TABLE 2

Studies assessing BMI and cardiorespiratory fitness: Effect on heart failure development

Study	N	Design^{^a}	End point	Main findings
Pandey et al¹⁹ Cooper Center Longitudinal Study	19,485	Patients stratified by BMI and peak METs into quintiles	Long-term risk of hospitalization for HF	Higher midlife BMI was significantly associated with greater risk of hospitalization for HF in older age. This association was attenuated after adjusting for cardiorespiratory fitness.
Kenchaiah et al²⁰ Physicians’ Health Study	21,094	Patients stratified by BMI and vigorous physical activity	New onset HF	Compared with lean participants, overweight and obese participants had increased HF risk. Vigorous physical activity conferred decreased HF risk. No interaction was found between BMI, vigorous physical activity, and HF risk.
Hu et al²¹	59,178	Patients stratified by physical activity and indicators of adiposity (eg, BMI, waist circumference, waist-to-hip ratio)	New onset HF	Higher BMI, waist circumference, or waist-to-hip ratio was associated with increased HF incidence in men and women. The protective effect of physical activity on HF risk was consistent in participants at all levels of BMI.
Kokkinos et al²²	20,254	Patients stratified by BMI and cardiorespiratory fitness in quartiles	New onset HF	Increased cardiorespiratory fitness was associated with progressively lower HF risk regardless of BMI. After adjusting for fitness, BMI was not a significant predictor of HF risk.
Pandey et al²³ Look AHEAD trial	5,109 (with DM)	Patients stratified by BMI and cardiorespiratory fitness into tertiles	New onset HF	High cardiorespiratory fitness was associated with lower risk of developing HFpEF. Sustained long-term improvement in fitness was associated with lower risk of HF after 4 years.

↵a All studies are retrospective.
AHEAD = Action for Health in Diabetes; BMI = body mass index; DM = diabetes mellitus; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; METs = metabolic equivalents