Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC).

Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54-1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39-1.94), Chinese, 1.39 (1.06-1.83), African, 1.67 (1.37-2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91-2.87) for MetS-PC versus 1.79 (1.46-2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12-1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12-1.39) and African Americans (HR = 1.16, 95%CI 1.01-1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17-1.64 compared with 1.46, 95%CI 1.23-1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort

Age- and sex- specific all-cause mortality risk greatest in metabolic syndrome combinations with elevated blood pressure from 7 U.S. cohorts

Background The association between metabolic syndrome (MetS) and all-cause mortality is well established but it is unclear if there are differences in mortality risk among the 32 possible MetS combinations. Hence, the purpose of this study is to evaluate the associations between different MetS combinations and its individual components with all-cause mortality, and to examine differences in the association by age and sex. Methods A merged sample of 82,717 adults from 7 U.S. cohorts was used. Results In our sample, MetS was present in 32% of men, 34% of women, 28% of younger adults (18–65 years) and 62% of older adults (>65 years) with 14,989 deaths over 14.6 ± 7.4 years of follow-up. Risk of all-cause mortality was higher in younger individuals with a greater number of MetS factors present, but in older adults having all 5 MetS factors was the only combination significantly associated with mortality. Regardless of age or sex, elevated blood pressure was the MetS factor most consistently present in MetS combinations that were significantly and most strongly associated with mortality. In fact, elevated blood pressure in the absence of other risk factors was significantly associated with mortality in men (HR, 95% CI = 1.56, 1.33–1.84), women (HR = 1.62, 1.44–1.81) and younger adults (HR = 1.61, 1.45–1.79). Conversely, waist circumference, glucose and triglycerides in isolation were not associated with mortality (p>0.05). Conclusion In a large U.S. population, different combinations of MetS components vary substantially in their associations with all-cause mortality. Men, women and younger individuals with MetS combinations including elevated blood pressure had stronger associations with greater mortality risk, with minimal associations between MetS and mortality risk in older adults. Thus, we suggest that future algorithms may wish to consider differential weighting of these common metabolic risk factors, particularly in younger populations.York University Librarie

Genetic variants and the metabolic syndrome: a systematic review

Several candidate gene studies on the metabolic syndrome (MetS) have been conducted. However, for most single nucleotide polymorphisms (SNPs) no systematic review on their association with MetS exists. A systematic electronic literature search was conducted until the 2nd of June 2010, using HuGE Navigator. English language articles were selected. Only genes of which at least one SNP–MetS association was studied in an accumulative total population =4000 subjects were included. Meta-analyses were conducted on SNPs with three or more studies available in a generally healthy population. In total 88 studies on 25 genes were reviewed. Additionally, for nine SNPs in seven genes (GNB3, PPARG, TCF7L2, APOA5, APOC3, APOE, CETP) a meta-analysis was conducted. The minor allele of rs9939609 (FTO), rs7903146 (TCF7L2), C56G (APOA5), T1131C (APOA5), C482T (APOC3), C455T (APOC3) and 174G>C (IL6) were more prevalent in subjects with MetS, whereas the minor allele of Taq-1B (CETP) was less prevalent in subjects with the MetS. After having systematically reviewed the most studied SNP–MetS associations, we found evidence for an association with the MetS for eight SNPs, mostly located in genes involved in lipid metabolis

Associations of plasma very-long-chain SFA and the metabolic syndrome in adults

Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms

Soluble ST2 levels and left ventricular structure and function in patients with metabolic syndrome

Background: A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. Methods: A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. Results: LV mass index (β=0.337, P<0 .001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. Conclusions: Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS

Risk of postoperative pulmonary complications in adult surgical patients with metabolic syndrome: a systematic review and meta-analysis protocol

Background: Metabolic syndrome (MetS) is defined as an accumulation of risk factors that include chronic hypertension, dyslipidaemia, insulin resistance and obesity and leads to an increased risk for diabetes, cardiovascular disease and stroke. MetS is widespread and estimated to affect up to a quarter of the global population. Patients with MetS who undergo surgery are associated with an increased risk of postoperative complications when compared with patients with a non-MetS profile. An emerging body of literature points to MetS being associated with a greater risk of postoperative pulmonary complications (PPC) in the surgical patient. PPC are associated with increased postoperative morbidity and mortality, Intensive care unit (ICU) admission, length of stay (ICU and hospital), health care costs, resource usage, unplanned re-intubation and prolonged ventilatory time. Methods/design: We will search for relevant studies in the following electronic bibliographic databases: EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus as well as scan the reference lists of included studies for potential additional literature. Two authors will independently screen titles and abstracts to identify potentially relevant studies for inclusion based on predefined inclusion and exclusion criteria. The Cochrane Collaboration Review Manager (Review Manager 5) statistical software will be used to conduct this systematic review and meta-analysis and generate forest plots to demonstrate comparison of findings across studies included for meta analysis. Subgroup and sensitivity analysis will be performed to assess the heterogeneity of included studies. A descriptive synthesis of the statistical data will be provided to summarise the results and findings of the systematic review and meta-analysis. Discussion: This review will be the first to report and summarise the risk for and incidence of PPC in adult patients with MetS undergoing surgery across a range of surgical specialities. The results have the potential to inform the development of evidenced-based interventions to improve the management of PPC in the surgical patient with MetS. Findings from this systematic review and meta-analysis will inform a subsequent Delphi study on priorities and responses to PPC in patients with MetS. We will also disseminate our results through publication in scientific peerreviewed journals, conference presentations and promotion throughout our network of surgical safety champions in clinical settings

Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials.

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and methodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo-controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe-controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL-C.ResultsLDL-C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non-MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non-MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) and HDL-C. Overall, the percentage change at Week 24 in LDL-C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection-site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab-associated reductions in LDL-C, apolipoprotein B, and non-HDL-C were significant vs control, and did not vary by MetS status

Peri-implant diseases and metabolic syndrome components: a systematic review

OBJECTIVE: Metabolic syndrome (MetS) is defined as a spectrum of conditions associated with an increased risk of developing CVD and type 2 diabetes. MetS include: hyperglycemia, hypertension, visceral obesity, dyslipidemia with elevated values of triglycerides (TG) and low levels of HDL. The aim of this review is to provide current knowledge of the relationship between MetS, its components and peri-implant diseases. MATERIALS AND METHODS: An electronic literature search was conducted in the English language in several databases. The Newcastle-Ottawa Scale was used for quality assessment of cohort and cross-sectional studies; while systematic reviews were evaluated through AMSTAR; results were reported according to the PRISMA Statement. RESULTS: A total of 272 records were identified through database searching, six studies were included for qualitative analysis. No study directly related to MetS was found, there was inconsistent and controversial evidence regarding association with cardiovascular disease. A higher risk of peri-implantitis was detected in people with hyperglycemia. CONCLUSIONS: Future research should be orientated in assessing the risk of peri-implant diseases, evaluating patient's therapeutic response, analyzing directionality of the relationship between MetS, its components and biologic implant complications. Few studies have investigated the possible relationship between systemic conditions and peri-implant diseases. The aim of this review is to present, in a systematic manner, current evidence and knowledge regarding possible association between cardiovascular disease and implant biologic complications. Out of the one-hundred-eighty-nine studies screened, just five studies were selected for qualitative analysis: three cohort studies (one prospective and two retrospectives) and two cross-sectional studies. According to their results, there is inconsistent and controversial evidence regarding association of cardiovascular disease and implant biologic complications. Future research should be orientated in conducting longitudinal studies, evaluating patients affected by cardiovascular disease rehabilitated with dental implants

A simulator for the control network of smart grid architectures

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Effect of metabolic syndrome and aging on Ca2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine

BACKGROUND: Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS: Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca2+ handling dysfunction in CAD