Weight fluctuations associated with mortality in patients with coronary artery disease

1. In patients with coronary artery disease (CAD), increased body-weight variability demonstrated a graded increased risk of cardiovascular events and death.

2. The association of increased cardiovascular events and mortality was higher in obese or overweight patients compared to those with normal weight.

Evidence Rating Level: 2 (Good)       

Study Rundown: Many patients prescribed weight reduction for the management of cardiovascular disease find it difficult to maintain the lower weight and experience cycles of weight loss and gain. The prognostic significance of these fluctuations is unknown and an area of controversy. This study explored the association of weight fluctuation with the risk of cardiovascular events in a large cohort of patients with known CAD. The primary outcome – any coronary event – demonstrated a graded increase with weight variability, with the strongest association in those with baseline obesity. Secondary outcomes – including any cardiovascular event, death, myocardial infarction (MI), and stroke – all were significantly higher with increased weight variability. New-onset diabetes was evaluated as an additional outcome and was significantly higher with increased weight variability. This data suggests that weight variability is an independent prognostic indicator in those with coronary artery disease.

The authors conducted a post hoc analysis using data of patients with CAD in the randomized Treating to New Targets (TNT) trial. This trial had a large cohort that excluded patients with a poor prognosis and included a sensitivity analysis (excluding patients with a history of heart failure) to reduce possible confounders. Limitations include the retrospective study design (precludes testing for causation), the use of BMI to measure obesity (insensitive to body composition), and the smaller sample size of the sensitivity analyses (underpowered for outcome assessment beyond a certain cutoff point).

Click to read the study in NEJM

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In-Depth [retrospective cohort study]: This post hoc analysis collected data on 9509 patients from the TNT trial with at least two post-baseline measurements of body weight. Patients were followed at 3, 6, 9, and 12 months and every 6 months thereafter. The main variability measure was absolute differences in successive weight. The primary outcome was any coronary event (a composite of coronary artery disease, nonfatal MI, resuscitated cardiac arrest, revascularization, or angina) evaluated as a time-dependent covariate. Secondary outcomes included any cardiovascular event, death, MI, and stroke, evaluated as a non-time-dependent covariate. New-onset diabetes was included as an additional outcome.

The median duration between first and last weight measurements was 4.7 years (median number of measurements, 12). Using body-weight as a time-dependent covariate, each 1 standard deviation (SD) increase in variability increased the risk of any coronary event (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01 to 1.07; p = 0.01), any cardiovascular event (HR, 1.04; 95% CI, 1.02 to 1.07; p < 0.01), and death (HR, 1.09; 95% CI, 1.07 to 1.12; p < 0.001). In the non-time-dependent covariate analysis, each 1 SD increase in variability increased the risk of any coronary event (HR, 1.04; 95% CI, 1.02 to 1.06; p < 0.001), cardiovascular event (HR, 1.04; 95% CI, 1.03 to 1.06; p < 0.001), death (HR, 1.03; 95% CI, 1.01 to 1.06; p = 0.01), MI (HR, 1.04; 95% CI, 1.00 to 1.07; p = 0.04), and stroke (HR, 1.05; 95% CI, 1.00 to 1.09; p = 0.03). Body-weight variability was also associated with an increase in new-onset diabetes (HR, 1.08; 95% CI, 1.02 to 1.14; p = 0.009). The strongest associations were found in those with the highest baseline BMI, and high body-weight variability was no significant in those with a normal BMI. Sensitivity analyses that excluded patients with only two measures of body-weight, a history of heart failure, or used other measures of variability yielded similar results.

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