An elevated systolic blood pressure response at 8 minutes in full contact exercise may identify hypertensive subjects

The aim of this study was to identify hypertension (HT) in karate competitors (KCs) in high intensity exercise. Values were compared with an exercise control group (EC). The 84 subjects were randomly divided into two groups: KC and EC. Resting blood pressure (BP) was measured the day before and immediately precompetition. A further three measurements were taken postexercise for all subjects at 1-, 2-, and 8- minute intervals. At rest, day one, mean BP of KC was 134/84 ± 3/2 mmHg vs. EC, 124/72 ± 1/2 mmHg and on day 2, was 141/79 ± 3/2 mmHg vs. EC, 125/72 ± 1/2 mmHg, respectively. Eight minutes postcompetition, BP of KCs was 140/77 ± 2/1 mmHg vs. EC 135/75 ± 2/1 mmHg. High blood pressure (HBP) was recorded in 60.5% of KCs on day 2, and essential HT that required medical therapy was subsequently diagnosed in 5% of KCs. Five percent of EC also had HBP, but subsequent medical examination reported normal values.

Volatile Blood Pressure Due To Baroreflex and Autonomic Failure

An 85-year-old male was hospitalized because of deterioration of his general condition and infection of the tracheostoma. He had had laryngectomy, bilateral neck dissection and radiation therapy for a laryngeal carcinoma 5 years earlier. Despite a good recovery, he could not get up because of a new onset of postural symptoms (dizziness, lightheadedness, collapse). Late onset of baroreflex failure and autonomic nervous system failure were diagnosed. Volatility of blood pressure (supine hypertension, upright hypotension) was treated with NaCl supplement during the day and a short-acting antihypertensive (clonidine) at night. With this regimen, the patient could walk without support.

Effect of nitric oxide donors on blood pressure and pulse pressure in acute and subacute stroke

High blood pressure (BP), pulse pressure (PP), and rate pressure product (RPP) areeach associated independently with a poor outcome in acute ischemic stroke. Whereas nitric oxide (NO) donors, such as glyceryl trinitrate (GTN), lower blood pressure in acute ischemic stroke, their effect on other hemodynamic measures is not known. We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke. Randomized controlled trials were identified from searches of the Cochrane Library, Pubmed, and Embase. Information on hemodynamic measures, including systolic BP (SBP), diastolic BP (DBP), and heart rate, were assessed, and hemodynamic derivatives of these were calculated: PP (PP SBP DBP), mean arterial pressure (MAP DBP PP/3), mid blood pressure (MBP (SBP DBP)/2), pulse pressure index (PPI PP/MAP), and RPP (RPP SBP HR). The effect of treatment on hemodynamic measures was calculated as the weighted mean difference (WMD) between treated and control groups with adjustment for baseline. Results: Three trials involving 145 patients were identified; 93 patients received the NO donor, GTN, and 52 control. As compared with placebo, GTN significantly reduced SBP (WMD -9.80 mmHg, p< 0.001), DBP (WMD -4.43 mmHg, p<0.001), MAP (WMD -6.41 mmHg, p< 0.001), MBP (WMD -7.33 mmHg,p<0.001), PP (WMD -6.11 mmHg, p<0.001 ) and PPI (WMD -0.03, p=0.04 ). 3 GTN increased HR (WMD +3.87 bpm, p<0.001) and non-significantly lowered RPP (WMD -323 mmHg.bpm, p=0.14). Conclusion: The NO donor GTN reduces BP, PP and other derivatives in acute and subacute stroke whilst increasing heart rate.

Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333)

Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation. Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke patients, although limited data have been published. Subjects were recruited 3-30 days post ischaemic stroke into a phase II randomised (1:1), double blind, placebo-controlled trial. Subjects received dexamphetamine (5mg initially, then 10mg for 10 subsequent doses with 3 or 4 day separations) or placebo in addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl-Meyer, FM), and functional scales (Barthel index, BI and modified Rankin score, mRS). Peripheral blood pressure (BP), central haemodynamics and middle cerebral artery blood flow velocity were assessed before, and 90 minutes after, the first 2 doses. 33 subjects were recruited, age 33-88 (mean 71) years, males 52%, 4-30 (median 15) days post stroke to inclusion. 16 patients were randomised to placebo and 17 amphetamine. Amphetamine did not improve motor function at 90 days; mean (standard deviation) FM 37.6 (27.6) vs. control 35.2 (27.8) (p=0.81). Functional outcome (BI, mRS) did not differ between treatment groups. Peripheral and central systolic BP, and heart rate, were 11.2 mmHg (p=0.03), 9.5 mmHg (p=0.04) and 7 beats/minute (p=0.02) higher respectively with amphetamine, compared with control. A non-significant reduction in myocardial perfusion (Buckberg Index) was seen with amphetamine. Other cardiac and cerebral haemodynamics were unaffected. Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and heart rate without altering cerebral haemodynamics.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Eph kinases and their ligands ephrins act in concert with sex hormones in regulating blood pressure

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN.

A randomised controlled trial comparing weight adjusted dose versus fixed dose prophylactic phenylephrine infusion on maintaining systolic blood pressure during caesarean section under spinal anaesthesia.

Background: Spinal anaesthesia is the standard of care for elective caesarean delivery. It has advantages over general anaesthesia. However the sympathetic blockade induced by spinal anaesthesia results in an 80 percent incidence of hypotension without prophylactic management. Current evidence supports co-loading with intravenous fluids in conjunction with the use of vasopressors as the most effective way to prevent and treat the hypotension. Phenylephrine is the accepted vasopressor of choice in the parturient. A prophylactic phenylephrine infusion combined with a fluid co-load is proven to be an effective and safe method of maintaining maternal hemodynamic stability. While most published studies have assessed the effectiveness of a prophylactic phenylephrine fixed dose infusion, few studies have assessed the effect of a prophylactic phenylephrine weight adjusted dose infusion on maintaining maternal hemodynamic stability following spinal anesthesia for a cesarean delivery. Objective: To compare the incidence of hypotension between women undergoing elective caesarean section under spinal anaesthesia, receiving prophylactic phenylephrine infusion at a fixed dose of 37.5 micrograms per minute versus a weight adjusted dose of 0.5 micrograms per kilogram per minute. Methods: One hundred and eight patients scheduled for non-urgent caesarean section under spinal anaesthesia were randomized into 2 groups; control group and intervention group using a computer generated table of numbers. Control group; Received prophylactic phenylephrine fixed dose infusion at 37.5 micrograms per minute. Intervention group; Received prophylactic phenylephrine weight adjusted dose infusion at 0.5 micrograms per kilogram per minute Results: The two groups had similar baseline characteristics in terms of ; Age, sex, weight and height. There was a 35.2% incidence of hypotension in the fixed dose group and an 18.6% incidence of hypotension in the weight adjusted dose group. This difference was found to be of borderline statistical significance p-value 0.05, and the difference in the incidence rates between the two groups was found to be statistically significant p= 0.03. The difference in the incidence of reactive hypertension and bradycardia between the two groups was not statistically significant: p-value of 0.19 for reactive hypertension and p-value of 0.42 for the incidence of bradycardia. There was also no statistically significant difference in the use of phenylephrine boluses, use of atropine, intravenous fluid used and the number of times the infusion was stopped. Conclusion: Among this population, the incidence of hypotension was significantly less in the weight adjusted dose group than in the fixed dose group. There was no difference in the number of physician interventions required to keep the blood pressure within 20% of baseline, and no difference in the proportion of reactive hypertension or bradycardia between the two groups. Administering prophylactic phenylephrine infusion at a weight adjusted dose of 0.5 micrograms per kilogram per minute results in a lower incidence of hypotension compared to its administration at a fixed dose of 37.5 micrograms per minute.

Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA Collaboration

Background and Purpose—High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods—Analyses included 1722 patients in hyperacute trials (recruitment 8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results—Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions—High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

A Systematic Review of Studies on Blood Pressure in Iranian Pediatric Population: First Report From the Middle East and North Africa

Context:Blood pressure (BP) tracks from childhood to adulthood, and has ethnic variations. Therefore, it is important to assess the situation of pediatric BP in different populations. This study aims to systematically review the studies conducted on BP in Iranian children and adolescents. Evidence Acquisition: We conducted a systematic review on published and national data about pediatric BP in Iran, our search was conducted in Pub Med, Medline, ISI, and Scopus, as well as in national databases including Scientific Information database (SID), IranMedex and Irandoc from 1990 to 2014. Results: We found 1373 records in the primary search including 840 from international and 533 from national databases. After selection and quality assessment phases, data were extracted from 36 papers and four national data sources. Mean systolic BP (SBP) varied from 90.1 ± 14 mmHg (95% CI 89.25, 90.94) to 120.2 ± 12.3 (118.98, 121.41) mmHg, and for diastolic BP (DBP) from 50.7 ± 11.4 (50.01, 51.38) to 79.2 ± 12.3 (77.95, 80.44) mmHg. The frequency of elevated BP had large variation in sub-national studies with rates as low as 0.4% (0.009, 1.98) for high SBP and as high as 24.1% (20.8, 27.67) for high DBP. At national level, three surveys reported slightly raised rates of elevated BP from 2009 to 2012. Conclusions: The findings provide practical information on BP levels in Iranian pediatric population. Although differences exist on the findings of various studies, this review underscores the necessity of tracking BP from childhood, and implementing interventions for primordial prevention of hypertension.

Systolic Blood Pressure and Its Determinants: Study in a Population Attending Pharmacies in a Portuguese Coastal City

Hypertension is a common condition causing cardio and cerebrovascular complications. Portugal has one of the highest mortality rates from stroke and a high prevalence of hypertension. Systolic Blood Pressure (SBP) is an important risk factor for cardiovascular events (myocardial infarction and stroke) and premature mortality, particularly in the elderly population. The present study aims to estimate the prevalence of hypertension in a Portuguese population living in a coastal city and to identify some of its determinants (namely gender, age, the body mass index and physical activity frequency). A total of 91 adults who attended three pharmacies of a coastal city in the center of Portugal, between May and August of 2013 were evaluated. Attendants who reported to have diabetes or taking antihypertensive drugs in the 2 previous weeks were excluded from the study. Sociodemographic factors, BMI, habits of exercise and BP were assessed. Hypertension was defined as blood pressure ≥140/90 mmHg. The majority of the studied population was constituted by women (75.8%), with a mean age of 54.2±1.6 years old, married or living in civil union and that had completed secondary school or had higher education (40%). They presented a mean BMI of 26.2±4.76 Kg/m2., and were sedentary. The mean BP was 127.0±17.77mmHg- 74.69 ± 9.53. In this population we found 4.3% of people with hypertension and 16.1% with normal high blood pressure. Men exhibit a tendency to present higher systolic blood pressure values than women. Of all the factors considered, SBP values also tended to be higher with age and higher BMI values. Despite the fact that the mean values of SBP did not present values higher than 140 mmHg we must be concerned because the studied population is undiagnosed for hypertension. Although this is a preliminary study, it might be a prelude to the upcoming research about the underlying factors responsible for the occurrence of SBP.