Abstract
BACKGROUND: The objective of this cohort study was to assess the predictive value of main arterial markers for cardiovascular death in middle-aged subjects with metabolic syndrome (MetS). METHODS: This prospective longitudinal study analyzed data from 5829 metabolic syndrome subjects without overt cardiovascular disease aged between 40 and 64 years and enrolled in the Lithuanian High Cardiovascular Risk primary prevention program. Initial assessment comprised the evaluation of aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT), carotid stiffness index, cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), aortic augmentation index adjusted for a heart rate of 75 bpm (AIXHR75), and endothelium-dependent flow-mediated dilatation (FMD). RESULTS: During the mean follow-up period of 6.35 ± 2.99 years, 170 subjects (2.9%) had died, with 41 out of these deaths (24.1%) related to cardiovascular causes. Cox proportional hazard regression analysis revealed associations between cardiovascular deaths and increases in aPWV (HR 1.34, 95% CI 1.14-1.58, p < 0.001), CAVI (HR 1.28, 95% CI 1.09-1.50, p = 0.002), and cIMT (HR 1.004, 95% CI 1.001-1.006, p = 0.003), as well as a decrease in ABI (HR 0.020, 95% CI 0.001-0.359, p = 0.008). However, after adjustment for age and gender, only aPWV remained a statistically significant predictor. Common survival tree analysis foregrounded the predictive significance of C-reactive protein (CRP), as the primary variable associated with an increased risk of cardiovascular death, followed by aPWV and smoking as secondary and tertiary variables. The analysis also demonstrated sex-related differences: in women, the primary predictive variable was aPWV, whereas in men, CRP was identified as the primary variable, followed by CAVI and cIMT. CONCLUSIONS: The findings of this study suggest that, among the markers of subclinical arterial damage, an increase in both aPWV and CAVI has a statistically significant predictive value for cardiovascular mortality in the middle-aged subjects with MetS. However, only aPWV demonstrated predictive value that was independent of age and gender.