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Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients.
Rimpelä, JM, Pörsti, IH, Jula, A, Lehtimäki, T, Niiranen, TJ, Oikarinen, L, Porthan, K, Tikkakoski, A, Virolainen, J, Kontula, KK, et al
BMC medical genetics. 2018;(1):110
Abstract
BACKGROUND Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10- 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. RESULTS In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = - 4.8%, P = 9.6 × 10- 9 for systolic and β = - 4.3%, P = 2.2 × 10- 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10- 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = - 0.8%, P = 0.4 for systolic and β = - 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = - 7.6 g/m2, P = 0.02). CONCLUSIONS rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology.
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Age threshold for moderate and severe periodontitis among Korean adults without diabetes mellitus, hypertension, metabolic syndrome, and/or obesity.
Han, K, Park, JB
Medicine. 2017;(33):e7835
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Abstract
The purpose of this study is to determine an appropriate age threshold at which to recommend the evaluation of moderate and severe periodontitis among Korean adults.This study involved a cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey from 2012 to 2014. Incidence rates of periodontitis with the 95% confidence interval (CI) were evaluated. The predictive accuracy of age for periodontitis was determined by calculating the area under curve (AUC) on the basis of the receiver operating characteristic (ROC) curve.The cutoff value of age was 43 years in men having periodontitis with an AUC of 0.70 with 95% CI of 0.69 to 0.72. The AUC was 0.72 (95% CI: 0.70-0.73), and the cutoff value of age (49 years) was identified for the moderate periodontitis in women. The cutoff values for age with AUCs and 95% CI for individuals with periodontitis were 46 years (0.72 [0.71-0.73]), 43 years (0.73 [0.72, 0.74]), 45 years (0.71 [0.70,0.72]), 43 years (0.73 [0.72, 0.74]), and 45 years (0.74 [0.72, 0.75]) for no obesity, no abdominal obesity, no diabetes mellitus, no hypertension, and no metabolic syndrome groups, respectively.This study proposed the guideline for the appropriate age threshold at which to recommend the evaluation of moderate and severe periodontitis for the general population and additionally added the guideline for the individuals without systemic disease including diabetes mellitus, hypertension, metabolic syndrome, and obesity. This study suggests that the participants with certain age may be recommended for the regular periodontal evaluation.
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The ticking time bomb in lifestyle-related diseases among women in the Gulf Cooperation Council countries; review of systematic reviews.
Alshaikh, MK, Filippidis, FT, Al-Omar, HA, Rawaf, S, Majeed, A, Salmasi, AM
BMC public health. 2017;(1):536
Abstract
BACKGROUND This study aims to review all published systematic reviews on the prevalence of modifiable cardiovascular disease risk factors among women from the Gulf Cooperation Council countries (GCC). This is the first review of other systematic reviews that concentrates on lifestyle related diseases among women in GCC countries only. METHOD Literature searches were carried out in three electronic databases for all published systematic reviews on the prevalence of cardiovascular disease risk factors in the GCC countries between January 2000 and February 2016. RESULTS Eleven systematic reviews were identified and selected for our review. Common reported risk factors for cardiovascular disease were obesity, physical inactivity, diabetes, metabolic syndrome and hypertension. In GCC countries, obesity among the female population ranges from 29 to 45.7%, which is one of the highest rates globally, and it is linked with physical inactivity, ranging from 45 to 98.7%. The prevalence of diabetes is listed as one of the top ten factors globally, and was reported with an average of 21%. Hypertension ranged from 20.9 to 53%. CONCLUSIONS The high prevalence of lifestyle-related diseases among women population in GCC is a ticking time bomb and is reaching alarming levels, and require a fundamental social and political changes. These findings highlight the need for comprehensive work among the GCC to strengthen the regulatory framework to decrease and control the prevalence of these factors.
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The role of PPARgamma in cardiovascular diseases.
Kvandová, M, Majzúnová, M, Dovinová, I
Physiological research. 2016;(Suppl 3):S343-S363
Abstract
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system - cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension. Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARgamma is very important in the regulation of several disorders such as diabetes mellitus, hypertension and/or metabolic syndrome.
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Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia.
Gosadi, IM
Saudi medical journal. 2016;(1):12-20
Abstract
Metabolic syndrome (MS) is a combination of factors that increases the risk of cardiovascular atherosclerotic diseases including diabetes, obesity, dyslipidemia, and high blood pressure. Cardiovascular diseases are one of the leading causes of death in the adult Saudi population where the increase in cardiovascular-related mortality is augmented by the rise in the prevalence of MS. Metabolic syndrome is a multi-factorial disorder influenced by interactions between genetic and environmental components. This review aims to provide a comprehensive assessment of studied environmental and genetic factors explaining the prevalence of MS in the Kingdom of Saudi Arabia. Additionally, this review aims to illustrate factors related to the population genetics of Saudi Arabia, which might explain a proportion of the prevalence of MS.
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Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial.
Brown, MJ, Williams, B, Morant, SV, Webb, DJ, Caulfield, MJ, Cruickshank, JK, Ford, I, McInnes, G, Sever, P, Salsbury, J, et al
The lancet. Diabetes & endocrinology. 2016;(2):136-47
Abstract
BACKGROUND Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control. METHODS We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18-80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete. FINDINGS Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to hydrochlorothiazide, and 150 to the combination group. 132 participants in the amiloride group, 134 in the hydrochlorothiazide group, and 133 in the combination group were included in the modified intention-to-treat analysis. 2 h glucose concentrations after OGTT, averaged at 12 and 24 weeks, were significantly lower in the amiloride group than in the hydrochlorothiazide group (mean difference -0·55 mmol/L [95% CI -0·96 to -0·14]; p=0·0093) and in the combination group than in the hydrochlorothiazide group (-0·42 mmol/L [-0·84 to -0·004]; p=0·048). The mean reduction in home systolic blood pressure during 24 weeks did not differ significantly between the amiloride and hydrochlorothiazide groups, but the fall in blood pressure in the combination group was significantly greater than that in the hydrochlorothiazide group (p=0·0068). Hyperkalaemia was reported in seven (4·8%) patients in the amiloride group and three (2·3%) patients in the combination group; the highest recorded potassium concentration was 5·8 mmol/L in a patient in the amiloride group. 13 serious adverse events occurred but the frequency did not differ significantly between groups. INTERPRETATION The combination of amiloride with hydrochlorothiazide, at doses equipotent on blood pressure, prevents glucose intolerance and improves control of blood pressure compared with montherapy with either drug. These findings, together with previous data about morbidity and mortality for the combination, support first-line use of amiloride plus hydrochlorothiazide in hypertensive patients who need treatment with a diuretic. FUNDING British Heart Foundation and National Institute for Health Research.
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Prognostic interactions between cardiovascular risk factors.
Vishram, JK
Danish medical journal. 2014;(7):B4892
Abstract
BACKGROUND Cardiovascular disease (CVD) still remains the leading cause of death worldwide, especially in Europe where the prevalence of hypertension is 60% higher compared with the United States and Canada and the clustering of hypertension and the metabolic disorders central adiposity, dyslipidemia and dysglycemia, known as the metabolic syndrome (MetS), affects 25% of the population. Despite the great initiatives of many primary prevention strategies, risk factor control is still poor. In an attempt to optimize risk factor control, two issues among others have been of great debate in the past decade: (1) the superiority of systolic blood pressure (SBP) as a risk factor in the elderly; and (2) the clinical relevance of MetS. However, in order to further elucidate these issues, we need to get a deeper understanding of how the cardiovascular risk factors interact with one another. Thus, prognostic interactions were used in the present PhD thesis to test the following hypotheses: Primary hypotheses: (1) The superiority of SBP over diastolic blood pressure (DBP) as a risk factor occurs at an earlier age if an individual presents with other cardiovascular risk factors. (2) The prevalence and prognostic significance of MetS differ according to age and gender. The first hypothesis is explored in paper 1 (for the endpoint fatal and nonfatal (total) stroke) and paper II (for mortality from coronary heart disease (CHD), stroke, and all-causes), while the second hypothesis is explored in paper III (for total CHD, total stroke, and CVD mortality). METHODS Using 34-42 cohorts from the MORGAM Project with baseline between 1982-1997, approximately 68 000-86 000 apparently healthy men and women aged 19-78 years, without CVD (papers I-III) and not receiving antihypertensive treatment (papers I-II) were included. During 12-13 years of follow-up, the incident events of total stroke were up to 1957, of total CHD were 4368, and of all-cause mortality were 7903. In papers I-II, event risk was analyzed by multivariate-adjusted Cox regressions including SBP and DBP simultaneously, as well as other cardiovascular risk factors and any significant interactions between variables. In paper III, MetS prevalence and prognostic significance was considered according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program - Adult Treatment Panel (NCEP-ATP III), and the influence of possible interactions between age and gender on MetS prevalence and prognostic significance was explored using logistic as well as multivariate-adjusted Cox regressions. MetS was analyzed separately for men and women in various age-groups. RESULTS Taking into account the significant interactions between cardiovascular risk factors, the results were as follows: Papers I-II: Age-related shifts were shown for the independent relative importance of SBP and DBP as risk factors for stroke (both total and fatal) and all-cause mortality, but not for CHD mortality where SBP remained significant in all ages. The prognostic shift to the superiority of SBP was significantly established in the 6th decade, and only for stroke mortality was this shift influenced by other cardiovascular risk factors, such that it occurred at an earlier age in men from high-risk countries and with a higher cholesterol level. However, from mid-age and onwards, a potential harmful effect of low DBP for the risk of total stroke and all-cause mortality was present. Paper III: The prevalence and prognostic significance of MetS showed great variations among countries and were influenced by both age and gender. With older age, the prevalence of MetS increased 5-fold in women from ages 19-39 years to 60-78 years and 2-fold in men. The CVD risk associated with MetS was (1) higher in women than in men especially when using the NCEP-ATP III criteria, and (2) independently of age in men whereas in women total CHD risk decreased significantly and the total stroke risk tended to increase (although not significant) with older age. CONCLUSION The present thesis elucidates through prognostic interactions the complex interplay between cardiovascular risk factors. Our results indicate the independent prognostic superiority of SBP in elderly Europeans, and only for stroke mortality risk this prognostic superiority of SBP was influenced by other cardiovascular risk factors such that it was established at an earlier age. The prevalence and prognostic significance of MetS differed according to both age and gender. In women, MetS was associated with higher relative event risks and the MetS associated relative CHD risk decreased with advancing age.
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Prevalence of premorbid metabolic syndrome in Spanish adult workers using IDF and ATPIII diagnostic criteria: relationship with cardiovascular risk factors.
Tauler, P, Bennasar-Veny, M, Morales-Asencio, JM, Lopez-Gonzalez, AA, Vicente-Herrero, T, De Pedro-Gomez, J, Royo, V, Pericas-Beltran, J, Aguilo, A
PloS one. 2014;(2):e89281
Abstract
BACKGROUND Metabolic Syndrome (MetS) is a complex disorder defined as a cluster of interconnected risk factors such as hypertension, dyslipidemia, obesity and high blood glucose levels. Premorbid metabolic syndrome (PMetS) is defined by excluding patients with previously diagnosed cardiovascular disease or diabetes mellitus from those suffering MetS. We aimed to determine the prevalence of PMetS in a working population, and to analyse the relationship between the diagnostic criteria of the International Diabetes Federation (IDF) and of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII). The relationship between the presence of PMetS and cardiovascular risk factors was also analysed. RESEARCH METHODOLOGY/FINDINGS A cross-sectional study was conducted in 24,529 male and 18,736 female Spanish (white western European) adult workers (20-65 years) randomly selected during their work health periodic examinations. Anthropometrics, blood pressure and serum parameters were measured. The presence of MetS and PMetS was ascertained using ATPIII and IDF criteria. Cardiovascular risk was determined using the Framingham-REGICOR equation. The results showed MetS had an adjusted global prevalence of 12.39% using ATPIII criteria and 16.46% using IDF criteria. The prevalence of PMetS was slightly lower (11.21% using ATPIII criteria and 14.72% using IDF criteria). Prevalence in males was always higher than in females. Participants with PMetS displayed higher values of BMI, waist circumference, blood pressure, glucose and triglycerides, and lower HDL-cholesterol levels. Logistic regression models reported lower PMetS risk for females, non-obese subjects, non-smokers and younger participants. Cardiovascular risk determined with Framingham-REGICOR was higher in participants with PMetS. CONCLUSIONS PMetS could be a reliable tool for the early identification of apparently healthy individuals who have a significant risk for developing cardiovascular events and type 2 diabetes.
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Frequency of cardiovascular risk factors before and 6 and 12 months after bariatric surgery.
Silva, MA, Rivera, IR, Barbosa, EM, Crispim, MA, Farias, GC, Fontan, AJ, Bezerra, RA, Sá, LG
Revista da Associacao Medica Brasileira (1992). 2013;(4):381-6
Abstract
OBJECTIVE To compare the frequency of cardiovascular risk factors (CVRFs) in obese patients of the Brazilian Unified Health System (Sistema Único de Saúde - SUS) with indication of bariatric surgery during the preoperative period and after the sixth month and the first year of the procedure. METHODS An observational, longitudinal, prospective, and analytical study was performed, with consecutive selection of obese patients with indication for surgery referred to preoperative cardiac evaluation. The protocol consisted of: medical history, physical examination, electrocardiogram, echocardiogram, and biochemical analysis. This study analyzed the following variables: weight, body mass index (BMI), waist circumference (WC), systemic arterial hypertension (SAH), diabetes mellitus type 2(DM), dyslipidemia (high LDL cholesterol; low HDL cholesterol; hypertriglyceridemia), and metabolic syndrome (MS). The chi-squared test and the Tukey-Kramer method were used for statistical analysis. RESULTS The sample was composed of 96 obese people, among which 86 were women, aged between 18 and 58 years old (median 35 years old). At the end of six months, significant reductions of 88%, 95%, 71%, 89%, and 80% in the frequency of SAH, high LDL cholesterol, hypertriglyceridemia, DM, and MS could already be observed. A significant and small reduction in the frequency of low HDL cholesterol (24%) and abnormal WC (31%) was observed only at the end of 12 months. After six months and one year, weight and BMI experienced reductions of 33.4kg and 44.3kg, and 13.1kg/m(2) and 17.2kg/m(2), respectively. CONCLUSION The positive impact on weight loss and the reduction in BMI, WC, and in the frequency of CVRFs are already extremely significant after six months and remain so one year after bariatric surgery.
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Genes for blood pressure: an opportunity to understand hypertension.
Ehret, GB, Caulfield, MJ
European heart journal. 2013;(13):951-61
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Hypertension (HTN) is quantitatively the major cardiovascular risk factor and responsible for ∼50% of cardiovascular morbidity and mortality. Blood pressure (BP) is also a classical complex genetic trait with heritability estimates of 30-50%. Although much is known about BP regulation, the intrinsic origin of essential HTN remains obscure although many environmental factors are known. Analyses of rare monogenic syndromes of HTN have focused attention on pathways that involve renal sodium handling, and steroid hormone metabolism including the mineralocorticoid receptor activity. The genetic basis of common essential HTN on the other hand is only just becoming accessible through high-throughput approaches. Unbiased genome-wide analyses of BP genomics have identified 43 genetic variants associated with systolic, diastolic BP, and HTN. It is highly likely based on current findings that there are hundreds of such loci with small effects on BP, opening a perspective on the genetic architecture of BP that was unknown before. It is our hope that the knowledge of these and further loci will lead to improved understanding of BP pathophysiology and to the identification of new targets for drug therapy.