Artery Cardiovascular Diseases Carotid Artery Diseases Carotid Intima-Media Thickness Coronary Angiography Coronary Artery Disease Ethnic Groups Female Humans Incidence Male Middle Aged Nonlinear Dynamics Obesity Predictive Value of Tests Proportional Hazards Models Prospective Studies Risk Factors Sex Factors Smoking Tomography, X-Ray Computed United States Vascular Calcification Vasodilation

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