Metabolically Healthy Obesity Versus Metabolic Obesity on Long-Term Major Adverse Cardiovascular Events and Mortality in Women with Suspected Ischemic Heart Disease

Background: Obesity and metabolic syndrome (MS) often co-exist; however, these conditions can exist independently as metabolically healthy obesity (MHO) and as metabolic obesity (MO). Methods: We investigated the association between metabolic status and body weight and risk of obstructive angiographic coronary artery disease (CAD), long-term major adverse cardiovascular events (MACEs), and all-cause mortality in women with signs/symptoms of ischemic heart disease (IHD) enrolled in the original cohort of the Women’s Ischemia Syndrome Evaluation (WISE) study (1997–2001) followed for mortality for a median of 8.6 years (range: 0–11.3 years). Normal weight (NW) was defined as a body mass index (BMI) < 25 kg/m2, overweight (OW) was defined as a BMI of 25–29 kg/m2, obesity (O) was defined as ≥30 kg/m2. MS was defined according to the NCEP ATP III Harmonized definition, metabolically healthy (MHO) was defined as obesity in the absence of MS, and MO was defined as MS in NW individuals. Results: 503 women were evaluated including 20.7% MH-NW, 14.7% MH-OW, 8.5% MHO, 6.2% MO, 21.9% MS-OW, 28.0% MS-O. Compared to MH-NW (reference), MHO was associated with a lower risk of MACEs (aHR 0.50; 95% CI 0.29, 0.85, p = 0.011) and mortality (aHR 0.50; 95% CI 0.27, 0.95, p = 0.035). MO was associated with higher odds of obstructive CAD (aOR 2.10; 95% CI 1.33, 3.33, p = 0.002) and a higher risk of MACEs (aHR 1.67, 95% CI 1.07, 2.59, p = 0.023). Conclusions: In women with suspected IHD, compared with MH-NW, MHO was associated with a lower risk of MACEs and mortality, whereas MO had higher odds of obstructive CAD and a greater MACE risk. These findings challenge simplistic BMI-based risk paradigms and emphasize the benefits of using metabolic status assessment over weight alone.