Age-specific risk and clustering patterns of metabolically unhealthy status associated with obstructive coronary artery disease in obese and non-obese adults

The burden of metabolic dysfunction and coronary artery disease (CAD) in young adults has rapidly increased. We aimed to investigate whether the association between metabolically unhealthy status and prevalent CAD varies by age in both obese and non-obese individuals, and whether specific metabolic clustering patterns are associated with an elevated likelihood of obstructive CAD among young adults. This hospital-based study involved patients with and without angiographically confirmed obstructive CAD (coronary stenosis ≥ 50%). The odds ratios (ORs) for CAD associated with metabolically unhealthy non-obesity (MUN) and metabolically unhealthy obesity (MUO) were estimated using multivariate logistic regression analysis across young (age ≤ 45 years), middle-aged (age 46–64 years) and elderly (age ≥ 65 years) adults. The exploratory metabolic clustering analysis included body mass index, mean arterial pressure, triglyceride-to-high-density lipoprotein cholesterol ratio, and glycated hemoglobin. Among 9,051 included participants, obstructive CAD was detected in 3,523 (38.9%) patients. The mean age of the study population was 50.06 ± 15.14 years; 62.1% of them were male and 15.2% were obese. Compared to individuals with metabolically healthy non-obesity, those with MUN and MUO exhibited significantly higher odds of CAD. Notably, young adults demonstrated the strongest associations (MUN: adjusted OR, 5.02 [95% CI 3.24–7.84]; MUO: adjusted OR, 5.06 [95% CI 3.11–8.29]), which were attenuated with aging. Numerical accumulation of metabolically unhealthy components was not only associated with amplified prevalent CAD risk, particularly among young adults, but also positively correlated with atherosclerotic plaque burden among CAD patients (median regression: β = 5.10, P for trend < 0.001). Furthermore, two distinct phenotypes were identified, corresponding to 7.96-fold and 2.35-fold increased odds for the presence of obstructive CAD among young adults, respectively. Metabolically unhealthy status, irrespective of obesity, is associated with a higher prevalence of obstructive CAD with the strongest effect observed among young adults. The two exploratory metabolic clusters showed markedly elevated odds of obstructive CAD in this age group, which warrants further investigation. Trial registration : www.clinicaltrials.gov (NCT 02496858; registration date: July 14, 2015).