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Abstract Background Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DIITM), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up. Method We conducted a prospective case–control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986–2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population. Results Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21–2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14–1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03–0.14) and 6% higher IL-6 (95% CI 0.02–0.11) in 605 controls with biomarker data available. Conclusion A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

Cardiovascular diseases are a major cause of human death worldwide. Excessive proliferation of vascular smooth muscle cells contributes to the etiology of such diseases, including atherosclerosis, restenosis, and pulmonary hypertension. The control of vascular cell proliferation is complex and encompasses interactions of many regulatory molecules and signaling pathways. Herein, we recapitulated the importance of signaling cascades relevant for the regulation of vascular cell proliferation. Detailed understanding of the mechanism underlying this process is essential for the identification of new lead compounds (e.g., natural products) for vascular therapies. [ABSTRACT FROM AUTHOR]

Exposure to multi-walled carbon nanotubes (MWCNTs) has been associated with detrimental cardiovascular outcomes; however, underlying mechanisms have not yet been fully elucidated. Thus, we investigated alterations in proatherogenic and proinflammatory signaling pathways in C57Bl6/ mice exposed to MWCNTs (1 mg/m 3 ) or filtered air (FA-Controls), via inhalation, for 6 h/day, 14d. Expression of mediators of cholesterol transport, namely the lectin-like oxidized low-density lipoprotein receptor (LOX)-1 and ATP-binding cassette transporter (ABCA)-1, inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1β/IL-6, nuclear-factor kappa-light-chain-enhancer of activated B cells (NF-κB), intracellular/vascular adhesion molecule(s) (VCAM-1, ICAM-1), and miRNAs (miR-221/-21/-1), associated with cardiovascular disease (CVD), were analyzed in cardiac tissue and coronary vasculature. Cardiac fibrotic deposition, matrix-metalloproteinases (MMP)-2/9, and reactive oxygen species (ROS) were also assessed. MWCNT-exposure resulted in increased coronary ROS production with concurrent increases in expression of LOX-1, VCAM-1, TNF-α, and MMP-2/9 activity; while ABCA-1 expression was downregulated, compared to FA-Controls. Additionally, trends in fibrotic deposition and induction of cardiac TNF-α, MMP-9, IκB Kinase (IKK)-α/β, and miR-221 mRNA expression were observed. Analysis using inhibitors for nitric oxide synthase or NADPH oxidase resulted in attenuated coronary ROS production. These findings suggest that subacute inhalation MWCNT-exposure alters expression of cholesterol transporter/receptors, and induces signaling pathways associated with inflammation, oxidative stress, and CVD in wild-type mice. [ABSTRACT FROM AUTHOR]

Tetrachlorobisphenol A (TCBPA), which is widely used as flame retardant, can be released into various environments, thereby being absorbed by wildlife or human beings through food chain's bio-magnification and causing some adverse influences on wildlife or human beings. However, limited data are currently available on TCBPA-associated cytotoxicity and related mechanisms. Here, the cytotoxicity induced by different concentrations of TCBPA (i.e., 5, 10 and 20 μM) was studied using Saccharomyces cerevisiae , a simple eukaryotic model organism. TCBPA treatment inhibited the growth and survival rate of yeast cell in a dose-dependent manner. Moreover, TCBPA promoted the increasing of intracellular oxidative stress by enhancing accumulation of intracellular reactive oxygen species (ROS). Meanwhile, lipid peroxidation degree (represented by malondialdehyde (MDA) content) and DNA damage degree (represented by 8-hydroxy deoxyguanosine (8-oxodG) content) in yeast cell also increased after TCBPA treatment. However, yeast cell mitochondrial membrane potential (Δψm) decreased after TCBPA treatment. It was noteworthy that there was no significant inhibitory effect on yeast cell growth or survival rate in 5 μM TCBPA-treated cells, but the intracellular MDA content and Δψm level changed significantly, suggesting the potential cell damage secondary to the relative low dose of TCBPA exposure. Results presented here would highlight our knowledge about TCBPA-associated cytotoxicity in organisms. [ABSTRACT FROM AUTHOR]

Background Drinking water (DW) is an important dietary source of magnesium. Recently, Israel has increased its use of desalinated seawater (DSW) as DW country-wide. Its negligible magnesium content, however, raises concern that consumption of DSW may be associated with hypomagnesemia and increase the risk of ischemic heart disease (IHD), diabetes mellitus (DM), and colorectal cancer (CRC). Objectives We tested whether there was a change in incidence of negative health outcomes (IHD, DM, and CRC) following the introduction of DSW supply in a population-based ecologic study in Israel. Methods A historical prospective analysis was applied to members aged 25–76 during 2004–2013 of Clalit Health Services (Clalit), the largest healthcare provider in Israel, using its electronic medical record database. Multivariable analyses were adjusted for age, sex, socioeconomic status, smoking status, and body mass index. Results An increased odds ratio was found for IHD (0.96, 95% CI 0.93–0.99 at baseline and 1.06, 95% CI 1.02–1.11 at the end of the follow-up period), but no time trend was observed. Conclusions We found that the risk for IHD increased during the study period. The risks for DM and CRC were unchanged. Long term studies are needed for assessing the risk for CRC due to the long latency. The higher risk for IHD has practical public health implications and raise the need to add magnesium to DSW. [ABSTRACT FROM AUTHOR]

Background Tungsten (W) interferes with molybdenum (Mo) binding sites and has been associated with prevalent cardiovascular disease (CVD). We evaluated if (1) W exposure is prospectively associated with incident CVD and (2) the association between urinary W levels and incident CVD is modified by urinary Mo levels. Methods We estimated multi-adjusted hazard ratios (HRs) for incident CVD outcomes by increasing W levels for 2726 American Indian participants in the Strong Heart Study with urinary metal levels measured at baseline (1989–1991) and CVD events ascertained through 2008. Results Increasing levels of baseline urinary W were not associated with incident CVD. Fully-adjusted HRs (95% CIs) of incident CVD comparing a change in the IQR of W levels for those in the lowest and highest tertile of urinary Mo were 1.05 (0.90, 1.22) and 0.80 (0.70, 0.92), respectively (p-interaction = 0.02); for CVD mortality, the corresponding HRs were 1.05 (0.82, 1.33) and 0.73 (0.58, 0.93), respectively (p-interaction = 0.03). Conclusions The association between W and CVD incidence and mortality was positive although non-significant at lower urinary Mo levels and significant and inverse at higher urinary Mo levels. Although prior cross-sectional epidemiologic studies in the general US population found positive associations between urinary tungsten and prevalent cardiovascular disease, our prospective analysis in the Strong Heart Study indicates this association may be modified by molybdenum exposure. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications. DPP-4 has the capability to inactivate not only incretins, but also a series of cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. Pre-clinical studies suggested that DPP-4 inhibitors may have potential cardiovascular protective effects in addition to their antidiabetic actions. In recent years, a number of clinical trials have been conducted to evaluate the effect of different DPP-4 inhibitors on the cardiovascular system. We herein review the available clinical studies in cardiovascular effects played by each DPP-4 inhibitor and discuss the prospective application of DPP-4 inhibitors on cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background The early intervention is a rational approach to reduce the cardiovascular disease mortality in cancer patients. Here, we tried to identify potential biomarkers for the endothelial damage caused by cisplatin, a typical chemotherapy compound, and explore its underlying mechanisms. Methods Microarray dataset GSE62523 were utilized to assess the gene differential expression from human micro-vascular endothelial cells (HMEC-1) treated with cisplatin. Then, the potential key genes were further validated by qRT-PCR and the γH2AX level was evaluated to monitor the DNA damages caused by cisplatin. Result For the ‘acute-exposure’ settings that HMEC-1 were treated with 12.9 μM cisplatin for 6, 24 and 48 h, ATF3, LRRTM2, VCAM1 and PAPPA were identified as potential key genes in endothelial damage, while for the ‘chronic-exposure’ settings that cells were exposed to 0.52 μM cisplatin twice a week, SULF2, ACTA2 and PRAP1 were identified. In addition, further in vitro validation showed that knockdown of ATF3 attenuated the γH2AX level in cells exposed to cisplatin for 6 or 24 h and knockdown of PRAP1 increased the γH2AX level in cells exposed to cisplatin for 2 days. Notably, ATF3 has the ability to regulate the expression of HIST1H1D, FBXO6, APP, MDM2, STAT1 and TRAF1, while PRAP1 regulates YWHAB, MDM2, ISG15, LYN and CUL1 during cisplatin-induced DNA damage repair process. Conclusion ATF3 and PRAP1 play important roles in cisplatin-induced DNA damage repair process. They may serve as potential early surrogate biomarkers of microvascular endothelial damage for cancer patients receiving chemotherapies. [ABSTRACT FROM AUTHOR]

Vertebrate stress responses are highly adaptive biological functions, maximizing survival probability in life-threatening situations. However, experiencing repeated and/or chronic stressors can generate physiological dysregulation and lead to disease. Because stress responses are multi-systemic and involve a wide range of physiological functions, identifying responses to stressors is best accomplished using integrated biomarker models. Allostatic load, defined as the physiological dysregulation that accumulates over the lifespan due to stressful experiences, is one such model. Allostatic load is measured using allostatic load indices, which are composites of biomarkers from multiple somatic systems. Previously, we reported the use of a 7-biomarker allostatic load index (albumin, CRH, cortisol, DHEA-S, glucose, IL-6, TNF-α) in western lowland gorillas housed at a single zoo. Herein, this index is expanded to examine allostatic load responses to lifetime stressors in gorillas from two additional zoos (n = 63) as well as two pooled samples. The index was created using quartile cut-points for each biomarker. Significant associations were observed between multiple predictor variables and allostatic load, including sex, age, number of stressful events (anesthetic events, zoo transfers, agonistic interactions with wounding, pregnancies), and rearing history (mother-reared, nursery-reared, wild-caught). Additionally, allostatic load was associated with indicators of morbidity (creatinine, cholesterol, triglycerides), age at death, and mortality risk. These results are consistent with those reported in human allostatic load research, suggesting allostatic load indices have potential as an investigative and clinical tool for gorillas and other great apes. [ABSTRACT FROM AUTHOR]

Alcohol abuse and its related diseases are the major risk factors for human health. Although the mechanism of alcohol-related disorders has been widely investigated, serum metabolites associated with long-term alcohol intake have not been well explored. In this study, we aimed to investigate the profiles of serum metabolites and lipid species of rats chronically exposed to alcohol, which may be involved in the pathogenesis of alcohol-associated disease. An 1 H NMR-based metabolomics and Q-TOF/MS-based lipidomics approach were applied to investigate the profile of serum metabolites and lipid species of rats administrated daily with alcohol (12% vol/vol, 10 ml/kg per day, i.g. ) for one year continuously. The rats administered with sterile water (10 ml/kg per day, i.g. ) were used as control. We found that alcohol affected mostly the lipid species rather than small molecule metabolites in the serum of both female and male rats. Among the modified lipids, glycerophospholipid, sphingolipid and glycerolipids metabolism pathways were profoundly altered. The prominent changes in lipid profiles included diacylglycerol (DG), lysophosphatidylcholine (LysoPC), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and triacylglycerol (TG). Moreover, fatty-acyl profile of lipids and total degree of unsaturation of fatty acid were also significantly altered by alcohol. The modified lipidomic profile may help to understand the pathogenesis of alcohol-associated diseases and also be of value for clinical evaluation of alcohol abuse, alcohol-associated disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability.Methods: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons.Results: Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC.Conclusions: An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD.Trial Registry: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: COPD is associated with cardiovascular disease (CVD), and coronary artery calcification (CAC) provides additional prognostic information. With increasing use of nongated CT scans in clinical practice, this study hypothesized that the visual Weston CAC score would perform as well as the Agatston score in predicting prevalent and incident coronary artery disease (CAD) and CVD in COPD.Methods: CAC was measured by using Agatston and Weston scores on baseline CT scans in 1,875 current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study. Baseline cardiovascular disease and incident cardiac events on longitudinal follow-up were recorded. Accuracy of the CAC scores was measured by using receiver-operating characteristic analysis, and Cox proportional hazards analyses were used to estimate the risk of incident cardiac events.Results: CAD was reported by 133 (7.1%) subjects at baseline. A total of 413 (22.0%) and 241 (12.9%) patients had significant CAC according to the Weston (≥ 7) and Agatston (≥ 400) scores, respectively; the two methods were significantly correlated (r = 0.84; P < .001). Over 5 years of follow-up, 127 patients (6.8%) developed incident CVD. For predicting prevalent CAD, c-indices for the Weston and Agatston scores were 0.78 and 0.74 and for predicting incident CVD, they were 0.62 and 0.61. After adjustment for age, race, sex, smoking pack-years, FEV1, percent emphysema, and CT scanner type, a Weston score ≥ 7 was associated with time to first acute coronary event (hazard ratio, 2.16 [95% CI, 1.32 to 3.53]; P = .002), but a Agatston score ≥ 400 was not (hazard ratio, 1.75 [95% CI, 0.99-3.09]; P = .053).Conclusions: A simple visual score for CAC performed well in predicting incident CAD in smokers with and without COPD.Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Purpose To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). Design Population-based cohort study. Participants A total of 518 participants aged 40 to 80 years (baseline visit 2007–2009 and second visit 6 years later, 2013–2015), with diabetes, clinical data, and VF information at both visits. Main Outcome Measures VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. Methods Incident DR was defined using the Modified Airlie House classification as “none or minimal” DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. Results Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (β = −0.60; 95% confidence interval [CI], −0.96 to −0.24; P = 0.001) and 23% (β = −1.00; 95% CI, −1.61 to −0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (β = −0.18; 95% CI, −1.00, 0.64; P = 0.660). Conclusions Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR. [ABSTRACT FROM AUTHOR]

C1q tumor necrosis factor-related protein 9 (CTRP9), a newly discovered adipokine, is the closest paralog of adiponectin. After proteolytic cleavage, it can release the globular domain (gCTRP9) that serves as the major circulatory isoform. Upon binding to adiponectin receptor 1 (AdipoR1) and N-cadherin, CTRP9 can activate a variety of signaling pathways to regulate glucose and lipid metabolism, vascular relaxation and cell differentiation. Circulating CTRP9 levels are significantly decreased in patients with coronary atherosclerosis disease. Data obtained from in vitro experiments and animal models suggest that CTRP9 exerts an atheroprotective effect by altering multiple pathological processes involved in atherosclerosis, including inflammation, foam cell formation, endothelial dysfunction, insulin resistance, and vascular smooth muscle cell dedifferentiation, proliferation and migration. In this review, we summarize the latest advances regarding the roles of CTRP9 in atherosclerosis with an emphasis on its potential as a novel therapeutic target in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background Studies reported that lipid-lowering treatment may increase the risk of diabetes, support the hypothesis that low-density lipoprotein cholesterol (LDLC) may be associated with type 2 diabetes (T2D). Objective The aim of this study was to assess the association between the LDLC levels and the incidence of T2D in an Iranian high-risk population not treated with lipid-lowering medications. Methods Mean 10-year follow-up data (1819) in non-diabetic first-degree relatives (FDR) of consecutive patients with T2D 30–70 years old, who were not treated with lipid-lowering drugs at baseline were examined. The diagnosis of T2D based on serial oral glucose tolerance test was the primary outcome. Cox proportional hazard model was used to estimate the hazard ratio (HR) for the incidence of T2D within tertiles of LDLC. Results A higher LDLC concentration was significantly associated with higher risk of T2D. Compared with the first tertile, the adjusted risk of T2D increased for the second (HR 1.20, 95% CI: 1.07, 1.35, P < 0.01) and third (HR 1.22, 95% CI: 1.08, 1.37, P < 0.01), tertiles of LDLC. Conclusions While these results await confirmation, a higher LDLC level was significantly associated with higher risk of T2D, independent of age, gender, fasting plasma glucose, waist circumference or blood pressure, in high-risk individuals in Iran. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists. Patients and methods A cohort of 106 patients with DM2, 42–83 years of age, and eGFR < 60 ml/min/m 2 were included. Age, sex, duration of diabetes, duration of attending our clinic, smoking habits, BMI, data regarding ischemic heart disease and induction of hemodialysis, urine albumin excretion (UAE) levels, eGFR (MDRD equation) and values of various biochemical parameters were recorded too. Follow-up period ranged from one to 25 years. Paired samples t -test and non-parametrical Kruskal–Wallis test were used for the analyses of the data. Results Fifty percent of patients had no further progression, 25.9% improvement, while 24.1% had worsening of the UAE levels. During the follow-up in the joined clinic, there was a smaller than the expected from the medical literature decrease in median eGFR, i.e. 2,3 ml/min/m 2 and a statistically significant improvement in glycosylated hemoglobin levels from 8.0% to 7.4% (p = 0.016). Time in years of follow-up in the joined clinic of our hospital appeared to be the most significant factor in the improvement or stabilization against deterioration of the UAE levels (p = 0.018). Conclusions Close follow-up of DM2 patients with eGFR < 60 ml/min/m 2 has resulted in a minor annual eGFR decrease. Monitoring of these patients in a specialized diabetic nephropathy clinic is beneficial for this group of patients for delaying the occurrence of end-stage renal disease. [ABSTRACT FROM AUTHOR]

Background Metabolic syndrome is a multisystem disorder which coined to describe the recognized clustering of metabolic and cardiovascular abnormalities including obesity, hypertension, dyslipidemia, and abnormalities of glucose homeostasis. Objective To assess the prevalence and associated factors of metabolic syndrome among psychiatric patients in Jimma University Specialized Hospital. Methods This study was conducted at Jimma University Specialized hospital psychiatric ward from May 15 to July 16, 2015. A cross-sectional study design and consecutive sampling technique were used. A single population proportion formula was used to include a total of 360 psychiatric patients. An interview administered structured questionnaire was used to collect socio-demographic and some clinical data. Anthropometric data were collected based on standard guild line for anthropometric measurement. Five milliliter of venous blood was collected from ante-cubital fossa after overnight fasting for 8 h. Semi-automated clinical chemistry analyzer (Temis Linear) was used for biochemical laboratory analysis. Data analysis was performed by using SPSS version-20 software. Binary and multiple logistic regressions were used to identify the association between dependent and independent variables. P value less than 0.05 was taken as statistically significant association. Results The prevalence of metabolic syndrome among psychiatric patients was 28.9%. Age greater than 30 years old (AOR: 5.2, CI: 2.3, 11.8, P. value < 0.05); being female (AOR: 7.1, CI: 3.3, 15.2, P. value < 0.05); regularly eating high protein and fat (AOR: 3.3, CI: 1.3, 8.2, P. value < 0.056) were independent determinant variables for high prevalence of metabolic syndrome among diabetic patients in the study area. The other independent variables such as family history of hypertension, chewing chat, Psychotropic drugs, duration of treatment, regularly eating fruits and vegetables had no statistically significant association with metabolic syndrome (P. value > 0.05). Conclusion and recommendation There was high prevalence of metabolic syndrome among the psychiatric patients. Therefore; close assessment, management and treatment of metabolic syndrome among patients with psychiatry problem is essential. [ABSTRACT FROM AUTHOR]

Tobacco use is the leading preventable cause of death worldwide and is a major risk factor for cardiovascular disease (CVD). Both prevention of smoking initiation among youth and smoking cessation among established smokers are key for reducing smoking prevalence and the associated negative health consequences. Proven tobacco cessation treatment includes pharmacotherapy and behavioral support, which are most effective when provided together. First-line medications (varenicline, bupropion, and nicotine replacement) are effective and safe for patients with CVD. Clinicians who care for patients with CVD should give as high a priority to treating tobacco use as to managing other CVD risk factors. Broader tobacco control efforts to raise tobacco taxes, adopt smoke-free laws, conduct mass media campaigns, and restrict tobacco marketing enhance clinicians' actions working with individual smokers. [ABSTRACT FROM AUTHOR]

Background: A high cardiorespiratory fitness (CRF) level is recommended to promote healthy aging. However, the association between CRF and very-long-term prognosis is unclear, and reverse causation may bias results in studies with shorter follow-up.Objectives: This study investigated the association between CRF and mortality in middle-aged, employed men free of cardiovascular disease (CVD).Methods: Participants from the Copenhagen Male Study, established in 1970 to 1971, were included and stratified into 4 age-adjusted maximal oxygen consumption (Vo2max) categories: below the lower limit of normal (lowest 5%); low normal (45%); high normal (45%); and above the upper limit of normal (top 5%). Vo2max was estimated by using a bicycle ergometer. Multivariable restricted mean survival time models were performed for all-cause and cardiovascular mortality using Danish national registers.Results: A total of 5,107 men with a mean age of 48.8 ± 5.4 years were included in the study. During the 46 years of follow-up, 4,700 (92%) men died; 2,149 (42.1%) of the men died of CVD. Compared with below the lower limit of normal CRF, low normal CRF was associated with 2.1 years (95% confidence interval [CI]: 0.7 to 3.4; p = 0.002), high normal with 2.9 years (95% CI: 1.5 to 4.2; p < 0.001), and above upper limit of normal with 4.9 years (95% CI: 3.1 to 6.7; p < 0.001) longer mean life expectancy. Each unit increase in Vo2max was associated with a 45-day (95% CI: 30 to 61; p < 0.001) increase in longevity. Estimates for cardiovascular mortality were similar to all-cause mortality. Results were essentially unchanged when excluding individuals who died within the first 10 years of follow-up, suggesting a minimal role of reverse causation.Conclusions: CRF was significantly related to longevity over the course of 4 decades in middle-aged, employed men free of CVD. The benefits of higher midlife CRF extend well into the later part of life. [ABSTRACT FROM AUTHOR]

Background: Reperfusion therapy led to an important decline in mortality after ST-segment elevation myocardial infarction (STEMI). Because the rate of cardiogenic shock has not changed dramatically, the authors speculated that a reduction in the incidence or fatality rate of mechanical complications (MCs), the second cause of death in these patients, could explain this decrease.Objectives: This study sought to assess time trends in the incidence, management, and fatality rates of MC, and its influence on short-term mortality in old patients with STEMI.Methods: Trends in the incidence and outcomes of MC between 1988 and 2008 were analyzed by Mantel-Haenszel linear association test in 1,393 consecutive patients ≥75 years of age with first STEMI.Results: Overall in-hospital mortality decreased from 34.3% to 13.4% (relative risk reduction, 61%; p < 0.001). Although the absolute mortality due to MC decreased from 9.6% to 3.3% (p < 0.001), the proportion of deaths due to MC among all deaths did not change (28.1% to 24.5%; p = 0.53). The incidence of MC decreased from 11.1% to 4.3% (relative risk reduction 61%) with no change in their hospital fatality rate over time (from 87.1% to 82.4%; p = 0.66). The proportion of patients undergoing surgical repair decreased from 45.2% to 17.6% (p = 0.04), with no differences in post-operative survival (from 28.6% to 33.3%; p = 0.74).Conclusions: Although the incidence of MC has decreased substantially since the initiation of reperfusion therapy in elderly STEMI patients, this reduction was proportional to other causes of death and was not accompanied by an improvement in fatality rates, with or without surgery. MCs are less frequent but remain catastrophic complications of STEMI in these patients. [ABSTRACT FROM AUTHOR]

Age-related arterial inflammation is associated with dysfunction of the arteries and increased risk for cardiovascular disease. To determine if aging increases arterial immune cell infiltration as well as the populations of immune cells principally involved, we tested the hypothesis that large elastic and resistance arteries in old mice would exhibit increased immune cell infiltration compared to young controls. Additionally, we hypothesized that vasoprotective lifestyle interventions such as lifelong caloric restriction or 8 weeks of voluntary wheel running would attenuate age-related arterial immune cell infiltration. The aorta and mesenteric vasculature with surrounding perivascular adipose was excised from young normal chow (YNC, 4–6 months, n = 10), old normal chow (ONC, 28–29 months, n = 11), old caloric restricted (OCR, 28–29 months, n = 9), and old voluntary running (OVR, 28–29 months, n = 5) mice and digested to a single cell suspension. The cells were then labeled with antibodies against CD45 (total leukocytes), CD3 (pan T cells), CD4 (T helper cells), CD8 (cytotoxic T cells), CD19 (B cells), CD11b, and F 4/80 (macrophages) and analyzed by flow cytometry. Total leukocytes, T cells (both CD4 + and CD8 + subsets), B cells, and macrophages in both aorta and mesentery were all 5- to 6-fold greater in ONC compared to YNC. Age-related increases in T cell (both CD4 + and CD8 + ), B cell, and macrophage infiltration in aorta were abolished in OCR mice. OVR mice exhibited 50% lower aortic T cell and normalized macrophage infiltration. B cell infiltration was not affected by VR. Age-related mesenteric CD8 + T cell and macrophage infiltration was normalized in OCR and OVR mice compared to young mice, whereas B cell infiltration was normalized by CR but not VR. Splenic CD4 + T cells from ONC mice exhibited a 3-fold increase in gene expression for the T helper (Th) 1 transcription factor, Tbet, and a 4-fold increase in FoxP3, a T regulatory cell transcription factor, compared to YNC. Splenic B cells and mesenteric macrophages from old mice exhibited decreased proinflammatory cytokine gene expression regardless of treatment group. These results demonstrate that aging is associated with infiltration of immune cells around both the large-elastic and resistance arteries and that the vasoprotective lifestyle interventions, CR and VR, can ameliorate age-related arterial immune cell infiltration. [ABSTRACT FROM AUTHOR]

Introduction Hormone therapy (HT) is an effective treatment for climacteric symptoms. Nevertheless, combined estrogen-progestin therapy and the oral route seem to entail higher risk of venous thromboembolism (VTE) than estrogen-only therapy and transdermal administration. The present study aimed to investigate the risk of thromboembolic events in postmenopausal women using non-oral estrogen compared to women using oral estrogen and control groups (women receiving placebo or non-users of HT), as well as to assess the thrombotic impact of estrogens alone vs. combined estrogen-progestin therapy. Materials and methods Systematic review of MEDLINE, Cochrane CENTRAL, EMBASE, and ClinicalTrials.gov according to PRISMA guidelines. Results Twenty-two studies were included in the meta-analyses (9 case-control studies, 9 cohort studies, and 4 randomized controlled trials). As compared to control groups, VTE risk was not increased with non-oral HT, including users of estrogens and estrogens plus progestins (OR 0.97 [0.9–1.06]), non-oral estrogen therapy (ET)-only (OR 0.95 [0.81–1.10]), and non-oral combined estrogen-progestin therapy (OR 0.92 [0.77–1.09]). Conversely, increased risk of VTE was observed as compared with control groups in users of oral HT, including users of estrogens and estrogens plus progestins HT (OR 1.72 [1.47–2.01]), oral ET-only (OR 1.43 [1.34–1.53]), and combined oral estrogen-progestin HT (OR 2.35 [1.9–2.9]). The comparison of non-oral vs. oral HT showed increased VTE risk with oral HT (OR 1.66 [1.39–1.98]). Conclusions VTE risk was increased in postmenopausal women with no previous thromboembolic events using oral HT. Non-oral HT did not significantly affect this risk. The quality of the evidence produced in our meta-analyses is low to moderate, and further clinical trials are needed to sort out the impact of different types of progestin and different estrogen doses and administration routes on VTE risk. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process. Moreover, several signaling and regulatory molecules are involved in the different steps of efferocytosis, and they include “Find-Me” signals (lysophosphatidylcholine), “Eat-Me” signals [phosphatidylserine, Mer tyrosine kinase (MerTK), and milk fat globule-EGF factor 8], and “Don't Eat-Me” signals [cluster of differentiation 47 (CD47)]. Regulation of efferocytosis is in a close nexus with inflammation, the key component in atherosclerosis. The predominance of pro-inflammatory and anti-inflammatory molecules plays a crucial role in lesion progression and regression, respectively. Polarization of macrophages towards the M1 phenotype causes them to secrete proinflammatory cytokines, while polarization towards the M2 phenotype causes them to secrete of anti-inflammatory cytokines, including interleukin-10 and transforming growth factor β, so tending to shift the balance towards resolution of the inflammation. Dysfunction of any regulatory signal may cause expansion of the necrotic core of an atherosclerotic plaque with ensuing conversion of the plaque into an unstable plaque with an increased susceptibility to rupture and to atherothrombotic complication. In this review we aim at elucidating the determinant factors and pathways of efferocytosis which can be considered as potential novel targets when striving to develop more personalized and efficient treatment regimens for patients with ACVD. [ABSTRACT FROM AUTHOR]

Although n-3 polyunsaturated fatty acids (PUFA) revealed promising therapeutic results in non-alcoholic fatty liver disease (NAFLD), which is considered as the most prevalent cause of chronic hepatic disease, inconsistencies are calling for further confirmatory trials to demonstrate therapeutic efficacy and safety. The study, registered as NCT02201160 on www.clinicaltrials.gov, was designed to compare two groups of NAFLD with a different severity, and to evaluate the efficacy of n-3 PUFA supplementation. Twenty young male participants of French Canadian origin with NAFLD were enrolled and classified into moderate (mNAFLD) and severe (sNAFLD) fatty liver groups, according to transaminase levels, ultrasonography, NAFLD Activity Score and Fatty Liver Index (FLI). The sNAFLD patients were assigned to consume 2 g of n-3 PUFA for 6 months. sNAFLD patients displayed higher insulinemia, insulin resistance (IR), oxidative stress (OxS), systolic blood pressure and the risk lipid indicators of cardiovascular diseases. Supplementation of n-3 PUFA for 6 months resulted in a significant increase in concentrations of eicosapentaenoic and docosahexaenoic acids in red blood cells along with an attenuation of hepatic steatosis as reflected by the reduction of the FLI, ALT and ALT/AST ratio. Moreover, the n-3 PUFA improved the lipid profile and carotid intima-media thickness, while reducing metabolic and OxS markers as well as raising adiponectin. In conclusion, NAFLD severity was essentially related to IR. Treatment with n-3 PUFA has an evidently beneficial effect on liver steatosis and related metabolic abnormalities. Furthermore, the cross association of omega-3 index with cardiometabolic markers may serve as a predictor for cardiovascular risk disorders in NAFLD. [ABSTRACT FROM AUTHOR]

Background: High added sugar (AS) intake is associated with obesity and poor diet quality. Guidelines recommended limiting AS to 5-10% of total energy intake, but palatability and feasibility of this AS intake level is uncertain.Objective: To compare adolescents' perceptions of hunger, fullness, and palatability in response to a low AS adequate fiber (LASAF; 5% total energy from AS and 13.5 g fiber/1000 kcal) and a high AS low fiber (HASLF; 25% total energy form AS and 8.2 g/1000 kcal) diet.Design: Adolescents (n = 32, age: 15.3 ± 1.6 yrs., BMI percentile: 47 ± 4, 15 male) completed a randomized, crossover, controlled feeding study. Participants consumed calorie-matched LASAF and HASLF diets for 7 days, separated by a 4 week washout. Body weight was monitored daily on each diet. Hunger, fullness, and palatability were assessed via 100 mm visual analogue scales at the end of each feeding period. Differences were assessed with paired sample t-tests. Data are expressed as mean ± SD.Results: Participants remained weight stable, and no difference in weight change between diet conditions was detected (LASAF: -0.06 ± 0.7 vs. HASLF: -0.02 ± 0.6 kg, p = 0.751). Less hunger (LASAF: 24.1 ± 14.6 vs. HASLF: 32.1 ± 17.6 mm, p = 0.024) and greater fullness (LASAF: 70.2 ± 12.3 vs. HASLF: 61.3 ± 18.1 mm, p = 0.006) were reported on the LASAF compared to the HASLF. Participants reported the diets to be equally palatable (LASAF: 39.6 ± 12.9 vs. HASLF: 37.2 ± 17.8 mm, p = 0.440).Conclusions: Adolescents perceive a LASAF diet to be as palatable as a HASLF diet, but more satiating. LASAF diets should be investigated as a strategy for weight control in adolescents. [ABSTRACT FROM AUTHOR]

Raspberries are a rich source of ellagitannins and anthocyanins. The aim of this work was to investigate whether raspberry consumption can improve vascular function and to understand which phenolic metabolites may be responsible for the effects. A 3 arm double-blind randomized controlled crossover human intervention trial was conducted in 10 healthy males. Flow-mediated dilation (FMD) was measured at baseline, 2 h, and 24 h post-consumption of 200 g and 400 g of red raspberries containing 201 or 403 mg of total (poly)phenols, or a matched control drink. Raspberry (poly)phenol metabolites were analyzed in plasma and urine by UPLC-QTOF mass spectrometry using authentic standards. Significant improvements in FMD were observed at 2 h (1.6% (95%CI 1.2, 1.9) and 1.2% (95% CI 0.8, 1.5)) and 24 h (1.0% (95% CI 0.6, 1.2) and 0.7% (95%CI 0.2, 0.9)) post-consumption of the 200 and 400 g raspberry drinks as compared to control, respectively. Plasma ellagic acid, urolithin A-3-glucuronide and urolithin A-sulfate correlated with the improvements in FMD at 2 and 24 h post consumption, respectively. Consumption of dietary achievable amounts of red raspberries acutely improves endothelial function up to 24 h and ellagitannins may be responsible for the observed effect. [ABSTRACT FROM AUTHOR]

Background and aims Obesity, hepatosteatosis, and hypertriglyceridemia are components of the metabolic syndrome and independent risk factors for cardiovascular disease. The lipid droplet-associated protein CIDEC (cell death-inducing DFFA-like effector C), known in mice as FSP27 (fat-specific protein 27), plays a key role in maintaining triacylglyceride (TAG) homeostasis in adipose tissue and liver, and controls circulating TAG levels in mice. Importantly, mutations and SNPs in CIDEC are associated with dyslipidemia and altered metabolic function in humans. Here we tested whether systemic silencing of Fsp27 using antisense oligonucleotides (ASOs) was atheroprotective in LDL receptor knock-out ( Ldlr –/– ) mice. Methods Atheroprone Ldlr –/– mice were fed a high-fat, high-cholesterol diet for 12 weeks while simultaneously dosed with saline, ASO-ctrl, or ASO-Fsp27. Results Data show that, compared to control treatments, silencing Fsp27 significantly reduced body weight gain and visceral adiposity, prevented diet-induced hypertriglyceridemia, and reduced atherosclerotic lesion size both in en face aortas and in the aortic root. Conclusions Our findings suggest that therapeutic silencing of Fsp27 with ASOs may be beneficial in the prevention and management of atherogenic disease in patients with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background and aims We examined the association between the American Heart Association's Life's Simple 7 (LS7) metrics and the risk of atrial fibrillation (AF) in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of adults free of cardiovascular disease (CVD) at baseline. Methods We analyzed data from 6506 participants. The LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were each categorized into ideal (assigned 2 points), intermediate (1 point) or poor (0 points). Scores were summed for a maximum of 14. A score of 0–8 was considered inadequate; 9-10, average and 11-14, optimal for cardiovascular health. Atrial fibrillation was ascertained using ICD-9 codes from hospital discharge records and Medicare claims data. Cox proportional hazard ratios (HR) and incidence rates of AF per 1000 person-years were calculated. Results During a median follow-up of 11.2 years (interquartile range: 10.6–11.7 years), 709 (11%) participants were hospitalized with a first AF episode. In the overall cohort, optimal scores at baseline were associated with a 27% lower risk for AF compared with inadequate scores (0.73 [0.59–0.91]). A similar finding was observed when the results were stratified by race/ethnicity (White, Chinese American, African American and Hispanic), though many of the associations were not statistically significant. There was no interaction by race/ethnicity ( p  = 0.15). Conclusions In the overall cohort, optimal LS7 status was associated with a lower risk of AF. These findings suggest that promoting ideal cardiovascular health may reduce the incidence and burden of AF. [ABSTRACT FROM AUTHOR]

Background and aims Obesity is frequently associated with non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR), inflammation and metabolic syndrome (MetS), all of which increase the risk of type 2 diabetes (T2DM). However, the role of these risk factors in mediating the effect of obesity remains unclear. We investigated the association between obesity and T2DM in the absence and presence of NAFLD, IR, inflammation and MetS components. Methods 29,836 obese subjects without diabetes were studied in a Korean health screening program. Obesity was defined by the appropriate ethnic-specific body mass index (BMI) threshold ≥25 kg/m 2 . Hazard ratios (HRs and 95% confidence intervals, CIs) for incident T2DM were estimated for the group with no hypertension, dyslipidemia, impaired fasting glucose, fatty liver, IR, or inflammation ( n  = 1717), compared to the reference group, with one or more of these factors ( n  = 19,757). Results Mean (SD) age at baseline was 37 (7) years and 1200 incident cases of diabetes occurred. Crude T2D incidence was 12.6/10,000 person-years in the group without metabolic abnormality and 143/10,000 person-years in the reference group. HR (95% CIs) for incident diabetes was 0.13 (0.06, 0.33) in the group without metabolic abnormality. Conclusions Obese subjects without components of the metabolic syndrome, IR, fatty liver and inflammation have an approximately 11-fold lower risk of incident type 2 diabetes than obese subjects who have these risk factors. These simple factors could be used to target limited resources in high risk obese subjects in the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. Background Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. Methods A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m 2 ), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τ ic ; a marker of cardiomyocyte size), and late gadolinium enhancement. Results At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m 2 ), a mean ECV of 0.32 ± 0.038, mean τ ic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m 2 ), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m 2 to 36 ± 6 g/m 2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τ ic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τ ic (β = 4.1 ± 1.5 g/m 2 per 100-ms increase in τ ic , p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 − ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. Conclusions A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036 ) [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationships of depression and anxiety symptoms with cardiovascular disease (CVD) risk factors and measures of vascular health in youth.Study Design: Participants (n = 202) were 8- to 18-year-olds from a cross-sectional study evaluating cardiovascular health across a wide range of body mass index values (normal weight to severe obesity). CVD risk measurement included blood pressure, fasting lipids, glucose, insulin, carotid artery intima-media thickness, compliance and distensibility, brachial artery flow-mediated dilation, carotid-radial artery pulse wave velocity, body fat percentage, and a metabolic syndrome cluster score. Anxiety and depression symptoms were self-reported on the Screen for Child Anxiety Related Disorders and Center for Epidemiological Studies Depression Scale for Children. Two sets of adjustment variables were used in evaluation of differences between those with and without anxiety or depression symptomatology for the CVD risk factor and vascular outcomes. The first set included adjustment for Tanner stage, sex, and race; the second was additionally adjusted for percent body fat.Results: Anxiety was not significantly associated with CVD risk factors or vascular health in either model. Depression was associated with high-density lipoprotein cholesterol, triglycerides, and metabolic syndrome cluster score; these relationships were attenuated when accounting for percent body fat.Conclusions: When accounting for body fat, we found no clear relationship of self-reported depression or anxiety symptoms with CVD risk factors or vascular health in youth. [ABSTRACT FROM AUTHOR]

In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early-onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin 17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education. [ABSTRACT FROM AUTHOR]

Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2. [ABSTRACT FROM AUTHOR]

Aims We explored the risks associated with metformin plus sulfonylurea (MET + SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET + DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. Methods This retrospective cohort study is based on the South Korean National Health Insurance Service–National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET + SU or MET + DPP4i between July 1, 2008 and December 31, 2013. The risk of hypoglycemia, CVD events and all-cause mortality was examined using Cox's proportional hazard modeling and propensity score matching. Results Overall, 5693 patients with a mean of 2.6 comorbidities in addition to diabetes were included. Compared with MET + SU, MET + DPP4i treatment was associated with a lower risk of hypoglycemia, CVD events and all-cause mortality; adjusted HRs (95% CI), 0.39 (0.18–0.83), 0.72 (0.54–0.97), and 0.64 (0.39–1.05), respectively. Propensity score matching showed comparable results. In further subgroup analyses according to comorbidity type and number, MET + DPP4i was associated with less CVD events and all-cause mortality compared to MET + SU. This increased with more complex comorbid status. Conclusions In T2D patients with comorbidities, MET + DPP4i treatment is associated with lower risks of CVD events and all-cause mortality compared with MET + SU, independent of type or number of comorbidities. A more complex comorbid status further increases this effect. [ABSTRACT FROM AUTHOR]

The PREDIMED clinical trial provided strong evidence that a Mediterranean dietary pattern (MedDiet) could help prevent cardiovascular disease (CVD) events in high risk middle-aged/older people. This report considers the feasibility of replicating PREDIMED in the U.S., including recommendations for dietary and behavioral principles. A 14-point Mediterranean diet Adherence Score (MEDAS) guided the PREDIMED MedDiet recommendations. At baseline MEDAS points were ~8.5. During intervention this score increased to nearly 11 in MedDiet vs. 9 in control. In the MedDiet groups, only about 0.5 points of the net 2 point MEDAS increase was attributable to the gratis supplements of olive oil or nuts. An issue in a U.S. replication is the large difference in typical U.S. versus Spanish diet and lifestyle. A typical U.S. diet would achieve a MEDAS of 1–2. A replication is scientifically feasible with an assumption such as that the MedDiet reflects a continuum of specific food choices and meal patterns. As such, a 2 point change in MEDAS at any point on the continuum would be hypothesized to reduce incident CVD. A conservative approach would aim for a randomized 4 point MEDAS difference, e.g. 5–6 points vs. an average U.S. diet group that achieved only 1–2 points. [ABSTRACT FROM AUTHOR]

Purpose Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis). We systematically reviewed the literature to determine the potential health advantages of increased water intake and identify specific subpopulations that need increased hydration. Materials and Methods We systematically reviewed published articles from 1972 through 2017 on PubMed® and the Cochrane Library. The data were reviewed independently by 2 individuals. Studies were included if they explored water intake in relation to the risk of a particular disease. Results Level 1 evidence supported increased fluid intake in patients with nephrolithiasis. There was no available evidence to support increased fluid intake in patients with cardiovascular disease, constipation, venous thromboembolism, headaches, cognitive function or bladder cancer. Dehydration may exacerbate some conditions, specifically chronic constipation and headache intensity. Increased fluid intake may have a role in preventing stroke recurrence but not in preventing primary stroke. Conclusions The available reviewed literature suggests no benefit to drinking 8 glasses of water per day in patients without nephrolithiasis. Also, excess fluid intake can exacerbate symptoms of overactive bladder. [ABSTRACT FROM AUTHOR]

Flavonoids are integral components of various vegetation and in foods; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans consisting of flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin exhibits significant heart related benefits as inhibition of LDL oxidation, endothelium-independent vasodilator effects, reduction of adhesion molecules and other inflammatory markers, the protective effect on nitric oxide and endothelial function under conditions of oxidative stress, prevention of neuronal oxidative and inflammatory damage and platelet antiaggregant effects. Searching for experimental evidence to validate the cardioprotective effects of quercetin, we review here the recent detailed in vivo studies. Quercetin and its derivatives lead to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence-based studies suggest mechanisms to observe cardiovascular diseases such as aging effects, hypertension, angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models including human are also used to elucidate the in vivo role of quercetin in cardiovascular diseases. The role of quercetin and its derivatives may go beyond their existence in food and has potential as a lead molecule in drug development programs. [ABSTRACT FROM AUTHOR]

Background Lifestyle factors are important in preventing cardiovascular disease (CVD) development. We aimed to systematically review guidelines on primary prevention of CVD and their recommendations on lifestyle advice or intervention, in order to guide primary prevention programs. Methods Publications in MEDLINE, CINAHL over 7 years since May 3, 2009 were identified. G-I-N International Guideline Library, National Guidelines Clearinghouse, National Library for Health Guideline finder, Canadian Medical Association InfoBase were searched. On the February 8, 2017, we updated the search from Websites of organizations responsible for guidelines development. Study Selection: 2 reviewers screened the titles and abstracts to identify Guidelines from Western countries containing recommendations for lifestyle advice and interventions in primary prevention of CVD. Data Extraction: 2 reviewers independently assessed rigor of guideline development using the AGREEII instrument, and one extracted recommendations. Results Of the 7 guidelines identified, 6 showed good rigor of development (range 45–86%). The guidelines were consistent in recommendations for smoking cessation, limiting saturated fat and salt intake, avoiding transaturated-fat and sugar, with particular emphasis on sugar-sweetened beverages. Guidelines generally agreed on recommendations for physical activity levels and diets rich in fruit, vegetables, fish and wholegrains. Guidelines differed on recommendations for specific dietary patterns and alcohol consumption. Recommendations on psychological factors and sleep are currently limited. Conclusions Current guidelines agree on the importance of lifestyle in the prevention of CVD with consensus on most factors including physical activity, smoking cessation and diet, which should be actively integrated in cardiovascular risk reduction programs aiming to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

The link between sodium and obesity has been accumulated over years. However, there has been few data reported on such sodium-obesity association from the general US population. This study is designed to assess the hypothesis that dietary sodium intake is independently and positively associated with obesity, central obesity, and measures of body composition among generally healthy US adults. We analyzed data on 9162 healthy participants aged 24 to 48 years (4813 men and 4349 women) with at least one valid diet recall from the 8-year National Health and Nutrition Examination Survey (1999-2006). Measures of body composition, including fat mass, lean mass, and total fat percent, were determined by dual-energy x-ray absorptiometry. We assessed the association between dietary sodium and obesity and measures of body composition by using multivariable logistic regression models. After adjustment for total energy intake and other prespecified confounders, high sodium intake (>2300 mg/d) was significantly associated with elevated risk of obesity and central obesity as compared with moderate sodium intake (1500-2300 mg/d). On average, each 1-g/d increment in dietary sodium intake resulted in a 15% (odds ratio, 1.15; 95% confidence interval, 1.00-1.33) increase in the risk of obesity and 24% (odds ratio, 1.24; 95% confidence interval, 1.11-1.39) increase in the risk of central obesity. After stratification by sex and ethnicity, significant associations between sodium and obesity/abdominal obesity were apparent only among women and non-Hispanic whites. In addition, all measures of body composition were positively associated with sodium consumption levels. We found that high sodium intake is independently associated with elevated risk of obesity and central obesity in the general US adult population. [ABSTRACT FROM AUTHOR]

The phytochemical study of Euphorbia helioscopia led to the isolation of 33 jatrophane diterpenoids ( 1 − 33 ), of which six ( 1 – 6 ) were new. This small jatrophane library was established to screen for potential lipid modulators. LDL-Uptake screening assay demonstrated that most of them improved LDL-Uptake rate in HepG2 cells, with compounds 16 , 21 and 26 exhibiting more outstanding effects. Further exploration found that these three compounds could increase LDLR protein level in HepG2 cells dose-dependently. SAR studies suggested that substituted patterns of C-9, steric hindrance between C-14 and C-15, and the long conjugated fragment from C-5 to the carbonyl (C-9) were essential for the activity. Moreover, compound 21 , a relatively abundant chemical in E. helioscopia , showed remarkable lipid-lowering effect in vivo, which makes it a promising lead for development of new lipid-lowering agents. [ABSTRACT FROM AUTHOR]

Red spinach ( Amaranthus tricolor ) has been reported to possess many benefits and medicinal properties and used as a part of traditional medicine in Ayurveda and Siddha. The aim of the study was to investigate the effects of Amaranthus tricolor on isoproterenol-induced oxidative stress, fibrosis, and myocardial damage in ovariectomized rats. Ovariectomy surgery was conducted to remove both ovaries from the rats. After recovery, rats were administered with ISO subcutaneously (50 mg/kg) twice a week and were treated with ethanolic extracts of A. tricolor . This investigation showed that the level of oxidative stress markers was significantly increased while the superoxide dismutase (SOD) activity decreased in ISO administered ovariectomized rats. A. tricolor extract and atenolol treatment prevented the rise of malondialdehyde, nitric oxide and advanced protein oxidation product. Moreover, elevated activities of AST, ALT, and CK-MB enzymes were also lowered by both atenolol and A. tricolor treatment. Increased uric acid and creatinine levels were also normalized by atenolol, and A. Tricolor treatment in ISO administered ovariectomized rats. ISO-induced ovariectomized rats also showed massive inflammatory cell infiltration, fibrosis and iron deposition in heart compared to sham rats. Atenolol and A. tricolor treatment prevented the inflammatory cells infiltration, fibrosis, and iron deposition. These results suggest that A. tricolor treatment may protect against ISO administered myocardial infarction in ovariectomized rats probably by preventing inflammation, oxidative stress, and fibrosis. Further research is warranted to examine molecular mechanism of cardioprotective effect of A. tricolor . [ABSTRACT FROM AUTHOR]

Background Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear. Objective We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY. Methods We analyzed baseline (1989–1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM 10 ), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants' monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR. Results Increased PM 10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m 3 ), the middle (28.5–31.0 μg/m 3 ; β = −0.0044, p  = 0.09) and highest (≥31 μg/m 3 ; β = −0.0054, p  = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = −0.00035, p  = 0.06) and smoking pack-years (β = −0.00011, p  = 1.4E−3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants. Conclusions PM 10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted. [ABSTRACT FROM AUTHOR]

Introduction Recently, epidemiological studies have found a link between air pollution (AP) and individual components of the metabolic syndrome (MetS), a condition predisposing to cardiometabolic diseases. However, very few studies have explored a possible association between air pollution and MetS. Objective We analyzed the effects of long-term exposure to airborne particulate matter and NO 2 on prevalence and incidence of MetS. Methods We used data of the population-based prospective Heinz Nixdorf Recall study (baseline 2000–2003) to investigate the association(s) between AP exposure and MetS prevalence at baseline ( n  = 4457) and MetS incidence at first follow-up visit ( n  = 3074; average follow-up: 5.1 years). Mean annual exposure to size-fractioned particulate matter (PM 10 , PM 2.5 , PM coarse , and PM 2.5 abs) and nitrogen dioxide (NO 2 ) was assessed using a land use regression model. MetS was defined as central obesity plus two out of four additional risk factors (i.e., elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure or elevated plasma glucose). We estimated odds ratios (ORs) of MetS prevalence and incidence per interquartile range (IQR) of exposure, adjusting for demographic and lifestyle variables. Results We observed a MetS prevalence of 20.7% ( n  = 922) and an incidence of 9.7% ( n  = 299). NO 2 was positively associated with MetS prevalence, with an OR increase per IQR of 1.12 (95%-CI 1.02–1.24, IQR = 6.1 μg/m 3 ). PM 10 and PM 2.5 were both borderline positively associated with MetS incidence, with ORs of 1.14 (95%-CI 0.99–1.32, IQR = 2.1 μg/m 3 ) and 1.19 (95%-CI 0.98–1.44, IQR = 1.5 μg/m 3 ) per IQR, respectively. Conclusion In summary, we found a weak positive association between air pollution and MetS. The strongest and most consistent effects were observed between NO 2 and prevalent MetS. [ABSTRACT FROM AUTHOR]

Proteinuria is a common adverse effect of renal injury in preeclampsia. To explore the effects of AKR1C3 in renal injury due to preeclampsia and to determine an optimal method to prevent proteinuria, glibenclamide treatment was used in unrestrained Wistar rats exposed to N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Successful rat models for preeclampsia were confirmed based on mean arterial pressure, a 24-h protein urine test, and by observing the structure of the kidney by transmission electron microscopy (TEM). Forty Wistar rats were randomly divided into L-NAME-induced preeclampsia (pregnant and L-NAME), treatment (pregnant, L-NAME, and glybenclamide), non-pregnant (L-NAME), and control (pregnant and 0.9% saline) groups. Rats that were 19 days into their pregnancies were then euthanized and their kidneys were collected. After exposure to L-NAME, the mean arterial pressure increased by ~25 mmHg, which was largely prevented by the co-administration of glibenclamide. At 24 h, protein levels in the urine of the L-NAME-induced preeclampsia group were higher than those of the control and treatment groups. AKR1C3 was downregulated in the kidney and podocytes, whereas glibenclamide increased the expression of AKR1C3 . The generation of reactive oxygen species (ROS) detected by ELISA was decreased by the glibenclamide co-administration. Compared with that in the L-NAME-induced preeclampsia group, the expression levels of AKR1C3 protein and mRNA significantly increased in the treatment group ([0.48 ± 0.09] vs.[1.05 ± 0.20];[0.05 ± 0.02] vs.[0.22 ± 0.06]; both P  < 0.05]). Therefore, AKR1C3 expression was decreased in the kidneys of L-NAME-induced preeclampsia rats, and glibenclamide may be useful for the treatment of preeclampsia by regulating the generation of ROS and preventing proteinuria. [ABSTRACT FROM AUTHOR]

Objective Middle-aged adults who are lonely have an elevated likelihood of death. Systemic inflammation may contribute to these increased odds. Using population-level data, this study tested if systemic inflammation is associated with loneliness in a broad age range of middle-aged adults in the United States. Methods This study used data from the Midlife in the US (MIDUS) survey Biomarker Project, which collected data on psychological, social, and physiological measures from a sample of middle-aged adults. This sample included the 927 participants who were 35–64 years at Biomarker Project data collection. MIDUS collected baseline data from 1995-1996 and a follow-up survey was conducted from 2004-2006. The baseline Milwaukee sample of African Americans was collected in 2005–2006 and the biomarker database was collected in 2004–2009. Biomarkers were obtained from a fasting blood sample. Self-reported loneliness was categorized as feeling lonely or not feeling lonely. Hierarchical regressions examined the association between biomarkers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein) and feeling lonely, adjusted for covariates. Results Twenty-nine percent of the sample reported feeling lonely most or some of the time. There was a positive significant relationship between loneliness and the three systemic inflammation biomarkers after controlling for covariates: interleukin-6 ( n  = 873) ( b [ se ] = 0.07 [0.03], p  = .014); fibrinogen ( n  = 867) ( b [ se ] = 18.24 [7.12], p  = .011); and C-reactive protein ( n  = 867) ( b [ se ] = 0.08 [0.04], p  = .035). Conclusions Feeling lonely is associated with systemic inflammation in middle-aged community-dwelling US adults. [ABSTRACT FROM AUTHOR]

Aims: Obesity promotes a variety of poor health outcomes, including type 2 diabetes (T2D). However, not all obese people are at an elevated risk of T2D. Obesity is closely linked to chronic inflammation. In addition, inflammation is an important contributor to T2D via the processes of insulin resistance and islet β-cell failure. Therefore, we hypothesize that white blood cells (WBC) count, a marker of subclinical inflammation, can be used as an indicator to identify whether or not obesity leads to increased risk of T2D. To investigate this hypothesis, we conducted a prospective cohort study in a general population.Methods: A total of 47,678 subjects were followed up from 2007 to 2016. WBC count was determined by automated hematology analyzer. T2D and obesity were defined in accordance with the criteria of the World Health Organization. Adjusted Cox proportional hazards regression models were used to assess relationships between obese status, WBC count and the incidence of T2D.Results: During the approximately ∼9-year follow-up period (median duration of follow-up: 3.48y), 1463 subjects developed T2D. In the final multivariate model, the hazard ratios (95% confidence interval) of T2D for obese participants with elevated WBC count, non-obese participants with elevated WBC count, and non-obese participants with low WBC count, when compared to obese participants with low WBC count were: 1.22(1.03-1.44), 1.37(1.12-1.66) and 0.99(0.83-1.20), respectively.Conclusions: This study demonstrated that WBC count can be used as an indicator to identify whether or not obesity leads to increased risk of T2D. [ABSTRACT FROM AUTHOR]

Background and Aims: Oxidized low-density lipoprotein (oxLDL) causes the development of atherosclerosis and kidney injury. Although circulating oxLDL levels were reportedly increased in type 2 diabetic patients with macroalbuminuria, it remains unclear whether albuminuria or the reduced glomerular filtration rate (GFR) is independently associated with the circulating oxLDL level. This study aimed to elucidate the association between the stage of diabetic nephropathy and serum malondialdehyde-modified LDL (MDA-LDL) and the ratio of MDA-LDL to LDL-cholesterol (MDA-LDL/LDL).Methods and Results: This retroactive cross-sectional study used data from 402 patients with type 2 diabetes. Patients undergoing hemodialysis were excluded. Serum MDA-LDL levels were significantly increased with increases in severity of albuminuria (103 ± 44 U/L, 109 ± 54 U/L, and 135 ± 72 U/L for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively; P for trend = 0.020) but not according to the estimated GFR (eGFR). An increased MDA-LDL/LDL ratio was significantly associated with both increased albuminuria (35 ± 13, 37 ± 14, and 40 ± 15 for normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively; P for trend = 0.003) and reduced eGFR (34 ± 13, 36 ± 13, 38 ± 12, and 51 ± 28 for grade 1, 2, 3 and 4, respectively; P for trend = 0.002). Multiple linear regression analysis showed that neither the albumin excretion rate nor eGFR but ln-transformed triglycerides and LDL-C levels were independent determinants of both serum MDA-LDL levels and MDA-LDL/LDL ratios.Conclusion: Serum MDA-LDL levels and MDA-LDL/LDL ratios were increased in those with dyslipidemia associated with diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD) is the most common mental health issue, afflicting around 33% of stroke survivors. PSD has a negative impact on the rehabilitation, recuperation of motor and cognitive deficits following stroke and significantly increases the chances of relapsing neurovascular events. It has been demonstrated that biological and psychological factors have a significant role in PSD. Numerous endeavors have been made to discover the risk factors and predictors of PSD. Screening and diagnosis also have gained attention; however, a suitable tool is yet to be developed. Medications are chosen based on their viability and reaction profile in the patients. Besides pharmacotherapy, psychotherapy treatment is also highly valued by both psychiatrists and stroke patients. Additional research is needed to examine the pathophysiology of PSD. This review attempts to highlight the existing evidence and gaps in the present knowledge of the predictors of PSD, incidence, prevalence, and etiology. Further, it also discusses the screening and diagnostic approaches, therapeutic modalities and management of PSD and the impact of pre-stroke depression on PSD. [ABSTRACT FROM AUTHOR]

This review describes trends in the burden of cardiovascular diseases (CVDs) and risk factors in India compared with the United States; provides potential explanations for these differences; and describes strategies to improve cardiovascular health behaviors, systems, and policies in India. The prevalence of CVD in India has risen over the past 2 decades due to population growth, aging, and a stable age-adjusted CVD mortality rate. Over the same time period, the United States has experienced an overall decline in age-adjusted CVD mortality, although the trend has begun to plateau. These improvements in CVD mortality in the United States are largely due to favorable population-level risk factor trends, specifically with regard to tobacco use, cholesterol, and blood pressure, although improvements in secondary prevention and acute care have also contributed. To realize similar gains in reducing premature death and disability from CVD, India needs to implement population-level policies while strengthening and integrating its local, regional, and national health systems. Achieving universal health coverage that includes financial risk protection should remain a goal to help all Indians realize their right to health. [ABSTRACT FROM AUTHOR]