Blood Pressure Lowering Effect Research Articles

Effects of blood pressure lowering in patients treated with intravenous thrombolysis before endovascular thrombectomy.

The effects of blood pressure (BP) lowering in patients treated with intravenous tissue plasminogen activator (IV tPA) before endovascular thrombectomy (EVT) are unclear. This study aims to investigate whether intensive and conventional BP management affect outcomes differently, depending on IV tPA administration before EVT. In this subgroup analysis of the Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control (OPTIMAL-BP; ClinicalTrials.gov Identifier: NCT04205305) trial, patients were divided into groups based on IV tPA use before EVT. Clinical outcomes of intensive (systolic BP target <140 mm Hg) or conventional BP management (systolic BP target 140-180 mm Hg) were compared among group. The primary efficacy outcome was a favorable outcome at 3 months (modified Rankin Scale score of 0-2). Primary safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 36 hours and stroke-related death within 3 months. Among the 302 patients, the IV tPA group included 98 (32.5%) and the non-IV tPA group comprised 204 subjects (67.5%). In the IV tPA group, intensive BP management significantly lowered the favorable outcome rate (intensive, 27.3% vs. conventional, 51.9%; adjusted odds ratio [aOR], 0.36; 95% confidence interval [CI], 0.13-0.93; p = 0.04). In the non-IV tPA group, the risk difference rate of favorable outcome was not significantly different between intensive and conventional BP management (44.1% vs. 55.9%; aOR, 0.62; 95% CI, 0.31-1.22; p = 0.17). Notably, the proportion of malignant cerebral edema within 36 hours in the IV tPA group was significantly higher in the intensive management group (18.2%) than in the conventional management group (1.9%; aOR, 10.72; 95% CI, 1.24-92.29; p = 0.03). sICH and mortality rates were not significantly different between intensive and conventional BP management in either study groups. Intensive BP management worsen 3-month functional outcomes after successful EVT without reducing sICH among patients who received IV tPA before EVT, indicating that BP lowering in this population should be cautious.

Alcohol consumption and ambulatory blood pressure-lowering effect in male patients on clinic blood pressure-guided antihypertensive treatment.

In the present analysis, we investigated the association between alcohol consumption and ambulatory blood pressure (BP) control in male patients after 8 weeks of antihypertensive therapy with two dihydropyridine calcium channel blockers. The study participants were hypertensive (clinic systolic/diastolic BP of 140-179/90-109 mmHg and 24-hour ambulatory systolic/diastolic BP ≥ 130/80 mmHg) patients enrolled in a randomized controlled trial and treated with amlodipine 5-10 mg or nifedipine gastrointestinal therapeutic system (GITS) 30-60 mg once daily. Alcohol consumption was classified as non-drinkers and drinkers. Non-dipping was defined as a BP drop from daytime to nighttime <10%. At baseline, the 131 alcohol drinkers, compared with 141 non-drinkers, had a significantly higher nighttime systolic/diastolic BP (129.3 ± 13.5/83.8 ± 9.5 vs. 125.7 ± 12.3/80.9 ± 8.2 mmHg, P ≤ 0.02), night-to-day ratio for both systolic (89.1 ± 8.5 vs. 87.0 ± 7.1%, P = 0.03) and diastolic BP (88.7 ± 8.8 vs. 86.5 ± 7.9%, P = 0.04) and prevalence of non-dippers for systolic (45.0% vs. 33.3%, P = 0.048) and diastolic BP (42.0% vs. 29.8%, P = 0.04). However, they had similar clinic and 24-hour and daytime ambulatory BP at baseline (P ≥ 0.07). Antihypertensive treatment significantly (P ≤ 0.001) reduced clinic and ambulatory systolic and diastolic BP from baseline in both alcohol drinkers and non-drinkers at 4 and 8 weeks of follow-up. However, in patients with a non-dipping pattern at baseline, the proportion of dippers for systolic/diastolic BP at 8 weeks of follow-up (36.5% vs. 58.5%) was significantly lower in 67 alcohol drinkers than in 52 non-drinkers (P = 0.035). Alcohol drinkers had higher nighttime BP and a higher prevalence of non-dippers than non-drinkers. Clinic blood pressure-guided antihypertensive treatment was insufficient in controlling nighttime BP or changing the non-dipping to dipping pattern in alcohol drinkers with sustained clinic and ambulatory hypertension. Alcohol drinkers had higher nighttime systolic and diastolic blood pressure than non-drinkers at baseline. Clinic blood pressure-guided antihypertensive treatment was insufficient in changing the non-dipping to dipping pattern in alcohol drinkers with sustained clinic and ambulatory hypertension.

The blood pressure lowering effect of beetroot juice is impaired in periodontitis and recovered after periodontal treatment

We have previously demonstrated that subgingival levels of nitrate-reducing bacteria, as well as the in vitro salivary nitrate reduction capacity (NRC), were diminished in periodontitis patients, increasing after periodontal treatment. However, it remains unclear if an impaired NRC in periodontitis can affect systemic health. To determine this, the effect of nitrate-rich beetroot juice (BRJ) on blood pressure was determined in 15 periodontitis patients before and 70 days after periodontal treatment (i.e., professional mechanical plaque removal, oral hygiene instruction, and subgingival instrumentation), as well as in a healthy control group of 15 individuals. Additionally, subgingival and tongue samples were taken to analyse the bacterial composition with Illumina sequencing of the 16S rRNA gene. In healthy individuals, the systolic and diastolic blood pressure (SBP and DPB) decreased significantly (both P < 0.01) 90 min after BRJ intake, but not in periodontitis patients. However, after periodontal treatment, this blood pressure-lowering effect was recovered (P < 0.05 for SBP; P < 0.01 for DBP). Lower levels of salivary nitrate after identical doses of BRJ intake indicated a potentially higher NRC in healthy individuals (P < 0.05). Periodontitis-associated bacteria decreased in tongue and subgingival samples after periodontal treatment (P < 0.01). In contrast, nitrate-reducing bacteria were associated with health in both habitats, but increased only in subgingival plaque after periodontal treatment (P < 0.001). This is the first study showing that periodontitis could limit the blood-pressure lowering effects of nitrate reduction by the oral microbiota. We propose that an impaired NRC represents a potential link between periodontitis and systemic conditions, which should be confirmed in future randomized controlled trials. Future work should also aim to determine if nitrate prebiotic supplementation and/or tongue cleaning could improve the treatment of periodontitis and its associated comorbidities.

Efficacy and Safety of Sacubitril/Valsartan Versus Amlodipine in Japanese Patients With Essential Hypertension: A Randomized, Multicenter, Open-Label, Noninferiority Study (PARASOL Study).

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has demonstrated a superior blood pressure-lowering effect compared with renin-angiotensin system inhibitors in several clinical trials. However, there has been no available evidence on the comparison between sacubitril/valsartan and calcium channel blockers (CCBs), a well-established class of antihypertensive drugs. In this open-label, multicenter study, we aimed to demonstrate the efficacy and safety of sacubitril/valsartan versus amlodipine, one of the most widely used CCBs, after 8 weeks of treatment. A total of 359 Japanese patients with essential hypertension (office systolic blood pressure [SBP] ≥150 to <180mmHg), aged 18-79, were randomly assigned to receive either once-daily sacubitril/valsartan 200mg or once-daily amlodipine 5mg in a 1:1 allocation ratio. The primary endpoint was the noninferiority of sacubitril/valsartan compared with amlodipine in mean change in 24-h SBP from baseline to Week 8, followed by a significance test as a secondary endpoint analysis. The mean change in 24-h SBP in sacubitril/valsartan was noninferior to that in amlodipine (between-treatment difference -0.62mmHg [95% confidential interval: -3.23 to 1.98; p = 0.003 for noninferiority; independent t-test with noninferiority margin 3.0mmHg]), with no significant difference observed (p=0.637). There was no significant difference in the incidence of adverse events (AEs). These results suggested that the blood pressure-lowering effect of sacubitril/valsartan is comparable to that of amlodipine, with no marked differences in tolerability between the two groups. Sacubitril/valsartan, a potent antihypertensive drug comparable to amlodipine, is expected to improve blood pressure control in clinical practice.

Systematic Review and Meta-Analysis in Randomized Controlled Trials of Anti-Hypertensive Drugs and the Risk of Cancer

This paper evaluates the potential carcinogenicity of anti-hypertensive medications by performing a meta-analysis on the risk of cancer associated with their use. The analysis incorporated data from 12 studies, encompassing a total of 16,711,997 observations, and focused on randomized controlled trials of anti-hypertensive drugs. The primary objective was to compare the cancer risk across different classes of these medications while considering their blood pressure-lowering effects. The meta-analysis employed a random-effects model to synthesize the results. The mean effect size was found to be 1.178, with a 95% confidence interval ranging from 1.027 to 1.351. A Z-test conducted to test the null hypothesis that the mean effect size equals 1 yielded a Z-value of 2.343 and a p-value of less than 0.019, leading to the rejection of the null hypothesis. This indicates a statistically significant association between the use of anti-hypertensive drugs and an increased risk of cancer. The heterogeneity among the included studies was significant, as evidenced by a Q-statistic of 85.118 with 11 degrees of freedom and a p-value of less than 0.001. The I-squared statistic was 87%, suggesting that 87% of the variance in observed effects was due to differences in true effects rather than sampling error. The tau-squared value, representing the variance of true effect sizes, was 0.040 in log units, while tau, the standard deviation of true effect sizes, was 0.201 in log units. Assuming a normal distribution of true effects, the prediction interval for the true effect size was estimated to be between 0.733 and 1.894, meaning that the true effect size in 95% of all studies would fall within this range. Overall, the findings suggest a potential risk of cancer associated with anti-hypertensive drugs, which warrants careful consideration when weighing their benefits and risks. The computations for the analysis were conducted using Comprehensive Meta-Analysis.

Blood glucose and blood pressure lowering effect of diets supplemented with whole unripe plantain flour and effects on altered biomolecules in diabetic/hypertensive rats

Plantain has been used in folklore for the management of diabetes and hypertension. The locals either make whole unripe plantain fruits into wet slurry or powdered form. This study seeks to evaluate fasting blood glucose (FABG) and blood pressure (BP) lowering ability of diets from whole (with peel) unripe plantain flour and their effect on biomarkers linked to the manifestation of diabetes and hypertension in diabetic/hypertensive (DH) rats. Cookies were formulated with whole unripe plantain flour and designated as Diet A-E. Then, organoleptic properties, amylose/amylopectin contents and glycemic index (GI) were determined. Experimental rats were sourced for DH induction and grouped as follows: Group-1: healthy rats; Group-2: DH rats; Group-3: DH rats administered acarbose/captopril; Group 4–7 rats fed with Diet A to D. The experiment lasted for 14 days. Our results revealed that the formulated diets had higher amylose, lower amylopectin content, and moderate GI. Also, DH rats fed with the formulated diets had reduced FABG, BP, decreased activity of carbohydrate-digesting enzymes, angiotensin-converting enzyme, and arginase with enhanced antioxidant status compared to untreated DH rats. Whole unripe plantain flour-supplemented diets exhibit health benefits, are safe and could serve as a functional food for diabetes and its complication management.

Impact of Deep Diaphragmatic Breathing with Virtual Reality on Blood Pressure in Patient with Hypertension: A mini Review

Virtual Reality (VR) offers a promising drug-free approach to relaxation for people with psychiatric issues. Studies show VR relaxation not only helps manage stress but also promotes positive emotions and decreases blood pressure. Compared to traditional relaxation techniques, VR requires less mental effort and delivers a more significant boost in positive feelings. The results of the current review indicate that VR with deep diaphragmatic breathing may be associated with a blood pressure-lowering effects for adult people with hypertension. Also VR technology can be used as a good facilitator of different practices for stress reduction and treatment of chronic pain (for example by meditation practices). The immersive and interactive nature of VR adds a positive effects for different modalities as it creates a semi-real environment and give the patient the sense of achievement.

The common component of traditional Chinese medicine formulations has a role in the treatment of hypertension.

Abstract. Hypertension is one of the most common cardiovascular diseases, but the control rate of hypertension is not high, only 16.8%, which a serious public health problem in our country. This article analyzes some commonly used traditional Chinese medicine formulations that effectively treat high blood pressure and lists the ingredients of these common drugs. Find common ingredients that includes: Rhizoma Gastrodiae, Uncaria, and Licorice. The study found that the active ingredients in the three herbs, such as gastrodin, gastrodia elata ethyl acetate extract routine and isoglycyrrhizin, have a significant effect on lowering blood pressure. This research can provide hypertensive patients with a better understanding of the reasons for taking these herbs and offer guidance on medication. It can also help patients recognize the necessity of combined Chinese medicine. However, the study only explore the blood pressure-lowering effects of the active ingredients but does not investigate the specific treatment of different types of hypertension using individual Chinese medicine preparations. In the future will refine the effects of these herbs in various types of hypertension.

Abstract 4116298: Once Weekly Utreglutide (GL0034), a Glucagon-like Peptide-1 Receptor Agonist, at 4 × 450 µg Doses Reduces Blood Pressure, Lipids, and Body Weight in Post-menopausal Females: A Phase I Study

Background: Utreglutide (GL0034), a novel, once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated significant reductions in body weight (BW) after a single dose ascending study in individuals with obesity . BW reductions after pharmacological treatment of obesity with GLP-1RA is associated with blood pressure (BP) lowering effects. Aim: This phase I study assessed the safety, tolerability, and cardio-metabolic effects of utreglutide after multiple ascending doses in post-menopausal female volunteers with overweight and obesity. Methods: In this randomized, double-blind, placebo-controlled study 12 post-menopausal female volunteers with overweight/obesity, aged 18 to 65 years old with a body mass index (BMI) ≥26 kg/m 2 were randomized (9:3) to subcutaneous utreglutide fixed doses (4 × 450 µg); or placebo once weekly for four weeks. Safety, tolerability, and key cardio-metabolic parameters were assessed. Biomarker measurements included oral glucose tolerance test (OGTT) insulin and glucose area under the curve (AUC), systolic- and diastolic BP, lipid profile (triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL), creatinine, potassium, BW and leptin. Results: Utreglutide was generally well tolerated and related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Reductions in OGTT AUCs of insulin ( p &lt;0.05) and glucose ( p &lt;0.01) were noted on Day 23 after four weeks treatment with Utreglutide. This was accompanied by a decrease ( p &lt;0.001) in mean systolic and diastolic BP on Day 23 from baseline (BL). On Day 23, significant reductions in TC ( p &lt;0.01), LDL ( p &lt;0.05) and non-HDL ( p &lt;0.05) were observed. BW reduction versus BL ( p &lt;0.001) was 2.0 kg and 1.8 kg respectively on Day 29 and End of Study (EoS). Leptin levels significantly reduced from BL on Day 23 ( p&lt; 0.01) and EoS ( p &lt;0.001). No significant changes were observed for TG, creatinine and potassium (Table). Conclusions: Once weekly utreglutide dosing for four weeks at a dose of 450 µg in post-menopausal females with overweight and obesity, demonstrated clinically relevant reductions of systolic and diastolic BP. This was associated with improved performance of OGTT AUC of insulin and glucose, lipids, BW and leptin with an overall good tolerability and with potential to demonstrate cardio-metabolic benefits.

Abstract 4134333: Blood pressure reduction in diabetic patients with resistant hypertension: results from the aprocitentan PRECISION study

Background: In patients with resistant hypertension (RHT), diabetes is a frequent comorbidity that increases the risk of cardiovascular events. The phase-3 PRECISION study demonstrated the efficacy of aprocitentan (APRO), a dual endothelin ET A /ET B receptor antagonist, to lower blood pressure (BP) in patients with RHT. In this pre-planned PRECISION post hoc analysis, we evaluated the BP lowering effect of APRO in diabetic patients. Methods: Eligible patients were hypertensive despite treatment with ≥3 antihypertensive medications from different classes. After ≥4 weeks of combination therapy (amlodipine/valsartan/hydrochlorothiazide), patients still hypertensive received single-blind placebo for a run-in period, followed by a 4-week double-blind part (APRO 12.5 mg, 25 mg, or placebo), a 32-week single-blind part (APRO 25 mg) and a 12-week double-blind withdrawal part (APRO 25 mg or placebo). The primary endpoint was change from baseline to Week 4 in mean trough office SBP. Results: Out of 730 patients, 395 (54%) had diabetes (APRO 12.5 mg, n=112; 25 mg, n=107; placebo, n=116). At Week 4, APRO reduced office SBP (12.5 mg: −14.6; 25 mg: −14.1 mmHg) vs placebo (−9.4 mmHg) in diabetic patients, with no treatment/diabetes status interaction (p=0.77). The reduction was maintained at Week 36 (−16.2 mmHg). APRO also reduced mean 24-hour ambulatory SBP at Week 4 (12.5 mg: −7.4 mmHg; 25 mg: −9.5 mmHg) vs placebo (−2.2 mmHg), most pronounced on night-time values (12.5 mg: −8.9 mmHg; 25 mg: −13.1 mmHg; placebo: −1.6 mmHg). At Week 40, after 4 weeks of withdrawal, office SBP increased in placebo patients (+3.6 mmHg) and remained stable with APRO 25 mg (+0.2 mmHg). A substantial reduction in urine albumin–creatinine ratio of 33% and 37% was observed at Week 4 for APRO 12.5 mg and 25 mg, respectively, compared with an increase of 11% for placebo. Edema/fluid retention were the most common adverse events; they were mild-to-moderate in most cases and dose dependent (9%, 23%, and 2% of patients receiving APRO 12.5 mg, 25 mg, and placebo, respectively, up to Week 4). During the study, 11 patients were hospitalized for heart failure (10 treated with APRO 25 mg and one with placebo). Among these, 6 had chronic kidney disease stage 3–4, and 5 had medical history of heart failure; no cases were fatal. Conclusion: APRO produced clinically relevant and sustained BP reduction in diabetic patients with RHT, consistent with the effect observed in the overall population.

Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta-Analysis.

Lowering blood pressure (BP) in persons with low diastolic BP could be harmful. Hence, we examined whether baseline diastolic BP modifies the effects of BP lowering on clinical outcomes in a meta-analysis of five large BP lowering trials. In a study-level meta-analysis based on individual participant data of the Systolic Blood Pressure Intervention Trial (N = 9361), the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (N = 2362), the Secondary Prevention of Small Subcortical Strokes (N = 3020), the African American Study of Kidney Disease and Hypertension (N = 1094) and the Modification of Diet in Renal Disease (N = 840) studies, we used DerSimonian-Laird random-effects models to examine the dependence of the effect of the BP lowering intervention on baseline diastolic BP for cardiovascular, all-cause mortality and kidney outcomes. Mean baseline age was 65 ± 10 years old. Mean baseline systolic and diastolic BP were 141 ± 17 and 79 ± 12 mm Hg, respectively. More intensive BP control resulted in lower risk of composite cardiovascular outcome (HR 0.79, 95% CI 0.72, 0.87) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.99) without evidence that the BP intervention effects differed by level of baseline diastolic BP (interaction p = 0.76 for cardiovascular composite and 0.85 for all-cause mortality). The mean baseline diastolic BP in the lowest and the upper three quartiles of baseline diastolic BP were 65 ± 6 mm Hg and 84 ± 9 mm Hg, respectively but the effects of the BP interventions on the outcomes were similar in both groups. Furthermore, there was no evidence of interaction of the BP intervention and baseline diastolic BP for kidney outcomes. Within the included diastolic BP range, there was no evidence that baseline diastolic BP modified the beneficial effects of intensive BP lowering.

The health benefits of fermented fruits and vegetables and their underlying mechanisms.

Fermented fruits and vegetables are rich in phenolic compounds, minerals, and vitamins, which have potential health benefits for the prevention of many diseases such as cardiovascular disease and Type 2 diabetes. There is a growing demand for the development of nondairy probiotic products based on fruits and vegetables in view of changing lifestyles (e.g., vegetarianism, veganism, and allergy to dairy products) and the rise of nutritional diet therapy. In this review, the processes and health potential of fermented fruits and vegetables are described. The study focuses on the role of bacteria and fungi in fermented fruits and vegetables, outlines the process of transformation of bioactive components, and systematically summarizes the possible mechanisms of antioxidant, anti-inflammatory, and blood pressure-lowering effects. The health effects of fermented fruits and vegetables depend mainly on the microorganisms present in the fermentation process and the bioactive components they produce, such as phenols, vitamins, and organic acids. These active compounds exert many health effects such as antioxidant, anti-inflammatory, anti-obesity, hypotensive, hypoglycemic, and other health benefits. Therefore, the development of fermented foods based on fruits and vegetables can be a promising way to adapt to the market demand and to reduce the wastage of agriculturally produced fruits and vegetables.

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD). We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD. CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups. In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.

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.

Cardiovascular effects of obstructive sleep apnoea and effects of continuous positive airway pressure therapy: evidence from different study models

INTRODUCTIONCardiovascular consequences of obstructive sleep apnoea (OSA) and the effects of continuous positive airway pressure (CPAP) therapy on blood pressure, endothelial dysfunction, and MACE (major adverse cardiovascular events) have been studied over decades using different study designs. However, clinical findings from different study models on cardiovascular outcomes are sometimes contradictory.METHODSA literature search was conducted in PubMed for randomised controlled trials, meta-analyses, population-based epidemiological studies and OSA cohort studies up to September 2023 investigating the cardiovascular effect of OSA and CPAP in adults with OSA on the following cardiovascular endpoints: blood pressure, arterial hypertension, endothelial function, and MACE (myocardial infarction, stroke, transient ischemic attack, cardiovascular death). The level of evidence for these outcomes was discussed on the basis of different study models.RESULTS AND CONCLUSIONSThere is high-level evidence of a causal relationship between OSA and arterial hypertension and endothelial dysfunction, as well as on higher MACE incidence among subgroups of patients with untreated OSA. The cardiovascular effects of OSA depend on the severity of OSA, symptoms, phenotype, and comorbidities. The blood pressure-lowering effect of CPAP is mainly observed in uncontrolled and treatment-resistant hypertension. The MACE risk reduction in OSA depends on good long-term CPAP adherence. Younger, sleepy patients with more severe OSA, higher hypoxaemic burden and without overt cardiovascular end-organ disease may particularly benefit from CPAP treatment in terms of cardiovascular risk reduction. Randomised controlled trials of CPAP or other effective OSA treatments in primary cardiovascular prevention and in patients at highest risk are lacking.

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.

Home blood pressure-lowering effect of esaxerenone versus trichlormethiazide for uncontrolled hypertension: a predefined subanalysis of the EXCITE-HT randomized controlled trial by basal calcium channel blocker versus angiotensin receptor blocker.

This prespecified subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to examine the non-inferiority of esaxerenone to trichlormethiazide as a second-line antihypertensive agent according to the basal antihypertensive agent used (angiotensin receptor blocker [ARB] or calcium channel blocker [CCB]). The primary endpoint, change in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to end of treatment was similar between the two groups (intergroup difference in least squares mean change [95% confidence interval]: -1.3 [-3.8, 1.3]/-0.2 [-1.6, 1.3] mmHg for ARB; -2.7 [-4.2, -1.2]/-0.8 [-1.7, 0.1] mmHg for CCB). The respective incidences of serum potassium levels <3.5 mEq/L and ≥5.5 mEq/L in the ARB subgroup were 3.4% and 4.2% for esaxerenone and 7.9% and 0% for trichlormethiazide; in the CCB subgroup, they were 2.8% and 0.6% for esaxerenone and 13.9% and 1.2% for trichlormethiazide, respectively. The incidence of uric acid level ≥7.0 mg/dL was numerically higher in the trichlormethiazide group than the esaxerenone group in both the ARB and CCB subgroups. The non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP was demonstrated regardless of whether the basal antihypertensive agent was an ARB or CCB. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns. Serum potassium levels tended to be higher when esaxerenone was combined with an ARB than with a CCB, but this can be mitigated if administered according to the package insert. A subgroup analysis of the EXCITE-HT study according to basal antihypertensive agent demonstrated the non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP regardless irrespective of the basal antihypertensive agent. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns.

A single-dose, randomized, crossover bioequivalence study of levamlodipine besilate tablets in healthy subjects.

Levamlodipine, the levorotatory form of amlodipine racemate, has a blood pressure-lowering effect that is twice that of the racemate. The study aims to establish a foundation for the clinical application of the test drug by conducting a phase I clinical bioequivalence trial, comparing its bioequivalence and safety with the reference drug in healthy Chinese subjects. Recruiting 26 healthy subjects for separate bioequivalence trials in both fasting and fed conditions. The subjects will orally administer 2.5-mg test drug and 5-mg reference drug. A chiral method was used for bioanalytics and liquid chromatography-tandem mass spectrometry was employed to quantify the (S)-amlodipine concentrations at various time points after administration. In fasting condition, the geometric mean ratios (GMRs) for the primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ are 100.24%, 103.63%, and 103.24%, respectively. The 90% confidence intervals (CIs) fall within the range of 80-125%, satisfying the established bioequivalence criteria. Similarly, upon oral administration of the drugs in the fed condition, the GMRs for Cmax, AUC0-t, and AUC0-∞ are 96.48%, 99.90%, and 99.62%, respectively. The corresponding 90% CIs are within the limits of 80-125%, meeting the predefined bioequivalence standards. Furthermore, both drugs exhibited favorable safety profiles. The results show that the two drugs are bioequivalent in healthy Chinese subjects under both fasting and fed conditions. The two drugs both had similar PK parameters and good safety.

Combination blood pressure lowering therapy in patients with type 2 diabetes: messages from the ADVANCE trial.

The Action in Diabetes and Vascular disease: preterAx and diamicroN Controlled Evaluation (ADVANCE) trial investigated the effects of intensive blood pressure (BP) lowering using a fixed combination of perindopril-indapamide versus placebo in type 2 diabetes (T2D). The study showed that combination perindopril-indapamide had significant benefits in reducing cardiovascular, renal, and mortality events, with consistent relative risk reductions across different patient subgroups. Secondary analyses of ADVANCE have identified novel risk markers in T2D including cessation of BP lowering therapy, absent peripheral pulses and cardiac biomarkers to name a few. ADVANCE also shed light on practical aspects of hypertension management, including the limitations of office BP, tolerability of combination BP lowering therapy across the range of BP levels and the interpretation of changes in serum creatinine after treatment initiation. This review article summarizes the findings of ADVANCE and its subsequent substudies, which have been foundational in our understanding of BP management and the use of combination BP lowering therapy in T2D.

8204 Rare Asymptomatic Presentation Of A Large Pheochromocytoma

Abstract Disclosure: A. Lorin: None. C.K. Persaud: None. M.H. Kemm: None. Background: Pheochromocytoma is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. It is associated with excessive release of catecholamines causing symptoms of hypertension, palpitations, diaphoresis, and headaches. These symptoms are particularly prominent with larger pheochromocytomas. We present the case of a large 13 cm pheochromocytoma (PCC) without the typical associated symptoms. Clinical Case: A 45-year-old male with medical history of osteoarthritis and gastroesophageal reflux presented to his primary care doctor with 2 months of intermittent right upper quadrant abdominal pain associated with nausea. Work up with CT abdomen/pelvis found a 9.3 cm heterogeneous right adrenal mass with mass effect on the right liver lobe, superior pole of the right kidney, duodenum, and pancreatic head. Hormonal testing was notable for plasma metanephrine 257.8 pg/mL (0-88), plasma normetanephrine 12063.7 pg/mL (0.0-218.9), 24 hr urine metanephrine 159 mcg/24 hr (58-276), 24 hr urine normetanephrine 22575 mcg/24 hr (156-729), and chromogranin A 5387 mg/mL (0-101.8). Given lab evaluation, diagnosis was made of pheochromocytoma, and patient was initiated on alpha blockade with doxazosin. Patient’s blood pressure and heart rate were at goal prior to doxazosin initiation and patient needed to be decreased from 1 mg daily to 0.5 mg daily due to side effects of low blood pressure and orthostatic hypotension. Patient had an uncomplicated open right adrenalectomy with pathology showing a 13 cm pheochromocytoma with invasion through the capsule into the periadrenal adipose tissue. Genetic testing revealed no known mutation variants associated with PCC. Labs drawn two weeks postoperatively showed resolution of elevated plasma metanephrine, normetanephrine, and chromogranin A. Conclusion: While the patient had an elevated plasma metanephrine, the normetanephrine was predominantly elevated. Such a hormone profile is more common in extra-adrenal PCCs, consistent with cluster 1 associated genes. This noradrenergic phenotype is likely a reason the patient did not have typical symptoms, despite the size of his pheochromocytoma. A proposed pathophysiologic mechanism for this is the dissociation of renal medulla from the cortex given the large size of the tumor. This would lead to lower local availability of corticosteroid to potentiate the conversion of norepinephrine to epinephrine, thus decreasing likelihood of classical PCC symptoms. Despite lack of expected symptoms and an imaging initially concerning for adrenocortical carcinoma, we should recognize the potential for a large adrenal tumor to represent PCC and evaluate accordingly. Presentation: 6/1/2024