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OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score =1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 mug/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure.; CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

International audience; BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

OBJECTIVE:GlycA, a novel NMR biomarker of inflammation, has been associated with incident cardiovascular disease (CVD) in the general population, but its association with CVD among HIV-infected individuals is unknown. We examined the associations between GlycA and subclinical coronary plaque among HIV-infected and HIV-uninfected men participating in MACS. DESIGN:Cross-sectional analysis of 935 men with plasma measurement of GlycA and noncontrast cardiac computed tomography (CT) and/or coronary CT angiography. METHODS:We used multivariable Poisson and linear regression to assess associations of GlycA with prevalent coronary atherosclerosis and plaque extent, respectively. RESULTS:Mean ± SD age was 54 ± 7 years; 31% were black; 63% HIV-infected. GlycA levels were higher in HIV-infected compared with HIV-uninfected men (397 ± 68 vs. 380 ± 60 μmol/l, P = 0.0001), and higher for men with detectable viral load vs. undetectable (413 ± 79 vs. 393 ± 65 μmol/l, P = 0.004). After adjusting for HIV serostatus, demographic and CVD risk factors, every 1SD increment in GlycA level was associated with a higher prevalence of coronary artery calcium (CAC >0) [prevalence ratio 1.09 (95% CI 1.03-1.15)] and coronary stenosis at least 50% [1.20 (1.02-1.41)]. These associations did not significantly differ after adjusting for traditional inflammatory biomarkers or by HIV serostatus. Among men with plaque, GlycA was positively associated with the extent of CAC and total plaque. CONCLUSION:HIV infection was associated with higher GlycA levels. In both HIV-infected and HIV-uninfected individuals, GlycA was significantly associated with several measures of subclinical coronary atherosclerosis, independent of other CVD risk factors and inflammatory biomarkers. These findings suggest the potential role of GlycA in CVD risk stratification among HIV patients.

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

Item does not contain fulltext BACKGROUND: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. METHODS: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2-19.0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. FINDINGS: The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0.0139 [95% CI 0.0105-0.0174] for ACR and 0.0065 [0.0042-0.0088] for eGFR) and heart failure (0.0196 [0.0108-0.0284] and 0.0109 [0.0059-0.0159]) than for coronary disease (0.0048 [0.0029-0.0067] and 0.0036 [0.0019-0.0054]) and stroke (0.0105 [0.0058-0.0151] and 0.0036 [0.0004-0.0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0.0227 (0.0158-0.0296) after omission of eGFR and ACR compared with less than 0.007 for any single modifiable traditional predictor. INTERPRETATION: Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. FUNDING: US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.

Purpose: Current European guidelines recommend that patients free from cardiovascular disease (CVD) but estimated to be at high (≥ 5%) 10-year risk of CVD mortality should be more vigorously pharmacologically treated than those at lower risk. The recommended target level of low-density lipoprotein cholesterol (LDL-C) is < 2.5 mmol/l, or < 1.8 mmol/l for those at very high risk (VHR; those with diabetes mellitus [DM] or a ≥ 10% 10-year mortality risk). We examined the use of lipid lowering therapy (LLT) and achievement of LDL-C level targets in routine clinical practice in Europe. Methods: The European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA) (NCT00882336) was a cross-sectional study conducted simultaneously in 12 European countries from May 2009 to January 2010, recruiting 7641 patients aged ≥ 50 years who were free of clinical CVD but had at least one cardiovascular risk factor (dyslipidaemia, hypertension, DM, smoking or obesity). Ten-year CVD mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE) algorithm. LDL-C levels were measured and use of LLT was noted, including the agents and doses used. Statin therapy was classified as low-intensity (LIS; pravastatin, simvastatin, lovastatin, fluvastatin, atorvastatin < 40 mg or rosuvastatin < 20 mg) or high-intensity (HIS; atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg). Results: We identified 3278 individuals who were receiving any form of LLT, of whom 3040 (92.7%) were receiving a statin. Of the 4363 patients not receiving LLT, 1741 (39.9%) had DM or a SCORE risk ≥ 5%. LDL-C levels were available for 3151 participants receiving LLT, for whom LDL-C levels were not at target (< 2.5 mmol/l) in 1931 (61.3%). Only 8.9% of patients on LLT were receiving HIS. Of the patients receiving LIS, only 39.8% had LDL-C levels < 2.5 mmol/l. A subset of 2970 patients were at VHR, of whom only 1469 (49.5%) were receiving any form of LLT. LDL-C levels were at target (< 1.8 mmol/l) in 17.1% of these patients. Only 9.1% of the VHR patients on LLT were receiving HIS. Of the VHR patients receiving LIS, only 17.1% had Conclusion: Approximately 40% of patients aged ≥ 50 years with at least 1 cardiovascular risk factor who are not currently receiving LLT are at high risk of CVD (DM or SCORE ≥ 5%). Furthermore, well over half of all those receiving LLT and more than 80% of VHR patients receiving LLT did not achieve recommended LDL-C levels. These results demonstrate that there is potential for major improvements in lipid level management in patients at risk of CVD in Europe.

Purpose: Cardiovascular disease (CVD) imposes a significant health burden throughout Europe. Cardiovascular risk can be assessed using validated risk prediction models, such as the European Systematic COronary Risk Evaluation (SCORE) algorithm that assesses 10-year risk of cardiovascular mortality. This is also recommended for guiding treatment options. Recently, the SCORE algorithm has been updated to incorporate high-density lipoprotein cholesterol (HDL-C) levels (SCORE-HDL), thus providing a more accurate estimate of risk. We have investigated the proportion of patients who would have their risk classification changed with the SCORE-HDL algorithm when compared to the original SCORE. Methods: The European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA) (NCT00882336) was a cross-sectional study conducted simultaneously in 12 European countries, recruiting 7641 patients aged ≥ 50 years who were free of clinical CVD but had at least one cardiovascular risk factor (dyslipidaemia, hypertension, diabetes mellitus, smoking or obesity). We calculated risk using international SCORE and SCORE-HDL algorithms in patients aged 50–65 years without diabetes and not receiving lipid-lowering therapy. Results: In total, risk was assessed in 2321 patients. According to SCORE, 447 were at low risk (LR), 1409 were at intermediate risk (IR) and 465 were at high risk (HR) of CVD mortality (LR: < 1%; IR: 1–5%; HR ≥ 5% 10-year risk). According to SCORE-HDL, 597 were at LR, 1328 were at IR and 396 were at HR. Of the 447 patients at LR according to SCORE, 11.9% were reclassified by SCORE-HDL as IR and none as HR. Of the 1409 patients at IR according to SCORE, 14.3% and 2.9% were reclassified as LR and HR, respectively. Of the 465 patients at HR according to SCORE, 23.4% and 0.2% were reclassified as IR and LR, respectively. Comparable proportions of males and females at IR according to SCORE were reclassified as HR by SCORE-HDL (3.6 and 2.4%, respectively). However, only 1.9% of males were reclassified from IR to LR, in contrast to 24.9% of females. Conclusions: Assessment of CVD risk using SCORE-HDL in our patient population (aged 50–65 years, with at least one cardiovascular risk factor but no history of CVD, without diabetes and not receiving lipid-lowering therapy) often resulted in cardiovascular risk reclassification when compared with the original SCORE. Reclassification into a lower risk category was more common than into a higher risk category, especially amongst females at IR according to SCORE. Most of our study cohort were categorized as LR or IR by both algorithms.

The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 mu g/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above similar to 110 mu g/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. (C) 2014 Elsevier Inc. All rights reserved.

Stranges S, Tabák AG, Guallar E, Rayman MP, Akbaraly TN, Laclaustra M, Alfthan G, Mussalo-Rauhamaa H, Viikari JSA, Raitakari OT, Kivimäki M (Health Sciences Research Institute, University of Warwick Medical School, Coventry; University College London, London, UK; Semmelweis University Faculty of Medicine, Budapest, Hungary; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; National Center for Cardiovascular Research (CNIC), Madrid, Spain; University of Surrey, UK; National Institute of Health and Medical Research (Inserm) U888. F-34000 Montpellier, France; National Institute for Health and Welfare, Helsinki, Finland; Hjelt Institute, University of Helsinki, Helsinki; University of Turku and Turku University Hospital, Turku; University of Turku, Turku; Finnish Institute of Occupational Health and University of Helsinki, Helsinki, Finland). Selenium status and blood lipids: the cardiovascular risk in young finns study. J Intern Med 2011; doi: 10.1111/j.1365-2796.2011.02398.x. Background. Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. Objectives. To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. Methods. Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). Results. Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1) ; 95% CI: 30.3 to 34.3, P

The object of this study was to summarize the available information on the incidence of invasive disease and meningitis caused by Haemophilus influenzae in Spain from 1985 to 1995, evaluating potential geographic differences.Systematic and exhaustive literature searches of computerized databases, manual review of obtained references, revision of relevant Spanish journals and proceedings of congresses and direct consultation with experts were carried out. Yearly incidence rates were estimated per 100,000 children less than 5 years of age, by year and geographical region.We encountered 16 studies, one covering the entire Spanish population and the rest limited to Catalonia, the Basque Country, the Valencian Community, Andalucia, Navarra or the Community of Madrid. In 1994, the incidence of invasive H. influenzae disease varied from 8.4 cases per 100,000 children under 5 years of age in Navarra to 26.3 cases per 100,000 children under 5 years of age in the Basque Country.Available data do not permit the nationwide estimation of the incidence rate, although it is possible to appreciate that important geographic differences exist. It is remarkable the lack of specific information for the majority of Spanish regions, as well as the lack of data to assess temporal trends.