Determinants Of Blood Pressure Research Articles

Dialysate sodium concentration: The forgotten salt shaker.

The concentration of sodium in dialysis fluid, a major determinant of extracellular fluid volume and blood pressure, plays a major role in the sodium balance in end-stage renal disease patients. A low dialysate sodium concentration (DNa) reduces interdialytic weight gain (IDWG) and blood pressure and might help ameliorate endothelial dysfunction and inflammation. However, low DNa can also increase the incidence of hypotensive episodes and muscle cramps. Sodium profiling, as typically prescribed in which the DNa is ramped up from above 140mEq/L to nonphysiological levels, might reduce hypotension in patients with hemodynamic instability but at the cost of the consequences of hypernatremia. Serum sodium concentrations of individual patients fall within a narrow range around a "sodium setpoint." The sodium gradient, the difference between the sodium set point and the DNa, is associated more robustly with clinical outcomes than DNa itself. Sodium concentration presents several issues: the influence of the net negative charge of plasma proteins on sodium flux across the dialysis membrane (Donnan equilibrium); and the clinically important problems in measuring sodium levels. This article presents a review of the clinical effects of DNa and of basic aspects of sodium balance in hemodialysis patients.

A2567 Direct renin inhibition using aliskiren prevents endothelial dysfunction in renal arteries of spontaneously hypertensive rats

Objectives: Renovascular tone is an important determinant of systemic blood pressure. Hypertension is a significant clinical problem leading to cardiovascular comorbidities. The direct renin inhibitor aliskiren, is a novel anti-hypertensive agent with similar efficacy to angiotensin II receptor blockers. In this study, we tested the hypothesis that i) increased blood pressure in spontaneously hypertensive rats (SHRs) is associated with endothelial dysfunction in renal arteries, and ii) aliskiren exerts protective effects by reducing local oxidative stress. Methods: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were randomly divided into aliskiren treatment group (10 mg/kg/day) or vehicle control group for eight weeks (n = 7). Bi-weekly monitoring of blood pressure was achieved using a tail-cuff method. Protein levels were determined by Western blotting. Results: Endothelium-dependent dilatations to acetylcholine were significantly reduced in intralobal renal arteries from SHR as compared with those from age-matched WKY rats (Figure left). Aliskiren treatment significantly improved acetylcholine-induced dilatation in SHR renal arteries while vehicle treatment had no effect. By contrast, aliskiren treatment did not modify endothelium-dependent dilatations in WKY rat renal arteries. Bone morphogenetic protein 4, an upstream activator of vascular inflammation, and cyclooxygenase (COX)-2 expression, were increased in SHRs. These increases were prevented by aliskiren. COX-1 levels were similar in both WKY rats and SHRs in the presence or absence of aliskiren. Conclusion: The direct renin inhibitor aliksiren exerts anti-hypertensive effects through suppression of the BMP4-COX2 axis.

Antihypertensive Treatment Patterns and Blood Pressure Control in Older Adults: Results from the Berlin Aging Study II.

Hypertension is highly prevalent in older adults and represents a major public health issue since recognition, awareness, treatment and control are insufficient. Analyses of prescription patterns in conjunction with clinical parameters can provide novel insights into the current practice of hypertension management and help to identify barriers to sufficient hypertension control. A cross-sectional analysis was conducted. Prevalence of hypertension, patterns of antihypertensive therapy, and determinants of blood pressure (BP) control were examined in the Berlin Aging Study II cohort, including 1654 community-dwelling older adults (60-85years of age). Of the participants, 75.9% had hypertension; 40.6% of these were not prescribed BP medications. Lack of hypertension awareness, younger age, absence of comorbidities, not being on a statin, and not having visited a physician in the past 3months were associated with lack of treatment. Forty-two percent of treated hypertensive individuals received monotherapy and 58.0% received combination therapy. Renin-angiotensin-aldosterone system (RAAS) inhibitors, and β-blockers were most commonly prescribed, while calcium channel blockers were least prescribed. Only 38.5% of treated hypertensive individuals had their BP controlled to < 140/90mmHg. Number and choice of BP medications were not predictive of BP control; neither were age, glycated hemoglobin (HbA1c), kidney function, or number of healthcare visits. However, female sex, lower low-density lipoprotein cholesterol (LDL-C) levels and current smoking, amongst others, were positively associated with BP control. There was evidence of significant effect modification by statins in the association of LDL-C and BP. The majority of older adults do not reach BP goals. Antihypertensive prescription patterns do not conform to current guidelines. Using more BP medications was not associated with higher odds of BP control. Lowering LDL-C might be favorable in terms of BP control.

Fine mapping of epistatic genetic determinants of blood pressure on rat chromosome 5.

Previously, using linkage analysis and substitution mapping, two closely-linked interactive blood pressure quantitative trait loci (QTLs), BP QTL1 and BP QTL2, were located within a 13.96 Mb region from 117894038 to 131853815 bp (RGSC 3.4 version) on rat chromosome 5 (RNO5). This was done by using a series of congenic strains consisting of genomic segments of the Dahl salt-sensitive (S) rat substituted with that of the normotensive Lewis (LEW) rat. The interactive nature of the two loci was further confirmed by the construction and characterization of a panel of S.LEW bicongenic strains and corresponding S.LEW monocongenic strains, which provided definitive evidence of epistasis (genetic interaction) between BP QTL1 (7.77 Mb) and BP QTL2 (4.18 Mb). The purpose of this work was to further map these interacting QTLs. A new panel of seven new S.LEW bicongenic strains was constructed and characterized for BP. The data obtained from these new strains further resolved BP QTL1 from 7.77 to 2.93 Mb. Further, BP QTL2 was traceable as not being a single QTL, but a composite of at least three QTLs, LEW alleles at two of which located within 2.26 Mb and 175 kb lowered BP but the third one located within 1.31 Mb increased BP. Lack of coding variation within any of the regions further mapped within the previous QTL2 suggests noncoding variation as likely responsible for the observed epistasis.

Magnitude and determinants of uncontrolled blood pressure among hypertensive patients in Ethiopia: hospital-based observational study.

Background:Hypertension is an important public health problem worldwide. There is lack of data on uncontrolled blood pressure in developing countries.Objectives:To determine the magnitude and predicting factors of uncontrolled blood pressure in hypertensive patients attending Gondar university hospital, Ethiopia.Methods:A hospital-based cross-sectional survey was conducted from July 2015 to March 2016. All hypertensive patients were followed and the blood pressure levels were measured. Binary logistic regression analysis was done to determine the predictors of uncontrolled blood pressure. A p-value of <0.05 was set at priori with 95% confidence interval to test the level of significance.Results:Of the total 578 hypertension patients, 543 (93.9%) fulfilled the study criteria and were included in the final analysis. The mean age of the participants was 55.96±14.6 years. Nearly two-third (58.2%) of the participants were females. More than one-tenth (11.4%) of the respondents had uncontrolled blood pressure. High salt intake carried six times more risk of uncontrolled blood pressure. Elderly individuals had lower risk as compared to young age group. However, comorbidities were not related with uncontrolled blood pressure.Conclusions:Blood pressure control was relatively high in the hospital studied. High salt intake was strongly linked with uncontrolled blood pressure. Individuals with high salt intake should be followed for their medication experience and disease knowledge.

Renin Activity and Aldosterone Assay Among Nigerians with Hypertension and Normotension: An Insight into Normative Values and Clinical Correlates.

Plasma renin activity (PRA) and aldosterone tend to differ between Blacks and Caucasians and studies are very scarce among Africans. We therefore aimed to determine the normative value of plasma renin activity and serum aldosterone among school teachers in Nigeria with normal blood pressure compared with their hypertensive counterparts and relevant clinical/ demographic associations. Plasma renin activity and serum aldosterone were measured using the kits provided by Diagnostic Biochem, Canada among randomly selected school teachers recruited as part of a study to assess their total cardiovascular risks. Mean serum values were compared between normotensive and hypertensive participants and were correlated with clinical and demographic parameters. Statistical analysis was done using SPSS 17.0, Chicago, Ill, USA. P <0.05 was taken as statistically significant. The mean PRA level of all study participants was 0.80 ± 0.85 ng/mL.h (mean ± SD) while the mean serum level of aldosterone was 93.9 ± 60.9 pg/ml. The mean aldosterone: renin ratio was 446.5 ± 958.2. The frequency of occurrence of hypertension was 29%. Only plasma renin activity was significantly correlated with systolic and diastolic blood pressure, age and the rate pressure product (a measure of cardiovascular risk). The finding of a higher mean PRA among hypertensive subjects is definitely related to the antihypertensive medications being taken including beta blockers and angiotensin converting enzyme inhibitors among others. The prevalence of high aldosterone/ renin ratio which could reflect the proportion of primary aldosteronism was 10.8%. Nigerians have a low renin activity compared to their Caucasian counterpart. PRA may be an important determinant of blood pressure among Nigerians. Appropriate drugs that target phenotypic status of PRA and aldosterone may be useful in the management of hypertension and the choice of pharmacotherapy among Nigerians.

2100 TL1 team approach to social and genetic determinants of nocturnal blood pressure

OBJECTIVES/SPECIFIC AIMS: The TL1 Team approach aims to train translational investigators capable of tackling complex and multifaceted diseases, such as hypertension, by beginning multidisciplinary, team-based training early in their graduate programs. METHODS/STUDY POPULATION: Leanne Dumeny is a graduate student in Genetics and Genomics studying how pharmacogenomics can be applied to improve clinical care and cardiovascular outcomes. Chu Hsiao is a graduate student in Anthropology studying how sociocultural experiences become biologically embodied. Both are in the Ph.D. phase of M.D.-Ph.D. training. Joining the seemingly disparate but complementary fields of anthropology and genomics facilitates understanding of the intersection between socially driven experiences and genetics on nocturnal blood pressure. Understanding both social determinants, such as racial discrimination, and biological determinants, such as genetics, is important because an interplay of gene-environment interactions influences many complex diseases. Rarely can 1 individual, or 1 discipline, tackle all the perspectives necessary to answer these types of complex questions. The TL1 Team curriculum teaches students to navigate the spectrum of translational research as a team, reflect on disciplinary limitations, and embrace collaborative research. RESULTS/ANTICIPATED RESULTS: This team project will investigate the relationship between racial discrimination and genetics using a large epidemiological cohort of African Americans in Mississippi. The data request application is currently under review. By the project’s end, the team anticipates their investigation will reveal novel associations between racial discrimination, genetic polymorphisms, and nocturnal blood pressure measurements. The investigators will have gained experience obtaining and analyzing large external data sets, working in diverse team settings, collaborating across state-lines, and publishing articles. Through this team approach, the students will also understand the barriers to working in multidisciplinary groups, and develop a foundation for approaching future collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: By joining anthropology with genomics, it becomes possible to understand the intersection between socially driven experiences of racial discrimination and genetics on nocturnal blood pressure. The successful training of this first cohort of team-applicants to the TL1 funding mechanism can impact how graduate education will be structured and could reframe graduate education to emphasize a team-based approach.

Determinants of Cardiometabolic Risk Factors in the First Decade of Life: A Longitudinal Study Starting at Birth.

The present prospective study assessed the association of birth weight (BW) and growth pattern on cardiometabolic risk factors in a cohort followed from birth to 10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the inclusion criteria and had all their data recorded at birth and at 5 years were enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric measurements, office and 24-hour blood pressure, and metabolic parameters were obtained. At 5 years, both BW and current weight were determinants of blood pressure and metabolic parameters; however, as the subjects got older, the impact of body size increased. Higher BW and maternal obesity increased the risk of becoming obese at 5 years while this was reduced if breastfeeding. Maternal obesity was the only factor associated with becoming obese at 10 years. Twenty-two children at 10 years had insulin values ≥15 U/L, some of whom were persistent from 5 years while in others it increased afterward. Subjects with insulin values ≥15 U/L showed significant higher values of office systolic blood pressure, triglycerides, and uric acid and lower values of high-density lipoprotein than did those with normal insulin values. Highest weight gain from 5 to 10 years and lowest BW were the main determinants of high insulin levels. In conclusion, although BW was a proxy of the events during fetal life and projected its influence later, the influence of gaining weight was a key determinant in the risk to develop obesity and metabolic abnormalities.

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis.

Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Mean office and 24-h BP fell by 15.4/6.6 and 5.5/3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P ≤ 0.01) and 0.86/0.42 mmHg (P ≤ 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P = 0.0006), ARV (P = 0.01), and VIM (P = 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN.

Vascular smooth muscle contraction in hypertension.

Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex-interacting systems such as the renin-angiotensin-aldosterone system, sympathetic nervous system, immune activation, and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin–myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase, protein Kinase C and mitogen-activated protein kinase signalling, reactive oxygen species, and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and non-coding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signalling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here, we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension.

Prevalence, awareness, treatment, and control of hypertension among rural and urban dwellers of the Far North Region of Cameroon.

To assess the prevalence and determinants of high blood pressure (BP) and awareness, treatment, and control rates in the Far North Region of Cameroon, where these variables have not been explored so far. In total, 889 individuals (41.5% women) aged at least 18 years participated in a cross-sectional survey conducted in Maroua (urban area) and Tokombere (rural area) from November 2014 to May 2015, using a multistage cluster sampling frame. Anthropometric variables, BP, and fasting capillary glucose were assessed in all participants. Hypertension was defined as BP at least 140/90 mmHg or antihypertensive therapy and BP control as BP less than 140/90 mmHg. Prevalence estimates were age standardized to the Cameroon population. The prevalence of hypertension was 37.8% (rural: 34%; urban: 41.2%; men: 38.8%; women: 37.9%). Hypertension was associated with urban environment (odds ratio: 1.42; 95%; confidence interval 1.06-1.89), age at least 70 years (4.06; 2.02-6.14), male sex (4.06; 2.02-6.14), abdominal obesity (2.36; 1.54-3.61), and high blood sugar (2.01; 1.31-3.08). Among individuals with hypertension, 18.6% (rural: 17.9%; urban: 19.5%) were aware of having high BP. Among those aware, 29.3% (rural: 17.3%; urban: 36.3%) reported receiving treatment, of whom 16.3% (rural: 22.6%; urban: 4.2%) had BP controlled. Awareness, treatment, and BP control levels were higher in women than men. Hypertension is highly prevalent in Far North Cameroon and awareness, treatment, and control rates are low. Efforts to improve detection, treatment, and control of hypertension in Cameroon are needed.

Determinants of High Blood Pressure and Quality of Management in Three Regions of Benin

Objective: The aim of this work was to determine the prevalence, associated factors and quality of high blood pressure (HBP) management in three regions of Benin in 2015. Methodology: This was a cross-sectional study, with two components. The first component included adults aged from 18 to 69 years, selected using a three-stage random sampling within the households. Data were collected thanks to the French version of the WHO STEPS instrument. Anthropometric data, including blood pressure, capillary fasting glucose and total cholesterol were measured according to standard procedures. The second component included Public Health Centers (PHC) selected by a random stratified multi-stage sampling. Data were collected on the structures and the processes of HBP management using the standardized tool for assessing the capacities of management of non-communicable diseases in peripheral health centers provided by the World Health Organization. Results: A total of 4816 participants were included in the first component. The mean age was 35.8 ± 12.7 years. The weighted prevalence of HBP was 27.9% (95% Confidence Interval (CI) [25.6 - 30.2]). It was higher in the 60 - 69 years compared to the lower age groups (Adjusted Odd-ratio (ORa) = 5; 95% CI [3.9 - 6.5)]). HBP was positively associated with urban residence (ORa = 1.26; 95% CI [1.24 - 1.28]), obesity (ORa = 1.46; 95% CI [1.43 - 1.50]), hyperglycemia (ORa = 1.13; 95% CI [1.10 - 1.15)]) and hypercholesterolemia (ORa = 1.64; 95% CI [1.59 - 1.70)]). A total of 27 PHC were included in the second component. Taking blood pressure and other anthropometric measurements was not routine in PHC. Several essential medicines were not available in the PHC. A low level of community involvement in the management of HBP was noted. Conclusion: This study confirms the high prevalence of HBP and shows inadequacies in its management in the targeted PHC. More appropriate prevention and control measures for HBP should be implemented.

Abstract P406: Sleep Health as an Important Determinant of Elevated Blood Pressure: A Population Based Study

Introduction: One mechanism elucidating the association between lack of sleep and elevated blood pressure includes over-activity of the sympathetic neurotransmitters which in turn raises the levels of adrenaline in the blood. Persistently raised adrenaline levels directly elevate heart rate, systolic blood pressure (SBP) and the diastolic blood pressure (DBP). We aimed at evaluating the association of sleep duration with blood pressure among the adult population in the United States after adjusting for the confounding effects of age, gender, BMI, income poverty ratio (IPR), and race. Methods: Our study was based on a population-based cross-sectional study design, comprising of a nationally representative sample of US adults derived from the National Health and Nutrition Examination Survey (NHANES) data cycle 2013-2014 (N=6266). Study population comprised of adults aged 16 years or above who had participated in both interview and medical examination components of the NHANES survey. Measurements on SBP, DBP, and BMI were obtained at the designated clinic by trained personnel, while age, gender, IPR, and race were recorded during the interview by self-report. Results: Of 6266 participants, aged between 16 to 80 years with a mean age of 45( + 9.2) years, a total of 2302 (34%) reported short sleep duration (&lt;6 hours per day) (Table 1). The outcome variables, SBP and DBP, were significantly different across short and normal sleep duration (p-value &lt;0.05) (Table 1). SBP and DBP were also significantly different among males and females (p-value &lt;0.0001) (Table 2). Both unadjusted and adjusted analyses showed a statistically significant association between sleep duration and DBP [b adjusted = -0.42, sd=0.16, 95%CI= -0.74, 0.08, p-value= 0.02]. When stratified by gender, the association was only significant for males [b adjusted = -0.50, sd=0.20, 95%CI= -0.90, -0.09, p-value = 0.02] (Table 3). Conclusion: Sleep health is a significant determinant of elevated blood pressure in our data even when BMI was held constant. Prospective studies are needed to augment the understanding of this association to seek early public health and behavioral interventions for the prevention of premature cardiovascular morbidity.

Abstract 122: 20-HETE Antagonists Normalize Large Artery Stiffness and Systolic Blood Pressure in Metabolic Syndrome

Large artery stiffness is a causal factor in development of systolic hypertension. 20-hydroxyeicosatetraeonic acid (20-HETE), a cytochrome CYP450-derived arachidonic acid metabolite, is known to be elevated in resistance arteries in hypertensive animal models and in obesity in humans, but the role of 20-HETE in regulation of large artery remodeling in metabolic syndrome has not been investigated. Unlike normal (Sprague-Dawley (SD)) rats, large arteries (aorta, carotid and &gt;100μM mesenteric arteries) of metabolic syndrome rats (JCR:LA-cp, JCR) express CYP4A and 4F, CYP450s which make 20-HETE in rats (2-fold increase vs. SD). Consequently, 20-HETE production is elevated in large arteries of JCR rats. We hypothesized that this elevated 20-HETE increases matrix metalloproteinase 12 (MMP12, an elastase) activation leading to increased degradation of elastin, increased large artery stiffness and increased systolic blood pressure. A 3-4 fold increase in 20-HETE production in large arteries of JCR vs. SD rats correlated with increased elastin degradation (3-6 fold) and increased arterial stiffness (~75%). 20-HETE antagonists blocked elastin degradation in JCR rats concomitant with blocking MMP12 activation. Importantly, 20-HETE antagonists and MMP12 inhibition (pharmacological and MMP12-shRNA-Lnv) significantly decreased (~60% vs. untreated JCR) large artery stiffness in JCR rats. 20-HETE antagonists also decreased systolic (182±3 mmHg JCR, 145±3 mmHg JCR+20-HETE antagonists) but not diastolic (125±4 mmHg JCR, 124±4 mmHg JCR+20-HETE antagonists) blood pressure in JCR rats. Whereas diastolic pressure was fully angiotensin II (Ang II)-dependent, systolic pressure was only partially Ang II-dependent, and large artery stiffness in JCR rats was Ang II-independent. These results suggest that 20-HETE-dependent regulation of systolic blood pressure may be a unique feature of metabolic syndrome related to high CYP4A/4F expression and resultant high 20-HETE production in large conduit arterial stiffness, which is a primary determinant of systolic blood pressure. These findings may have implications for management of systolic hypertension in patients with metabolic syndrome.

P1337Identification of 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese individuals by exome-wide association studies

P1337Identification of 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese individuals by exome-wide association studies

Prevalence and Determinants of Hypertension and High Normal Blood Pressure Among Young Adult Saudi Females: Insights Into Preventive Strategies.

This study aimed to determine the prevalence of hypertension and high normal blood pressure and their risk factors among young adult Saudi females. A prospective cross-sectional study was conducted in a women's university. A questionnaire evaluated the subjects' demographic data and risk factors for hypertension and the blood pressure, height, and weight were recorded. In all, 4.1% of the participants were hypertensive and 6.2% had high normal blood pressure. Significant predictors of hypertension/high normal blood pressure were increased body mass index, increased heart rate, walking fewer days per week, and dietary factors. Attention to these risk factors through educational programs is warranted to reduce disease burden in the community.

Expressions of irisin and urotensin II and their relationships with blood pressure in patients with preeclampsia

ABSTRACTThe aims of this study are to observe irisin and urotensin II (UII) levels in serum and placenta in normal pregnant and preeclamptic women and investigate the relationship between expressions irisin and UII, and their association with blood pressure. A total of 67 pregnant subjects were recruited, including 31 healthy and 36 preeclamptic pregnant women. Serum irisin and UII concentrations were measured. Expressions of fibronectin type III domain-containing protein 5 (FNDC5) (irisin precursor) and UII in placenta specimens were performed. There was no significant difference of serum irisin levels between severe preeclamptic (SPE)) patients, mild preeclamptic (MPE) patients and normal controls, while serum UII was significantly higher in preeclamptic women than normal pregnancy. There was no relationship between serum UII and irisin levels. In patients with preeclampsia, serum irisin was negatively associated with systolic and diastolic blood pressure(r = −0.350, P = 0.004, r = −0.307, P = 0.011), while serum UII was positively associated with systolic blood pressure (r = 0.291, P = 0.031). Serum irisin, UII, urinary protein level, BMI and serum creatinine were the independent determinants of blood pressure in preeclampsia by multiple regression analysis. Protein expression of FNDC5 and UII was upregulated in placenta of patients with SPE and positively correlated with systolic blood pressure and urinary protein level. We firstly verify that serum irisin and placental irisin precursor expressions have differently correlated with blood pressure. Expressions of irisin and urotensin II have relationships with blood pressure in patients with preeclampsia

Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure in Japanese by exome-wide association studies.

We performed exome-wide association studies to identify genetic variants that influence systolic or diastolic blood pressure or confer susceptibility to hypertension in Japanese. The exome-wide association studies were performed with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays and with 14,678 subjects, including 8215 individuals with hypertension and 6463 controls. The relation of genotypes of 41,843 single nucleotide polymorphisms to systolic or diastolic blood pressure was examined by linear regression analysis. After Bonferroni's correction, 44 and eight polymorphisms were significantly (P < 1.19 × 10−6) associated with systolic or diastolic blood pressure, respectively, with six polymorphisms (rs12229654, rs671, rs11066015, rs2074356, rs3782886, rs11066280) being associated with both systolic and diastolic blood pressure. Examination of the relation of allele frequencies to hypertension with Fisher's exact test revealed that 100 of the 41,843 single nucleotide polymorphisms were significantly (P < 1.19 × 10−6) associated with hypertension. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that five polymorphisms (rs150854849, rs202069030, rs139012426, rs12229654, rs76974938) were significantly (P < 1.25 × 10−4) associated with hypertension. The polymorphism rs12229654 was thus associated with both systolic and diastolic blood pressure and with hypertension. Six polymorphisms (rs12229654 at 12q24.1, rs671 of ALDH2, rs11066015 of ACAD10, rs2074356 and rs11066280 of HECTD4, and rs3782886 of BRAP) were found to be associated with both systolic and diastolic blood pressure, with those at 12q24.1 or in ACAD10 or BRAP being novel determinants of blood pressure in Japanese.

Fenofibrate Attenuates Hypertension in Goldblatt Hypertensive Rats: Role of 20-Hydroxyeicosatetraenoic Acid in the Nonclipped Kidney

BackgroundThere is vast evidence that the renin-angiotensin system is not the sole determinant of blood pressure (BP) elevation in human renovascular hypertension or the relevant experimental models. This study tested the hypothesis that kidney deficiency of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway of arachidonic acid metabolism, is important in the pathophysiology of the maintenance phase of 2-kidney, 1-clip (2K1C) Goldblatt hypertension. Materials and MethodsIn 2K1C Goldblatt rats with established hypertension, angiotensin II, angiotensin 1-7, 20-HETE concentrations and gene expression of CYP4A1 enzyme (responsible for 20-HETE formation) of the nonclipped kidney were determined. We examined if 14 days׳ administration of fenofibrate, a lipid-lowering drug, would increase CYP4A1 gene expression and renal 20-HETE formation, and if increased 20-HETE concentrations in the nonclipped kidney would decrease BP (telemetric measurements). ResultsCYP4A1 gene expression, 20-HETE and angiotensin 1-7 concentrations were lower and angiotensin II levels were higher in the nonclipped kidney of 2K1C rats than in sham-operated rats. Fenofibrate increased CYP4A1 gene expression and 20-HETE concentration in the nonclipped kidney and significantly decreased BP in 2K1C rats but did not restore it to normotensive range. The treatment did not change BP in sham-operated rats. ConclusionsOur results suggest that alterations in the RAS and CYP-dependent ω-hydroxylase metabolites of arachidonic acid in the nonclipped kidneys are both important in the pathophysiology of the maintenance phase of 2K1C Goldblatt hypertension. Therefore, fenofibrate treatment effectively attenuated hypertension, probably via stimulation of 20-HETE formation in the nonclipped kidney.

Greater adherence to the dietary approaches to stop hypertension (DASH) dietary pattern is associated with lower blood pressure in healthy Iranian primary school children.

The dietary determinants of children blood pressure (BP) are poorly understood. We examined the association between adherence to the dietary approaches to stop hypertension (DASH) dietary pattern and BP in healthy Iranian primary school children. This cross-sectional study was conducted among a representative sample (n = 407) of healthy Shirazi students aged 6-12 years. Subjects' systolic and diastolic BP were measured by a validated oscillometric BP monitor. Usual dietary intakes over the past 12 months were assessed using a valid and reproducible 168-item semi-quantitative food frequency questionnaire via face-to-face interviews. A DASH score was calculated for each subject based on his/her energy-adjusted intakes of 8 major dietary components emphasized or minimized in the DASH dietary pattern. The higher the DASH score of a subject, the more his/her adherence to the DASH dietary pattern. After controlling for several potential confounders in the analysis of covariance models, multivariable-adjusted means of systolic and mean BP of subjects in the highest tertile of DASH score were significantly lower than those in the lowest tertile (for systolic BP: mean difference -6.2mmHg, P = 0.010; and for mean BP: mean difference -5.4mmHg, P = 0.013). Furthermore, a similar but statistically insignificant difference was found in terms of multivariable-adjusted means of diastolic BP (mean difference -3.9mmHg, P = 0.146). The findings suggest that greater adherence to the DASH dietary pattern is associated with lower BP in healthy Iranian primary school children. However, future prospective studies of adequate methodological quality are warranted to confirm these findings.