Abstract

Introduction: Obesity is associated with a varying spectrum of metabolic risk, from the metabolically healthy obesity (MHO) phenotype, to metabolically unhealthy obesity (MUO) with the development of metabolic syndrome (MetS) and diabetes (DM). The longitudinal association of metabolic risk with CVD phenotypes (CHD, HF) has not been well characterized. Hypothesis: Persistent MHO is independently associated with heart failure (HF) but not coronary heart disease (CHD), and regression from MUO to MHO mitigates CVD risk. Methods: We conducted a prospective analysis of 10,011 Visit 4 (1996-98) ARIC participants free of HF and CHD (mean age 63, 21% Black, 56% female). Metabolic risk among those with obesity (BMI ≥ 30 kg/m 2 ) was categorized as MHO (no MetS or DM), MUO (MetS present) and MUO with DM, with same categorizations among those without obesity. We used Cox regression models to estimate associations of cross-categories of metabolic risk status at Visit 2 (1990-92) and Visit 4 with risk of HF and CHD after Visit 4 through 12/21/19. (Reference: persistent metabolically healthy normal weight). Results: Between Visits 2 and 4, 56% of those with MHO transitioned to MUO. There were 2212 HF and 1648 CHD events, median follow-up of 20.5 years. Persistent MHO status was associated with increased risk for HF (HR:1.59, 95% CI: 1.19-2.13) but not CHD (HR: 1.08, 95% CI: 0.74-1.58) (Table). Persistent MUO with DM had the highest risk for HF (HR: 5.30, 95% CI: 4.38-6.41) and CHD (HR: 3.77, 95% CI: 3.00-4.74). Among those with MUO at Visit 2, progression to MUO with DM at Visit 4 was linked to greater risk for HF and CHD, while regression to MHO was associated with an attenuated risk for CVD. Similar patterns were seen for those without obesity (data not shown). Conclusions: Transitions in metabolic risk status are common and associated with divergent patterns of CVD risk. Progression from MHO to MUO and even persistent MHO are linked to HF risk, whereas regression from MUO to MHO may attenuate CVD risk. Primordial prevention of obesity is warranted to stave off HF.

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