Lack of association between lymphotoxin-α, galectin-2 polymorphisms and coronary artery disease: A meta-analysis

ObjectivePrevious case–control studies suggested the single nucleotide polymorphisms of lymphotoxin-α (LTA) gene and galectin-2 (LGASL2) gene are associated with coronary artery disease and myocardial infarction. However, other studies did not confirm this relationship. The objective was to assess the relationship of LTA gene, LGALS2 gene and coronary artery disease, using a meta-analysis.MethodsDatabases, including PubMed, EMbase, CBM and CNKI, were searched to get the genetic association studies. Data were extracted by two authors and pooled odds ratio (OR) and 95% confidence interval (CI) were calculated.ResultThe meta-analysis included 20640 (LTA-A252G) and 10552 (LGALS2-C3279T) cases, 15388 (A252G) and 10545 (C3279T) controls. The pooled OR of 252G was 1.02 (95%CI: 0.97–1.07) compared to wild type allele in dominant model, and was 1.00 (95%CI: 0.94–1.07) in recessive model. The pooled OR of 3279T was 0.95 (95%CI: 0.89–1.01) compared to wild type allele in dominant model, and was 0.89 (95%CI: 0.78–1.00) in recessive model. None of the polymorphisms was found to associate with coronary artery disease.ConclusionIn present study, the LTA gene and LGALS2-C3279T are not associated with coronary artery disease.     

Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in coronary disease: Case–control study and a meta-analysis

ObjectiveMatrix metalloproteinase-3 and its gene, MMP3, have been implicated in atherosclerotic diseases of coronary arteries. We conducted a haplotype analysis to examine the role of common variation of MMP3 in myocardial infarction (MI) and a meta-analysis to combine available evidence on the association between the 5A/6A polymorphism (rs3025058) and coronary diseases.Methods and resultsGenotype distributions of haplotype-tagging single nucleotide polymorphisms (rs522616, rs650108, rs569444, rs635746) and rs3025058 were not significantly different between a group with MI (n = 3657) and a control group (n = 1211) (p ≥ 0.24). Five major haplotypes were established, and their frequencies were not substantially different between the case and control groups (p ≥ 0.11). In a meta-analysis of 15 studies (10,061 cases, 8048 controls), the overall risk of coronary disease was not different between the carriers of the 5A allele and 6A6A genotype of rs3025058 (OR, 1.00; 95% CI, 0.85–1.19). Moderate trends of a reduced risk in the 5A allele carriers of European ancestry (OR, 0.87; 95% CI, 0.76–1.00) and an increased risk in the 5A allele carriers from East Asia (OR, 1.33; 95% CI, 0.94–1.90) were observed.ConclusionsIndividual polymorphisms and haplotypes of MMP3 were not associated with MI in a German case–control study. Evidence was obtained to suggest different risk effects of rs3025058 between Europeans and East Asians.     

FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

ObjectiveWe investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans.MethodsIn this case–control study, CAD patients (n = 756, 40–79 years) and healthy controls (n = 890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide.ResultsAmong four SNPs, only rs174537G > T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P = 0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P = 0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F_2α in both control and CAD groups.ConclusionThe rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.     

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction

ObjectiveEnhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event.MethodsConsecutive patients (n = 372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up.ResultsThe decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p < 0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r = 0.46; p < 0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p < 0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p < 0.05).ConclusionExcessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI.     

Association of ADIPOQ variants, total and high molecular weight adiponectin levels with coronary artery disease in diabetic and non-diabetic Brazilian subjects

ObjectiveTo investigate the association of ADIPOQ variants, total and high molecular weight adiponectin (HMW) adiponectin levels with the prevalence of diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary angiography in Brazilian subjects with high cardiovascular risk.Methods603 subjects undergoing coronary angiography were studied in regard to their glycemic status and presence of CAD (lesions > 0%). We evaluated baseline concentrations of total and HMW adiponectin and three ADIPOQ variants: ? 11391G > A (rs17300539), + 45T > G (rs2241766) and + 276G > T (rs1501299).ResultsThe G-allele of rs2241766 was associated with higher levels of total and HMW adiponectin, and the A-allele of rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of total and HMW adiponectin were independently associated with CAD. The G-allele of rs2241766 (OR 2.45, 95% C.I. 1.05–6.04, p = 0.04) and the G-allele of rs1501299 (OR 1.89, 95% C.I. 1.04–3.45, p = 0.03) were associated with CAD, and these associations were independent of circulating levels of adiponectin.ConclusionsIn Brazilian subjects with high cardiovascular risk, CAD was associated with lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms were associated with CAD. The rs2241766 variant was associated with total and HMW adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.     

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

ObjectiveTo evaluate possible subclinical atherosclerosis using biomarkers and ultrasound-guided methods in a group of adolescents having fathers with premature atherosclerosis.MethodsThirty-three subjects whose fathers had a history of premature coronary artery disease and 30 counterparts whose fathers had no history of coronary artery disease were included in the study.ResultsThe homocysteine levels, high-sensitivity C-reactive protein levels, and cardiac chamber sizes and functions did not differ between the two groups. The carotid stiffness index β (CSI), the intima-media thickness (CIMT) and aortic pulse wave velocity (PWV) values were higher in the group with a family history of coronary artery disease, but only the difference in the CSI was statistically significant (CSI 3.07 ± 1.33 vs 3.88 ± 1.25, P = 0.015; CIMT 0.53 ± 0.09 mm vs 0.57 ± 0.08 mm, P = 0.068; PWV 3.49 ± 0.53 m/s vs 3.78 ± 0.63 m/s, P = 0.053).ConclusionAmong several markers of subclinical atherosclerosis, the CSI was significantly higher in adolescents who had a family history of premature atherosclerosis. The small sample size, the multifactorial nature of atherosclerosis or the insufficient power of these methods may explain these results.     

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

BackgroundImatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs.AimTo investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML.MethodsOne hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C > T (rs1128503), c.3435C > T (rs1045642) and c.2677G > T/A (rs2032582) were evaluated by PCR-RFLP.ResultsABCB1 polymorphisms were not related with a risk for CML in this sample population (p < 0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p > 0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43–97.3, p = 0.022).ConclusionsThe ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients.     

CRP and CD14 polymorphisms correlate with coronary plaque volume in patients with coronary artery disease--IVUS substudy of the ENCORE trials

BackgroundSeveral proinflammatory single-nucleotide polymorphisms (SNPs) have been linked to the progression of atherosclerosis and coronary artery disease (CAD). Plaque size and its destabilization by inflammatory processes are major determinants of ischemia and acute coronary syndromes. Intravascular ultrasound (IVUS) allows for quantification of plaque size in vivo. We therefore investigated the relation of plaque size with mutations of proinflammatory genes in patients with CAD.MethodsIn 196 patients with stable CAD enrolled in the ENCORE trials coronary plaque and vessel volume was assessed by IVUS. 173 patients were successfully genotyped for polymorphisms of proinflammatory genes CD14 C(?260)T and CRP C(+1444)T using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach.ResultsBaseline characteristics were comparable for all genotype groups. Higher ratios of plaque volume/vessel volume were observed in patients with the CRP 1444TT (n = 11) and CD14 260TT (n = 33) genotypes (p = 0.016 and p = 0.026, respectively).ConclusionIn patients with stable coronary artery disease the CRP 1444TT and CD14 260TT variants are associated with larger coronary plaque volume independently of concomitant cardiovascular risk factors.     

IL6, IL10 and TGFB1 gene polymorphisms in coeliac disease: differences between DQ2 positive and negative patients

Predisposition to coeliac disease (CD) might be partially due to an individual pattern of hyper-inflammatory biased immune response. One of these patterns of intense response may be linked to the haplotype carrying HLA-DQ2 alleles and TNF −308A allele. However, 10 % of CD patients do not express the DQ2 heterodimer and these do not usually carry the TNF −308A allele. A similar response might be achieved by genes codifying other cytokines.ObjectivesTo study biallelic polymorphisms in genes codifying for TNFα, IL10, IL6 and TGFβ1 in DQ2 negative CD patients and to compare the results with DQ2 positive patients and healthy controls, in order to establish whether any of these polymorphisms have a role in CD susceptibility.MethodsTNF −308 (G > A), IL-6 −174 (G > C) and TGFB1 codon 10 (+ 869, T > C) and codon 25 (+ 915, G > C) polymorphisms and IL-10 haplotype of polymorphisms in positions −1082 (G > A), −819 (C > T) and −592 (C > A) were typed by a SSP-PCR technique.ResultsThe distribution of allele frequencies for TNF −308 is different between DQ2 positive CD patients and controls and the same occurs for haplotype frequencies of the IL10 promoter (−1082, −819, −592): The frequencies of the TNF −308A allele (p = 0.027), TNF −308A carriers (p = 0.031) and of IL10GCC haplotype are increased (p = 0.013) in DQ2 positive CD patients. However, the IL6 −174 allele G is more frequent in DQ2 negative patients than in healthy controls (p = 0.018), DQ2 negative controls (p = 0,018), and DQ2 positive patients (p = 0.008).ConclusionsDQ2 negative CD patients show an increased frequency of genotypes associated to IL6 high production. These were mainly allele G homozygous for the IL6 gene (−174) polymorphism. The IL6 −174GG genotype (homozygous) may be an additional risk marker for CD in DQ2 negative patients, representing an alternative susceptibility factor for CD when TNF −308A is negative.     

Decreased lipoprotein lipase activity and increased postprandial concentrations of triglyceride-rich lipoproteins in offspring of elderly survivors of myocardial infarction

Background and aimA family history of myocardial infarction (MI) is an independent risk factor for future coronary events. Decreased plasma lipoprotein lipase (LPL) activity is associated with delayed clearance of triglyceride-rich lipoproteins (TRL) and low fasting HDL cholesterol. The aim of the study was to investigate the relations between plasma LPL activity, postprandial TRL and HDL cholesterol in offspring of MI patients.Methods and resultsA case-control study was performed in 17 healthy middle-aged offspring of MI patients and 13 healthy age-and sex-matched controls. Fasting blood samples were collected and each subject was given a standardized oral fat load (1 g fat/kg body weight) with subsequent blood samples collected for an 8-h period. Offspring of MI patients had significantly lower postheparin LPL activity (62.9 mU/ml ± 22.8 mU/ml) (mean ± SD) than healthy controls (93.0 mU/ml ± 21.7 mU/ml) (p = 0.002). Decreased postheparin LPL activity was accompanied by significantly increased and delayed clearance of postprandial TRL and subsequent lower fasting HDL cholesterol in offspring of MI patients. Postheparin LPL activity was associated with HDL cholesterol (r = 0.40, p = 0.036) and trend analysis revealed a decrease in incremental area under the curve (AUCi) for chylomicrons with increasing LPL activity (p = 0.013).ConclusionsOffspring of MI patients had decreased postheparin LPL activity accompanied by increased postprandial TRL and subsequent decreased HDL cholesterol, an unfavourable lipid profile which may contribute to their increased risk for future coronary events.     

Adenosine improves post-procedural coronary flow but not clinical outcomes in patients with acute coronary syndrome: a meta-analysis of randomized trials

AimsAdjunctive therapy with adenosine has been shown to improve coronary flow in patients with acute coronary syndromes (ACS); it is unclear, however, whether adenosine can effectively reduce adverse clinical events. The aim of our study was to perform a meta-analysis of all randomized controlled trials (RCTs) investigating angiographic and clinical outcomes in ACS patients undergoing PCI or thrombolysis and receiving adjunctive adenosine therapy vs. placebo.MethodsMedline/CENTRAL/EMBASE and Google Scholar database were scanned. The meta-analysis included ten RCTs (N = 3821). All-cause mortality was chosen as primary endpoint. Secondary endpoints were re-infarction (MI), heart failure (HF) symptoms (NYHA class III/IV), no-reflow (defined as TIMI 0 flow) and >50% ST-resolution.ResultsAdenosine compared to placebo was associated with a significant reduction of post-procedural no-reflow (OR [95% CI] = 0.25 [0.08–0.73], p = 0.01); however, at a median follow-up of 6 months, prior treatment with adenosine did not confer significant benefits in terms of reduction of mortality (OR_Fixed [95% CI] = 0.87 [0.69–1.09], p = 0.23), as well as re-MI (p = 0.80), HF symptoms (p = 0.44) and ST-resolution (p = 0.09). Separate analyses conducted in the subgroups of ST-elevation MI patients treated with either PCI or thrombolysis confirmed the findings found in the overall population.ConclusionsThis meta-analysis shows that adenosine adjunctive therapy does not improve survival nor reduce the rates of re-MI and HF symptoms in patients with ACS treated with PCI or thrombolysis. The beneficial effect on post-procedural coronary flow was not associated with consistent advantages on clinical outcomes.     

Glycated apolipoprotein B and myocardial infarction

AimsTo evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes.MethodsThe design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data.ResultsApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P = 0.009 and P = 0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95 % CI 0.93–4.33) in non-diabetic and 2.88 (0.85–9.68) in diabetic subjects (chi-square test for trend; non-diabetics P = 0.03, diabetics P = 0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P > 0.10).ConclusionApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.     

Gene-nutrient interactions and gender may modulate the association between ApoA1 and ApoB gene polymorphisms and metabolic syndrome risk

ObjectiveDyslipidemia is a key feature of the metabolic syndrome (MetS), which is determined by both genetic and dietary factors.MethodsWe determined the relationships between ApoA1 and ApoB polymorphisms and MetS risk, and whether dietary fat modulates this in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).ResultsApoB rs512535 and ApoA1 rs670 major G allele homozygotes had increased MetS risk (OR 1.65 [CI 1.24, 2.20], P = 0.0006; OR 1.42 [CI 1.08, 1.87], P = 0.013), which may be, partly, explained by their increased abdominal obesity and impaired insulin sensitivity (P < 0.05) but not dyslipidemia. Interestingly these associations derived primarily from the male GG homozygotes (ApoB rs512535 OR 1.92 [CI 1.31, 2.81], P = 0.0008; ApoA1 rs670 OR 1.50 [CI 1.05, 2.12], P = 0.024). MetS risk was exacerbated among the habitual high-fat consumers (>35% energy) (ApoB rs512535 OR 2.00 [CI 1.14, 3.51], P = 0.015; OR 1.58 [CI 1.11, 2.25], P = 0.012 for ApoA1 rs670). In addition a high monounsaturated fat (MUFA) intake (>14% energy) increased MetS risk (OR 1.89 [CI 1.08, 3.30], P = 0.026 and OR 1.57 [CI 1.10, 2.40], P = 0.014 for ApoB rs512535 and ApoA1 rs670, respectively). MetS risk was abolished among the habitual low-fat consumers (<35% energy). Saturated and polyunsaturated fat intake did not modulate MetS risk.ConclusionApoB rs512535 and ApoA1 rs670 may influence MetS risk. Apparent modulation of these associations by gender and dietary fat composition suggests novel gene-gender-diet interactions.     

Association of the six transmembrane protein of prostate 2 gene polymorphisms with metabolic syndrome in Han Chinese population

AimThe six-transmembrane protein of prostate 2 (STAMP2) has been demonstrated to play a potential role in the pathogenesis of metabolic syndrome (MetS). The present study was designed to investigate the association of STAMP2 gene polymorphisms with MetS in Han Chinese population.MethodsA case-control study enrolled 350 Han Chinese subjects in two groups: 182 MetS patients and 168 control subjects. The clinical and biochemical characteristics were determined. Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756 and rs10263111 in STAMP2 gene were genotyped. The association of STAMP2 gene polymorphisms with MetS was analyzed.ResultsSNPs rs1981529 and rs10263111 were found to be significantly associated with MetS phenotype in male population (P = 0.014 and 0.025). Moreover, SNP rs1981529 was found to be associated with high density lipoprotein-cholesterol in male cases and with body mass index in female cases (P = 0.014 and 0.049). SNP rs10263111 was found to be associated with both waist circumference and diastolic blood pressure in total cases (P = 0.044 and 0.033). Haplotype analysis yielded significant association of STAMP2 gene with MetS in total (global P = 0.0109) and male population (global P = 0.0004).ConclusionOur findings revealed that STAMP2 gene polymorphisms are likely to significantly contribute to the risk of MetS in male Han Chinese population.     

Knowledge of cardiovascular risk factors and awareness of non-pharmacological approach for risk prevention in young survivors of acute myocardial infarction. The cardiovascular risk prevention project "Help Your Heart Stay Young"

Background and aimsKnowledge of cardiovascular disease (CVD) risk factors in young patients who experienced myocardial infarction (MI) is poorly described.Methods and resultsKnowledge of traditional CVD risk factors, non-fatal cardiovascular events and of non-pharmacological factors able to reduce CVD risk and education level were evaluated by questionnaires in subjects who visited their family doctors. Sixty-one participants with history of MI in age <50 years (MI+) were compared with 3749 subjects with age <50 years, from the same population source, but without history of MI (MI−). MI+ were more frequently men (p < 0.01), did not have significantly higher prevalences of family history of CVD, diabetes and hypertension. MI+ individuals reported previous non-fatal stroke (13% vs. 0.5%, p < 0.001), overweight, diabetes, and hypercholesterolemia (all p < 0.001) more frequently than controls, whereas prevalence of arterial hypertension, smoking habit and physical inactivity did not differ between the two groups; MI+ and MI− individuals did not differ in terms of the proportion of those who were unaware of being hypertensive, diabetic or hypercholesterolemic. MI+ participants reported more frequently lower education level than controls (p < 0.05). Knowledge of non-pharmacological approach for CVD risk reduction was similar in MI+ and MI−. In a logistic multivariate analysis, male gender (adjusted odds ratio = 5.8) and high cholesterol level (adjusted odds ratio 2.8, both p < 0.01) were independent correlates of MI+. CVD risk factors distribution was similar between participants with juvenile MI+ and MI in age ≥50 years (n = 167) extracted from the same population source; however, stroke was reported more frequently in juvenile MI+ than in those who had MI at age ≥50 years/old (13% vs. 4%, p < 0.01).ConclusionsJuvenile non-fatal MI was associated with metabolic CVD risk factors, with higher cerebrovascular co-morbidity and lower education level.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Triple nutrient supplementation improves survival, infarct size and cardiac function following myocardial infarction in rats

Background and aimWe evaluated the impact of triple nutrient supplementation (TNS: carnitine, taurine and coenzyme Q₁₀) vs. carnitine alone (CARN) or placebo on survival, infarct size, cardiac function and metabolic gene expression using a model of myocardial infarction (MI) in rats.Methods and resultsMale Wistar rats were randomized to three groups divided in two independent studies prior to ligation of the left anterior descending coronary artery (LAD): TNS vs. Placebo and TNS vs. CARN. Nutrient supplementation [l-carnitine (300 mg/day), coenzyme Q₁₀ (15 mg/kg body weight/day) and taurine (0.1 M)] was administered daily for four weeks prior to and for 10 days after MI. At that time, cardiac function and infarct size were measured. Metabolic gene (mRNA) expression in the peri-infarct tissue of left ventricle from TNS, placebo or corresponding time-control rats (TNS or placebo without LAD ligation) was measured 10 days after MI.When compared to placebo, TNS significantly improved survival (60% vs. 34%, p < 0.02), cardiac function, and reduced infarct size (30 ± 7% vs. 42 ± 9%, p < 0.001). Although CARN improved survival like TNS (45% vs. 50%, not significant), it did not reduce infarct size (32 ± 14% vs. 19 ± 10%, p < 0.05) or delay myocardial remodeling. In the placebo group, MI was associated with a significantly altered pattern of metabolic gene expression (glucose transporter 1, liver carnitine palmitoyl transferase 1, medium-chain acyl-CoA dehydrogenase; p < 0.01 for all three) in the left ventricle peri-infarct tissue. In contrast, gene expression was normalized in the group receiving TNS.ConclusionsOur results support the potential cardioprotective impact of TNS during myocardial ischemia. In contrast to carnitine supplementation alone, TNS improved survival as well as cardiac function, gene expression and delayed remodeling.     

Akt2 Gene common allelic variants in insulin resistance and the metabolic syndrome

Background and aimSeveral lines of evidence indicate that glucose homeostasis may be under the control of Akt2 and it can therefore be seen as a candidate gene for human insulin resistance (IR) and related phenotypes. The aim of our study was the identification of Akt2 common allelic variants that might modulate susceptibility to IR and related metabolic abnormalities.Methods and resultsThe Akt2 gene (exons, 5′ and 3′ regulatory regions) was re-sequenced in samples of 50 blood donors from the Gargano region. Two single nucleotide polymorphisms (SNPs) in 5′ (rs11669332 and rs969531) and two in 3′ (rs2304186 and C1658T) regulatory regions were exploited in an association study using 661 healthy unrelated Caucasian individuals from the same region.Individuals being homozygous for the T allele of rs11669332 (an Akt2 promoter) showed lower systolic blood pressure (p = 0.04), total/HDL cholesterol ratio (p = 0.02) and the metabolic syndrome score (p = 0.04), while carriers of the A allele of rs969531 (in 5′-UTR) showed higher systolic blood pressure (p = 0.027). The association between phenotypic traits and possible haplotypes was tested as well. However, no haplotype affecting the risk of metabolic abnormalities was found.ConclusionsTwo variants in 5′ regulatory region of Akt2 gene are associated and may modulate susceptibility to IR and related metabolic abnormalities.     

Qualitative characteristics of HDL in young patients of an acute myocardial infarction

AimRecently, the concept that high density lipoprotein (HDL) quality is an important parameter for atheroprotection is gaining ground, though little data exists so far to support it. In an attempt to identify measurable qualitative parameters of HDL associated with increased risk for premature myocardial infarction (MI), we studied the structural characteristics of HDL from patients who survived an MI at a young age (≤35 years).Methods and resultsWe studied 20 MI patients and 20 healthy control subjects. HDL of patients had reduced apolipoprotein A-I (apoA-I), apolipoprotein M, and paraoxonase 1 levels and significantly elevated apolipoprotein C-III (apoCIII) levels (all p < 0.05). Specifically, the HDL apoA-I/apoC-III ratio was 0.24 ± 0.01 in patients versus 4.88 ± 0.90 in controls (p < 0.001). These structural alterations correlated with increased oxidation potential of HDL of the MI group compared to controls (2.5-fold, p = 0.026). Electron microscopy showed no significant difference in average HDL particle diameter between the two groups though a significant difference existed in HDL diameter distribution, suggesting the presence of different HDL subpopulations in MI and control subjects. Indeed, non-denaturing two-dimensional electrophoresis revealed that MI patients had reduced pre-β1_α, pre-β1_b and α₂, and elevated α₁, α₃, and pre-α₄ HDL.ConclusionsReduction in the HDL apoA-I/apoC-III ratio, changes in the HDL subpopulation distribution and an increase in HDL oxidation potential correlated with the development of MI in young patients. The possibility that such changes may serve as markers for the early identification of young individuals at high risk for an acute coronary event should be further explored.     

Relation between plasma homocysteine, gene polymorphisms of homocysteine metabolism-related enzymes, and angiographically proven coronary artery disease

BackgroundHyperhomocyteinemia (HHcy) is a risk factor for coronary artery disease (CAD), and methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms may contribute to plasma total homocysteine (tHcy) variation. We investigated the association of polymorphisms 1298A→C in the MTHFR gene, 2756A→G in the MTR gene, and 66A→G in the MTRR gene with tHcy levels and with CAD in patients undergoing coronary angiography.MethodsCAD patients (n = 151) and control subjects (n = 79) were compared regarding the prevalence of the polymorphisms, risk factors, and biochemical parameters.ResultsThe mean tHcy concentration was significantly higher in CAD patients than in control subjects (P < 0.001). HHcy (tHcy ≥ 15 μmol/l) conferred an OR of CAD of 4.1 (95% CI 2.2–7.5, P < 0.001). In both cases and controls, smokers had a higher tHcy level than non-smokers and demonstrated a markedly increased risk for CAD (OR = 2.5, 95% CI 1.7–3.3, P < 0.001). The allele frequencies of the MTHFR 1298A→C, MTR 2756A→G, and MTRR 66A→G mutations were 36.7%, 15.7%, and 36.6%, respectively. The 1298C allele frequency was significantly higher in the CAD group than in controls (P < 0.05) and showed a significant association with CAD in heterozygote carriers. There was no statistically significant difference between cases and controls in the frequencies of the A2756G alleles/genotypes in the MTR gene and of the A66G alleles/genotypes in the MTRR gene. The contributions to tHcy levels of the three common mutations were statistically significant. The heterozygosity of the MTHFR 1298AC genotype, MTR 2756G allele, and MTRR 66G allele yielded an OR of 3.4, 2.0, and 2.1, respectively, for having HHcy.ConclusionWe suggest that HHcy confers a risk for CAD, and smokers with tHcy are at a greatly increased risk. Our finding supports an important role of the MTHFR gene in CAD and provides evidence of polygenic regulation of tHcy.