The impact of long-term changes in metabolic status on cardiovascular biomarkers and microvascular endothelial function in middle-aged men: A 25-year prospective study

Abstract

Background: The aim of this analysis was to examine long-term effects of changes in metabolic status on microvascular endothelial function and cardiovascular diseases (CVD) biomarkers among physically active middle-aged men. Methods: Metabolically healthy men (n = 101, mean age 59.7 years), free of symptoms and treatment, have been prospectively observed for their lifestyle and CVD risk factors (observation period 24.7 years). At the latest follow-up (2011/2012) a set of CVD biomarkers was measured using enzyme-linked immunosorbent assay. Microvascular endothelial function was evaluated by means of the reactive hyperemia index (RHI) using Endo-PAT2000 system. At follow-up the participants were divided into metabolically healthy (0-1 metabolic parameters) and metabolically unhealthy (≤2 metabolic parameters) groups. Metabolic syndrome was defined according to the NCEP ATP III definition. Results: Traditional metabolic risk factors were significantly associated with hsCRP, ox-LDL, Il-6, leptin and adiponectin/leptin ratio. Reactive hyperemia index was negatively related to body mass (p < 0.01), waist circumference (p < 0.05), triglycerides (p < 0.01), TG/HDL ratio (p < 0.01), uric acid (p < 0.05), sICAM-1 (p < 0.05) and Il-6 (p < 0.05), and positively to HDL-C (p < 0.01) and leisure-time physical activity (p < 0.01). Men who maintained metabolically healthy status (n = 47) through the observation had significantly lower hsCRP and uric acid (p < 0.05), higher adiponectin/leptin ratio (p < 0.05), higher mean RHI and lower prevalence of endothelial dysfunction (p < 0.05) as compared to the metabolically unhealthy group (n = 54). Regular physical activity level was significantly higher among metabolically healthy individuals during the whole observation. Conclusions: Even subtle changes in metabolic profile influence inflammatory biomarkers and microvascular endothelial function. Leptin, adiponectin/leptin ratio and hsCRP are significant predictors of metabolic profile. Interleukine-6 and sICAM-1 may be used as indicators of early endothelial dysfunction in asymptomatic men. High leisure-time physical activity level is an important contributor of metabolically healthy profile through middle adulthood.