George Hatzis

Genetic variability on adiponectin gene affects myocardial infarction risk: The role of endothelial dysfunction

BACKGROUND Adiponectin is an adipokine with an important role in cardiovascular system conferring anti-inflammatory and anti-atherogenic effects. Two common single nucleotide polymorphisms (SNP) on adiponectin gene, rs2241766 and rs1501299, have been associated with insulin resistance and diabetes mellitus risk however their effects on cardiovascular risk remain unclear. We examined the impact of rs2241766 and rs1501299 on circulating adiponectin levels, endothelial function and cardiovascular disease risk. METHODS We recruited in total 594 subjects; 462 patients with angiographically confirmed coronary artery disease (CAD) and 132 controls matched for age and gender. rs2241766 and rs1501299 were genotyped by polymerase chain reaction and restriction endonuclease digestion. Serum adiponectin levels were determined by enzyme-linked immunosorbent assay. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery. RESULTS rs2241766 had no effects on circulating adiponectin levels or FMD. In subjects without CAD, carriers of the T/T alleles at rs1501299 had lower adiponectin levels (p=0.001) and impaired endothelial function (p<0.05). After multivariate adjustment none of the SNPs had any effect on CAD risk. However, carriers of the T allele at rs1501299 were at increased myocardial infarction (MI) risk, independently of classic risk factors (OR=2.558 [95%CI=1.587-4.123], p=0.0001). The number of T alleles in both SNPs was strongly associated with MI history (p=0.0001). CONCLUSIONS rs1501299 polymorphism of adiponectin gene affects circulating adiponectin levels and endothelial function in subjects without CAD. Presence of the T variant at rs1501299 on adiponectin gene is independently associated with increased myocardial infarction risk.

The association of the 174G > C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus

AIMS To evaluate the association of 174G>C polymorphism on interleukin-6 (IL-6) gene with diabetic nephropathy in patients with type 2 diabetes. METHODS A total of 393 Greek subjects with type 2 diabetes (mean age 66.5±10.0years, men n=203, women n=190) were examined. Diabetic nephropathy was defined as presence of microalbuminuria and/or proteinuria. The IL-6 174G>C polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme digestion. High sensitivity C-reactive protein was assayed by particle-enhanced immunonephelometry. RESULTS The genotype distribution (%) was GG: 49.1, GC: 26.8 and CC: 24.1, with no gender difference. The CC homozygotes had lower albumin excretion (mg/24h) in comparison with the GC genotype [CC: 8.9 (4.0-20.9) vs GC: 21.95 (9.1-53.35), P=0.004]. Participants with the GC genotype tended to have more frequently nephropathy than those with the GG or the CC genotype [GC: 44.55% vs GG: 35.1% and CC: 28.3%, P=0.07)]. The CC homozygotes in comparison with GC heterozygotes had lower odds to have nephropathy (odds ratio: 0.51, 95% confidence intervals=0.28-0.91, P=0.02), even after adjustment for sex, age, duration of diabetes, body mass index, smoking, hypertension, lipids and glycated hemoglobin, (P=0.01). CONCLUSION In type 2 diabetes states, CC homozygotes have lower albumin excretion and are protected from nephropathy in comparison with GC genotypes.

Socioeconomic status and risk factors for cardiovascular disease: Impact of dietary mediators

It is well known that cardiovascular disease is the leading cause of mortality in the western societies. A number of risk factors such as family history, diabetes, hypertension, obesity, diabetes, smoking and physical inactivity are responsible for a significant proportion of the overall cardiovascular risk. Interestingly, recent data suggest there is a gradient in the incidence, morbidity and mortality of cardiovascular disease across the spectrum of socioeconomic status, as this is defined by educational level, occupation or income. Additionally, dietary mediators seem to play significant role in the pathogenesis of cardiovascular disease, mediating some of the discrepancies in atherosclerosis among different socioeconomic layers. Therefore, in the present article, we aim to review the association between socioeconomic status and cardiovascular disease risk factors and the role of different dietary mediators.

Methionine-induced homocysteinemia impairs endothelial function in hypertensives: the role of asymmetrical dimethylarginine and antioxidant vitamins.

BACKGROUND Nitric oxide synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is synthesized by the methylation of arginine as part of the methionine/homocysteine cycle. However, the mechanisms regulating ADMA synthesis in hypertension are unclear. METHODS We investigated the role of ADMA and antioxidants in endothelial dysfunction during methionine-induced homocysteinemia in hypertensives. Thirty-nine hypertensives and forty-nine normotensive controls underwent methionine loading (100 mg methionine/kg BW), after being randomized to receive vitamin C (2 g) and E (800 IU) or placebo. Endothelium-dependent dilation (EDD) was evaluated by plethysmography (baseline and 4-h post-methionine loading (4-h PML)). RESULTS Hypertensives had higher homocysteine at baseline (P < 0.001) and 4-h PML (P < 0.05), whereas methionine increased homocysteine in all groups. EDD was decreased in both vitamins and placebo groups in controls (P < 0.01 for both) and vitamins- and placebo-treated hypertensives (P < 0.05 and P < 0.01, respectively). In controls, ADMA was increased in both vitamin- and placebo groups (P < 0.01 for both) at 4-h PML. Hypertensives had higher ADMA at baseline (P < 0.01 vs. normotensive) and remained unchanged at 4-h PML (P = NS in placebo and vitamins treated). CONCLUSIONS ADMA is elevated in hypertensives but remains unchanged after methionine loading, suggesting that ADMA plays an important role in endothelial dysfunction in hypertensives, but it is not responsible for homocysteine-induced endothelial dysfunction in these patients.

Genetic variability of matrix metalloproteinase genes in cardiovascular disease.

It is well established that matrix metalloproteinases (MMPs) contribute to the degradation of the extracellular matrix of coronary plaque and contribute to the thinning of the fibrous cap. As a result, the atheromatous plaque becomes unstable and prone to rupture with consequent clinical manifestations including acute coronary syndromes. Moreover, genetic polymorphisms of MMPs have been found to be associated with the concentration of circulating MMPs, and over the past decade, considerable efforts have been devoted to explore the relationships between MMPs polymorphisms and myocardial infarction risk among various populations. However, existing studies have yielded inconsistent results. Some observations have suggested that genetic variation that affects the expression of MMPs may contribute to the occurrence of myocardial infarction, whereas others reported no support for an association of MMPs polymorphisms with myocardial infarction susceptibility. Furthermore, the interpretation of these studies has been complicated by the use of different populations or different control sources. Therefore, further studies are required to evaluate the role of matrix metalloproteinases and especially the associated genetic polymorphisms in cardiovascular disease.

HIGH LEVELS OF FIBRINOGEN, BUT NOT FIBRINOGEN GENETIC VARIANTS PREDICT CORONARY ARTERY DISEASE IN SUBJECTS WITH HYPERTENSION AND DIABETES MELLITUS TYPE 2

It is well established that hypertension (HTN) and diabetes mellitus (DM) are strongly associated with coronary artery disease (CAD). In addition, controversial data exist related to the role of fibrinogen genetic variants in atherosclerosis-CAD. Therefore, we examined the effects of the rs180070

The role of C-reactive protein genetic variability in the onset of carotid artery disease and renal function impairment in patients with diabetes mellitus type 2.

The role of diabetes mellitus (DM) in cardiovascular disease is well established and currently is considered as an equivalent of coronary artery disease. Studies have also reported that DM is associated with the prevalence of occlusive carotid artery disease (AD) [1] as well as the grade carotid artery stenosis [2]. In addition, DM is related to impaired renal function via several mechanisms [3]. During the last years novel data have arisen for the role of genetics in the initiation and progression of carotid AD [4–8] as well as for impaired renal function [9,10]. However, scarce data exist regarding genetic polymorphisms in patients with diabetes mellitus and their role in carotid artery disease and renal function. Thus, in the present study we examined the potential role of a single nucleotide polymorphism (SNP) on C-reactive protein (CRP) gene in the onset of carotid AD and impaired renal function in patients with diabetes mellitus type 2. Our study population consisted of 430 patients with DM2 (documented for carotid AD or not). Subjects were characterized as patients with DM2 if fasting plasma glucose levels were ≥126 mg/dl, or 2-hour post glucose loading plasma levels were ≥200 mg/d according to the American Diabetes Association [11]. Carotid artery disease was evaluated based on history of transient ischemic attack or stroke, important degree of carotid stenosis in Doppler ultrasonography or blowing existence or interventional procedure of carotid revascularization. Subjects were considered to have systemic hypertension if their systolic and/or diastolic blood pressure was ≥140 and/or ≥90 mmHg on two different occasions. Moreover subjects were considered to have systemic hypertension if they were currently being treated with anti-hypertensive drugs or when a significant history of hypertension was present [12]. Subjects were considered to have dyslipidemia if total cholesterol levels ≥200 mg/dl were revealed in biochemical tests or if they were already treated with antihyperlipidemic agents [13]. Current smokers were regarded as subjects smoking 1–10 cigarettes/day for at least the last year [14]. In the exclusion criteriawe included any acute or chronic inflammatory disease, malignancies, and renal or liver failure. Glomerular filtration rate (GFR) was measured by the appropriate formula. The studywas approvedby the institutional ethics committees, and an informed consent was given by all the participants. Venous blood samples were centrifuged at 3500 rpm at 4 °C for 15 min, and plasma or serum was collected and stored at −80 °C until assayed. Serum concentrations of lipids were determined by using colorimetric enzymatic method in a Technicon automatic analyzer RA-

THE ASSOCIATION OF A3872G POLYMORPHISM ON C-REACTIVE PROTEIN WITH PERIPHERAL ARTERIAL DISEASE AND WAIST HIP RATIO INDEX IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Recent data consider inflammatory biomarkers and waist hip ratio (WHR) index prognostic agents of advanced atherosclerosis. C- reactive protein (CRP) contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). However, the impact of common polymorphisms of inflammatory genes on the

ARTERIAL STIFFENING IS ASSOCIATED WITH CEREBRAL MICROVASCULAR DAMAGE IN UNTREATED HYPERTENSION

Arterial stiffening is associated with the incidence of stroke however little is known about its relationship with cerebral microvascular damage. Retinal arterioles provide important information on cerebral microvascular function thus we sought to investigate the relationship of retinal alterations

ASSOCIATIONS OF CYSTATIN-C WITH PRECLINICAL ORGAN DAMAGE IN UNTREATED HYPERTENSION

methods: The study population consisted of 319 untreated hypertensive patients, and 193 matched control subjects. In all participants, flow mediated dilation (FMD), carotid-femoral pulse wave velocity (cf-PWV), intima-media thickness of carotid arteries (C-IMT), augmentation index, ankle-brachial index (ABI). The left cardiac indices, regarding left ventricular geometry and function, were assessed by echocardiography. Left ventricular mass index (LVMI) was calculated by Devereux’s formula. Serum cystatin-C levels were measured by the ELISA method.