Unmasking the role of hypertension in atherosclerosis among patients with obesity: a cardiometabolic dysfunction perspective.

Abstract

Vascular alterations in obesity may arise primarily from associated metabolic and inflammatory disturbances rather than from excess adiposity per se. This study evaluated the relative strength of association of individual BioSHaRE-EU Healthy Obese Project-defined cardiometabolic abnormalities and low-grade inflammation with carotid-iliofemoral subclinical atherosclerosis in adults with obesity. In this cross-sectional analysis from the CARFARE registry (NCT04040777), asymptomatic adults with obesity (BMI ≥ 30 kg/m²) underwent standardized clinical evaluation and carotid-iliofemoral ultrasonography. Atherosclerosis was defined by the presence of ≥1 plaque according to Mannheim criteria. Metabolic status was classified as metabolically healthy or unhealthy obesity, with individual evaluation of hypertension, elevated fasting glucose, hypertriglyceridemia, and low HDL cholesterol. Inflammation was estimated through absolute neutrophil count. Associations were assessed using multivariable logistic regression adjusted for established cardiovascular risk factors. Sensitivity analyses included parsimonious models focused on hypertension and cardiovascular risk factors, and restriction of assessment to Mannheim-defined carotid territories. Among 2033 participants, overall atherosclerosis prevalence was 56.5% (95% CI 54.3-58.7%), higher in metabolically unhealthy than healthy obesity (64.5% vs. 35.5%, p < 0.0001). In multivariable analysis, hypertension (OR 1.88, 95% CI 1.44-2.44, p < 0.0001) and low HDL cholesterol (OR 1.33, 95% CI 1.04-1.69, p = 0.0225) were independently associated with subclinical atherosclerosis, along with age, male sex, and smoking. In the parsimonious clinically oriented model, hypertension remained independently associated with subclinical atherosclerosis (adjusted OR 1.97, 95% CI 1.52-2.53; p < 0.001), with effect estimates comparable to the primary analysis. The magnitude and direction of the association were consistent across primary, parsimonious, and Mannheim-restricted analyses. In individuals with obesity, hypertension showed the largest effect estimate for association with subclinical atherosclerosis among evaluated cardiometabolic abnormalities and low-grade inflammation. These findings suggest that blood pressure elevation may represent a clinically informative indicator of vascular vulnerability in obesity, without implying a causal relationship. Graphical Abstract.