Associations of time-varying obesity and metabolic syndrome with risk of incident heart failure and its subtypes: Findings from the Multi-Ethnic Study of Atherosclerosis

Objective: Most previous studies have examined associations between metabolic disorders measured at a single point in time and risk of heart failure (HF). However, there are many situations where the values of exposures vary over time before HF occurs. We aimed to examine the associations of time-varying obesity and metabolic syndrome (MetSyn) measured at multiple points in time with HF. Methods: A total of 6750 participants in the Multi-Ethnic Study of Atherosclerosis from 2000 were included in the study. Follow-up was completed through December 2015. MetSyn was defined using the American Heart Association criteria. Incident HF was diagnosed by clinical criteria. Subtypes HF (reduced ejection fraction (HFrEF) and preserved (HFpEF) were classified by left ventricular EF. Results: A total of 331 HF cases were identified during 82,609 person-years of observation. The incidence (95%CI) of total HF was 4.0 (3.4–4.4) per 1000 person-years. Of the total HF cases, 45.6% were HFrEF (n = 151), 40.8% HFpEF (n = 135), and 13.6% were unclassified HF subtypes (n = 45). After adjusting for key covariates, time-varying obesity (BMI ≥ 30 kg/m²) and MetSyn were significantly associated with HF, with a stronger association for HFpEF than for HFrEF. The corresponding hazards ratios (HR, 95%CI) were 1.97 (1.43–2.72) and 1.86 (1.43–2.42) for HFpEF, and 1.46 (1.07–1.98), and 1.39 (1.06–1.82) for HFrEF respectively. Time-varying large waist circumference was significantly associated with for HFpEF, but not with HFrEF. Conclusion: Time-varying obesity and MetSyn were significantly associated with HF risk, with a stronger association with HFpEF than with HFrEF. Continued effort to control these risk factors is recommended.