Reduction In Systolic Blood Pressure Research Articles

Differences in the effects of exercise on blood pressure depending on the physical condition of the subject and the type of exercise: a systematic review and meta-analysis.

Although hypertension is a major cause of cardiovascular disease, the control of blood pressure (BP) is insufficient worldwide. Exercise is an effective treatment for reducing BP, but the differences in the blood pressure lowering effects of exercise according to the underlying pathophysiological condition, the type of exercise, and the geographic region are not fully understood. An umbrella review with a meta-analysis of 435 randomized controlled trials that investigated the BP-lowering effects of exercise was performed using Ovid MEDLINE and the Cochrane Library, covering the period from inception to August 1, 2023. A random effects model meta-analysis was performed to estimate the effect size across multiple studies. Exercise significantly reduced systolic BP in healthy subjects (-3.51 mmHg, 95% confidence interval: -3.90, -3.11; p < 0.001) and in those with lifestyle-related diseases including hypertension (-5.48 mmHg, -6.51, -4.45; p < 0.001), but not in those with cardiovascular diseases (-1.16 mmHg, -4.08, 1.76; p = 0.44). According to the type of exercise, all types significantly reduced systolic BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases. According to the region, in Oceania, there were no reductions in systolic BP. In Asia, systolic BP was reduced in patients with cardiovascular diseases. In conclusion, any type of exercise reduced BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases, and the region affected the effect of exercise. When using exercise to reduce hypertension, it is important to consider the patient's pathophysiological condition and the region.

Effect of nebivolol monotherapy or combination therapy on blood pressure levels in patients with hypertension: an updated systematic review and multilevel meta-analysis of 91 randomized controlled trials.

To systematically appraise and summarize the available evidence from published randomized controlled trials considering the effect of nebivolol on blood pressure in patients with hypertension. Literature search was performed through Medline (via PubMed), Cochrane Library and Scopus until December 15, 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. In total, 7,737 participants with hypertension, who were treated with nebivolol, were analyzed across 91 RCTs. Nebivolol was associated with significantly greater reduction in office systolic and diastolic BP compared to placebo (MD = - 6.01 mmHg; 95% CI = [- 7.46, - 4.55] and MD = - 5.01 mmHg; 95% CI = [- 5.91, - 4.11], respectively). Moreover, resulted a similar reduction in systolic BP (MD = - 0.22 mmHg; 95% CI = [- 0.91, 0.46]) and a significantly greater reduction in diastolic BP compared to the active comparator (MD = - 0.71 mmHg; 95% CI = [- 1.27, - 0.16]). When considering the effect of nebivolol on 24-hour ambulatory BP, notable reductions were observed compared to placebo. In contrast, compared to the active comparators, there was no significant difference in systolic BP reduction, but a significant reduction in diastolic BP favoring nebivolol. Based on moderator analyses, the impact of nebivolol on the pooled estimates remained independent of the dose of nebivolol, age, male sex, trial duration, body mass index (BMI), baseline diabetes, heart failure, and baseline systolic and diastolic BP. Nebivolol, compared to placebo, showed a significant BP reduction and was non-inferior to other active comparators in terms of BP reduction.

Safety, tolerability and blood pressure lowering of the innovative guanylyl cyclase a-receptor activator MANP in an ethnically diverse resistant hypertension population: a phase 1B clinical trial

Abstract Background/Introduction MANP is a novel atrial natriuretic peptide (ANP) analog bioengineered as a particulate guanylyl cyclase A receptor (GC-A) activator with superior receptor binding, resistance to neprilysin degradation, natriuretic, aldosterone suppressing and blood pressure (BP) lowering properties than native ANP. MANP is now under clinical development for resistant hypertension (RH). The rationale for its design was the fundamental role of the ANP/GC-A system in BP homeostasis through which GC-A activation with MANP leads to BP reduction through renal, vascular, and hormonal mechanisms mediated by the second messenger cGMP. Purpose We investigated the safety, tolerability, cGMP activation and BP reductions of MANP compared to placebo in subjects with RH. Methods We performed a double-blind, placebo controlled randomized trial in 36 RH patients comprised of approximately 50% non-African Americans (NAA) and 50% AA. MANP was administered in 6 cohorts receiving ascending subcutaneous (SQ) doses of MANP once daily from 3 ug/kg to a maximal dose of 7 ug/kg or placebo for 5 days and then followed for 21 days after dosing. Endpoints included safety, cGMP activation and changes in systolic BP (SBP), aldosterone (Aldo) levels and glomerular filtration rate (GFR). Results MANP was safe and well tolerated. One patient in the 7 ug/kg cohort was discontinued due to symptomatic hypotension. Compared to baseline, plasma cGMP increased in all MANP groups on Day 1 and Day 5 with no change in the placebo group. The maximal SBP reduction in the MANP group on Days 1 (D1) and 5 (D5) was -17.5 (D1) and -16 mmHg (D5) with 3 ug/kg (lowest dose) and -39.5 (D1) and -36.3 mmHg (D5) with 7 ug/kg (highest dose); Changes in the Placebo group were -6.3 (D1) and -16.7 mmHg (D5). Notably, the SBP reductions in AA were greater than NAA in the 4 and 7 ug/kg cohorts. After the 1-hour timepoint on both the first and fifth days, Aldo and percentage of Aldo reduction generally remained suppressed compared to baseline. Twenty-one days after MANP dosing, SBP remained lower in three groups receiving SQ MANP (4, 4.5 and 7 ug/kg) compared to placebo in association with a preservation of GFR. There were no reported drug related serious adverse events. Conclusions This clinical trial demonstrates that once a day SQ administration of MANP in RH subjects activates cGMP, without attenuation over 5 days, and reduces SBP and preserves GFR. At higher doses of MANP, SBP reductions were greater in AA compared to NAA. MANP also demonstrated Aldo inhibiting actions compared to placebo. Importantly, MANP was overall safe and well-tolerated. Our findings support the continued clinical development of MANP as a novel GC-A activating peptide for the treatment of RH.

Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive

Abstract Background Zilebesiran is an investigational RNA interference therapeutic targeting hepatic angiotensinogen synthesis. In KARDIA-1, a single subcutaneous (SC) dose of zilebesiran monotherapy significantly reduced 24-hr mean ambulatory and office systolic blood pressure (SBP) from baseline to Months 3 and 6 versus placebo. The Phase 2 KARDIA-2 study assessed efficacy and safety of zilebesiran with a standard oral antihypertensive in patients with uncontrolled hypertension. Purpose Uncontrolled hypertension is a leading cause of cardiovascular morbidity and mortality, and medication non-adherence affects blood pressure control. Developing effective, long-lasting treatments is crucial for patients with hypertension uncontrolled by standard therapy. Methods KARDIA-2 enrolled adults with mild-to-moderate hypertension who were untreated or receiving stable therapy with ≤2 antihypertensives. Patients discontinued prior antihypertensive medication and were randomized 10:7:4 to open-label, once-daily oral treatment with 40 mg olmesartan, 5 mg amlodipine, or 2.5 mg indapamide. After ≥4 weeks on protocol-specified medication, patients with a 24-hr mean ambulatory SBP of 130–160 mmHg were randomized 1:1 in a double-blind manner to a single SC dose of zilebesiran 600 mg or placebo as add-on therapy. The primary endpoint was change from baseline to Month 3 in 24-hr mean ambulatory SBP versus placebo for each group. Efficacy and safety were also assessed in pre-specified subgroups: age (&amp;lt;65; ≥65 years), sex, race (Black; other), baseline 24-hr mean ambulatory SBP (&amp;lt;145; ≥145 mmHg), and baseline estimated glomerular filtration rate (≥60; &amp;lt;60 mL/min/1.73m2). Results The primary analysis included 667 patients (median age [range] 59 [27–75] years; 57% male, 28% Black). At Month 3, least-squares mean differences (LSMD) (95% confidence interval [CI]) between zilebesiran and placebo for the olmesartan, amlodipine, and indapamide groups were −4.0 (−7.6, −0.3), −9.7 (−12.9, −6.6), and −12.1 (−16.5, −7.6) mmHg, respectively, for 24-hr mean ambulatory SBP (all p&amp;lt;0.05). LSMD (95% CI) in office SBP for the same groups were −7.0 (−10.4, −3.6), −10.2 (−13.5, −6.9), and −18.5 (−22.8, −14.2) mmHg, respectively, (all p&amp;lt;0.001). SBP reductions were consistent across subgroups, except for a trend towards an attenuated response observed in Black patients (Figs 1, 2). More patients receiving zilebesiran (49–58%) than placebo (39–48%) experienced ≥1 adverse event through Month 6, with low rates of hyperkalaemia, hypotension, or acute kidney injury reported across all groups. Conclusion In KARDIA-2, a single dose of zilebesiran significantly reduced SBP versus placebo at Month 3 on top of a standard oral antihypertensive, with encouraging safety data. SBP reduction was consistent across most subgroups. Treatment with zilebesiran combined with standard antihypertensives may be effective for a broad population of patients with hypertension uncontrolled on monotherapy.

Trends in hypertension prevalence and control in England over the last 3 decades: Health Survey of England 1994-2019

Abstract Globally, raised blood pressure (BP) contributes to more than 10.8 million avoidable deaths from cardiovascular (CV) and renal disease. Understanding national BP control trends amongst hypertensive patients will help inform the effectiveness and gaps in existing pathways and policies. We used data from 13 nationally representative health surveys in England between 1994-2019 to compare nationwide trends in BP control and hypertension awareness over 25 years. We used ‘period’ definitions to define hypertension and BP control (i.e. using existing guidance at the time of the survey) to account for changes in BP targets and definitions. Analyses were also conducted using ‘current definitions’ (i.e. definition of hypertension and BP control targets as per NICE 2023), applied across the entire duration. Sample weights, accounting for oversampling and survey nonresponse, and other relevant transformations were applied. Python and STATA 18 were used to conduct analyses and Join Point regression software was used to compare trends. In England, between 1994-2019, the prevalence of hypertension initially increased sharply by 8% from 23.3% when the BP cut off was lowered in 1999. Thereafter for the next 12 years it remained static at 32-34%, and since 2011 has plateaued at 31-32%, showing only marginal improvement of 1.5% over this 25-year period (Figure 1). This is consistent with population-wide mean systolic (S) and diastolic (D) BPs, and amongst those with and without hypertension. Population-wide there was a reduction in SBP (8.5mmHg) and DBP (3.8mmHg) over the period. There was significantly greater reduction in SBP (11.9 vs 9.5mmHg) and DBP (4.1 vs 2.5mmHg) amongst those with diagnosed hypertension as compared to those without. Using the current target of below 140/90mmHg when evaluating BP control over this period suggests that we have improved. However, when we use ‘period definitions’ of BP targets at that time, it seems that over last 25 years there has been ‘no change’ in the proportion of diagnosed hypertensives with uncontrolled BPs (Figure 2). Additionally, although appearing to increase over the period, there has been no significant change in proportions of those with hypertension who are unaware of this condition since BP cut-offs were lowered in 1999. These findings indicate that in England, over last 25 years, whilst there have been some improvements in population wide mean SBP and DBP with slight reduction in hypertension prevalence, the proportions of those with known hypertension with uncontrolled BPs have remained static. This is despite improvement in medications and practice. Furthermore, there has been little progress in detection of those hypertensive patients who are unaware about and untreated for their condition. Clearly, these call in question the effectiveness of the current policies and clinical practice pathways and provide huge opportunity to improve population wide CV riskSytolic and Diastolic BP trendsTrends in the prevalence of BP control

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of &amp;lt;10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Assessing the efficacy of renal denervation in patients with resistant arterial hypertension: a systematic review and meta-analysis

Abstract Background/Introduction Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood. Purpose Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN. Methods We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of &amp;lt; 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine. Results Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups. Conclusion In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

Effect of incremental exercise training interventions in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation is recommended after myocardial infarction (MI) to improve prognosis, quality of life and control of cardiovascular risk factors. However, the specific impact of different exercise training interventions remains incompletely understood. Purpose To study the health outcomes of three incremental exercise training interventions during a Cardiac Rehabilitation Program (CRP) following MI. Methods We implemented a post-MI Phase 2 CRP in 2022. After initial exercise testing, a 3-month, individualized aerobic and strength ambulatory training program was provided by Cardiologists and Physical Medicine and Rehabilitation physicians (Group 1, n=58). Additionally, a subset of patients received one session of supervised teaching of aerobic and strength training by physiotherapists (Group 2, n=19), and another subset received 8-20 sessions of in-hospital supervised training (Group 3, n=13). Exercise testing was repeated at the end of Phase 2 and peak oxygen consumption (peak VO2) was measured. We analysed quality of life (SF-36), depression (PHQ2), anxiety (GAD2), adherence to Mediterranean diet (PREDIMED) and pharmacological treatment (Morisky-Green), and weekly physical activity (IPAQ). Health outcomes were compared at the beginning and after Phase 2 CRP. Results The cohort comprised 90 patients who completed Phase 2 CRP (mean age 61.2±10.8 years, 84.4% male and 47.8% smokers). Reductions in systolic blood pressure (-10.3±13.8mmHg), LDL cholesterol (-60.7±35.4mg/dL), weight (-2.8±6.6kg, -3±7.8%) and body mass index (-1±2.2) were attained (p&amp;lt;0.05). Smoking abstinence was accomplished in 88.4% of smokers and most patients achieved an LDL&amp;lt;55mg/dL (81.1%). Improvements in quality of life (SF-36 +10.4±19.4 points, p&amp;lt;0.001) and anxiety and depression symptoms (PHQ2 -0.5±1.6 points and GAD2 -0.6±1.6 points, p&amp;lt;0.01) were noted. An increase in peak VO2 (+5.12±5.44ml/kg/min, +23.5±27.4% from baseline, p&amp;lt;0.001) and predicted functional capacity (+13.4±23.8%, p&amp;lt;0.001) was achieved. Patients increased their reported weekly physical activity by 2520.3±2935.4 METS/week (+132% from baseline, p&amp;lt;0.001) and most of them were adherent to Mediterranean diet (91.1%) and pharmacological treatment (95.6%). Patients achieved similar health outcomes regardless of their exercise training group, except for patients in Group 3, who experienced a more pronounced improvement in peak VO2 (+8.1±6.4ml/kg/min, +37.8±34.7% from baseline; p&amp;lt;0.05) and a trend towards higher increase in predicted functional capacity (+21.7±19.2%, p&amp;lt;0.25) and greater weight loss (-5.5±9.4kg, -5.9±9.6%; p&amp;lt;0.2). Conclusions Supervised in-hospital training during a Phase 2 CRP provides superior physical fitness improvements and more pronounced weight loss in MI patients. However, a Phase 2 CRP based on ambulatory training provides similar benefits regarding other health outcomes, such as control of cardiovascular risk factors and quality of life amelioration.Exercise training interventions in a CRP

Dapagliflozin enhances arterial and venous compliance during exercise in heart failure with preserved ejection fraction

Abstract Background Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. Purpose This study tested the hypothesis that SGLT2i dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. Methods In this secondary analysis from the RCT trial, patients with HFpEF underwent invasive hemodynamic exercise testing at baseline and following treatment for 24 weeks with dapagliflozin or placebo. Patients were required to display pulmonary capillary wedge pressure (PCWP) ≥25 mmHg during exercise at the time of baseline evaluation. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated (eSBV) from hemodynamic indices fit to a comprehensive cardiovascular model. Results A total of 37 patients completed the study and were included in this analysis (21 dapagliflozin and 16 placebo). Patients were predominantly women (24/37, 65%) and older (mean age 67 years). There was no statistically significant effect of dapagliflozin on resting BP, but dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mmHg, 95% CI: -33.9 to -3.7, P=0.016) (Figure 1A). Dapagliflozin improved exertional total arterial compliance (TAC) index (ETD, 0.06 mL/mmHg/m2, 95% CI: 0.003 to 0.11, P=0.039) (Figure 1B) and aortic root characteristic impedance (ETD, -2.6 mmHg/ml*sec, 95% CI: -5.1 to -0.03, P=0.048) during peak exercise, with no significant effect on systemic vascular resistance. Dapagliflozin reduced eSBV at rest and during peak exercise (ETD, -292 mmHg, 95% CI: -530 to -53, P=0.018) (Figure 1C), and improved venous capacitance evidenced by a decline in ratio of eSBV to total blood volume (ETD, -7.3%, 95% CI -13.3 to -1.3, P=0.020). Each of these effects of dapagliflozin during peak exercise were also observed during matched 20W exercise intensity. Improvements in TAC index and eSBV were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in eSBV during exercise (r=0.40, P=0.019) (Figure 2A). Decreases in BP were correlated with reduction in PCWP during exercise (r=0.56, P&amp;lt;0.001) (Figure 2B). Conclusion In patients with HFpEF, treatment with dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with SGLT2i in HFpEF.

Do more with less? Impact of personalized very low doses of amlodipine in the PERSONAL-CovidBP trial

Abstract Introduction The Personal-CovidBP study1 tested remote patient use of a drug-device combination of a smartphone application (App) to record blood pressure (BP), novel personalized milligram-by-milligram drug (amlodipine) dose, and relevant side effects daily during the COVID-19 pandemic. Purpose In supplementary data analyses, we examined the effect of using small doses (1 mg) and small increments (1-2 mg) of amlodipine on the BP response and side effects. Methods In this community-based trial with remote monitoring and remote medical management from the investigational site, hypertensive participants aged 18 years + with poor BP control (prior 7 day mean of 135 mmHg systolic BP or above and/or 85 mmHg diastolic BP and above) were enrolled to intervention with open label dose titration over 14 weeks, allowing personalized dosing of liquid amlodipine (1–2 mg steps from 1–10 mg daily). Results 205 patients were enrolled into the intervention group between October 2020 and July 2021. Average BP in intervention fell from 141/87 to 131/81 (difference −10/6 p &amp;lt; 0.001). Even low doses or small increments: 1 or 2 mg amlodipine or 5 mg to 6 mg, produced meaningful BP responses. Here we report that the addition of amlodipine during the study reduced blood pressure regardless of being amlodipine naive at baseline (n=141), or receiving amlodipine 2.5mg or 5mg at baseline (n=62). The response slopes were comparable, and mean reductions in SBP were consistent across groups: -11.7 (95% CI: -12.9 to -10.6); -9.4 (-11.1 to -7.7); respectively (Figure 1). For the amlodipine naive, the majority (76%) achieved BP control at low doses (&amp;lt;1 to 3mg) with occurrence of side effects increasing with dose (Figure 2). Conclusions Our real-world remote care study demonstrated that very low doses of amlodipine as little as 1 mg were effective and for 1mg-3mg gained BP control in the majority and were associated with fewer side effects which is consistent with previous meta-analyses.2 Personalized treatment titration was effective even at very low doses and also regardless of whether amlodipine naive or not at baseline.Changes in SBP- baseline amlodipine useAmlodipine dose at control vs oedema

Relationships among intensive blood pressure control, morning blood pressure surge and 24-hour blood pressure variability

Abstract Objectives This study aimed to investigate the relationships between cardiovascular outcomes and blood pressure (BP) reduction, 24-hour BP variability (BPV), morning BP surge (MBPS), and visit-to-visit BPV. Methods This study involved 897 participants from the Systolic Blood Pressure International Trial (SPRINT), for whom biochemical and demographic data, medication history, and various blood profile information were collected. Univariate and multivariate linear regression models were used to assess the impact of intensive BP management on 24-hour BPV and the MBPS. Results Among the 897 participants (average age 71.48 ± 9.42 years; 640 males), 453 received intensive treatment. Those in the intensive group were more likely to be on ACE inhibitors, CCBs, or diuretics. This group showed significant reductions in 24-hour systolic and diastolic BP, as well as in both short-term and long-term BPVs, such as average real variability (ARV) and MBPS. The analysis demonstrated strong associations between intensive BP management and improvements in various BPV measures, including systolic ARV, diastolic BP ARV, and cumulative BP loads. A significant correlation was also found between intensive BP lowering and the primary composite outcome of the SPRINT study. Conclusions This study highlighted the significant associations between intensive BP management and reductions in the MBPS and 24-hour BPV, which affect both short-term and long-term health outcomes. The primary benefits of intensive BP control appear to stem from direct BP reduction rather than changes in BPV. However, further extensive randomized controlled trials are needed to confirm these findings.

Nationwide trends in blood pressure control among those with and without diabetes in England over last 2 decades: Health Survey of England 2003-2019

Abstract Diabetes and hypertension are both risk factors for cardiovascular disease (CVD), and often co-exist. Over recent decades practice guidance and health policy efforts have been made to improve population wide blood pressure (BP) control, particularly amongst those with diabetes, to reduce CVD. However, the nationwide impact of these ongoing efforts is yet to be documented comprehensively in England. We used data from 11 serial nationally representative health surveys of England between 2003 and 2019 and compared BP control and presence of untreated hypertension amongst those with and without diabetes. These cross-sectional, randomly sampled surveys included 94,100 individuals cumulatively. We applied sample weights, accounting for oversampling and survey nonresponse, and transformations mitigating for survey equipment changes during this period. We used ‘period definitions’ to define those with diabetes and quantify BP control at the time of each coinciding survey, facilitating accurate comparison of trends over the sixteen-year period, while accounting for changes in understanding, variations in definitions, and shifts in medical practices. Python and STATA were used to conduct analyses and Join Point regression software was used to develop and compare trends. In England, from 2003-2019, the prevalence of hypertension amongst those with diabetes and without diabetes decreased from 74.4% to 66.5% and from 32.6% to 27.1% (7.9% vs. 5.5%), respectively. This corresponded to reductions in population-wide mean systolic (S) and diastolic (D) BPs: compared to those without diabetes, those with diabetes had greater reduction in both SBP (7.9mmHg vs. 4.8mmHg) and DBP (2.7mmHg vs. 1.9mmHg) (Figure1). Both groups showed similar temporal improvement in BP-control amongst those with diagnosed hypertension, with those with diabetes showing better improvement in BP control compared to those without diabetes (14% vs. 12%). There was a significant difference in proportions of those with undiagnosed (unaware) hypertension amongst those with and without diabetes (11.4% vs. 30.0% respectively) (Figure2). Notably, there was no change in proportion of those with hypertension unaware about the condition (i.e. detection rate for hypertension in either of the group did not show any improvement over time). These results suggest that we have been able to improve BP control over this period amongst those with and without diabetes, however, those without diabetes (more than 90% of population) have shown significantly poorer improvement. In addition, around one third of hypertensive patients amongst the no-diabetes group are unaware of the condition, and overall, the detection rates for hypertension in both groups have not improved in the last two decades. Lessons learnt from improving BP control amongst those with diabetes should be applied across the entire population, and newer strategies need to develop to improve detection of those with hypertension and are unaware.

Nationwide trends in major cardiovascular risk factors in England in the last 2 decades: Health Survey of England 2003-2019

Abstract Cardiovascular disease (CVD) accounts for a quarter of deaths annually in the UK, with more than 7.6 million people living with the disease. Hypertension, diabetes, and obesity are among the most prevalent modifiable risk factors for CVD, and the strategies to reduce the incidence and prevalence of these CV risk factors are deemed the most effective to reduce this immense toll. In the UK, over the last few decades, several health policy decisions and pathways have been developed to reduce this toll. We used data from 11 nationally representative, cross-sectional surveys from the Health Survey of England between 2003 and 2019 to evaluate trends in the prevalence of these CV risk factors and whether there has been any population-wide improvement in them. These surveys have cumulative information on 94,100 adults, and we applied sample weights, accounting for oversampling and nonresponse. We used "period definitions and cut-offs" to define those with diabetes. For example, for undiagnosed diabetes, we used glycated haemoglobin cut-off equivalent of 7% or more for years before 2011 and the current diagnostic threshold of &amp;gt; 6.5% thereafter. This was done to facilitate and compare the trends after accounting for changes in medical practice and understanding across this period. Similarly, hypertension was defined as doctor-diagnosed hypertension or in its absence regular use of antihypertensive medications or blood pressure ≥ 140/90mmHg (period diagnostic threshold remains unchanged during). Python and STATA were used to conduct analyses, and Join Point regression software was used to develop and compare trends. In England, from 2003-2019, mean population BMI consistently increased over this period, rising by 0.8kg/m2 from 27.6 to 28.8 kg/m2. Obesity prevalence (BMI ≥30kg/m2) increased by 5.4% from 22.6% to 28.0%. Concurrently, mean glycated haemoglobin increased by 0.36% from 6.18% to 6.54%, surpassing the current diabetes diagnostic threshold. Diabetes period prevalence surged from 4.2% to 11.6%, a trend consistent when the current diagnostic threshold was alternatively applied across all periods. Conversely, doctor-diagnosed and total hypertension (including those who are unaware) prevalence exhibited a slight decrease (1.4% and 3%, respectively), mirrored by reductions in population-wide mean systolic and diastolic blood pressure by 4.6mmHg and 1.9mmHg. These results suggest that, with the total population in England standing at 56.3 million in 2019, an estimated 15.8 million adults were within the obese BMI range, 6.5 million had diabetes and 17.6 million had hypertension. The obesity epidemic is likely fuelling the increase in diabetes prevalence. These findings underscore the importance of prioritising obesity reduction in public health initiatives, aiming to subsequently curb diabetes prevalence. Hypertension still remains a major CV risk factor, affecting almost one third of the adult population.

Blood pressure-lowering and risk of cancer: an individual participant-level data meta-analysis and mendelian randomisation studies

Abstract Background The current body of randomised evidence concerning the effect of blood pressure lowering on the risk of cancer remains limited. Purpose We leveraged the strengths of both randomised controlled trials (RCTs) and genomic information to examine this question. Methods Individual-level data from 314,016 participants from 42 RCTs were pooled to investigate the effect of blood pressure lowering on the risk of cancer through one-stage individual participant data (IPD) meta-analysis. The primary outcome was incident cancer, defined as the first occurrence of any cancer diagnosed after randomisation. Pre-specified subgroup analyses were conducted to assess heterogeneity in effect by follow-up time and baseline age groups, sex, body mass index categories, smoking status and previous use of antihypertensive drugs. Secondary outcomes were cause-specific cancer death and site-specific cancer risk comprising breast, colorectal, kidney, lung, prostate, and skin. Cox proportional hazard regression, stratified by trials, were used for statistical analyses. For site-specific cancers, analyses were complemented with Mendelian randomisation analyses using naturally randomised genetic variants associated with blood pressure lowering, retrieved from genome-wide association studies involving participants of European ancestry. Results Over a median of 4 years (interquartile range 2), 17,954 participants in RCTs were diagnosed with cancer of any type and 4,878 participants were reported to have died with cancer as the cause of death. In the IPD meta-analysis that compared the treatment arm with the comparator, no associations were identified between reductions in either systolic or diastolic blood pressure and the risk of incident cancer (hazard ratios [HRs] per 5 mmHg reduction in systolic and per 3 mmHg diastolic blood pressure were 1.03 (95% confidence interval [CI] 0.99-1.06) and 1.03 [0.98-1.07], respectively). We also found no pattern of increasing or decreasing relative risk for incident cancer during the follow-up period, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on the risk of cause-specific cancer death was identified for either systolic or diastolic blood pressure lowering. Considering site-specific cancers, we also found no evidence of effect, except for a possible link with lung cancer risk, with HRs of 1.17 [99.5% CI 1.02-1.32] for systolic blood pressure and 1.17 [99.5% CI 0.98-1.36] for diastolic blood pressure lowering. In Mendelian randomisation studies, no association was observed for genetically determined systolic and diastolic blood pressure and all the considered site-specific cancers, including overall lung cancer and its subtypes. Conclusion We found no consistent randomised evidence to suggest that blood pressure-lowering has a substantial effect, whether increasing or decreasing, on incident cancer, cause-specific cancer death, or selected site-specific cancers.

The relationship between lung MIBG uptake and clinical response to renal denervation

Abstract Background Renal denervation (RDN) reduces the sympathetic overdrive and can optimize blood pressure control in patients with difficult-to-treat hypertension (DTH). However, a substantial proportion of patients undergoing RDN do not show a clinical response to the procedure, making it critical to identify novel and more accurate predictors. The metaiodobenzylguanidine (MIBG) scintigraphy allows non-invasive assessment of sympathetic nerve activity. Yet, studies evaluating the heart and kidney MIBG uptake as predictors of clinical response to RDN provided conflicting results, and a comprehensive evaluation of the MIBG uptake in different organs of DTH patients undergoing RDN is lacking. Purpose To explore if a more comprehensive evaluation of MBG uptake in the kidneys, heart and lungs can predict the clinical response to RDN. Methods Eighteen patients with DTH underwent evaluation of their clinical and pharmacological history, office and ambulatory BP values and levels of cardiovascular risk factors. A rest echocardiography, carotid vascular ultrasound and MIBG scintigraphy were also performed before RDN. The patient’s pharmacological history and office and ambulatory BP values were re-evaluated after 3 months from RDN. We considered responders (R) those subjects with a significant reduction of the office BP values on stable BP-lowering treatment or a reduced burden of BP-lowering medications while maintaining optimal control of the office BP. Results Ten patients could be classified as R (1 woman, mean age 49±10 years), while 7 were non-responders (NR, 2 women, mean age 53±8 years). The reduction in office systolic and diastolic BP (baseline vs 3 months) was significantly larger in R vs NR (p=0.01 for both). The burden of BP-lowering medications after the procedure was reduced by 39% in R, compared to 2% in NR (p&amp;lt;0.01). Responders had a higher baseline HR and prevalence of carotid atherosclerosis than NR (p&amp;lt;0.05 for both). In early MIBG acquisitions, the lung/mediastinum ratio on both sides showed higher MIBG uptake in R vs NR (p&amp;lt;0.05). There was a higher MIBG uptake in the right vs. left lung in the whole population and in R vs NR. In late acquisitions, only the left side showed a significant difference between R and NR (p&amp;lt;0.05). The associations between the lung/mediastinum ratio MIBG uptake and response to RDN remained significant after adjusting for the baseline clinical predictors of the RDN response. All other MIBG scintigraphy parameters were similar between groups. Conclusions Our results suggest that RDN might be less effective in patients with an advanced burden of hypertension-mediated target organ damage and confirm a higher HR as a reliable predictor of the clinical response to the procedure. We also document a novel association between the lung/mediastinum ratio MIBG uptake and response to RDN that, if confirmed in future studies, might provide a novel marker to improve the selection of patients undergoing RDN.

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with &amp;gt;10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p&amp;lt;0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Efficacy of online japanese intensive cardiac rehabilitation for secondary prevention for coronary artery disease: a comprehensive program including exercise, nutrition, mindfulness, and group support

Abstract Background/Introduction While comprehensive programs for cardiac rehabilitation are recommended for patients with coronary artery disease (CAD), systematic programs including nutrition, stress-management, and behavior change have not been clearly established. Purpose To comprehensively change the lifestyle of patients with CAD as secondary prevention, we developed an online based educational program "intensive cardiac rehabilitation for Japanese patients with CAD (J-ICR)" modifying ICR, a regimen covered by health insurance in the United States, to the program that has affinity with Japanese. Methods Online J-ICR program is set up as sessions for maintenance-phase CAD patients using an online application. J-ICR has 12 sessions held weekly for 3 hours per session, total 36 hours, aimed to integrate 4 components: 1) exercise guidance based on exercise prescription which contain aerobic exercise, resistance training, and multi-component exercise through online platforms, 2) dietary education focusing on "the Japan Diet", 3) stress management utilizing mindfulness, and 4) group support to enhance patient and medical-staff interaction. Twenty-two participants were randomly separated to Early Phase group and Late phase group. For verification of the efficacy of this program, we survey the adherence to the program and compared the changes in risk factor of CAD at 3 months defining Early phase group as intervention group and Late phase group as control. (Fig.1). Results After excluding 3 participants who withdrawn to participate, the remaining 19 participants were conducted the evaluation and 10 participants were in intervention group and 9 participants in control group, respectively. As for patient characteristics, the mean age was 66 years old, and all participants were male. History of CVD was comprising 8 cases of myocardial infarction and 15 cases of angina pectoris. As for the risk factors of CVD, there were not significant differences in mean low density lipoprotein (LDL) cholesterol (Intervention group 71.5mg/dl vs Control group 83.4mg/dl; p=0.12) or systolic blood pressure (SBP) (126mmHg vs 130mmHg; p=0.40) at base line between two groups. The average participating rate in program was 93.8% and there was no dropped out participant during the program in investigation group. After 3months, LDL cholesterol was not significantly decreased in both groups (mean reduction of Intervention group -0.3mg/dl, p=0.93 and control group -3.8mg/dl, p=0.43, respectively). However, there was significant reduction of SBP in intervention group (mean reduction 5.6mmHg, p=0.02) but in control group (mean reduction 2.4mmHg, p=0.42). (Fig.2). Conclusions This randomized controlled study showed the good adherence of J-ICR program and it suggested that J-ICR program has the effect on lowering systolic blood pressure at 3 months. Longer follow up data and the results of more participants are warranted to clarify the efficacy in real world prevention of CVD.

Semaglutide for the treatment of resistant hypertension

Abstract Background Treatment options for resistant hypertension (RH) are often limited by medication intolerance and adverse effects. Novel approaches to treatment are required. The disease of obesity affects 70% of patients with RH. Purpose To determine if a weight centric approach using semaglutide improved BP control in patients with RH. Methods Individual participant data from three randomised placebo-controlled trials (STEP 1, 3 and 4) examining the effect of semaglutide 2.4mg on body weight over 68 weeks were included. Participants on &amp;gt;4 anti-hypertensive medications or those with systolic BP (SBP) &amp;gt;130mmHg at baseline and 3 anti-hypertensive medications including a diuretic were considered to have RH. Firstly, the change in SBP comparing those on semaglutide to placebo was analysed with baseline systolic BP as a covariate in an ANCOVA model. Then, the RH group was subdivided into those with SBP above or below 130mmHg at baseline and BP response to semaglutide assessed. Analyses were performed using R Software version 4.0.3. Results In the pooled analysis of 3136 trial participants, 111 met the criteria for RH. Compared to placebo, participants on semaglutide had a SBP reduction of -4.93mmHg, adjusted for SBP baseline to -3.16mmHg (95%CI -8.69 to 2.37). For those with RH and a baseline SBP &amp;gt; 130mmHg on semaglutide, the SBP change was -10.94mmHg. This change was 4.54mmHg for those with a SBP &amp;lt; 130mmHg. The diastolic BP changes were -3.62 and 2.79mmHg respectively (Figure 1). At trial completion, 36% of those on semaglutide did not meet the criteria for RH. Conclusions The effect of semaglutide on BP for patients with RH is modest. A greater BP reduction is evident for those with a higher baseline SBP. Targeting excess body weight with semaglutide is a viable treatment option for patients with RH and uncontrolled BP.

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): &amp;lt;45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups &amp;lt;45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group &amp;lt;45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p&amp;lt;0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p&amp;lt;0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p&amp;lt;0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p&amp;lt;0.001). Between group differences in eGFR changes were statistically significant (adjusted p&amp;lt;0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR &amp;lt;45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Systematic Review: Comparative Efficacy and Safety of Losartan vs. Candesartan for the Treatment of Hypertension

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease (CVD) and remains a leading cause of morbidity and mortality globally. Effective management of hypertension is essential for preventing comp lications such as stroke, myocardial infarction, and heart failure. Angiotensin II receptor blockers (ARBs) like losartan and candesartan are well-established therapeutic options for blood pressure (BP) control and are widely prescribed due to their favorable side-effect profiles and organ-protective properties. Despite being members of the same drug class, these ARBs differ in their pharmacokinetics, receptor binding affinity, and clinical efficacy. This systematic review aims to provide a detailed comparison of the efficacy and safety of losartan versus candesartan in managing hypertension. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases, retrieving studies published from 2000 to 2024 that compared the two ARBs directly in hypertensive populations. A total of 25 randomized controlled trials (RCTs) and observational studies, comprising more than 12,000 participants, were included in the analysis. The primary outcomes evaluated were the reduction in systolic and diastolic blood pressure, cardiovascular event prevention, and adverse event profiles. The results suggest that both losartan and candesartan effectively lower BP, but candesartan consistently demonstrated greater reductions in both systolic and diastolic BP compared to losartan. Candesartan also appeared to have superior cardiovascular outcomes, with a lower incidence of major cardiovascular events such as stroke, myocardial infarction, and heart failure hospitalizations. The safety profiles of both drugs were comparable, though losartan was associated with a slightly higher incidence of cough and discontinuation due to adverse events. Overall, candesartan may offer a slight clinical advantage over losartan, particularly in patients requiring more potent or sustained BP control. However, both drugs remain valuable options in the management of hypertension. Further long-term studies are recommended to confirm these findings and to investigate the potential benefits of each drug in specific patient subgroups.