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Am J Epidemiol. 2018 Jun 1;187(6):1319-1326. doi: 10.1093/aje/kwx360.

Accounting for Time-Varying Confounding in the Relationship Between Obesity and Coronary Heart Disease: Analysis With G-Estimation: The ARIC Study.

Author information

Cardiovascular Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran.
School of Health, Guilan University of Medical Sciences, Rasht, Iran.
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Endocrinology, AJA University of Medical Sciences, Tehran, Iran.
Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.


In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study was performed in a subset of participants from the Atherosclerosis Risk in Communities (ARIC) Study (1987-2010), a US study designed to investigate risk factors for atherosclerosis. General obesity was defined as body mass index (weight (kg)/height (m)2) ≥30, and abdominal obesity (AOB) was defined according to either waist circumference (≥102 cm in men and ≥88 cm in women) or waist:hip ratio (≥0.9 in men and ≥0.85 in women). The association of obesity with CHD was estimated by G-estimation and compared with results from accelerated failure-time models using 3 specifications. The first model, which adjusted for baseline covariates, excluding metabolic mediators of obesity, showed increased risk of CHD for all obesity measures. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model produced negligible changes in the hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95% confidence interval (CI): 0.83, 1.47) for general obesity, 1.65 (95% CI: 1.35, 1.92) for AOB based on waist circumference, and 1.38 (95% CI: 1.13, 1.99) for AOB based on waist:hip ratio, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratios for both measures were further from the null than those derived from standard models.

[Available on 2019-06-01]

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