Circulating Adipocyte Fatty Acid-Binding Protein Levels and Cardiovascular Morbidity and Mortality in Patients With Coronary Heart Disease

Abstract

Objective— Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. Methods and Results— Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1–120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22–3.92, P <0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18–1.95; P =0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98–1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17–2.62, P =0.007). Conclusion— Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

“…In addition, prospective studies have shown that FABP4 can predict the development of metabolic syndrome and type 2 diabetes . Since metabolic syndrome and insulin resistance are closely linked with CVD, a strong association between circulating FABP4 levels and this pathology has also been proposed , Miyoshi et al 2010, Bao et al 2011, von Eynatten et al 2012, Fuseya et al 2014 (Fig. 2).…”

“…Recently, FABP4 has been proposed as a prognostic biomarker in patients with acute coronary syndrome (Reiser et al 2015). In addition, FABP4 is an important predictor of cardiovascular outcomes in patients with either coronary heart disease or acute ischaemic stroke (Holm et al 2011, von Eynatten et al 2012. Along with its potential role Endocrine and paracrine effects of FABP4 linked to obesity-induced HF and CVD.…”

Adipokines and cardiovascular disease: A comprehensive review

“…AFABP levels positively correlate with metabolic and inflammatory cardiovascular risk factors, which include atherogenic dyslipidemia, hyperglycemia, hypertension and also some laboratory markers of inflammation (s-CRP and IL-6). For people with pre-existing coronary heart disease, a significantly higher concentration of AFABP4 predicted increased risk of cardiovascular death, nonfatal myocardial infarction or stroke 48 . Expression of the adipocyte fatty-acid-binding protein (FABP4) gene in macrophages can be induced by oxidized LDL cholesterol and decreased by administration of lipid-lowering drugs (statins), which inhibit cholesterol synthesis 49 .…”

Adipocyte fatty acid binding protein levels in patients with coronary artery disease and its relationship to alternative biomarkers

“…In a recent study, circulating A-FABP levels and CV morbidity and mortality in patients with coronary heart disease were examined [32]. This study included a ten-year follow-up with > 200 major CV events and reported that circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease.…”