Abstract
BackgroundSymptomatic peripheral artery disease (PAD) is an atherosclerotic occlusive disease affecting the lower extremities. The cause of symptomatic PAD is atherosclerosis, vascular dysfunctions, impaired angiogenesis and neointima formation. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein, which is highly expressed in the heart and arteries and recently introduced as a potential mediator of pathological vascular remodeling and neointima formation. We aimed to investigate the relationship between serum MFAP4 (sMFAP4) and symptomatic PAD outcomes.MethodsA total of 286 PAD patients were analyzed if they had either intermittent claudication or critical lower-extremity ischemia (CLI) and followed for 7 years. The level of serum MFAP4 (sMFAP4) was measured by alphaLISA. Kaplan–Meier, Cox proportional hazard and logistic regression analysis were used to analyze the associations between upper tertile sMFAP4 and symptomatic PAD outcomes.ResultsPatients with upper tertile sMFAP4 had an odds ratio (OR) of 2.65 (p < 0.001) for having CLI diagnosis. Further analysis indicated that patients with upper tertile sMFAP4 had a hazard ratio (HR) of 1.97 (p = 0.04) for cardiovascular death during the 7-years follow-up. However, analysis of 2-year primary patency showed that patients with upper tertile sMFAP4 had decreased risk of vascular occlusion after reconstructive surgery with HR of 0.15 (p = 0.02).ConclusionssMFAP4 has potential as a prognostic marker for cardiovascular death, primary patency of reconstructed vessels and CLI diagnosis in symptomatic PAD patients. Confirmation of observations in larger cohorts is warranted.
Highlights
Symptomatic peripheral artery disease (PAD) is an atherosclerotic occlusive disease affecting the lower extremities
Logistic regression was used to analyze the risk of a critical lower-extremity ischemia (CLI) diagnosis and hazard ratios (HRs) with 95% confidence intervals were calculated for upper tertile serum MFAP4 (sMFAP4) with age, sex, body mass index (BMI) and smoking as covariates
Analysis of clinical variables between these two groups showed, that there was a significant difference when considering age (p = 0.01), male sex (p = 0.02), smoking (p = 0.03), CLI/intermittent claudication (IC) diagnosis (p < 0.001), whereas there was a tendency for BMI-association to Microfibrillar-associated protein 4 (MFAP4) tertiles
Summary
Symptomatic peripheral artery disease (PAD) is an atherosclerotic occlusive disease affecting the lower extremities. The cause of symptomatic PAD is atherosclerosis, vascular dysfunctions, impaired angiogenesis and neointima formation. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein, which is highly expressed in the heart and arteries and recently introduced as a potential mediator of pathological vascular remodeling and neointima formation. Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects the blood vessels other than those in the coronary circulation. The cause of symptomatic PAD is atherosclerosis, vascular dysfunctions, impaired angiogenesis and neointima formation and the prevalence is increased with age and is a growing health problem worldwide. Symptomatic PAD can present as intermittent claudication (IC) or as critical lower-extremity ischemia (CLI). The proportion of diagnosed CLI patients is approximately 40% of hospitalized PAD patients [11]. The clinical manifestations of the disease are seen after the establishment of the flow-limiting atherosclerotic plaque and symptoms
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