Association between early-stage systemic metabolic disorder and incident cardiometabolic treatment and cardiovascular hospitalisation in Japanese adults

Background Systemic metabolic disorder (SMD) is an emerging clinical framework that conceptualises visceral adiposity–driven metabolic abnormalities as a progressive multisystem disorder. The European Atherosclerosis Society (EAS) has recently proposed a staging system for SMD to guide intervention according to severity. However, its clinical utility in Asian populations remains uncertain. Purpose To examine the association between early-stage SMD and cardiometabolic treatment initiation and cardiovascular hospitalisation in a Japanese population. Methods This study included Japanese adults who underwent annual health examinations in 2019, with linked insurance claims data from 2019–2023. Individuals receiving treatment for hypertension, dyslipidaemia, or diabetes, with HbA1c ≥6.5% or fasting glucose ≥126 mg/dL, or with cardiovascular disease or chronic kidney disease at baseline, were excluded. Early-stage SMD was defined according to Stage 1 of the EAS consensus1 as pre-diabetes alone (HbA1c ≥5.7% or fasting glucose ≥101 mg/dL), or overweight (body mass index (BMI) ≥23 kg/m² or waist circumference ≥90/85 cm for women/men; Japanese-specific cut-offs) with ≥1 of the following: hepatic steatosis (fatty liver index ≥60), hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), or dyslipidaemia (triglycerides ≥150 mg/dL or non–high-density lipoprotein cholesterol ≥131 mg/dL). The association between SMD and initiation of pharmacological treatment for hypertension, dyslipidaemia, or diabetes over 4 years was evaluated using logistic regression adjusted for age, sex, exercise habit, alcohol consumption, and smoking. The association between SMD and cardiovascular hospitalisation was assessed using Cox proportional hazards models. Results Among 60,319 participants (mean age 44.8 years; 76.0% men; mean BMI 23.0 kg/m²), the prevalence of Stage 1 SMD at baseline was 52.3%. During the 4-year follow-up, 15.3% initiated pharmacological treatment for at least one cardiovascular risk factor. This proportion was higher among individuals with SMD than among those without SMD (20.6% vs. 9.4%; odds ratio (OR) 2.12, 95% confidence interval (CI) 2.01–2.23, p<0.001). The association was consistent across age strata (<45 years: OR 2.33, 95% CI 2.14–2.54, p<0.001; ≥45 years: OR 1.99, 95% CI 1.87–2.12, p<0.001). Individuals with SMD were at increased risk of requiring combined pharmacological treatment for multiple cardiovascular risk factors (Figure 1). SMD was associated with cardiovascular hospitalisation (overall: hazard ratio (HR) 1.93, 95% CI 1.47–2.53, p<0.001; <45 years: HR 1.81, 95% CI 1.00–3.38, p=0.048; ≥45 years: HR 1.92, 95% CI 1.42–2.60, p<0.001). Conclusions Early-stage SMD was associated with clustered progression of cardiovascular risk factors and increased cardiovascular hospitalisation. These findings support the clinical utility of early SMD staging for risk stratification in Japanese adults.Figure 1.Cardiometabolic treatment patterns