Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk

ObjectiveChronic inflammation plays a role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is a novel cardiometabolic risk factor. Whether dietary fat intake modulates MetS risk conferred by elevated C3 concentrations is unknown. Our objective is to investigate the relationship between C3 concentrations and risk of the MetS and its phenotypes, and to further examine whether dietary fat intake modulates these relationships.MethodsBiochemical, dietary and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).ResultsElevated C3 concentrations (>median) were associated with increased risk of impaired insulin sensitivity [OR 1.78, CI 1.34–2.36, P < 0.0001], insulin resistance [OR 1.73, CI 1.31–2.89, P = 0.0001], abdominal obesity [OR 2.15, CI 1.43–3.24, P = 0.0002] and low HDL cholesterol [OR 1.40, CI 1.05–1.86, P = 0.02] compared to low C3 concentrations. Increased MetS risk conferred by elevated C3 concentrations [OR 3.11, 95% CI 2.52–3.82, P < 0.0001] was further accentuated among high dietary fat consumers [OR 4.80, 95% CI 2.77–8.33, P < 0.0001] (particularly of saturated [OR 4.05, 95% CI 2.33–7.05, P < 0.0001] and monounsaturated fat [OR 4.48, 95% CI 2.62–7.56, P < 0.0001]), and smokers [OR 3.83, 95% CI 2.12–6.94, P < 0.0001], however this effect was abolished in abdominally lean individuals [OR 1.46, 95% CI 0.69–3.14, P = 0.33].ConclusionsDietary fat (intake and composition), abdominal obesity and smoking modulate the relationship between elevated plasma C3 concentrations and MetS risk.     

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue

ObjectiveThe objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.MethodsAll eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software.ResultsIn overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients.ConclusionACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.     

Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans

BackgroundIt has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, ?0.08 mm, 95% CI ?0.13, ?0.04; P = 0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) was superior to placebo (WMD, ?0.04 mm, 95% CI ?0.05, ?0.03; P < 0.00001), no antiplatelet medication (WMD, ?0.12 mm, 95% CI ?0.21, ?0.03; P = 0.008), aspirin monotherapy (WMD, ?0.06 mm, 95% CI ?0.12, 0.00; P = 0.04) or dual antiplatelet therapy (WMD, ?0.16 mm, 95% CI ?0.30, ?0.02; P = 0.03) in preventing the progression of carotid IMT. Cilostazol resulted in a significant decrease in total cholesterol (WMD ?8.47 mg/dl, 95% CI ?14.18, ?2.75; P = 0.004) and LDL-C (WMD ?8.25 mg/dl, 95% CI ?14.15, ?2.36; P = 0.006) and favorable trends in reducing triglyceride (WMD ?15.83 mg/dl, 95% CI ?32.14, 0.48; P = 0.06).ConclusionIt suggests that cilostazol may have beneficial effects in preventing the progression of carotid atherosclerosis and improving pro-atherogenic lipid profile, especially in patients with T2DM. Whether the anti-atherosclerotic effect of cilostazol is independent of improving pro-atherogenic dyslipidemia is worth further investigation.     

Coffee consumption and risk of coronary heart disease: a meta-analysis

Background and aimsDuring the past three decades the relationship between habitual coffee drinking and coronary heart disease (CHD) has been assessed in numerous studies, with conflicting results. The aim of this study was to systematically examine the data published on the association between habitual coffee consumption and risk of CHD.Methods and resultsThirteen case–control and 10 cohort studies were included. Case–control studies incorporated 9487 cases of CHD and 27,747 controls, and cohort studies included a total of 403,631 participants that were followed for between 3 and 44 years. The summary of odds ratios (OR) for the case–control studies showed statistically significant associations between coffee consumption and CHD for the highest intake group (>4 cups/day), OR 1.83 (95% CI 1.49–2.24; P < 0.0001), and for the second highest category (3–4 cups/day), OR 1.33 (95% CI 1.04–1.71; P < 0.0001), while no significant association emerged for low daily coffee intake (≤2 cups/day), OR 1.03 (95% CI 0.87–1.21; P = 0.45). The analysis of long-term follow-up cohort studies did not show any association between the consumption of coffee and CHD, with a relative risk (RR) of 1.16 (95% CI 0.95–1.41; P = 0.14) for the highest category, and 1.05 (95% CI 0.90–1.22; P = 0.57) and 1.04 (95% CI 0.90–1.19; P = 0.60) for the second and third highest categories, respectively. These results did not differ substantially when controlling for region of origin, fatal and non-fatal events, year of publication, and number of years of follow-up.ConclusionsDespite a significant association between high consumption of coffee and CHD reported among case–control studies, no significant association between daily coffee consumption and CHD emerged from long-term follow-up prospective cohort studies.     

Sensitivity of A1C to diagnose diabetes is decreased in high-risk older Southeast Asians

ObjectiveTo determine the effect of ageing on the performance of glycosylated haemoglobin A1C (A1C) for the diagnosis of diabetes mellitus (DM) in Southeast Asians.MethodsA1C was measured in 511 subjects (mean age of 52.4 years; range 14–93) undergoing the 75-g oral glucose tolerance test (OGTT). Using receiver operating curve (ROC) analysis, the performance of A1C for the diagnosis of diabetes (using different standard criteria) was compared between 4 groups: < 45 (n = 156), 45–54 (n = 132), 55–64 (n = 122), ≥ 65 years (n = 101).ResultsSubjects aged ≥ 65 years had the highest false-negative rates with fasting plasma glucose (60.8%) and A1C (35.1%), the smallest area under ROC curve (0.723, 95% CI 0.627–0.820), the lowest sensitivity (58.7%, 95% CI 50.4–65.7) and specificity (71.1%, 95% CI 57.3–82.6) of A1C 6.5%, compared to the younger age groups.ConclusionOGTT is preferable for diagnosis of DM in older Southeast Asian adults.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction

IntroductionElevation of total white blood cells (WBC) count is associated with higher mortality in patients with acute coronary syndromes. However, it is unknown which specific subset of leukocytes best correlates with increased risk of adverse outcome.Methods and resultsWe prospectively studied the predictive value of WBC subtypes for long-term outcome in 1037 patients with acute myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte counts, and high-sensitivity C-reactive protein (CRP) were obtained in each patient. The median duration of follow up was 23 months (range, 6–42 months). Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5–3.3; P < 0.0001), neutrophil (HR 2.7, 95% CI 1.8–4.1; P < 0.0001) and monocyte (HR 1.9, 95% CI 1.3–2.8; P = 0.001) counts in the upper quartile, and lymphocyte count in the lower quartile (HR 1.5, 95% CI 1.1–2.3; P = 0.03), were all independent predictors of mortality. Comparing nested models, adding other WBC data failed to improve model based on neutrophil count. In contrast, adding neutrophil count to the models based on total WBC (P = 0.01), on monocyte count (P < 0.0001) or on lymphocyte count (P < 0.0001) improved the prediction of the models. Neutrophil count in the upper quartile (≥9800 μL^?1) remained a strong independent predictor of mortality after adjustment for left ventricular systolic function and for CRP (HR 2.2, 95% CI 1.6–3.0; P < 0.0001).ConclusionOf all WBC subtypes, elevated neutrophil count best correlates with mortality in patients with AMI. Neutrophil count provides additive prognostic information when combined with CRP.     

Angiotensin-converting enzyme gene insertion/deletion polymorphisms and the susceptibility to allergic rhinitis

BackgroundAngiotensin-converting enzyme (ACE) gene I/D polymorphism might be linked to the risk of the allergic rhinitis (AR).ObjectiveIn the present study, we assessed the association of ACE gene I/D polymorphisms with AR susceptibility using a meta-analysis.Materials and methodsWe carried out a retrieval of studies and included the eligible studies if they met the criteria. After the data extraction, the Stata software was used to analyse the genotype frequencies.ResultsIn total, five studies with 561 patients and 603 controls were included. However, the genotype distribution among the control of one study was not consistent with the Hardy–Weinberg equilibrium. After pooling all studies, the results indicated an association between ACE gene I/D polymorphism and AR risk in the overall analysis (II vs. others: OR = 0.70, 95% CI = 0.54–0.92, P = 0.010; D vs. I: OR = 1.29, 95% CI = 1.08–1.54, P = 0.005). In the further analysis of the East Asians, no association between ACE gene I/D polymorphism and AR risk was observed.ConclusionACE gene I/D polymorphisms were not associated with the risk of AR in East Asians. These results need to be confirmed in the following studies.     

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

BackgroundStudies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.Methods19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.ResultsCYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p = 0.009], CV death [RR: 3.21, CI: 1.65–6.23; p = 0.001], MI [RR: 1.36, CI: 1.12–1.65; p = 0.002], ST [RR: 2.41, CI: 1.69–3.41; p < 0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p = 0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p = 0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p = 0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p = 0.06], ST [RR: 0.88, CI: 0.52–1.47; p = 0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p = 0.62] in both groups.ConclusionIn CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.     

Interleukin-18 and the risk of future cardiovascular disease among initially healthy women

ObjectiveElevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce.Methods and resultsIn a prospective nested case–control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls. IL-18 levels were higher at baseline among those who developed CVD (274.1 pg/mL versus 233.8 pg/mL, P < 0.001), and were associated with future CVD (relative risk (RR) for highest versus lowest quartile 2.53; 95% CI, 1.47–4.35, P < 0.001). While that risk was attenuated after adjustment for traditional cardiovascular risk factors (RR 1.60; 95% CI, 0.77–3.34, P = 0.13), those with IL-18 levels at or above a threshold of the 90th percentile (442 pg/mL) remained at elevated risk after adjustment (RR 2.40; 95% CI, 1.05–5.56, P = 0.04). Levels of IL-18 above this threshold modify the fully adjusted risk of future CVD conferred by elevated levels of total cholesterol (P_interaction = 0.02).ConclusionsIn this population of apparently healthy women, IL-18 levels associate with increased risk of cardiovascular disease, but that risk is attenuated in models adjusting for traditional cardiovascular risk factors. Very high levels of IL-18 interact with hypercholesterolemia to alter CVD risk.     

Effect of thiazolidinediones on in-stent restenosis in patients after coronary stenting: a meta-analysis of randomized controlled trials

BackgroundRecent experimental studies have demonstrated that thiazolidinediones (TZDs) therapy inhibits proliferation and migration of vascular smooth muscle cells, accelerates endothelium reparation and attenuates neointimal hyperplasia. It implies that TZDs therapy may have beneficial effects on in-stent restenosis (ISR). Several small-sample clinical trials have evaluated the effect of TZDs therapy on ISR, however, the results were inconsistent across trials.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials to evaluate the effect of TZDs therapy on in-stent restenosis in patients undergoing coronary stenting. Eight trials involving 366 patients were included in this study. TZDs therapy was associated with a significant reduction in the risk of ISR in both diabetic (RR 0.37, 95% CI 0.23–0.59; P < 0.0001) and non-diabetic patients (RR 0.16, 95% CI 0.05–0.45; P = 0.0006). TZDs therapy was associated with a significant reduction in late lumen loss (WMD ?0.54 mm, 95% CI ?0.87 mm, ?0.22 mm; P = 0.001), percent diameter stenosis (WMD ?15.7%, 95% CI ?19.4%, ?12.0%; P < 0.00001), neointimal area/volume (SMD ?0.76, 95% CI ?1.13, ?0.39; P < 0.0001) and target lesion revascularization (RR 0.32, 95% CI 0.18–0.57; P = 0.0001).ConclusionsOur study suggests that TZDs therapy is an effective strategy in preventing ISR in both diabetic and non-diabetic patients undergoing coronary stenting. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-restenotic effect of TZDs therapy.     

Age and living in an urban environment are major determinants of diabetes among South Kivu Congolese adults

ObjectivesThis study aimed to determine the risk factors for diabetes mellitus (DM) in the eastern part of the Democratic Republic of Congo.MethodologyMultilevel sampling identified 200 households (444 adults aged ≥ 20 years) from 20 neighbourhoods in the city of Bukavu, and 90 households (255 adults aged ≥ 20 years) from 10 villages in the Kaziba (South Kivu) chiefdom (the South Kivu VITARAA study). DM was defined as a personal history of the disorder or a casual glycaemia greater or equal to 200 mg/dL. Standardization according to age and sample readjustment based on the urban–rural distribution of the population was applied accordance with the typical Congolese population. The probability of DM was assessed by multiple logistic regressions.ResultsTotal prevalence of DM was 3.5%. DM was significantly more prevalent in urban areas (age-standardized prevalence: 4.0%) than in rural areas (1.7%). City-dwelling DM patients were characterized by higher rates of indices of abdominal obesity (P < 0.05) whereas, in rural areas, no patients were obese. In the study group as a whole, only 25.0% of diabetic patients were obese. On multivariate analyses, only age [adjusted OR (95% CI): 4.79 (1.60–14.25); P = 0.004] was independently associated with the prevalence of DM, while the effect of obesity was not significant [2.64 (0.99–7.02); P = 0.051].ConclusionAge and living in an urban environment appeared to be major determinants of DM in South Kivu. Also, obesity prevalence was relatively low in these diabetic patients, confirming the peculiar, relatively lean, phenotype of type 2 DM in indigenous sub-Saharan Africans.     

Risk factors for foot ulcers—A cross sectional survey from a primary care setting in Brazil

AimsTo identify the prevalence of higher risk of foot ulceration and associated factors among patients with diabetes mellitus (DM) at primary health care services.MethodsIndividuals with DM, registered at primary health care services in a municipality in southern Brazil, were interviewed and underwent foot examinations. Their risk of ulceration was classified in accordance with the recommendations of the International Working Group on the Diabetic Foot. Poisson bivariate and multivariate analyses were performed and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were calculated.ResultsThe prevalence of higher risk of foot ulceration among the 337 interviewees was 27.9% (95% CI 23.1–32.9). The following factors were associated with this risk: having been diagnosed with DM for more than 10 years (Adjusted-PR 1.669; 95% CI 1.175–2.373; p = 0.004); having had previous diagnoses of acute myocardial infarction (Adjusted-PR 1.873; 95% CI 1.330–2.638; p < 0.001) and stroke (Adjusted-PR 1.684; 95% CI 1.089–2.604; p = 0.019); presenting interdigital mycosis (Adjusted-PR 1.539; 95% CI 1.030–2.300; p = 0.035) and calluses (Adjusted-PR 1.654; 95% CI 1.117–2.451; p = 0.012).ConclusionsThe prevalence of higher risk of ulceration was high, which reinforces the importance of continued education for health care professionals in order to prevent complications in the feet of these patients.     

Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis

BackgroundTo evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.MethodsWe meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.ResultsCompared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): ?5.31%, 95% CI ?7.09 to ?3.53%, P < 0.001] and higher carotid IMT (pooled MD: 0.12 mm, 95% CI 0.09–0.15 mm, P < 0.001) and femoral IMT (pooled MD: 0.35 mm, 95% CI 0.18–0.51 mm, P < 0.001). FCH patients had lower FMD and increased IMT (pooled MD: ?3.60%, 95% CI ?6.69 to ?0.50%, P = 0.023; and 0.06 mm, 95% CI 0.04–0.08 mm, P < 0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86–7.92%, P < 0.001) and decreased carotid IMT (pooled MD of change: ?0.025 mm, 95% CI ?0.042 to ?0.009 mm, P = 0.003). Changes of both FMD and IMT with statins correlated with the duration × treatment intensity product in FH patients (both P < 0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43–3.69%, P = 0.013). No significant publication bias was detected.ConclusionArterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.     

Long-term follow-up of participants in a health promotion program for treated hypertensives (ADAPT)

Background and aimsImprovements in a lifestyle modification program for hypertensives were maintained 1 year later. Longer follow-up in such studies is limited; we therefore re-assessed participants after an additional 2 years in which there was no contact with program facilitators.Methods and resultsParticipants randomised to usual care (N = 118) or a 4-month lifestyle program (N = 123) were previously assessed after 4 months and 1 year. After a further 2 years, diet, alcohol intake, physical activity, weight, waist girth, ambulatory blood pressure (BP), blood lipids, glucose and insulin were measured (usual care N = 64; program N = 76). Statistically significant net changes, relative to usual care, included blood cholesterol (−0.2 mmol/L, 95% CI 0.1–0.4); physical activity (53 min/week, 95% CI 15–91); dietary saturated fat (−1.9% energy, 95% CI −0.1 to −3.8); fish (3.2 serves/month, 95% CI 0.7–5.7); vegetables (9.1 serves/month, 95% CI 3.2–15.1); and sweet foods (−6.2 serves/month, 95% CI −1.1 to −11.3). Between-group changes in weight (−0.7 kg, 95% CI −1.8–0.4), BP (systolic 1.4 mmHg, 95% CI −0.7–3.5)/diastolic 1.0 mmHg, 95% CI −0.3–2.4) and Framingham risk (usual care: men 12.1%, women 3.7%; program: men 12.2%; women 3.5%) did not differ significantly.ConclusionContinued reinforcement with long-term follow-up is needed in lifestyle modification programs.     

Interleukin-18 promoter polymorphism associates with the occurrence of sudden cardiac death among Caucasian males: the Helsinki Sudden Death Study

ObjectiveThe increased plasma concentrations of pro-atherogenic and cardiomyocyte hypertrophic cytokine interleukin 18 (IL-18) predict mortality in patients with coronary heart disease (CHD) in addition to predicting the outcome of heart failure. The IL-18 gene has a functional ?137 G/C polymorphism (rs187238) in the promoter region. The C allele carriage is associated with attenuated IL-18 production. The effect of IL-18 genotype on SCD is unknown. We studied the association of the IL-18 gene ?137 G/C polymorphism with the occurrence of sudden cardiac death (SCD).MethodsUsing the TaqMan 5′ nuclease assay, we genotyped two independent consecutive and prospective autopsy series which were included in the Helsinki Sudden Death Study.ResultsOf the 663 men, 359 (54.1%) had the wild-type GG-genotype, 261 (39.4%) were heterozygotes (CG) and 43 (6.5%) were CC homozygotes. Compared to the GG homozygotes, the C allele carriers (i.e. subjects having CC or CG genotypes) had a lower adjusted risk for SCD from any cause (odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31–0.77, p = 0.002), for SCD due to CHD (OR 0.51; 95% CI, 0.32–0.82, p = 0.005), and for SCD caused by non-coronary heart diseases (OR 0.34; 95% CI 0.13–0.90, p = 0.030).ConclusionIL-18 promoter ?137 G/C polymorphism, which regulates the expression of IL-18, is an important predictor of SCD from any cause as well as SCD in patients with and without underlying CHD.     

Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 27)

PurposeThe aims of this study were to report the prevalence of various microvascular complications and to identify the various clinical and biochemical characteristics related to these complications in subjects with newly diagnosed type II diabetes.MethodsOf the 5999 subjects enumerated, 1414 subjects with diabetes (both known and newly diagnosed) were analyzed for the study. Among the diabetic subjects, 248 (17.5%) were newly diagnosed with diabetes and the remaining had history of diabetes. All subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography), neuropathy (vibration pressure threshold), and nephropathy (microalbuminuria).ResultsThe prevalence of any form of microvascular complication was 30.2% (95% confidence interval [CI] = 24.5–35.9). The prevalence of diabetic retinopathy was 4.8%, and that of diabetic nephropathy and neuropathy was 10.5%. The risk factors for developing any form of microvascular complication were increasing age (odds ratio [OR] = 1.07, 95% CI = 1.04–1.11, P < .0001), increasing systolic blood pressure (OR = 1.03, 95% CI = 1.01–1.06, P = .001), and increasing hemoglobin (OR = 1.39, 95% CI = 1.09–1.79, P = .011). The risk factors for diabetic retinopathy and diabetic nephropathy were increasing systolic blood pressure (OR = 1.06 [P = .001] for retinopathy and OR = 1.04 [P = .012] for nephropathy) and increasing hemoglobin (OR = 2.20 [P = .007] for retinopathy and OR = 1.57 [P = .023] for nephropathy). The risk factor for diabetic neuropathy was increasing age (OR = 1.12, P < .0001).ConclusionsNearly one third of the newly diagnosed type II diabetes subjects had some form of microvascular complication; nephropathy, and neuropathy being commoner than retinopathy.     

Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL,PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs

BackgroundWhile several type 2 diabetes mellitus (T2DM) susceptibility loci identified through genome-wide association studies (GWAS) have been replicated in many populations, their association in Arabs has not been reported. For this reason, the present study looked at the contribution of ENNP1 (rs1044498), IGF2BP2 (rs1470579), KCNJ11 (rs5219), MLXIPL (rs7800944), PPARγ (rs1801282), SLC30A8 (rs13266634) and TCF7L2 (rs7903146) SNPs to the risk of T2DM in Lebanese and Tunisian Arabs.MethodsStudy subjects (case/controls) were Lebanese (751/918) and Tunisians (1470/838). Genotyping was carried out by the allelic discrimination method.ResultsIn Lebanese and Tunisians, neither ENNP1 nor MLXIPL was associated with T2DM, whereas TCF7L2 was significantly associated with an increased risk of T2DM in both the Lebanese [P < 0.001; OR (95% CI): 1.38 (1.20–1.59)] and Tunisians [P < 0.001; OR (95% CI): 1.36 (1.18–1.56)]. Differential associations of IGF2BP2, KCNJ11, PPARγ and SLC30A8 with T2DM were noted in the two populations. IGF2BP2 [P = 1.3 × 10^?5; OR (95% CI): 1.66 (1.42–1.94)] and PPARγ [P = 0.005; OR (95% CI): 1.41 (1.10–1.80)] were associated with T2DM in the Lebanese, but not Tunisians, while KCNJ11 [P = 8.0 × 10^?4; OR (95% CI): 1.27 (1.09–1.47)] and SLC30A8 [P = 1.6 × 10^?5; OR (95% CI): 1.37 (1.15–1.62)] were associated with T2DM in the Tunisians, but not Lebanese, after adjusting for gender and body mass index.ConclusionT2DM susceptibility loci SNPs identified through GWAS showed differential associations with T2DM in two Arab populations, thus further confirming the ethnic contributions of these variants to T2DM susceptibility.     

Diabetes and impaired fasting glucose in rural and urban populations in Futa Jallon (Guinea): prevalence and associated risk factors

AimThe authors present the results of the first survey conducted among the population of the Futa Jallon province in Guinea on the prevalence of diabetes mellitus (DM) and impaired fasting glucose (IFG) and associated risk factors for diabetes.MethodA random sample of the study population selected by cluster house sampling method included 1537 Guineans (807 women and 730 men) aged 35 years and above in urban (Labé) and rural (Fellö Koundoua-Tougué) areas. Participants were examined and administered a capillary whole blood glycemia test.ResultsThe mean age of subjects was 49.4 years. Participation rate was 77%. Overall crude diabetes and IFG prevalence were 6.1% and 13.4%, respectively. The age-adjusted prevalence of diabetes using the standardized age distribution of Segi was 6.7% (95% CI: 5.5–7.9%). Subjects in the urban area had twice as much DM as in the rural area (OR 2.0, 95% CI: 1.3–3.2). Out of the 94 subjects with DM, 66 had no prior history of disease. Urban location, age, waist to hip ratio, excess waist circumference, hypertension, raised systolic and diastolic blood pressures were significantly positively associated with DM. In multivariate analysis, only age (P = 0.002) and waist circumference (P < 0.05) remained independently associated with DM.ConclusionThe prevalence of DM was higher than expected in urban and rural areas. The data support the conclusion that prevalence of DM is expected to increase with the aging of the population. The factors associated with diabetes are potentially modifiable. Therefore, primary prevention through lifestyle modifications may play a critical role in the control of DM.     

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease

BackgroundCytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G > A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD).MethodsBetween July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization.ResultsThe baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n = 291; homozygous *2/*2, n = 57) and non-carriers (n = 306) of the CYP2C19*2 variant. During the follow-up period (11.42 ± 4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n = 306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR] = 5.191; 95% confidence interval [CI] = 1.936–13.917; P = 0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR = 1.208; 95% CI 0.517–2.822; P = 0.662).ConclusionsThe homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD.