Role of microcirculatory function and plasma biomarkers in determining the development of cardiovascular adverse events in patients with peripheral arterial disease: A 5-year follow-up

OBJECTIVE: The aim of this long-term follow-up study was to investigate the association of local and systemic cardiovascular complications with endothelium-dependent and-independent microvascular relaxations and blood biomarkers and biochemicals in patients with peripheral arterial disease (PAD) caused by atherosclerosis. METHODS: This prospective study included 67 patients with PAD who had not undergone any endovascular intervention, peripheral arterial surgery, or major amputation. Changes in the microvascular blood flow were measured using laser Doppler imaging after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). The biochemical markers of high sensitivity C reactive protein (hs-CRP), nitric oxide (NO), total antioxidant capacity (TAC), asymmetric dimethyl arginine (ADMA), and hydrogen sulfide (H(2)S) levels were measured from blood samples. All the patients were followed up for 5 years to determine the development of cardiovascular adverse events (CVAEs) and major amputation. At the end of the follow-up period, the patients were classified into two groups: those who had a CVAE [CVAE (+)] and those who did not experience CVAE [CVAE (−)]. Parameters such as demographic features, atherosclerotic risk factors, chronic ischemia category, microvascular endothelial functions, and plasma biomarkers were compared between the groups. RESULTS: A total of 67 patients comprising 61 (91%) males and 6 (9%) females with a mean age of 62.3±9.7 years were included. During the follow-up period, 29 patients had CVAE (43.3%) and 38 patients did not have CVAE (56.7%). There was no difference between the groups in terms of ACh and SNP-induced vasodilation responses. Plasma high density lipoprotein (HDL) cholesterol values were lower in the CVAE (+) group [(CVAE+HDL: 38.4±9.1), (CVAE−HDL: 44.7±11.1), p=0.02]. Plasma hs-CRP values were significantly higher in the CVAE (+) group [(CVAE+ hs-CRP: 14.3±20.6), (CVAE−hs-CRP: 5.9±10.9), p=0.004]. No significant difference was observed between the groups in terms of plasma biomarkers and other biochemical levels. CONCLUSION: Based on the study findings, it was concluded that only low plasma HDL and high hs-CRP levels were risk factors for the development of CVAEs during follow-up of patients with PAD.