Could Tumor Necrosis Factor Serve as a Marker for Cardiovascular Risk Factors and Left Ventricular Hypertrophy in Patients with Early-Onset Coronary Artery Disease?

Introduction: Tumor necrosis factor (TNF), a pro-inflammatory cytokine, can be produced by cardiomyocytes, leading to metabolic disorders in the myocardium. The objective of this study was to assess the relationship between plasma levels of the TNF cytokine and the presence of known biochemical and clinical risk factors for cardiovascular disease, along with the parameters of cardiac morphology in patients diagnosed with coronary artery disease (CAD) at a young age. Materials and Methods: The study group included 75 men aged up to 50 years and 25 women aged up to 55 years. The plasma TNF concentration was measured by use of the ELISA assay. Echocardiography and electrocardiographic examinations were performed in all patients. Results: We observed positive correlations for TNF with the BMI ratio, weight, waist and hip circumference. We also found negative correlations for TNF with HDL levels and ApoA concentrations, and positive correlations with the ApoB/ApoA1 ratio, Apo B, IL6, LDL and TG concentrations. These results suggest an association between higher plasma TNF concentrations and components of metabolic syndrome, including dyslipidemia. TNF may be a potential risk factor for impaired diastolic function. Conclusions: While TNF may be useful for diagnosing certain risks in CAD patients, the TNF measurement cannot be used as a surrogate test for echocardiography.

The circulating vascular endothelial growth factor is only marginally associated with an increased risk for atherosclerosis.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) is a protein that plays a role in the formation and function of blood vessels, promotes increased vascular permeability or migration of monocytes through endothelial layers. We have tested the hypothesis that plasma levels of VEGF-A may be associated with biochemical and radiological parameters as a marker of cardiovascular risk in Caucasian patients with early-onset CAD. METHODS: The study group included 100 patients: 75 men not older than 50 years and 25 women not older than 55 years at the moment of CAD diagnosis. The control group (patients without CAD) comprised 50 healthy cases. ELISA test was used to measure plasma concentrations of VEGF. Doppler ultrasound of carotid and peripheral arteries was carried out in each patient. Serum glucose, complete lipid profile, ApoA1, ApoB, Lp(a) and blood count were measured in each case. RESULTS: Only very weak correlations of plasma VEGF levels with biochemical cardiovascular risk factors in the CAD subjects have been demonstrated. In the study group, VEGF concentration was significantly positively correlated with the same blood parameters as white blood cells, platelets, plateletcrit, apolipoprotein B, total and LDL cholesterol fraction. The plaque of common carotid arteries and bifurcation was present in 39% of CAD patients, however, there was no significant association between VEGF plasma concentration and any measured parameters in Doppler ultrasound of carotid and peripheral arteries. CONCLUSIONS: The circulating VEGF is only marginally associated with an increased risk for atherosclerosis.

Associations between IL-6 and Echo-Parameters in Patients with Early Onset Coronary Artery Disease.

BACKGROUND: Over the last two decades, many studies have investigated the association between interleukin 6 (IL-6) and pathogenesis and progression of coronary artery disease (CAD). Patients with CAD manifested at a young age are a particularly interesting group. They differ from older patients, not only in terms of the severity of coronary artery atherosclerosis, but also risk factor profiles, short- and long-term prognosis after myocardial infarction (MI). The role of IL-6 in younger patients with CAD is less well-known. Therefore, our study aimed to analyze the relationship between IL-6 level and other inflammations, atherosclerosis, and cardiac function parameters in early onset CAD patients. METHODS: The study covered 100 patients with early onset CAD and a group of 50 healthy participants. Plasma levels of IL-6 and basic biochemical parameters, anthropometric, echocardiographic, and arteries Doppler ultrasound measurements were performed. RESULTS: We did not observe a significant difference in IL-6 concentration in plasma between patients with early onset CAD and a control group, but IL-6 level was negatively correlated with echocardiographic measurements of ascending aorta diameter, left ventricular shortening fraction, and right ventricular end-diastolic diameter in our patients. CONCLUSIONS: In patients with early onset CAD, plasma IL-6 level is associated with other inflammation parameters and with cardiac function, potentially contributing to right ventricular remodeling and left ventricular systolic dysfunction. This suggests possible prognostic benefits of long-time observation of IL-6 level after the acute coronary syndrome.

Is plasma-soluble CD36 associated with density of atheromatous plaque and ankle-brachial index in early-onset coronary artery disease patients?

BACKGROUND: CD36 is a major macrophage scavenger receptor for oxidised low-density lipoprotein particles. Soluble CD36 (sCD36) is circulating as a ligand-bound complex and may be present in microparticles shed from cells such as platelets, monocytes/macrophages, or adipocytes. Positive association of plasma sCD36 with insulin resistance has been reported, and it has been proposed that sCD36 might represent a marker of macrophage activation and inflammation leading to atherosclerosis. Recently we have identified an association between CD36 polymorphism and low thickness of atheromatous plaque, suggesting its protective effect against atherosclerosis development. AIM: To obtain insight into the relationship between plasma concentration of sCD36 and radiological parameters of atherosclerosis in patients with early-onset coronary artery disease (CAD). METHODS: The study group comprised 70 clinically stable patients (18 women and 52 men) with early CAD (aged no more than 50 years for men and 55 years for women). Fasting blood sample was taken for serum glucose, lipid profile, ApoA1, ApoB, Lp(a), and plasma sCD36 protein measurements. Each subject's weight, height, waist and hip circumference, and systolic and diastolic blood pressure were measured, and the body mass index, waist-to-hip ratio, and mean arterial pressure were calculated. Doppler ultrasound examinations of carotid and peripheral arteries were performed in all patients. Thickness of intima-media complex (IMC) of common carotid (CCA) and brachial arteries, as well as density and thickness of atheromatous plaque at CCA bifurcation, were measured with M'Ath programme. Plasma concentrations of CD36 antigen were measured by ELISA. Correlations between quantitative variables and sCD36 plasma concentration were assessed with the Spearman rank correlation coefficient (Rs). Associations between qualitative variables and sCD36 plasma concentration were tested with the Mann-Whitney U test. RESULTS: We observed no significant correlations between sCD36 concentration and radiological parameters of atherosclerosis. We found only borderline significant negative correlation of sCD36 concentration with thickness of IMC of left brachial artery. We also observed a significantly negative correlation with CCA plaque density, but only in the female subgroup and on the right side. Borderline higher sCD36 plasma concentrations were observed in patients with lower ankle-brachial index value (< 0.9). CONCLUSIONS: The results of the study show no strong associations and do not prove either detrimental or beneficial influence of sCD36 on radiological parameters of atherosclerosis. Further research is necessary to assess the association of high plasma sCD36 concentrations with the risk of plaque instability in patients with early-onset CAD.

Is plasma soluble CD36 associated with cardiovascular risk factors in early onset coronary artery disease patients?

BACKGROUND AND PURPOSE: This is the first study to investigate the relationship between plasma concentration of soluble CD36 (sCD36) and CD36 gene polymorphisms as well as clinical and echocardiographic parameters in patients with early onset coronary artery disease (CAD). METHODS: sCD36 concentrations were measured by the ELISA kits. CD36 sequence alterations detected by the DHPLC technique comprised single nucleotide substitutions: rs3173798, rs3211892, rs5956 and rs141680676. RESULTS: There were significant negative correlations between sCD36 and red blood cell count, hemoglobin, hematocrit and glucose concentration, ApoB/ApoA1 ratio, patients' weight and waist circumference, BMI, WHR, systolic blood pressure, MAP values, left ventricular end-diastolic diameter and volume, left atrium diameter, right ventricular end-diastolic diameter. There were significant positive correlations between sCD36 and patients' age, mean corpuscular volume of erythrocytes, HDL-cholesterol, ApoA1 concentrations. Significantly higher CD36 plasma levels were found in female subgroup. There was no association between CD36 genotypes and sCD36 concentrations. Multiple linear regression analysis revealed that significant independent predictors of higher plasma sCD36 level were female gender, older age, lower serum glucose and lower RBC. CONCLUSION: The presented data suggest possible protective effects of higher sCD36 concentration in relation to metabolic syndrome components in CAD patients. Higher sCD36 concentration is also associated with lower risk of left ventricular hypertrophy, but on the other hand is a potential risk factor of impaired left ventricle diastolic function.

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease.

INTRODUCTION: CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy. MATERIAL AND METHODS: The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique. RESULTS: IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A' in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher RV5(6) and RV5(6) + SV1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes. CONCLUSIONS: Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.

Is CD36 gene polymorphism in region encoding lipid-binding domain associated with early onset CAD?

CD36 is a fatty acid translocase in striated muscle cells and cardiomyocytes. Some study suggested that alterations in CD36 gene may be associated with coronary artery disease (CAD) risk. The aim of the current study was to compare the frequency of CD36 variants in region encoding lipid-binding domain in Caucasian patients with early-onset CAD, no-CAD adult controls and neonates. The study group comprised 100 patients with early onset CAD. The genetic control groups were 306 infants and 40 no-CAD adults aged over 70years. Exons 4, 5 and 6 including fragments of flanking introns were studied using the denaturing high-performance liquid chromatography technique and direct sequencing. Changes detected in analyzed fragment of CD36: IVS3-6 T/C (rs3173798), IVS4-10 G/A (rs3211892), C311T (Thr104Ile, not described so far) in exon 5, G550A (Asp184Asn, rs138897347), C572T (Pro191Leu, rs143150225), G573A (Pro191Pro, rs5956) and A591T (Thr197Thr, rs141680676) in exon 6. No significant differences in the CD36 genotype, allele and haplotype frequencies were found between the three groups. Only borderline differences (p=0.066) were found between early onset CAD patients and newborns in the frequencies of 591T allele (2.00% vs 0.50%) and CGCGCGT haplotype (2.00% vs 0.50%) with both IVS3-6C and 591T variant alleles. In conclusion, CD36 variants: rs3173798, rs3211892, rs138897347, rs5956, rs143150225 rs141680676 and C311T do not seem to be involved in the risk of early-onset CAD in Caucasian population.

CD36 gene is associated with thickness of atheromatous plaque and ankle-brachial index in patients with early coronary artery disease.

BACKGROUND: CD36 is a multifunctional molecule engaged in the removal of oxidised LDL from plasma. It is unclear whether mutation of the CD36 gene protects against, or increases, the risk of hypercholesterolaemia, atherosclerosis and its complications. AIM: To search for associations between the CD36 gene polymorphisms and radiological markers of atherosclerosis progress in Caucasian patients with coronary artery disease (CAD) diagnosed at a young age. METHODS: The study group comprised 70 patients with early CAD. Doppler ultrasound of carotid and peripheral arteries was carried out and genomic DNA was isolated from each patient. RESULTS: We found two single nucleotide substitutions in introns (IVS3-6 T/C - rs3173798 and IVS4-10 G/A - rs3211892) and two synonymous polymorphisms in exon 6 (G573A - rs5956 and A591T). The allele frequencies were: 10.7% for the IVS3-6C, 3.6% for the IVS4-10A, 3.6% for the 573A, and 2.1% for the 591T. The 573A allele of CD36 rs5956 polymorphism is associated with low thickness of atheromatous plaque. The 591T allele is associated with lower ankle-brachial index. CONCLUSIONS: The 573A allele has a protective effect against atherosclerosis development and the 591T allele is a cardiovascular risk factor. Assessment of their functional implications requires further research.

Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age.

This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≤ 50 years old and the women were ≤ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism was associated with higher prevalence of obesity and diabetes, higher hsCRP, lower Lp(a) serum concentrations, and younger age at myocardial infarction. The A allele of the IVS4-10 G/A polymorphism was associated with older age of myocardial infarction and higher white blood cell count. The functional role of CD36 polymorphisms in CAD development needs further research.

[Resistance to activated protein C in a patient with multiple myocardial infarctions and stroke--a case report]. / Opornosc na aktywowane bialko C u chorej z trzykrotnym zawalem miesnia sercowego i udarem niedokrwiennym mózgu.

A case of a 49-year-old female with a history of two myocardial infarctions (MI) and ischaemic stroke is presented. The patient was admitted to the hospital due to a third acute MI. Laboratory investigations revealed resistance to activated protein C due to factor V Leiden mutation. Diagnosis and treatment of patients with this condition are discussed.