Gender-Related Differences in the Prevalence of Cardiovascular Disease Risk Factors and their Correlates in Urban Tanzania.

\ud Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. The age-adjusted prevalence of obesity (BMI > or = 30) was 13% and 35%, among men and women (p = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% (p < 0.0001), and high WHR (men: >0.9, women: >0.85) was 51% and 73% (p = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9-10.1), 14.2-fold increased odds for abdominal adiposity (95% CI: 5.8-34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4-5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome (p = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3-1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.\u

Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle

Background and Aims. Simple clinical algorithms including the Fatty Liver Index (FLI) and Lipid Accumulation Product (LAP) have been developed as a surrogate marker for Non-Alcoholic Fatty Liver Disease (NAFLD). These algorithms have been constructed using ultrasonography, a semi-quantitative method. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as measured quantitatively by proton magnetic resonance spectroscopy (1H-MRS). Methods. Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment in the course of research studies. Values of FLI and LAP were determined, and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5 %) and of actual liver fat content, as measured by 1H MRS. The discriminative ability of FLI and LAP was estimated using the area under the Receiver Operator Characteristic curve (AUROC). Since FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Results. FLI and LAP discriminated between patients with and without hepatic steatosis with an AUROC of 0.79 (IQR= 0.74, 0.84) and 0.78 (IQR= 0.72, 0.83), although quantitative prediction of liver fat content was unsuccessful. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort. Conclusions. FLI and LAP may be used clinically, and for metabolic and epidemiological research, to identify patients with hepatic steatosis, but not as surrogates for liver fat content

Dyslipidemia and changes in lipid profiles associated with rheumatoid arthritis and initiation of anti–tumor necrosis factor therapy

Objective To investigate the frequency of lipid testing in clinical practice and to explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors with RA treatment. Methods Patients in this retrospective database study were ages ≥18 years and had ≥2 physician diagnoses for RA or osteoarthritis (OA; comparator group) between March 2004 and March 2008. Outcomes of interest included the percentage of RA and OA patients receiving lipid tests, lipid profiles (total cholesterol, low‐density lipoprotein [LDL] cholesterol, and high‐density lipoprotein [HDL] cholesterol) of RA versus OA patients, and lipid profiles of RA patients before and after initiation with a tumor necrosis factor (TNF) inhibitor. We used multivariable regression to control potential confounders between the cohorts. Results Over a median ≥2‐year followup, fewer RA patients than OA patients had ≥1 lipid test (62.0% [95% confidence interval (95% CI) 61.5–62.5] versus 69.8% [95% CI 69.5–70.1]). Mean total cholesterol and LDL cholesterol were each 4 mg/dl lower in the RA cohort ( P < 0.0001); HDL cholesterol was similar between the cohorts. Across the RA cohort, 25.2% of patients had suboptimal LDL cholesterol levels (≥130 mg/dl). Among RA patients not receiving lipid‐lowering therapy who initiated TNF inhibitor therapy (n = 96), mean total cholesterol and LDL cholesterol increased by 5.4 and 4.0 mg/dl, respectively. Conclusion Patients with RA were less likely to be tested for hyperlipidemia and had more favorable lipid profiles than patients with OA. TNF inhibitor therapy modestly increased all lipid parameters. Additional studies are needed to determine the effect of traditional CV risk factors and inflammation and the impact of biologic agents on CV outcomes in RA patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93521/1/21693_ftp.pd

Endothelial function in patients with metabolic syndrome and erectile dysfunction : a question of Angiopoietin imbalance?

Erectile dysfunction (ED) is a highly prevalent disease whose aetiology is mostly vasculogenic. It is nowadays considered a marker of future cardiovascular events reflecting the underlying endothelial dysfunction, the common link with the metabolic syndrome (MetS). The recent association between MetS, endothelial dysfunction and peripheral artery disease, but not with coronary artery disease (CAD), suggests that the pathophysiologies of CAD and peripheral artery disease may be distinct. Moreover, several recent studies support an emerging role for an imbalance of angiogenic growth factor levels like Angiopoietin 1 and 2 in cardiovascular disease, considering its intimate association with chronic low-grade inflammation. We aim to find a correlation between Angiopoietins levels and systemic and local endothelial function in MetS and ED patients. Forty-five MetS patients with ED were enrolled. ED severity was assessed by International Index of Erectile Function questionnaire (IIEF5) and penile duplex Doppler ultrasound (PDDU). Endothelial function was assessed by Peripheral arterial tonometry (PAT), and serum asymmetric dimethylarginine (ADMA), Ang1 and Ang2 levels. Obesity and hypertension were the most frequent MetS parameters (91.1 and 88.9% respectively). Severe ED was present in 35.6% of patients. Penile haemodynamic was impaired in 77.5%. Endothelial dysfunction (PAT criteria) was present in 40.9% of patients. Ang2 levels were significantly higher in men with abdominal obesity. We observed an inverse correlation between Ang1 and peak systolic velocity, and in patients with penile arterial dysfunction, Ang1 levels were significantly higher and Ang2/Ang1 ratio significantly lower, than patients with normal arterial function. Neither ADMA nor PAT parameters were correlated with ED severity evaluated by IIEF5 or PDDU exam. In conclusion, there is an imbalance of angiopoietins in MetS and ED patients. The absence of correlation with PAT or ADMA levels suggests that angiopoietins may be early markers of endothelial dysfunction in this population of higher cardiovascular risk

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors

Endocrine disruptors and obesity

The purpose of this review is to summarise current evidence that some environmental chemicals may be able to interfere in endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine disrupting chemicals, termed “obesogens”, can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer

Accounting for photodegradation dramatically improves prediction of carbon losses in dryland systems

Traditional models of decomposition fail to capture litter mass loss patterns in dryland systems. This shortcoming has stimulated research into alternative drivers of decomposition, including photodegradation. Here, we use aboveground litter decomposition data for dryland (arid) sites from the Long-term Intersite Decomposition Experiment Team data set to test hypotheses (models) about the mechanisms and impacts of photodegradation. Incorporating photodegradation into a traditional biotic decomposition model substantially improved model predictions for mass loss at these dryland sites, especially after four years. The best model accounted for the effects of solar radiation via photodegradation loss from the intermediate cellulosic and lignin pools and direct inhibition of microbial decomposition. Despite the concurrent impacts of photodegradation and inhibition on mass loss, the best photodegradation model increased mass loss by an average of 12% per year compared to the biotic-only decomposition model. The best model also allowed soil infiltration into litterbags to reduce photodegradation and inhibition of microbial decomposition by shading litter from solar radiation. Our modeling results did not entirely support the popular hypothesis that initial lignin content increases the effects of photodegradation on litter mass loss; surprisingly, higher initial lignin content decreased the rate of cellulosic photodegradation. Importantly, our results suggest that mass loss rates due to photodegradation may be comparable to biotic decomposition rates: Mass loss due to photodegradation alone resulted in litter mass losses of 6–15% per year, while mass loss due to biotic decomposition ranged from 20% per year during early-stage decomposition to 3% per year during late-stage decomposition. Overall, failing to account for the impacts of solar radiation on litter mass loss under-predicted long-term litter mass loss by approximately 26%. Thus, not including photodegradation in dryland decomposition models likely results in large underestimations of carbon loss from dryland systems

CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease

Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcriptional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed chloride channel accessory 2 (CLCA2) expression in prostate xenografts developed in MeS animals. CTBP1 bound to CLCA2 promoter and repressed its transcription and promoter activity in PCa cell lines. Furthermore, we found that CTBP1 formed a repressor complex with ZEB1, EP300 and HDACs that modulates the CLCA2 promoter activity. CLCA2 promoted PCa cell adhesion inhibiting epithelial–mesenchymal transition (EMT) and activating CTNNB1 together with epithelial marker (CDH1) induction, and mesenchymal markers (SNAI2 and TWIST1) repression. Moreover, CLCA2 depletion in PCa cells injected subcutaneously in MeS mice increased the circulating tumor cells foci compared to control. A microRNA (miRNA) expression microarray from PCa xenografts developed in MeS mice, showed 21 miRNAs modulated by CTBP1 involved in angiogenesis, extracellular matrix organization, focal adhesion and adherents junctions, among others. We found that miR-196b-5p directly targets CLCA2 by cloning CLCA2 3′UTR and performing reporter assays. Altogether, we identified a new molecular mechanism to explain PCa and MeS link based on CLCA2 repression by CTBP1 and miR-196b-5p molecules that might act as key factors in the progression onset of this disease.Fil: Porretti, Juliana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Dalton, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Massillo, Cintia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Scalise, Georgina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Elble, Randolph. Southern Illinois University; Estados UnidosFil: Gerez, Esther Noemi. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Invest. Sobre Porfirinas y Porfirias. Grupo Vinculado Al Cipyp - Ffyb; ArgentinaFil: Accialini, Paula Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cabanillas, Ana Maria de Los A.. Universidad Nacional de Córdoba; ArgentinaFil: Gardner, Kevin. Columbia University; Estados UnidosFil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Metabolic Syndrome and Cognitive Decline in Elderly Latinos: Findings from the Sacramento Area Latino Study of Aging Study

To investigate the effect of metabolic syndrome on cognitive function in an elderly Latino population and to determine whether inflammation modifies this association. DESIGN : A longitudinal cohort study. SETTING : Sacramento area and the surrounding California counties from 1998 to 1999. PARTICIPANTS : One thousand six hundred twenty-four Latinos aged 60 and older who participated in the Sacramento Area Latino Study of Aging. MEASUREMENTS : Baseline metabolic syndrome was calculated using the Third Adult Treatment Panel of the National Cholesterol Education Program. Cognitive function was measured using the Modified Mini-Mental State Examination (3MS) and the Delayed Word-List Recall (DelRec), a verbal memory test. The effect of metabolic syndrome on cognitive change scores was examined using random effects models; in addition, the effect of the individual components of the syndrome on cognitive change was examined. RESULTS : Of the 1,624 participants, 718 (44%) had metabolic syndrome at baseline. Those with metabolic syndrome had worse 3-year change scores on 3MS ( P =.04) and DelRec ( P =.03). Multivariate adjustment attenuated the results for DelRec but not for 3MS. This association was especially pronounced in participants with a high serum level of inflammation, resulting in an average 3MS score 0.64 points lower per year ( P =.03) for those with metabolic syndrome. Individual components of metabolic syndrome were not associated with cognitive decline except for elevated glucose on the DelRec ( P =.02) and high blood pressure on 3MS ( P =.05). CONCLUSION : Metabolic syndrome and inflammation may both contribute to cognitive decline in older people of diverse backgrounds. The results also suggest that, in elderly Latinos, the composite measure of metabolic syndrome is a greater risk for cognitive decline than its individual components.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65598/1/j.1532-5415.2007.01139.x.pd

Plasma homocysteine and the risk of venous thromboembolism: insights from the FIELD study

Background The lipid-lowering effect of fenofibrate is accompanied by a rise in plasma homocysteine, a potential risk factor for venous thromboembolism (VTE). This study investigated the relationship between homocysteine and the risk of VTE in patients treated with fenofibrate. Methods and results The relationship between homocysteine and deep-vein thrombosis or pulmonary embolism was investigated in 9522 participants of the 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. All subjects received fenofibrate during a 6-week active run-in phase before randomization. A Cox proportional-hazards model was used to assess the effect of homocysteine on risk of venous thromboembolic events. During active-drug run-in, homocysteine rose on average by 6.5 μmol/L, accompanied by a substantial rise in plasma creatinine (+12%). Fenofibrate-induced changes in homocysteine and creatinine were fully reversible in the placebo group but persisted in the treatment group until reversing at the end of therapy. During follow-up, 1.8% had at least one episode of deep-vein thrombosis or pulmonary embolism: 103 on fenofibrate and 68 on placebo (log-rank P=0.006). In multivariate analysis, every 5 µmol/L higher baseline homocysteine was associated with 19% higher risk of VTE. Fenofibrate treatment was associated with 52% higher risk, but the change in homocysteine with fenofibrate was not significantly associated with VTE after adjustment for baseline homocysteine. Conclusions Hyperhomocysteinemia is prospectively associated with VTE. Fenofibrate may predispose individuals with high pretreatment homocysteine towards VTE. The fenofibrate-induced increase in homocysteine did not, however, explain the risk associated with fenofibrate therapy