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

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.