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Najafipour H.,Kerman Medical University | Sanjari M.,Kerman Medical University | Shokoohi M.,Kerman Medical University | Haghdoost A.-A.,Kerman Medical University | And 5 more authors.
Journal of Diabetes | Year: 2015

Background: The goal of this research was to measure the age-sex standardized prevalence of pre-diabetes (pre-DM) and diabetes (DM), and the effectiveness of diabetes management (using HbA1C as the indicator) in an urban area in Iran. Methods: Using a randomized cluster household survey, we recruited 5900 individuals whose age ranged from 15 to 75 from Kerman for assessing coronary artery disease risk factors (KERCADRS) including diabetes. In 2010 and 2011, all of the participants were interviewed by trained staff for medical history and physical activities, and were then examined for blood pressure and anthropometric measures. Venus blood sample was also collected for fasting plasma glucose and HbA1c. Results: The age-sex standardized prevalence of pre-diabetes, diagnosed and undiagnosed was 18.7%, 6.3% and 2.7%, respectively. Diabetes increased by age (from 14.7% in the 15-24 years old group to 28.4% in the 65-75 years old group), particularly after 40 years. Occasional opium users had the highest prevalence of Pre-DM (34.6%). Seventy-nine percent of the depressed and 75.5% of the anxious participants with diagnosed-DM were identified as uncontrolled-DM. More than 60% of diagnosed diabetic cases had impaired HbA1c. Overweight and obesity (adjusted odds ratio (AOR) 1.6) and low physical activity (AOR 1.5) were the most preventable risk factors associated with diabetes. Conclusion: Considerable prevalence of diabetes, susceptibility in progressing to diabetes and uncontrolled diabetes among individuals living in Kerman, suggested ineffective prevention and treatment of diabetes in urban areas in Iran. Successful experience regarding primary health-care in rural areas should be expanded to urban settings. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Nelson C.P.,University of Leicester | Nelson C.P.,National Health Research Institute | Hamby S.E.,University of Leicester | Hamby S.E.,National Health Research Institute | And 70 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.) Copyright © 2015 Massachusetts Medical Society.

Najafipour H.,Kerman Medical University | Nasri H.R.,Kerman Medical University | Afshari M.,Kerman Medical University | Moazenzadeh M.,Kerman Medical University | And 6 more authors.
International Journal of Public Health | Year: 2014

Objectives: Hypertension (HTN) is an important cause of cardiovascular related morbidity and mortality. This study aimed at providing the prevalence of pre-HTN, diagnosed and undiagnosed HTN, along with its control and associated factors in an adult population.Methods: 5,900 participants aged 15–75 years took part in the study. HTN was verified by examination, self-reported history or using anti-hypertensive drug(s). Pre-hypertension and hypertension were defined as 120–139/80–89 mmHg and >140/>90 mmHg for systolic/diastolic BP, respectively.Results: The prevalence of hypertension was 18.4 % from which 10.5 %were diagnosed and 7.9 % were undiagnosed. The prevalence of pre-HTN was 35.5 %. HTN increased by age (2.4 % in 15–24 to 49 % in 55–64 years). The men had higher pre-HTN (42.7 vs. 28.1 %) and undiagnosed HTN (11.3 vs. 4.6 %). Of those diagnosed, 56.3 % had uncontrolled BP levels. Smoking, anxiety, obesity, and positive family history of HTN were the most significant predictors for HTN.Conclusions: Hypertension affected almost one-fifth of the population. Given the poor control in diagnosed hypertensive patients, it is alarming that the current health system in urban areas in Iran is not effective enough to control the epidemic spread of non-communicable diseases. © 2014, Swiss School of Public Health.

Saleheen D.,University of Pennsylvania | Saleheen D.,Center for Non Communicable Diseases | Scott R.,Institute of Metabolic Science | Javad S.,Institute of Metabolic Science | And 10 more authors.
The Lancet Diabetes and Endocrinology | Year: 2015

Background: Although HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity-a prototypical measure of HDL function-has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain. Methods: We measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40-79 years, assessed in 1993-97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants. Findings: Cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=-0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51-0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70-0·90) for a per-SD change in cholesterol efflux capacity. Interpretation: HDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease. Funding: US National Institutes of Health, UK Medical Research Council, Cancer Research UK. © 2015 Saleheen et al.

Zanoni P.,University of Pennsylvania | Khetarpal S.A.,University of Pennsylvania | Larach D.B.,University of Pennsylvania | Hancock-Cerutti W.F.,University of Pennsylvania | And 53 more authors.
Science | Year: 2016

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

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