Metabolically healthy obesity and the risk for subclinical atherosclerosis

Although obesity and metabolic abnormalities are known risk factors for cardiovascular disease, the risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as metabolically healthy obese (MHO), remains unclear. We examined the association between body mass index categories and the development of subclinical carotid atherosclerosis in a cohort of metabolically healthy individuals.

We conducted a cohort study of 6453 men without subclinical carotid atherosclerosis or metabolic abnormalities at baseline, who underwent repeated health check-up examinations that included carotid ultrasound. A metabolically healthy state was defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance <2.5. Subclinical carotid atherosclerosis was assessed using ultrasound.

During the follow-up period of 34,797.9 person-years, subclinical carotid atherosclerosis developed in 1916 participants. Comparing overweight and obese with normal weight participants, the multivariable adjusted hazard ratios (95% confidence intervals) for incident subclinical carotid atherosclerosis were 1.24 (1.12-1.38) and 1.54 (1.38-1.72), respectively. The association persisted after further adjustment for metabolic variables. This association was also evident in MHO men without abdominal obesity (waist circumference > 90 cm) and it did not differ across any clinically relevant subgroups evaluated.

In a large cohort study of strictly defined metabolically healthy participants, the MHO phenotype was associated with an increased risk of incident subclinical carotid atherosclerosis, providing evidence that the MHO phenotype is not protective from cardiovascular risk.