A study based on the Look AHEAD trial examined how weight loss and physical activity impact the risk of HF, MI, and T2DM.
Type 2 diabetes mellitus (T2DM) is associated with a doubled increase in cardiovascular events, including heart failure (HF) and myocardial infarction (MI). The Look Action for Health in Diabetes (AHEAD) randomized controlled trial included T2DM patients with overweight and obesity and concluded that reduced body-mass index was associated with a lowered risk of HF and atherosclerotic cardiovascular disease (CVD). However, body mass index is a heterogeneous measure of body size. Due to the differences in cardiometabolic and cardiovascular phenotypes, the association between body mass index and fat mass and lean mass is unknown.
The Look AHEAD trial evaluated lifestyle intervention focused on weight loss and increased physical activity in 5145 patients with T2DM, overweight and obesity. This study is a post hoc analysis of the Look AHEAD trial, which included 5103 participants without HF at baseline that were followed up for 12.4 years. This study seeks to determine the association between body composition changes in fat mass and lean mass with the risk of HF and MI. The primary outcome was the incident of HF hospitalization and outpatient diagnosis of HF that was clinically adjudicated over 12.4 years of follow-up. The secondary outcome was the incident MI event, both fatal and nonfatal, during the follow-up period.
Patients were included with sufficient baseline data to determine the fat mass, lean mass, waist circumference, and cardiovascular events incidence. The fat mass and lean mass were estimated using validated demographics and anthropometric equations. Anthropometric equations were validated amongst participants who had a DXA scan to assess body composition measures at baseline, 1-year, and 4-year. A generalized linear model was utilized to compare the baseline characteristics across the groups. Multivariable-adjusted Cox proportional hazard analysis was conducted to determine the independent association of body composition parameters with the risk of HF. Patients from the Look AHEAD trial were excluded if data were missing on left ventricular ejection fraction (LVEF), which was used to determine the incidence of HF events and patients with a history of atherosclerotic CVD.
Fat mass and lean mass were validated using prediction equations that positively correlated with DXA measures (R2=0.87 and R2=0.90, respectively). During the 12.4 follow up period, the hospitalization incident due to HF was associated with 257 participants, of which 129 incidences were associated with heart failure with preserved ejection fraction (HFpEF,) 104 heart failure with reduced ejection fraction (HFrEF,) and 24 with missing LVEF. After adjustment for baseline demographics and cardiovascular risk factors, a short-term 1-year reduction in fat mass was significantly associated with a reduced risk of HF (HR: 0.74, 95% CI: 0.64-0.86). However, a short-term 1-year reduction in lean mass was not significantly associated with a risk in HF. Waist circumference was significantly associated with a reduced risk of HFpEF, but not with HFrEF (HR, 0.61, 95% CI, 0.44-0.83).
Additionally, during the 12.4 year follow-up period, there were 351 incidents of MI (event rate per 1000-person years = 5.43). Higher baseline fat mass and waist circumference were associated with a lower risk of MI, while baseline lean mass was not significantly related to MI risk. Changes in body composition during the short-term 1-year and intermediate 4-year did not show a significant risk of MI.
This post-hoc analysis of the Look AHEAD trial concluded that higher baseline measures of fat mass, lean mass, and weight circumference were significantly associated with a higher risk of HF. However, higher fat mass and weight circumference were associated with a reduced risk of MI. Additionally, longitudinal follow-up indicated that a reduction in fat mass was associated with a reduced risk of HF. The decrease in waist circumference was associated with a reduced risk of HFpEF. Thus, loss of fat mass and waist circumference through central adiposity are important modifiable targets for preventing HFpEF in patients with T2DM. This study had a long-term follow-up period with a patient population of various income and ethnic backgrounds. However, patients had to tolerate a treadmill test or maximal exercise test to be included in the study, potentially leading to selection bias. Further studies, including patients unable to tolerate maximal exercise tests, and other studies assessing the relationship between fat mass and weight circumference on MI’s risk, should be conducted.
- Higher fat mass, lean mass, and weight circumference was significantly associated with a higher risk of HF.
- Reducing waist circumference through central adiposity can reduce the risk of HFpEF, but similar risk reduction may not be seen with HFrEF.
- Further studies need to be conducted to determine the relationship between fat mass and waist circumference and the risk of MI.
Look AHEAD Research Group et al.” “The Look AHEAD study a description of the lifestyle intervention and the evidence supporting it” obesity
Patel, Kershaw V., et al.” “Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes: Findings From the Look AHEAD Trial” Circulation
Shana Indawala, PharmD Candidate, University of South Florida Health, Taneja College of Pharmacy