Small Reduction In Blood Pressure Research Articles

The Effect of Non-Oil Seed Legume Intake on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Hypertension is a primary modifiable risk factor for CVD, whereby even small reductions in blood pressure (BP) can decrease risk for CVD events. Modification of dietary patterns is an established, nonpharmacologic approach for the prevention and management of hypertension. Legumes are a prevailing component of dietary patterns associated with lower BP in observational research, but there is a need to understand the effects of legume consumption on BP. This study aimed to synthesize evidence from randomized controlled trials (RCTs) for the effects of non-oil seed legume consumption on systolic blood pressure (SBP) and diastolic blood pressure (DBP) (PROSPERO registration: CRD42021237732). We searched CINAHL, Cochrane, Medline, and PubMed scientific databases from inception through November 2022. A random-effects meta-analysis was conducted to assess the mean differences (MDs) for each outcome variable between legume-based and comparator diets. This review included 16 RCTs and 1092 participants. Studies ranged in duration (4-52 wk), participant age (17-75 y), and weekly legume dose (450-3150 g) in whole or powdered form. No significant overall effect between legume consumption and BP amelioration was observed in the meta-analysis (SBP-MD: -1.06 mm Hg; 95% CI: -2.57, 0.4410 mm Hg; I2 = 45%; DBP-MD: -0.48 mm Hg; 95% CI: -1.06, 0.10 mm Hg; I2 = 0%). The certainty of evidence was determined as low for SBP and DBP. Significant subgroup differences in SBP were found when studies were grouped according to participant BMI, with SBP reduction found for participants with overweight/obese BMI (MD -2.79 mm Hg, 95% CI: -4.68, -0.90 mm Hg). There is a need for large, high-quality trials to clearly define the benefits and mechanisms of legume consumption in BP management. Consideration of the relevance in individuals with obesity, overweight, and hypertension may also be warranted. This trial was registered at PROSPERO as CRD42021237732.

Calcium supplementation for prevention of primary hypertension.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of thereviewto evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the preventionof primary hypertension. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and theUS National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eightstudies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; sevenstudies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Calcium supplementation for prevention of primary hypertension.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of thereviewto evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the preventionof primary hypertension. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and theUS National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eightstudies; I2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; sevenstudies ; I2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies = 8; I2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Interaction between Renal Sodium‐Glucose Cotransporter 2 and Renin‐Angiotensin System in a PCOS Rat Model

Introduction : Polycystic Ovary Syndrome (PCOS) is characterized by androgen excess, oligo/anovulation, and polycystic ovaries. PCOS is co-prevalent with insulin resistance (IR), increased blood pressure (BP), and a dysfunctional renin-angiotensin system (RAS). The RAS has both a vasoconstrictive arm with angiotensin-converting enzyme (ACE) and a vasodilatory arm with ACE2. While PCOS patients require multiple medications to control their comorbidities, it is unknown how these medications interact with each other. ACE inhibitors (ACEi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) seem to influence each other in male rodents. However, how androgens influence these interactions in females is unknown. We have a well-established rat model that mimics PCOS, including IR, increased BP, and overactive RAS. Using this model, we tested the hypothesis that SGLT2i would attenuate the RAS and that ACEi would decrease renal SGLT2 expression in a rat model of PCOS. Methods : In Experiment 1, four-week old female Sprague Dawley (SD) rats implanted with DHT pellets (7.5mg/90 days) or control were randomized to drinking water with and without the SGLT2i empagliflozin at a dose of 10 mg/kg/day during the last 3 weeks of the study (n=10/group). At 3 months of DHT, fasting plasma was collected for the homeostatic model assessment of IR (HOMA-IR). BP was measured by radiotelemetry. Renal cortex and medulla were collected for quantitative real-time polymerase chain reaction (qRT-PCR) and western blot for ACE and ACE2. In Experiment 2, four-week old female SD rats implanted with DHT pellets (7.5mg/90 days) or control were randomized to drinking water with and without the ACEi enalapril at a dose of 250 mg/mL throughout the study (n=10/group). At 3 months of DHT, kidneys were collected for qRT-PCR for SGLT2. Results : PCOS rats had increased IR, BP, and renal expression of ACE and ACE2 compared to controls. SGLT2i had no impact on IR while causing a small reduction in BP in both groups. SGLT2i decreased cortical ACE mRNA and protein (1.03 ± 0.08 vs 1.37 ± 0.04, P<0.05) in PCOS, and had no impact in controls. SGLT2i also decreased cortical ACE2 protein (1.02 ± 0.05 vs 1.18 ± 0.03, P<0.05) in PCOS, but not in controls. SGLT2i decreased mRNA and protein of medullar ACE and ACE2 in both groups. In Experiment 2, cortical SGLT2 mRNA was increased in PCOS compared to controls. ACEi increased SGLT2 mRNA in controls (30.32 ± 8.03 vs 1.00 ± 0.32, P<0.01) with no effect in PCOS. Conclusions In summary, PCOS rats had increased IR, BP, and intrarenal ACE. Without impacting IR, SGLT2i attenuated both intrarenal ACE and ACE2 expression in PCOS. This suggests ACEi could work synergistically with SGLT2i to reduce BP. PCOS rats have increased SGLT2 mRNA, suggesting a differential response to SGLT2i between PCOS rats and controls, such as shown with cortical ACE. ACEi also increased cortical SGLT2 mRNA in controls, but androgen excess appeared to blunt this effect. Overall, this suggests that there could be a differential response in hyperandrogenemic women taking both SGLT2i and ACEi compared to a woman with normal androgen levels.

Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension.

Renin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension isunknown. To evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension. The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. We included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension. Two review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. We include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors forthe outcomes: all-cause mortality:risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence;total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; verylow-certainty evidence;adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants; moderate-certainty evidence;serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence;and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants;low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggestedthat RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants; and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants, to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect. AUTHORS' CONCLUSIONS: For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ forall-cause mortality andmyocardial infarction. We have low to moderate certainty that they do not differ foradverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty. More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessingmorbidity and mortality outcomes, but also on blood pressure-lowering effect.

Systemic hypertension in obstructive sleep apnea.

There is consistent epidemiological evidence that sleep disordered breathing and systemic arterial hypertension are deeply associated, being linked through a bidirectional complex interaction among multiple mechanisms including autonomic nervous system alterations, inflammation, hormonal and hemodynamic components, sleep alterations. However there are several unanswered questions not only from a pathophysiological perspective, but also regarding the effects of obstructive sleep apnea (OSA) treatment on arterial blood pressure values. At present, while many studies have supported the possibility to obtain at least a small blood pressure reduction with OSA treatment, in particular in hypertensive patients, large trials have not clearly confirmed a significant anti-hypertensive effect, nor a beneficial effect of this intervention on cardiovascular endpoints including cardiovascular mortality. Aim of the present review article is to address the relationship between OSA and hypertension in the light of the latest evidence in the field. Moreover we will discuss research topics which need to be investigated in the future, in order to better clarify still pending issues with the aim of obtaining an early diagnosis, a more suitable phenotyping including comorbidities, and better strategies to improve patients' compliance and adherence to treatment.

A review of interventions ≥ 6 months by pharmacists on adherence to medicines in cardiovascular disease: Characteristics of what works and what doesn't.

Nonadherence to cardiovascular medicines occurs in 60% of subjects with chronic cardiovascular disease and leads to poor outcomes. In an attempt to improve adherence and cardiovascular outcomes, interventions are often used. Interventions may involve a pharmacist, but it is not always clear whether these are effective. The primary objective of this review is to determine whether interventions by pharmacists, alone, discussing adherence to medicines, improve adherence to medicines for cardiovascular disease. Subsequently, the review links the characteristics of the individual studies with effectiveness or lack of effect. The second objective of this review is to consider whether any improvement in adherence with interventions by pharmacist is associated with better clinical outcomes. A literature search of PubMed and CINAHL for 'pharmacist', 'medicine' with 'adherence' or 'compliance' or 'persistence' was undertaken. To be included in this review, papers had to be of a pharmacist working alone and in person in an intervention of subjects with hypertension, hyperlipidemia (prior to or after a coronary artery event) or heart failure. The paper had to be published in a peer review journal, with a measure of adherence to medicines. The effectiveness of the intervention had to be evaluated after ≥6 months. Only 3 out of 8 interventions by pharmacists in hypertension, and 5 out of 12 interventions in subjects with hyperlipidemia led to improved adherence to medicines. In contrast, all 6 interventions by a pharmacist in subjects with heart failure were successful in improving adherence. One characteristic of successful interventions by pharmacists to improve adherence to cardiovascular medicines is that they must be more than brief/single interventions. A second characteristic is that the intervention should not involve subjects who are already highly adherent, as it is unlikely adherence can be improved in this population. Only 2 of 3 successful interventions in hypertension were associated with small reductions in blood pressure, and only one intervention in hyperlipidemia was shown to decrease LDL-cholesterol to a small extent. In subjects with heart failure, 5 of the 6 successful studies of the successful interventions by pharmacists to increase adherence also showed improved clinical outcomes. When planning an intervention to improve adherence to medicines and cardiovascular outcomes in subjects with hypertension or hyperlipidemic, by a pharmacist alone, or as part of a multi-faceted interventions, it is essential to use an intervention that has been shown to be effective, as most interventions are not effective at improving adherence or only improve adherence and clinical outcomes to a small extent. In heart failure, there is well documented evidence of interventions by pharmacists that do improve clinical outcomes, which should be adopted widely.

New Glucose-Lowering Agents for Diabetic Kidney Disease.

The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents. This review elaborates on the main results of renoprotective effects of these 3 treatment classes. In conclusion, currently available trials have demonstrated renoprotective effects for certain glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin. Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective effect. Nevertheless, larger studies with respect to renoprotective effects of these 3 drug classes are currently being performed, and thus, no conclusions for all of these agents can yet be made.

Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia.

Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced ex vivo preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact, unanesthetized rats. Using a lentivirus that expresses ArchT under the Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ∼65% of transduced neurons were C1 (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3.0 AAV2 (CaMKII-ArchT), which transduced C1 neurons and larger numbers of unidentified glutamatergic and GABAergic cells. Under anesthesia, ArchT photoactivation reduced sympathetic nerve activity and BP and silenced/strongly inhibited most (7/12) putative C1 neurons. In unanesthetized PRSx8-ArchT-treated rats breathing room air, bilateral ArchT photoactivation caused a very small BP reduction that was only slightly larger under hypercapnia (6% FiCO2), but was greatly enhanced during hypoxia (10 and 12% FiO2), after sino-aortic denervation, or during isoflurane anesthesia. The degree of hypotension correlated with percentage of ArchT-transduced C1 neurons. ArchT photoactivation produced similar BP changes in CaMKII-ArchT-treated rats. Photoactivation in PRSX8-ArchT rats reduced breathing frequency (FR), whereas FR increased in CaMKII-ArchT rats. We conclude that the BP drop elicited by ArchT activation resulted from C1 neuron inhibition and was unrelated to breathing changes. C1 neurons have low activity under normoxia, but their activation is important to BP stability during hypoxia or anesthesia and contributes greatly to the hypertension caused by baroreceptor deafferentation. Finally, C1 neurons are marginally activated by hypercapnia and the large breathing stimulation caused by this stimulus has very little impact on resting BP.SIGNIFICANCE STATEMENT C1 neurons are glutamatergic/peptidergic/catecholaminergic neurons located in the medulla oblongata, which may operate as a switchboard for differential, behavior-appropriate activation of selected sympathetic efferents. Based largely on experimentation in anesthetized or reduced preparations, a rostrally located subset of C1 neurons may contribute to both BP stabilization and dysregulation (hypertension). Here, we used Archaerhodopsin-based loss-of-function optogenetics to explore the contribution of these neurons to BP in conscious rats. The results suggest that C1 neurons contribute little to resting BP under normoxia or hypercapnia, C1 neuron discharge is restrained continuously by arterial baroreceptors, and C1 neuron activation is critical to stabilize BP under hypoxia or anesthesia. This optogenetic approach could also be useful to explore the role of C1 neurons during specific behaviors or in hypertensive models.

Calcium supplementation for prevention of primary hypertension.

Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure. As small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges, this review intends to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomised controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. We also reviewed reference lists from retrieved studies and contacted authors of relevant papers. We applied no language restrictions. We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We included 16 trials with 3048 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was mean difference (MD) -1.43 mmHg (95% confidence interval (CI) -2.15 to -0.72) and -0.98 mmHg (95%CI -1.46 to -0.50) respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years (7 trials with 399 participants) was -2.11 mmHg (95%CI -3.58 to -0.64) / -2.61 mmHg (95% CI -3.74, -1.49). The effect on systolic and diastolic blood pressure for those 35 years or more (9 trials with 2649 participants) was -0.96 mmHg (95%CI -1.83 to -0.09) / -0.59 mmHg (95%CI -1.13 to -0.06). The effect on systolic and diastolic blood pressure for women (6 trials with 1823 participants) was -1.45 mmHg (95% CI -2.78 to -0.12) / -0.92 mmHg (95% CI -1.71 to -0.14). The effect on systolic and diastolic blood pressure for men (5 trials with 617 participants) was -2.07 (95%CI -3.56 to -0.59] / -1.91 (95%CI -2.80 to -1.02).The quality of evidence for each of these outcomes was high. The effect is consistent in both genders regardless of baseline calcium intake.The effect on systolic blood pressure was 0.08 mmHg (95% CI -2.16 to 2.32) with doses less than 1000 mg, -1.14 mmHg (95% CI -2.01 to -0.27) with 1000 - 1500 mg, and -2.79 mmHg (95% CI -4.71 to -0.86) with more than 1500 mg. The effect on diastolic blood pressure was -0.54 mmHg (95% CI -2.23 to 1.15), -0.71 mmHg (95% CI -1.37 to -0.06) and -1.43 mmHg (95% CI -2.22 to -0.64) respectively. The quality of evidence for each of these outcomes was high.None of the studies reported adverse events. An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. These results should be interpreted with caution, since the proposed biological mechanism explaining the relationship between calcium and blood pressure has not been fully confirmed. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease.There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Chronic central nervous system MC3/4R blockade attenuates hypertension induced by nitric oxide synthase inhibition but not by angiotensin II infusion.

We examined whether central melanocortin 3 and 4 receptor (MC3/4R) blockade attenuates the blood pressure (BP) responses to chronic L-NAME or angiotensin II (Ang II) infusion in Sprague-Dawley rats implanted with telemetry transmitters, venous catheters, and intracerebroventricular cannula into the lateral ventricle. After 5 days of control measurements, L-NAME (10 μg/kg/min IV, groups 1 and 2) or Ang II (10 ng/kg/min IV, groups 3 and 4) were infused for 24 days, and starting on day 7 of L-NAME or Ang II infusion, the MC3/4R antagonist SHU-9119 (24 nmol/d, n=6/group; groups 1 and 3) or vehicle (saline 0.5 μL/h, n=6/group; groups 2 and 4) was infused intracerebroventricularly for 10 days. A control normotensive group also received SHU-9119 for 10 days (n=5). L-NAME and Ang II increased BP by 40±3 and 56±5 mm Hg, respectively, although heart rate was slightly reduced. MC3/4R blockade doubled food intake and reduced heart rate (≈40 to ≈50 bpm) in all groups. MC3/4R blockade caused only a small reduction in BP in normotensive group (4 mm Hg) and no change in rats receiving Ang II, although markedly reducing BP by 21±4 mm Hg in L-NAME-treated rats. After SHU-9119 infusion was stopped, food intake, heart rate, and BP gradually returned to values observed before SHU-9119 infusion was started. Ganglionic blockade at the end of L-NAME or Ang II infusion caused similar BP reduction in both groups. These results suggest that the brain MC3/4R contributes, at least in part, to the hypertension induced by chronic L-NAME infusion but not by Ang II.

Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients

Obstructive sleep apnea (OSA) may lead to the development of hypertension and therapy with continuous positive airway pressure (CPAP) can promote reduction in blood pressure. The objective of this study is to review systematically the effects of CPAP on blood pressure in patients with OSA. The search was conducted in the following databases, from their beginning until February 2013: MEDLINE, Embase, Cochrane CENTRAL, Lilacs and PEDro. In addition, a manual search was performed on references of published studies. Randomized clinical trials (RCTs) that used CPAP compared with placebo CPAP or subtherapeutic CPAP for treatment of patients with OSA and that evaluated office SBP and DBP and 24-h ambulatory blood pressure were selected. Sixteen RCTs were included among 3409 publications, totaling 1166 patients. The use of CPAP resulted in reductions in office SBP [-3.20 mmHg; 95% confidence interval (CI) -4.67 to -1.72] and DBP (-2.87 mmHg; 95% CI -5.18 to -0.55); in night-time SBP (-4.92 mmHg; 95% CI -8.70 to -1.14); in mean 24-h blood pressure (-3.56 mmHg; 95% CI -6.79 to -0.33), mean night-time blood pressure (-2.56 mmHg; 95% CI -4.43 to -0.68) and 24-h DBP (-3.46 mmHg; 95% CI -6.75 to -0.17). However, no significant change was observed in daytime SBP (-0.74 mmHg; 95% CI -3.90 to 2.41) and daytime DBP (-1.86 mmHg; 95% CI -4.55 to 0.83). Treatment with CPAP promoted significantly but small reductions in blood pressure in individuals with OSA. Further studies should be performed to evaluate the effects of long-term CPAP and the impact on cardiovascular risk.

Renal Nerve Ablation for Resistant Hypertension

Sympathetic renal denervation, or renal nerve ablation (RNA), has become the new buzz word in hypertension and interventional cardiology. Recent advances in catheter-based approaches have allowed sympathetic fiber interruption through transvascular techniques that are minimally invasive and can be delivered expeditiously and safely. Radiofrequency (RF) energy sources are currently the preferred modalities, but other sources of energy, such as cryoablation, microwave, high-intensity focus ultrasound, and local neurotoxic agent infusion, are under intense investigation. Results thus far have been encouraging and offer promise for the future. The role of the sympathetic nervous system (SNS) in the development of resistant hypertension and cardiovascular disease has long been known, and a great deal of work has been done through the years trying to explore potential interventions to interrupt the sympathetic influence on systemic vasculature and target organs. In this article we attempt an overview of time-dependent interventions on the SNS and examine approaches used in humans and in the many experimental models that offer a better understanding of the role of sympathetic activity in cardiovascular disease. Naturally we focus on methods and techniques addressing sympathetic renal denervation in patients with drug-resistant hypertension, examine the current state of the art, and attempt a look into the future. In 1889, after meticulous experiments on dogs, Bradford1 reported that stimulation of dorsal and splanchnic nerves causes changes in blood pressure (BP) and kidney size measured by plethysmography. Whether BP increased or decreased depended on the anatomic area stimulated, as well as the electric impulse frequency, but outcomes were consistent and reproducible. Neurosurgical treatment of hypertension was independently suggested by researchers in 1923.2 Adson, however, was the first to performed surgical sympathectomy for the treatment of malignant hypertension in 1925.3 During the following years and in the 1930s, Peet in Ann Arbor, Page and …

Antiplatelet and Lipid-lowering Drugs in Hypertension.

Antiplatelet therapy, and low-dose acetylsalicylic acid (ASA) in particular, is recommended in hypertensive patients with previous cardiovascular events and is considered in hypertensive patients with reduced renal function or a high cardiovascular (CV) risk, provided blood pressure is well-controlled. Acetylsalicylic acid is not recommended in low-to-moderate risk hypertensive patients in whom absolute benefit and harm are equivalent. Further trials evaluating antithrombotic therapy including newer agents in hypertension are needed. Women at high and moderate risk of pre-eclampsia are advised to take a low dose of ASA daily from 12 weeks of gestation until delivery. In addition to their lipid-lowering effects, statins induce a small blood pressure reduction. The 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines recommend using statin therapy in hypertensive patients at moderate-to-high CV risk to achieve the target low-density lipoprotein (LDL) cholesterol value <3 mmol/l (115 mg/dl). For individuals with manifest CV disease or at very high CV risk, a more aggressive LDL target of <1.8 mmol/l (70 mg/dl) is recommended.

Canagliflozin – something new for type 2 diabetes, but is it safe and efficacious?

Introduction: Inhibition of the sodium-glucose cotransporter 2 (SGLT2), to promote the excretion of glucose, is a new paradigm in the treatment of type 2 diabetes.Areas covered: Canagliflozin is an SGLT2 inhibitor, which has been the subject of two recent clinical trials, which are evaluated.Expert opinion: Studies with canagliflozin, in subjects with type 2 diabetes, have shown that its use is associated with reductions in HbA1c and body weight and small reductions in blood pressure and triglycerides, while increasing high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. As monotherapy in Japanese subjects, or in comparison with glimepiride in CANTATA-SU (CANagliflozin Treatment and Trial Analysis versus SUlphonylurea), canagliflozin causes a low incidence of hypoglycemia, and this is an advantage over glimepiride. However, one of the disadvantages with canagliflozin, which was also highlighted in CANTATA-SU, is that canagliflozin can cause urogenital infections, which are not observed with other antidiabetic drugs. The Federal Drug Administration has recently approved canagliflozin for use in type 2 diabetes, while directing that a clinical outcome safety trial be undertaken. We are concerned that canagliflozin has been approved for use in type 2 diabetes prior to a clinical outcome study of efficacy being undertaken and without the outcome of further safety testing.

Hypertension Analysis of Stress Reduction Using Mindfulness Meditation and Yoga: Results From the Harmony Randomized Controlled Trial

The HARMONY study was a randomized, controlled trial examining the efficacy of an 8-week mindfulness-based stress reduction (MBSR) program for blood pressure (BP) lowering among unmedicated stage 1 hypertensive participants. Participants diagnosed with stage 1 hypertension based on ambulatory BP were randomized to either immediate treatment of MBSR for 8 weeks or wait-list control. Primary outcome analysis evaluated whether change in awake and 24-hour ambulatory BP from baseline to week 12 was significantly different between the 2 groups. A within-group before and after MBSR analysis was also performed. The study enrolled 101 adults (38% male) with baseline average 24-hour ambulatory BP of 135±7.9/82±5.8mm Hg and daytime ambulatory BP of 140±7.7/87±6.3 mmHg. At week 12, the change from baseline in 24-hour ambulatory BP was 0.4±6.7/0.0±4.9mm Hg for the immediate intervention and 0.4±7.8/-0.4±4.6mm Hg for the wait-list control. There were no significant differences between intervention and wait-list control for all ambulatory BP parameters. The secondary within-group analysis found a small reduction in BP after MBSR compared with baseline, a finding limited to female subjects in a sex analysis. MBSR did not lower ambulatory BP by a statistically or clinically significant amount in untreated, stage 1 hypertensive patients when compared with a wait-list control group. It leaves untested whether MBSR might be useful for lowering BP by improving adherence in treated hypertensive participants. NCT00825526.

Ramipril

Ramipril

Challenges in the management of hypertension in Asia

Hypertension is common in Asian populations and is a major cause of cardiovascular diseases. Even a small reduction in blood pressure can lead to a substantial decrease in the risk of stroke. The prevalence of hypertension appears to be increasing in many countries, partly because of ageing of the population, but also because of increasing obesity. While much effort has gone into promoting the awareness of hypertension, the rates of detection, treatment, and control remain low. As hypertension is very prevalent in the general population, it makes sense to adopt population approaches towards the detection and treatment of hypertension, and its prevention. As obesity is a major cause of hypertension in Asia, tackling it will help to lower the incidence of hypertension in the future. Lowering sodium contents in foods and promotion of regular physical activity will also help to lower blood pressure at the population level. Asians appear to respond well to calcium channel blockers but have a higher incidence of dry cough with angiotensin-converting enzyme inhibitors.The costs of long-term follow-up and treatment impose a certain economic burden, whether on the individual or on the health provider.

Discrepancies between Office and Ambulatory Blood Pressure: Clinical Implications

Background Recent trials have documented no benefit from small reductions in blood pressure measured in the clinical office. However, ambulatory blood pressure is a better predictor of cardiovascular events than office-based blood pressure. We assessed control of ambulatory blood pressure in treated hypertensive patients at high cardiovascular risk. Methods We selected 4729 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Patients were aged ≥55 years and presented with at least one of the following co-morbidities: coronary heart disease, stroke, and diabetes with end-organ damage. An average of 2 measures of blood pressure in the office was used for analyses. Also, 24-hour ambulatory blood pressure was recorded at 20-minute intervals with a SpaceLabs 90207 device. Results Patients had a mean age of 69.6 (±8.2) years, and 60.8% of them were male. Average time from the diagnosis of hypertension to recruitment into the Registry was 10.9 (±8.4) years. Mean blood pressure in the office was 152.3/82.3 mm Hg, and mean 24-hour ambulatory blood pressure was 133.3/72.4 mm Hg. About 60% of patients with an office-pressure of 130-139/85-89 mm Hg, 42.4% with office-pressure of 140-159/90-99 mm Hg, and 23.3% with office-pressure ≥160/100 mm Hg were actually normotensive, according to 24-hour ambulatory blood pressure criteria (<130/80 mm Hg). Conclusion We suggest that the lack of benefit of antihypertensive therapy in some trials may partly be due to some patients having normal pressure at trial baseline. Ambulatory monitoring of blood pressure may allow for a better assessment of trial eligibility.

Physical Activity and Blood Pressure in 11 Year Old Children

Cardiovascular disease (CVD) is the leading cause of adult death in Western societies. The pathological processes associated with its development are initiated early in life; for example, elevated blood pressure (BP) can be seen in childhood, and has been shown to track into adulthood. There is a well-established relationship between physical activity (PA) and BP in adults, but few studies have investigated this in children, using an objective measure of PA. PURPOSE: To establish whether there is an association between objectively measured PA and BP in children. METHODS: Children aged 11 to 12 were recruited from a large birth cohort- the Avon Longitudinal Study of Parents and Children, and asked to wear a uniaxial accelerometer for seven days. Accelerometer counts per minute (cpm) and minutes per day spent in moderate to vigorous physical activity (MVPA) were derived, and children included if they had data for at least 10 hours on at least three days. The means of two BP readings taken using an automatic BP monitor were calculated. Data on a number of possible confounders were also available. RESULTS: Analyses were based on 5505 children. Associations between PA and BP after minimal and full adjustment for possible confounders are shown below:TableaAdjusted for age, gender (N=5505) bAdjusted for age, gender, BP measurement factors, social factors, maternal factors, current size, birthweight, gestation, puberty (N=2675). When cpm and MVPA were entered into models simultaneously, associations with cpm remained similar, while those with MVPA were reduced. CONCLUSIONS: Increases in PA at age 11 were associated with small reductions in BP, and the amount was more important than the intensity of activity.