Serum FABP4 concentration is independently associated with atherosclerosis in a general population without medication.
Masato FuruhashiSatoshi YudaAtsuko MuranakaMina KawamukaiMegumi MatsumotoMarenao TanakaNorihito MoniwaOhnishi HirofumiShigeyuki SaitohKazuaki ShimamotoTetsuji Miura
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Cardiovascular disease (CVD) is reported to be higher in elderly diabetics. Serum heart-type fatty acid binding protein (H-FABP) is a serum marker of myocardial ischemia. We aimed to investigate the association between serum H-FABP level and conventional cardiovascular risk factors, inflammatory markers and subclinical atherosclerosis in elderly diabetics without overt CVD.A total of 50 elderly diabetic patients without overt CVD and 30 age-, sex- and body mass index (BMI)-matched healthy controls were enrolled. Anthropometric and biochemical parameters, serum H-FABP, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and carotid intima-media thickness (CIMT) were measured. Logistic regression analyses (adjustments for age, sex, hypertension, smoking, diabetes, BMI, blood pressure, lipid, blood glucose, hemoglobin A1c, hs-CRP and fibrinogen) were performed to evaluate the association between H-FABP and cardiovascular risk factors and atherosclerosis indices.Serum fibrinogen (421.50±85.52 mg/dL vs 319.17±30.77 mg/dL, p=0.023), CIMT (0.70±0.12 mm vs 0.59±0.06 mm, p<0.001) and hs-CRP (5.72±4.50 mg/dL vs 1.60±0.72 mg/dL, p<0.001) were significantly higher in diabetic patients than controls. The mean serum H-FABP level did not differ between groups (1571.79±604.60 ng/mL vs 1500.25±463.35 ng/mL, p=0.905). H-FABP was positively correlated with fibrinogen (r2=0.473, p<0.001), hs-CRP (r2=0.323, p=0.003) and CIMT (r2=0.467, p<0.001). After full adjustments, the serum H-FABP level was independently associated with an increase in the fibrinogen level (odds ratio [OR] =4.21, 95% confidence level [CI] =1.49-11.90).Serum H-FABP was similar in the elderly diabetic patients without known CVD when compared with the nondiabetic control group. H-FABP does not possess a high diagnostic value as a cardiovascular marker when used alone; however, it may add supplementary information in patients with a high fibrinogen level.
Lipid Profile
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Background: Adipocyte fatty acid-binding protein (A-FABP) is a cardiometabolic predictor of cardiovascular (CV) disease in humans. We evaluated the association between serum A-FABP levels and future CV events in patients with coronary artery disease (CAD). Methods: A total of 106 CAD patients were enrolled in this study between January and December 2012 and were followed-up until June 30, 2017. The primary endpoint was the incidence of major adverse CV events. Results: During a median follow-up period of 53 months, 44 CV events occurred. Patients with CV events presented higher systolic blood pressure (p = 0.020), total serum cholesterol (p = 0.047), and serum A-FABP levels (p < 0.001) compared with patients without CV events. Kaplan-Meier analysis showed that the cumulative incidence of CV events in the high A-FABP group (median A-FABP concentration of >17.63 ng/mL) was higher than that in the low A-FABP group (log-rank p < 0.001). Multivariate Cox analysis showed that triglycerides (hazard ratio (HR): 1.008, 95% confidence interval (CI): 1.001-1.016, p = 0.026) and serum A-FABP levels (HR: 1.027, 95% CI: 1.009-1.047, p = 0.004) were independently associated with CV events. Conclusion: Serum A-FABP level is a biomarker for future CV events in patients with CAD. Further prospective studies are needed to confirm the mechanisms underlying this association.
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Atherosclerosis is a chronic disorder with a complex pathology. Apart from classical risk factors such as: hypertension, elevated serum lipids, cigarette smoking, diabetes and obesity, other new risk factors involved in atherosclerosis development have been discovered. These new factors include molecules associated with inflammation such as C-reactive protein (CRP), and also eleveted homocysteine (Hcy).To estimate the frequency of enhanced CRP and Hcy levels in two groups of patients: in patients with diagnosed coronary heart disease (CHD group) and without CHD symptoms (control), matched for serum cholesterol levels, age, sex, body mass index and blood pressure.335 subjects: 182 females, 153 males, aged between 42-63. In all studied subjects serum levels of total and HDL-cholesterol, triglycerides, Hcy and CRP levels were determined.HCY-levels lower than 10 mmol/l were observed in 53.3% of the controls and in 27.7% of the group diagnosed with coronary heart disease. Hcy above 15 mmol/l was observed in 29.7% of CHD group and in only 5% of the controls. 78.5% of controls had CRP levels concentrations not higher than 2 mg/l. CRP levels above 3 mg/l were observed only in 9.9% of controls and in up to 66.5% of the patients with coronary heart disease.CRP and Hcy levels have been recognized as parameters that strongly differentiate patients with classically diagnosed heart disease from people without clinical symptoms of the illness but with similar serum lipid levels, similar BMI and blood pressure.
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Introduction: Mac-2 binding protein (M2BP) is secreted from many cell types. Recently, serum M2BP levels were reported to be useful as a glycoprotein biomarker for liver fibrosis and several types of malignant tumors. Hypothesis: We hypothesized that expression of M2BP might change in the process of atherosclerosis. Hence, the present study was designed to investigate a possible association of the serum M2BP level with cardiovascular risk factors and whether M2BP is a candidate for a marker of progression of atherosclerosis. Methods: Outpatients with one or more cardiovascular risk factors (n=156) and healthy controls without cardiovascular risk factors (n=20) were enrolled. Subjects with liver dysfunction, a history of hepatic disease, malignant neoplasm, or cardiovascular events were excluded. Blood was sampled and serum levels of hyperglycosylated-M2BP were measured by glycan-based immunoassay. Vascular function was assessed by pulse wave velocity (PWV) and flow-mediated dilation (FMD). Results: Serum M2BP levels were positively correlated with cardiovascular risk factors (age, BMI, systolic blood pressure, fasting blood sugar, and HbA1c) and inversely correlated with HDL-cholesterol and estimated-GFR. The M2BP levels were also correlated with CRP, urinary albumin to creatinine ratio, and PWV. The M2BP levels in subjects with hypertension, dyslipidemia, or abnormal glucose metabolism were higher than those in subjects without hypertension, dyslipidemia, or abnormal glucose metabolism (P<0.01, respectively). Moreover, the M2BP levels were associated with accumulation of cardiovascular risk factors. Multiple logistic regression analysis with endpoint of high M2BP (above mean value) revealed that hypertension and dyslipidemia were significantly associated with high M2BP. Subjects with high M2BP showed significantly decreased FMD than those with low M2BP (p<0.05). Conclusions: Serum M2BP levels were increased with age and accumulation of cardiovascular risks factors. Although the spectrum was narrow as compared to that in cases of hepatic fibrosis, significant correlations with cardiovascular risk markers suggest that serum M2BP reflects silent atherosclerosis in subjects with cardiovascular risk factors.
Atherosclerotic cardiovascular disease
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HDL is strongly inversely related to cardiovascular risk. Hepatic HDL uptake is controlled by ecto-F1-ATPase activity, and potentially inhibited by mitochondrial inhibitor factor 1 (IF1). We recently found that IF1 is present in serum and correlates with HDL-cholesterol (HDL-C). Here, we have evaluated the relationship between circulating IF1 and plasma lipoproteins, and we determined whether IF1 concentration is associated with the risk of coronary heart disease (CHD). Serum IF1 was measured in 648 coronary patients ages 45-74 and in 669 matched male controls, in the context of a cross-sectional study on CHD. Cardiovascular risk factors were documented for each participant, including life-style habits and biological and clinical markers. In controls, multivariate analysis demonstrated that IF1 was independently positively associated with HDL-C and apoA-I (r = 0.27 and 0.28, respectively, P < 0.001) and negatively with triglycerides (r = -0.23, P < 0.001). Mean IF1 concentration was lower in CHD patients than in controls (0.43 mg/l and 0.53 mg/l, respectively, P < 0.001). In multivariate analyses, following adjustments on cardiovascular risk factors or markers, IF1 was negatively related to CHD (P < 0.001). This relationship was maintained after adjustment for HDL-C or apoA-I. This study identifies IF1 as a new determinant of HDL-C that is inversely associated with CHD.
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The aim of this study was to investigate the prospective association of circulating adipocyte fatty acid-binding protein (A-FABP) levels with the development of subclinical atherosclerosis in patients with type 2 diabetes in an 8-year prospective study.A total of 170 patients with newly diagnosed type 2 diabetes were recruited in the study and 133 patients completed the follow-up of 8 years. Baseline plasma A-FABP levels were measured with enzyme-linked immunosorbent assays. The role of A-FABP in predicting the development of subclinical atherosclerosis over 8 years was analyzed using multiple logistic regression.Of the 133 patients without subclinical atherosclerosis at baseline, a total of 100 had progressed to subclinical atherosclerosis over 8 years. Baseline A-FABP level was significantly higher in patients who had progressed to subclinical atherosclerosis at year 8 compared with ones who had not developed subclinical atherosclerosis after adjustment for sex (15.3 [12.1-23.2] versus 13.3 [10.0-18.9] ng/ml, P = 0.021). High baseline A-FABP level was an independent predictor for the development of subclinical atherosclerosis in patients with type 2 diabetes (odds ratio: 16.24, P = 0.022).Circulating A-FABP levels predict the development of subclinical atherosclerosis in type 2 diabetes patients.
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Lipoprotein(a)
Serum Albumin
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Background : Resistin is an adipokine that mediates insulin resistance in obese mice. In human, however, circulating resistin levels are not associated with obesity or insulin resistance. Although the function of human resistin is enigmatic, it has recently been reported that human resistin plays a role in hepatocyte low-density lipoprotein (LDL) receptor suppression. Objectives : Aim of this study was to determine if serum levels of resistin are associated with the response to lipid-lowering therapy and the prognosis in coronary artery disease (CAD). Methods : One hundred and eighty two patients without diabetes who underwent percutaneous coronary intervention for CAD participated in this study. We measured pre-procedural serum resistin levels. After procedures, we treated the patients with atorvastatin 20mg and evaluated response to the statin therapy at 6-month follow-up. We also performed 6-month follow-up coronary angiography (CAG) in all patients and quantitative coronary angiographic analysis was conducted. Results : After adjusting age, sex, BMI, hypertension and smoking, serum levels of resistin had positive correlation with total cholesterol (Pearson’s partial correlation coefficient (r)=0.170, p =0.015) and LDL (r=0.159, p =0.023) at baseline. However, there was no correlation between baseline serum levels of resistin and the decrement of LDL after statin therapy (r= 0.07, p =0.36). Although, serum resistin (odds ratio 1.714, 95%CI 1.266-2.319) and hypertension (odds ratio 4.617, 95%CI 1.535-13.887) were independent predictors of coronary artery disease in multivariate logistic regression analysis, we found no relationship between baseline serum levels of resistin and decrement in minimal lumen diameter of target vessel at follow-up CAG (r=0.003, p =0.96). Conclusions : Higher baseline serum resistin levels and the positive correlation between serum resistin and baseline LDL in CAD patients suggest that resistin may affect coronary atherosclerosis via lipid metabolism pathway. However, serum resistin is not associated with the response to lipid-lowering therapy and the prognosis in CAD. The different mechanism of restenosis after DES implantation might explain the irrelevance of resistin level and restenosis.
Resistin
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Abstract Background Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. Methods A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan–Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. Results During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076–3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409–4.650; p = 0.002). The Kaplan–Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). Conclusions Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.
Carbohydrate Metabolism
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