Normal-weight obesity subtypes and 10-year risks of major vascular diseases in 0.3 million adults

Background & aims: Obesity directly contributes to the progression of cardiovascular disease, but little is known about the association and risk attribution of normal-weight obesity subtypes with the incidence of major vascular events (MVEs) and their subtypes. Methods: This is a prospective cohort study based on the China Kadoorie Biobank (CKB). A total of 308,071 individuals with no prior vascular diseases or cancer were included at baseline. The incidence of MVEs and their subtypes were recorded during follow-up. Adjusted hazard ratios (HRs) for each disease were yielded by Cox regression. Results: During a median follow-up of 10.3 years, 62,040 MVEs occurred, with the adjusted HRs (95 % confidence intervals) were 1.11 (1.09–1.13) for normal-weight general obesity (NWGO), 1.27 (1.23–1.31) for normal-weight central obesity (NWCO), and 1.30 (1.27–1.33) for normal-weight central and general obesity (NWCGO). For subtypes of MVEs, increased waist circumference (WC) was associated with excess risk of ischaemic heart disease (IHD) independent of body fat percent (BF%) levels (HR range: 1.30–1.69 in men; 1.36–1.55 in women), while the risk plateaued with rising BF% within each WC quartile. However, even in men with lower WC (≤78 cm [median]), the risks of cerebrovascular disease (CeVD), particularly ischaemic stroke (IS), were increased with higher BF% (all P < 0.01). Conversely, in women, independent dose–response associations were primarily observed between increasing WC and CeVD, with the highest risk observed for IS (HR 1.38, 1.31–1.47). Conclusions: This study provided novel, sex-specific evidence that normal-weight obesity subtypes were associated with distinct risks of subtypes of MVEs, with elevated risks predominantly attributable to WC in women and both WC and BF% in men.