Determinants Of Blood Pressure Research Articles

Adiposity measurements in association with metabolic syndrome in older men have different clinical implications

Obesity is a major public health problem, and measuring adiposity accurately and predicting its future comorbidities are important issues. Therefore, we hypothesized that 4 adiposity measurements, body mass index (BMI), waist circumference (WC), waist-to-height ratio, and body fat percentage, have different physiological meanings and distinct associations with adverse health consequences. This study aimed to investigate the relationship of these 4 measurements with metabolic syndrome (MetS) components and identify the most associated factor for MetS occurrence in older, non-medicated men. Cross-sectional data from 3004 men, all 65 years of age and older, were analyzed. The correlation and association between adiposity measurements and MetS components were evaluated by Pearson correlation and multiple linear regression. Based on multivariate logistic regression, BMI and WC were significantly associated with MetS and were selected to build a combined model of receiver operating characteristic curves to increase the diagnosis accuracy for MetS. The results show that BMI is independently associated with systolic and diastolic blood pressure; WC and body fat percentage are associated with fasting plasma glucose and log transformation of triglyceride; BMI and WC are negatively associated with high-density lipoprotein cholesterol (HDL-C); and WC is a better discriminate for MetS than BMI, although the combined model (WC + BMI) is not significantly better than WC alone. Based on these results, we conclude that the 4 adiposity measurements have different clinical implications. Thus, in older men, BMI is an important determinant for blood pressure and HDL-C. Waist circumference is associated with the risk of fasting plasma glucose, HDL-C, triglyceride, and MetS occurrence. The combined model did not increase the diagnosis accuracy.

A cluster-randomized controlled trial to study the effectiveness of a protocol-based lifestyle program to prevent type 2 diabetes in people with impaired fasting glucose.

BackgroundEffective diabetes prevention strategies that can be implemented in daily practice, without huge amounts of money and a lot of personnel are needed. The Dutch Diabetes Federation developed a protocol for coaching people with impaired fasting glucose (IFG; according to WHO criteria: 6.1 to 6.9 mmol/l) to a sustainable healthy lifestyle change: ‘the road map towards diabetes prevention’ (abbreviated: Road Map: RM). This protocol is applied within a primary health care setting by a general practitioner and a practice nurse. The feasibility and (cost-) effectiveness of care provided according to the RM protocol will be evaluated.Methods/DesignA cluster randomised clinical trial is performed, with randomisation at the level of the general practices. Both opportunistic screening and active case finding took place among clients with high risk factors for diabetes. After IFG is diagnosed, motivated people in the intervention practices receive 3–4 consultations by the practice nurse within one year. During these consultations they are coached to increase the level of physical activity and healthy dietary habits. If necessary, participants are referred to a dietician, physiotherapist, lifestyle programs and/or local sports activities. The control group receives care as usual. The primary outcome measure in this study is change in Body Mass Index (BMI). Secondary outcome measures are waist circumference, physical activity, total and saturated fat intake, systolic blood pressure, blood glucose, total cholesterol, HDL cholesterol, triglycerides and behaviour determinants like risk perception, perceived knowledge and motivation. Based on a sample size calculation 120 people in each group are needed. Measurements are performed at baseline, and after one (post-intervention) and two years follow up. Anthropometrics and biochemical parameters are assessed in the practices and physical activity, food intake and their determinants by a validated questionnaire. The cost-effectiveness is estimated by using the Chronic Disease Model (CDM). Feasibility will be tested by interviews among health care professionals.DiscussionThe results of the study will provide valuable information for both health care professionals and policy makers. If this study shows the RM to be both effective and cost-effective the protocol can be implemented on a large scale.Trial registrationISRCTN41209683. Ethical approval number: NL31342.075.10.

Low Physical Activity Is a Determinant for Elevated Blood Pressure in High Cardiovascular Risk Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity, including hypertension. Beyond the severity of nocturnal hypoxia, other factors such as metabolic abnormalities but also sedentary behaviors and insufficient physical activity may contribute to elevated blood pressure (BP). To clarify the respective role of these factors as determinants of BP in OSA patients, we examined the relationship between BP and anthropometrics, severity of sleep apnea, and objectively measured physical activity and sedentary behaviors. Ninety-five adults presenting with OSA (apnea-hypopnea index > 10 events/h) and high cardiovascular risk (63.3 ± 8.8 y; body mass index: 29.9 ± 4.9 kg/m(2); apnea-hypopnea index: 41.3 ± 17.5/h; cardiovascular risk score: 13.5 ± 3.7%) were included. Physical activity and sedentary behaviors were objectively assessed by actigraphy, and self-measured home BP monitoring was measured. Logistic regression models adjusted for sex, age, and body mass index were built to identify the predictors of self-measured morning and evening BP. Physical activity was significantly related to obesity but not to the severity of sleep apnea or sleepiness. Sedentary behaviors were associated with self-measured morning and evening systolic BP (r = 0.32, P = .002; r = 0.29, P = .004). Steps per day were inversely associated with evening BP (r = -0.27, P = .01). Univariate analysis identified steps/d and time spent in vigorous physical activity as determinants for evening self-measured BP. In multivariate analysis, only steps/d were identified as a significant determinant of evening BP. Physical activity is the major determinant for evening BP in adults with OSA presenting high cardiovascular risk. Our results emphasize the need for lifestyle counseling programs in combination with CPAP to encourage regular physical activity in OSA subjects to obtain better BP control. (ClinicalTrials.gov registration NCT01226641.)

Plasminogen Activator Inhibitor-1

Hypertension is the most common reversible risk factor for stroke, myocardial infarction, and heart failure, affecting >60 million individuals in the United State alone and 1 billion globally.1 According to the World Health Organization, hypertension is now the leading cause of preventable death worldwide.2 Importantly, the prevalence and complications of hypertension increase significantly with age. However, despite the availability of many antihypertensive agents of distinct pharmacologic classes and evidence-based guideline recommendations for stepwise, multidrug regimens, control of hypertension remains suboptimal, with target blood pressure achieved in <50% of patients.1 Although patient noncompliance and submaximal dosing of antihypertensive agents contribute to lack of blood pressure control, there is an unmet need for new approaches for treatment of hypertension. In this issue of Circulation , Boe et al3 report that pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1) is protective against the development of hypertension, cardiac hypertrophy, and periaortic fibrosis (ie, arteriosclerosis) in mice treated with N ω-nitro-l-arginine methyl ester (l-NAME) to inhibit endothelial nitric oxide synthase. Article see p 2318 Because the molecular basis for primary or essential hypertension is unknown, the treatment of hypertension, excluding secondary or identifiable hypertension with known causes (eg, chronic renal disease, renovascular, hyperaldosteronism, Cushing syndrome, pheochromocytoma), has been based primarily on targeting the underlying physiologic determinants of blood pressure—namely, intravascular volume (eg, diuretics), neurohormonal drive (eg, centrally acting agents, renin angiotensin system blockade), systemic vascular resistance (eg, vasodilators), and cardiac inotropy and chronotropy (eg, beta blockers; Figure). Another hallmark of hypertension is vascular remodeling of both small (inward eutrophic remodeling that decreases lumen area and increases systemic vascular resistance) and large …

Literature search and review related to specific preparatory work in the establishment of Dietary Reference Values for Phosphorus, Sodium and Chloride

Literature search and review related to specific preparatory work in the establishment of Dietary Reference Values for Phosphorus, Sodium and Chloride

PP16 The Contribution of Changes in Diet and other Risk Factors to recent Favourable Trends in Blood Pressure in Middle-Aged Irish Adults

BackgroundRecent declines in cardiovascular mortality in Ireland and other developed countries are partially attributable to favourable secular trends in blood pressure (BP). However the underlying causes of these BP trends...

Hypoxia-Inducible Factor-1α in Vascular Smooth Muscle Regulates Blood Pressure Homeostasis Through a Peroxisome Proliferator–Activated Receptor-γ–Angiotensin II Receptor Type 1 Axis

Hypertension is a major worldwide health issue for which only a small proportion of cases have a known mechanistic pathogenesis. Of the defined causes, none have been directly linked to heightened vasoconstrictor responsiveness, despite the fact that vasomotor tone in resistance vessels is a fundamental determinant of blood pressure. Here, we reported a previously undescribed role for smooth muscle hypoxia-inducible factor-1α (HIF-1α) in controlling blood pressure homeostasis. The lack of HIF-1α in smooth muscle caused hypertension in vivo and hyperresponsiveness of resistance vessels to angiotensin II stimulation ex vivo. These data correlated with an increased expression of angiotensin II receptor type I in the vasculature. Specifically, we show that HIF-1α, through peroxisome proliferator–activated receptor-γ, reciprocally defined angiotensin II receptor type I levels in the vessel wall. Indeed, pharmacological blockade of angiotensin II receptor type I by telmisartan abolished the hypertensive phenotype in smooth muscle cell-HIF-1α-KO mice. These data revealed a determinant role of a smooth muscle HIF-1α/peroxisome proliferator–activated receptor-γ/angiotensin II receptor type I axis in controlling vasomotor responsiveness and highlighted an important pathway, the alterations of which may be critical in a variety of hypertensive-based clinical settings.

Relationship between copeptin and nocturnal blood pressure in young and healthy adults

Purpose: Copeptin is a vasopressin related stress hormone. We investigated whether copeptin is associated with 24-hour ambulatory blood pressure (BP) levels in young and healthy adults. Method: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors (GAPP) study is a population based cohort study of healthy adults aged 25-41 years in the Principality of Liechtenstein. Individuals with BMI >35 kg/m2 and prevalent cardiovascular disease were excluded. Copeptin was assayed using an immunoluminometric assay (BRAHMS GmbH). Ambulatory BP monitoring was performed using a validated, fully automatic, non-invasive device (Schiller BR-102 plus). Results: Of 1443 individuals included in this study, 53% were female. The median age was 38 years, BMI was 24.2 kg/m2, and 21% were active smokers. The median copeptin levels were 3.7 (interquartile range [IQR]: 2.5, 5.7) and 2.3 pmol/l (IQR: 1.6, 3.4) in men and women, respectively. In multivariable regression models, log-transformed copeptin was significantly associated with systolic and diastolic BP during sleep, as shown in the Table. However, copeptin was not associated with daytime BP levels. The relationship between copeptin and nighttime BP seemed to be stronger in men compared to women (p for interaction 0.005). View this table: Multivariable linear regression analysis Conclusion: In this large population based study of healthy adults, the stress hormone copeptin was significantly associated with elevated nighttime but not daytime BP levels. Our data therefore suggest that stress may be involved in BP elevations during sleep.

Childhood determinants of blood pressure and prehypertension in adolescents - results from the SAPALDIA youth study

Background: Hypertension has become the leading risk factor contributing to the global disability adjusted life years. Adolescent hypertension is increasing, possibly due to the obesity epidemic, and is known to track into adulthood. The SAPALDIA Youth Study, a nested study within the adult Swiss Air Pollution And Lung and Heart Disease In Adults cohort (SAPALDIA), aims to investigate early life factors and cardiovascular health in adolescents, with a special focus on active tobacco exposure. Methods: 288 SAPALDIA offspring (mean age 15 years, sd 3.5) underwent clinical examination and reported on early life, health and lifestyle, smoking habits and disease history. Parental determinants and disease status were taken from the SAPALDIA adult cohort data. The mean of two blood pressure measurements, following standard protocols, was calculated for analyses. Prehypertension in childhood was defined as average systolic (SBP) or diastolic blood pressure (DBP) levels ≥90th percentile but <95th percentile for gender, age, and height, respectively in adolescents ≥120/80 mmHg (2). Descriptive and multi-level regression analyses were performed to investigate the independent impact of early life determinants on blood pressure and prehypertension. Results: Prehypertensive values were found in 24%. We confirmed the impact of BMI on SBP (1 mmHg/10 percentile points, 95% CI 0.04,0.14, DBP 0.02 mmHg, 95%Ci -0.02; 0.06), and of high physical activity (≥60 min strenuous activity/day, SBP -3mmHg, 95% CI -6.0; 0.1, DBP -2.2 mmHg, -4.5; 0.1) and found a borderline significance for weekly smoking on SBP (SBP 3.6 mmHg; 95% CI -0.82; 8.0; DBP 2.3 mmHg, 95% CI -1.2; 5.7). Additional adjustment for parental education, smoking and cardiovascular risk strengthened the adverse association seen for weekly smoking. Associations with DBP proved less significant. Similar results were found in analyses with prehypertension. Conclusion: A high percentage of youth presented with prehypertension. Considering the impact of modifiable risk factors, and the high risk of prehypertension turning into clinical hypertension, screening for prehypertension and risk factors in youth should be given full attention to reduce the population risk by optimal metabolic control and lifestyle modification. Reference: 1. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics 2004

Prevalence of prediabetes in healthy adults using hemoglobin A1c versus fasting plasma glucose - The GAPP study

Purpose: According to current guidelines, both hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) are appropriate tools to screen for prediabetes and established diabetes. However, the correlation between HbA1c and FPG in this context is not well studied, especially among young and healthy adults. Methods: The Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors (GAPP) study is a population based cohort of healthy adults aged 25-41 years in the Principality of Liechtenstein. Main exclusion criteria are a prevalent cardiovascular disease, a prior diagnosis of diabetes and a body mass index (BMI) >35 kg/m2. FPG and HbA1c were assayed using a Roche Cobas 6000 (F.Hoffmann – La Roche) and high-performance liquid chromatography (Bio-Rad D-10), respectively. Prediabetes was defined according to the current guidelines as FPG between 5.6 and 6.9 mmol/l and/or HbA1c between 5.7 and 6.4%. Results: Of 1568 subjects who completed the baseline examination, 839 (53.5%) were women, mean age was 36.4±4.9 years and the mean BMI was 24.7±3.7 kg/m2. Obesity (BMI ≥30 kg/m2) was present in 156 (9.9%) participants. The correlation coefficient between HbA1c and FPG was 0.25 (p<0.0001). Overall, 476 (30.4%) had prediabetes. The prevalence was 36.6% among men and 25.2% among women (p<0.0001). A diagnosis of prediabetes was present in 427 (27.2%) by HbA1c criteria only, 98 (6.3%) by FPG criteria only and 49 (3.1%) by both criteria, as shown in Table 1. Compared with men, women were more likely to be diagnosed with prediabetes by HbA1c criteria, and less likely to be diagnosed by FPG criteria (p<0.0001, Table 1). View this table: Table 1 Conclusion: The prevalence of prediabetes among young and healthy adults is highly dependent on the test used and is much higher using HbA1c criteria, especially among women. If confirmed, our findings may have important implications for screening recommendations in the population.

Determinants of achieving early blood pressure control with monotherapy in a primary care setting.

This study sought to identify the determinants of early blood pressure (BP) control associated with monotherapy in hypertensive individuals being managed in the primary care setting. The Valsartan Intensified Primary Care Reduction of Blood Pressure (VIPER-BP) study, was a multicenter, randomized controlled trial of an intensive approach to BP management. During a standardized run-in, 2185 participants commenced monotherapy (valsartan 80mg/d) for 14 to 28days. A total of 1978 participants aged 59±12years (60% men) completed the run-in phase. Of these, 15.1%, 43.5%, and 41.4% participants had an initial BP target of ≤125/75, 130/80, and 140/90mmHg, respectively. A total of 416 of 2185 participants (19.0%) subsequently achieved their individual BP target during run-in with a mean BP change of -22.6±12.1/-12.9±8.2mmHg vs -4.2±16.2/-3.0±9.6mmHg for the rest (P<.001). These early responders were more likely to be women (adjusted odds ratio, 1.41; 95% confidence interval, 1.10-1.80), had lower BP at baseline, were less likely to have been treated previously (or for less time), and had a less stringent BP target. An initial period of monotherapy achieved BP control in a high proportion of hypertensive individuals with key groups (including women and de novo cases) more likely to show an early BP response.

Glucagon-Like Peptide-1 Secretory Function as an Independent Determinant of Blood Pressure: Analysis in the Tanno-Sobetsu Study

AimsRoles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation.Methods and ResultsWe recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUCGLP-1), an index of GLP-1 secretory function. Multiple linear regression analysis indicated that AUCGLP-1 was an independent negative predictor of systolic BP (SBP), while AUCGLP-1 was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUCGLP-1 to divide the study subjects into high and low GLP-1 response groups, AUCGLP-1 was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group.ConclusionsThe results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.

Prevalence and determinants of controlled hypertension in a German population cohort

BackgroundData of the German population-based cohort SHIP (Study of Health in Pomerania) were analysed to examine treatment rates, antihypertensive substances prescribed, and the proportion of hypertensive study participants reaching target values for blood pressure as well as determinants.MethodsThe study population was defined using baseline data of the cohort (collected between 1997 and 2001). Participants with blood pressure values ≥140/90 mmHg and/or antihypertensive medication with known hypertension and participants with risk-comorbidity (diabetes, stroke, angina pectoris, and/or myocardial infarction) and blood pressure values ≥130/80 mmHg were included. The analysis of treatment and target values was based on the 5-year follow-up of the cohort (collected between 2002 and 2006). Logistic regression was used to identify determinants for a normotensive blood pressure.Results3278 SHIP-participants with hypertensive blood pressure values were included (mean age: 55.5 years; SD 13.6, range 21–80 years). The raw hypertension prevalence was 50.9% (N = 1761). 58.7% (N = 1074) of all hypertensive patients reported some form of antihypertensive treatment. Thereof 65.1% (N = 728) received combination therapy. Of the patients without risk-comorbidity, 42.1% (N = 489) reached their target blood pressure values at the time of the 5-year follow-up of the cohort. Of the patients with any risk-comorbidity this proportion was only 21.7% (N = 131). Significant determinants for reaching the target values were being female and having antihypertensive combination therapy. Increasing age, having risk-comorbidities, and obesity were negatively associated with reaching the target values.ConclusionsBoth the proportion of participants receiving therapy and the number of participants reaching their target blood pressure values are very low. Combination therapy is associated with better blood pressure control as compared to mono therapy. However, even in the subgroup of hypertensive patients under combination therapy only 36% (both patients with and without comorbidity) reach target values.

L-Homoarginine and L-arginine are antagonistically related to blood pressure in an elderly population

Production of nitric oxide by the vascular endothelium is crucial for the maintenance of vascular tone, an important determinant of blood pressure. L-Arginine and its homolog L-homoarginine are competitive substrates of nitric oxide synthase (NOS), whereas asymmetric dimethylarginine (ADMA) is a NOS inhibitor. We evaluated the relationships between physiological levels of these amino acids and blood pressure. The relationship between blood pressure and plasma levels of L-arginine, L-homoarginine, and ADMA was studied in participants of the Hoorn study, a population-based cohort study of elderly participants (n = 746, aged 50-87, 49.5% men). In linear regression models adjusted for age, sex, L-arginine, and ADMA, a positive association was observed between L-homoarginine and SBP [3.90 mmHg per 1-SD increment of L-homoarginine (95% confidence interval, CI 2.28-5.52)] and DBP [1.83 (0.95-2.72)]. In these models, L-arginine was not significantly associated with SBP [-0.68 mmHg per 1-SD increment of L-arginine (95% CI -2.23 to 0.88)], but a significant inverse association with DBP was observed [-1.17 (-2.02 to -0.32)]. These associations were slightly attenuated after further adjustment for glucose or BMI, but not after adjustment for other cardiovascular risk factors (lipids, smoking, inflammation markers, microalbuminuria, prior cardiovascular disease, and antihypertensive medication). ADMA was not significantly associated with either SBP or DBP. In elderly participants, plasma levels of L-homoarginine and L-arginine are independently associated with clinically relevant differences in blood pressure in an antagonistic fashion.

Protein intake in type 1 diabetes

Protein intake in type 1 diabetes

Arterial stiffness to predict hypertensive response to antiangiogenic drugs.

e13589 Background: Targeting angiogenesis with anti-VEGF receptors is a new approach for cancer treatment. The most common side effect is arterial hypertension. We hypothesize that pre-existing large artery remodeling with increased arterial stiffness is a determinant of blood pressure (BP) increase under antiangiogenic (AAD) and that AAD may alter mechanical properties of large arteries independently of BP increase. Methods: 49 patients (mean age=57[15] years, mean bSBP=128[22] mmHg and mean DBP=75[11] mmHg; treated for a cancer with an indication to start AAD (Sorafenib, Sunitinib or Bevacizumab) were included in this longitudinal study. Arterial evaluation was assessed at baseline (BL) before the introduction of AAD and every two weeks for 2 months (V1 to V4) with aortic stiffness (PWV) and central BP measurements by aplanation tonometry (SphygmoCor), carotid distensibility with high resolution echotracking system (ArtLab). Results: 43% of the patients developed hypertension between BL and V1. Using linear mixed model analysis with random effects, PWV significantly increased between BL and V1 (BL-V1, adjusted slope 0.89 m/s, F value=6.8, p=0.04) after adjustment to age and mean BP, carotid distensibility decreased significantly during follow-up (BL-V1, adjusted slope= -4.4, p=0.04; BL-V2, adjusted slope= -5.23, p=0.001) after adjustment to age and mean BP. The determinants of BP increase were studied between BL and V1 since anti-hypertensive drugs were introduced after V1. Using multivariate analysis, BL PWV was an independent determinant of the delta brachial SBP (β= -1.36 [-2.61; 0.11], p=0.034) with age (β=0.25 [0.04; 0.47], p=0.02). Conclusions: AAD induce functional alterations of large arteries, increasing arterial stiffness, independently of BP increase. In addition, pre-AAD administration arterial properties influence the hypertensive response to AAD.

Exploratory analysis of angiotensin converting enzyme (ACE) and aldosterone (Ald) serum levels as prognostic and predictive biomarkers on the NCIC CTG BR24 trial.

8048 Background: Benefit from angiogenesis inhibitors (AI) has been linked to high blood pressure. One of the main determinants of blood pressure is the renin-angiotensin axis. We undertook an exploratory, retrospective analysis of ACE and Ald serum levels on specimens banked during the conduct of the BR24 study. The aim was to evaluate these markers for their prognostic significance and their predictive value regarding Cediranib (Ced) treatment. Methods: The NCIC CTG BR24 study randomized advanced non-small cell lung cancer patients (pts) to carboplatin and paclitaxel (CP) +/- Ced. ACE and Ald serum levels were retrospectively tested on baseline samples using commercial ELISA kits. A graphic method, differentiating treatment effect by the range of marker, was used to determine cutoff points (JCO 2010, 28: 5247). Exploratory analyses were performed to correlate biomarkers levels with pts characteristics and overall survival (OS). Association between categorical variables was assessed by Chi-square test or Fisher’s exact test; time to event correlation with biomarkers was tested using a Cox regression model. Potential confounding factors including medications were integrated into the statistical model. Results: Biomarker data was available in 226 of 296 randomized pts. The tested pts vs. all the randomized pts were more likely to have a lower performance status (PS, p=0.03), a normal LDH (p=0.05) and to be ever-smokers (p=0.015). The determined cutoffs were ACE: 115ng/ml and Ald: 250 pg/ml. High ACE was associated with a better PS (p=0.03). High ACE levels were prognostic for longer OS (adjusted HR 0.52 [95%C.I. 0.29-0.92], p=0.025). High ACE pts had no OS benefit (HR 1.27 [95% C.I. 0.78–2.08], p=0.34), while low ACE predicted OS benefit from the addition of Ced to CP (HR 0.64 [95%CI 0.42-0.97], p=0.03). Interaction p value=0.03; this remained significant after adjustment in multivariate analyses. Ald levels were neither prognostic nor predictive. Conclusions: This exploratory analysis suggests high ACE serum levels maybe prognostic for better OS, while low ACE may predict benefit from Ced when added to CP.

MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension

Hypertension is a common hereditary syndrome with unclear pathogenesis. Chromogranin A (Chga), which catalyzes formation and cargo storage of regulated secretory granules in neuroendocrine cells, contributes to blood pressure homeostasis centrally and peripherally. Elevated Chga occurs in spontaneously hypertensive rat (SHR) adrenal glands and plasma, but central expression is unexplored. In this report, we measured SHR and Wistar-Kyoto rat (control) Chga expression in central and peripheral nervous systems, and found Chga protein to be decreased in the SHR brainstem, yet increased in the adrenal and the plasma. By re-sequencing, we systematically identified five promoter, two coding and one 3'-untranslated region (3'-UTR) polymorphism at the SHR (versus WKY or BN) Chga locus. Using HXB/BXH recombinant inbred (RI) strain linkage and correlations, we demonstrated genetic determination of Chga expression in SHR, including a cis-quantitative trait loci (QTLs) (i.e. at the Chga locus), and such expression influenced biochemical determinants of blood pressure, including a cascade of catecholamine biosynthetic enzymes, catecholamines themselves and steroids. Luciferase reporter assays demonstrated that the 3'-UTR polymorphism (which disrupts a microRNA miR-22 motif) and promoter polymorphisms altered gene expression consistent with the decline in SHR central Chga expression. Coding region polymorphisms did not account for changes in Chga expression or function. Thus, we hypothesized that the 3'-UTR and promoter mutations lead to dysregulation (diminution) of Chga in brainstem cardiovascular control nuclei, ultimately contributing to the pathogenesis of hypertension in SHR. Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (∼18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension.

Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population

BackgroundThe aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.MethodsThe study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7.ResultsIn men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008).ConclusionIn conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.

Low calcium intake is associated with increased blood pressure among Filipino women

The role of dietary calcium (Ca) as a determinant of blood pressure (BP) has not been firmly established, especially in developing countries like the Philippines where Ca intake is low and hypertension (Htn) prevalence is high. We examined how Ca intake relates to BP among Filipino women using data from 1,997 women (ages 35–68y) in the 2005 Cebu Longitudinal Health and Nutrition Survey. Dietary Ca intake was measured using two 24‐hr recalls (mean: 309 mg/d). Major dietary sources of Ca were fish (37%), creamers/milk/milk products (23%), and vegetables (11%). About 27% of women had Htn (BP&gt;;=140/90 mmHg). Regression analyses adjusted for age, smoking, energy intake, and other confounders showed that low Ca intake (lowest quartile) is associated with higher BP and odds of having Htn. Women with low Ca intake had 3.8 mmHg (95% CI: 1.6–6.1) higher systolic BP and 46% higher odds of having Htn [OR 1.46 (1.11–1.92)]. For diastolic BP, the effect of low Ca intake increased as WC increased (p for interaction &lt;0.1). For example, for women with 75cm WC, the effect of low Ca intake was 1.6 (.1–3.1) while for those with 95cm WC, the effect is 3.8 (1.5–6.0) mmHg. Although Ca intake has been associated with fat metabolism and deposition, the biological mechanism of this interaction is yet to be elucidated. Results suggest that increasing Ca intake may help decrease BP in this population and preventing high WC may enhance this benefit. R01TW008288