Polymorphisms of −174G>C and −572G>C in the Interleukin 6 (IL-6) Gene and Coronary Heart Disease Risk: A Meta-Analysis of 27 Research Studies

OBJECTIVE: Elevated serum IL-6 level is a risk factor for coronary heart disease (CHD). The -174 G>C and -572 G>C polymorphisms in the IL-6 gene have previously been shown to modulate IL-6 levels. But the association between the -174 G>C and -572 G>C polymorphisms and the risk of CHD is still unclear. A meta-analysis of all eligible studies was carried out to clarify the role of IL-6 gene polymorphisms in CHD. METHODS AND RESULTS: PubMed, EMBASE, Vip, CNKI and CBM-disc were searched for eligible articles in English and Chinese that were published before October 2010. 27 studies involving 11580 patients with CHD and 17103 controls were included. A meta-analysis was performed for the included articles using the RevMan 5.0 and Stata 10.0 softwares. Overall, the -174 C allele was not significantly associated with CHD risk (ORs = 1.04, 95%CI = 0.98 to 1.10) when compared with the -174 G allele in the additive model, and meta-analysis under other genetic models (dominant, recessive, CC versus GG, and GC versus GG) also did not reveal any significant association. On the contrary, the -572 C allele was associated with a decreased risk of CHD when compared with the -572 G allele (ORs = 0.79, 95%CI = 0.68 to 0.93). Furthermore, analyses under the recessive model (ORs = 0.69, 95% = 0.59 to 0.80) and the allele contrast model (genotype of CC versus GG, ORs = 0.49, 95% = 0.35 to 0.70) yielded similar results. However, statistical significance was not found when the meta-analysis was restricted to studies focusing on European populations, studies with large sample size, and cohort studies by using subgroup analysis. CONCLUSIONS: The -174 G>C polymorphism in the IL-6 gene is not significantly associated with increased risks of CHD. However, The -572 G>C polymorphism may contribute to CHD development. Future investigations with better study design and large number of subjects are needed

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

INTERNATIONAL JOURNAL OF CARDIOLOGY

A case of uncontrolled hypertension with a vitreoretinal hemorrhage due to a retinal artery macroaneurysm of the right eye and chorioretinal scars of the left eye as initial symptom of hypertension is presented. End organ damage was undiagnosed until an intraocular hemorrhage appeared in the right eye. The hemorrhage and retinal macroaneursym disappeared spontaneously with proper medical therapy for hypertension. (C) 2003 Elsevier Ireland Ltd. All rights reserved

INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY RESEARCH

Recent studies indicate that abdominal fat accumulation is related to impaired endothelial function in young healthy volunteers. The aim of this study was to determine the acute effect of gastrointestinal lipase inhibitor on brachial flow-mediated vasodilatation and hemodynamic parameters in young obese women. The study population was composed of 42 female obese patients (mean age 29 +/- 4 years, age range between 18 and 34 years). Flow-mediated endothelial-dependent vasodilatation was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Brachial artery diameter (3.46 +/- 0.72 mm to 3.82 +/- 0.84 mm) and flow-mediated vasodilation (7.6 +/- 0.8% to 9.8 +/- 1.6%) changed significantly after 12 weeks of therapy (p 0.05). The results of this study demonstrate that orlistat improved endothelial function, weight, body mass index and systolic and diastolic blood pressure in young women

JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

Introduction Experimental and clinical studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and prognosis of coronary heart disease (CHD). The aim of this study was to investigate the genotype distribution and the allele frequencies of three RAS genes polymorphisms and their effects on premature CHD in a Turkish population. Materials and methods One-hundred and fifteen Turkish patients with premature CHD and 128 controls were included into the study. Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT(1)) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results The patients group showed an increased frequency of the ACE D allele compared with controls (65% vs. 35%, p=0.0001). There was a significant association between the DD genotype and premature CHD (ACE DD vs. ID and II; odds ratio [OR]=2.82 [CI 95% 1.33-2.91, p=0.002]). Also, we observed increased premature CHD risk associated with higher frequencies of the AGT MM genotype in patients when compared with controls (AGT MM VS. TT and MT OR=1.92 [Cl 95% 1.11-3.33, p=0.018]). We found a significant association between AT(1)-receptor AA genotype and decreased risk of premature CHD (AT1R AA vs. AC and CC, OR= 0.57[CI 95% 0.34-0.95, p=0.03]). Conclusions We demonstrated that increased premature CHD risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Also, our results suggest that family history, smoking, diabetes, hypertension, obesity and ACE DD genotype were independent risk factors for premature CHD

JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

Objectives. The aim of this study was to assess the effects of losartan treatment on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation (MR) secondary to mitral valve prolapse or rheumatic heart disease. Methods. Twenty-seven patients (14 males, 13 females, mean age 51 +/- 11, range 21-76) with moderate MR due to mitral valve prolapse or rheumatic heart disease were examined by means of Doppler echocardiography. The subjects were submitted to treadmill exercise tests using the modified Bruce protocol at baseline, after six hours and after the six-week treatment period to be evaluated based on their exercise tolerance. Mitral Regurgitant Volume (MRV), effective regurgitant orifice diameter, left atrial volume, left ventricle (LV) end-diastolic volume index, IV end-systolic volume index, IV ejection fraction (LVEF), left ventricle mass index were calculated at baseline and after six weeks of treatment with single dose of losartan (50 mg/day). Results. Total treadmill exercise time increased from 477.7 +/- 147.9 to 535.7 +/- 149.0 seconds after six hours (p < 0.01) and to 559.6 +/- 142.8 seconds after six weeks of treatment. Also, metabolic equivalent values increased following six hours of first dose and six weeks of losartan treatment (from 10.9 +/- 2.9 to 11.8 +/- 3.1, p=0.006 and 12.4 +/- 3.1, p=0.002; respectively). However, peak exercise systolic blood pressure (BP) was reduced after six hours and six weeks of treatment, and resting diastolic BP did not change after six hours but reduced at the end of the treatment period. MR volume decreased significantly from 29.3 +/- 14.1 ml to 25.1 +/- 14.8 ml, (p=0.025) without significant change in regurgitant orifice diameter (0.72 +/- 0.37 cm vs. 0.66 +/- 0.37 cm, p=NS), left atrium diameter and area while LVEF increased from 51.70 +/- 13.37 to 54.11-11-75 (p=0.015) with losartan. Conclusion. We conclude that the angiotensin II receptor antagonist losartan improves exercise tolerance and echocardiographic parameters in patients with moderate MR