Metabolically Healthy Obesity and Ischemic Heart Disease: A 10-Year Follow-Up of the Inter99 Study

Abstract Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart disease (IHD) irrespective of metabolic health. Design: In all, 6238 men and women from the Danish prospective Inter99 study were followed during 10.6 (standard deviation = 1.7) years. Setting: General community. Participants: Participants were classified according to body mass index and four metabolic risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less pronounced (HR, 1.8; 95% CI, 0.7 to 4.8). Being metabolically healthy but overweight was not associated with higher risk of IHD in men (HR, 1.1; 95% CI, 0.5 to 2.4), and in women the risk was only slightly increased and insignificant (HR, 1.5; 95% CI, 0.8 to 3.0). A substantial proportion of metabolically healthy individuals became metabolically unhealthy after 5 years of follow-up. When these changes in exposure status were taken into account, slightly higher risk estimates were found. Conclusions: Being obese is associated with higher incidence of IHD irrespective of metabolic status, and we question the feasibility of denoting a subgroup of obese individuals as metabolically healthy. We studied the risk of ischemic heart disease (IHD) in the Inter99 cohort and found that metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men.