Changes In Systolic Blood Pressure Research Articles

Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.

Blood pressure development plays a major role in both the etiology and prediction of gestational hypertensive disorders. Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography—mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values < 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value < 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.

Seasonal variation in the effect of antihypertensive treatment with the irbesartan/hydrochlorothiazide combination.

There is increasing awareness of seasonal variation in blood pressure (BP). In the present analysis, we investigated seasonal variation in the antihypertensive treatment effect of the irbesartan/hydrochlorothiazide combination in patients with stage 2 and 3 hypertension. The study participants were hypertensive patients enrolled in a 12-week therapeutic study. Antihypertensive treatment was initiated with irbesartan/hydrochlorothiazide 150/12.5 mg/day, with possible uptitration to 300/12.5 mg/day and 300/25 mg/day at 4 and 8 weeks of follow-up, respectively. The month of treatment commencement was classified as spring/summer (May to August) and autumn/winter (September to December). Of the 501 enrolled patients, 313 and 188 commenced antihypertensive treatment in spring/summer and autumn/winter, respectively. The mean changes in systolic/diastolic BP at 8 and 12 weeks of follow-up were greater in patients who commenced treatment in autumn/winter (-32.3/-16.5 and -34.2/-16.7 mmHg, respectively) than those who commenced treatment in spring/summer (-28.4/-13.9 and -27.1/-12.8 mmHg, respectively), with a between-season difference of 3.9 (95% confidence interval [CI], 1.4-6.4, P = 0.002)/2.6 (95% CI, 0.9-4.2, P = 0.002) mmHg and 7.0 (95% CI, 4.7-9.3, P < 0.0001)/3.9 (95% CI, 2.4-5.4, P < 0.0001) mmHg, respectively. Further subgroup analyses according to several baseline characteristics showed a greater between-season difference in the changes in systolic BP in patients aged ≥55 years than in those <55 years (n = 255, 12.6 mmHg vs. n = 246, 6.9 mmHg, P = 0.02), especially in patients who did not use antihypertensive medication at baseline (n = 94, 15.4 mmHg vs. n = 132, 5.4 mmHg, P = 0.006). In conclusion, there is indeed seasonality in the antihypertensive treatment effect, with a greater BP reduction in patients who commenced treatment in cold than warm seasons.

The role of nitric oxide in the dorsomedial periaqueductal gray (dmPAG) column in cardiovascular responses in urethane-anesthetized male rats.

The dorsomedial periaqueductal gray (dmPAG) is a mesencephalic area and has numerous functions including cardiovascular regulation. Because nitric oxide (NO) is present in the dmPAG, here we investigate, the probable cardiovascular effect of NO in the dmPAG. Five groups (n=6 for each group) were used as follows: (1) control; (2) L-NAME (NG -nitro-L-arginine methyl ester, a NO synthase inhibitor, 90 nmol); (3) L-arginine (L-Arg, a precursor for NO, 60 nmol); (4) Sodium nitroprusside (SNP, a NO donor, 27 nmol); and (5) L-Arg + L-NAME. The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery. Drugs were injected using a stereotaxic instrument. The changes (∆) in systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated at different times and compared to the control group. Microinjection of L-NAME significantly increased ∆SBP, ∆MAP, and ∆HR more than saline (from p < 0.05 to p < 0.001). L-Arg only significantly increased ∆HR (p < 0.05). In the L-Arg + L-NAME group, the above parameters also significantly increased (from p < 0.01 to p < 0.05) but not as significantly as with L-NAME alone. Microinjection of SNP significantly decreased ∆SBP and ∆MAP more than in the control and L-NAME groups (from p < 0.01 to p < 0.001), but ∆HR did not change significantly. The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.

Implementing DASH-Aligned Meals and Self-Measured Blood Pressure to Reduce Hypertension at Senior Centers: A RE-AIM Analysis.

Low-income, minority seniors face high rates of hypertension that increase cardiovascular risk. Senior centers offer services, including congregate meals, that can be a valuable platform to reach older adults in underserved communities. We implemented two evidence-based interventions not previously tested in this setting: DASH-aligned congregate meals and Self-Measured Blood Pressure (SMBP), to lower blood pressure (BP) at two senior centers serving low-income, racially diverse communities. The study enrolled congregate meal program participants, provided training and support for SMPB, and nutrition and BP education. DASH-aligned meals delivered 40% (lunch) or 70% (breakfast and lunch) of DASH requirements/day. Primary outcomes were change in BP, and BP control, at Month 1. Implementation data collected included client characteristics, menu fidelity, meal attendance, SMBP adherence, meal satisfaction, input from partner organizations and stakeholders, effort, and food costs. We used the RE-AIM framework to analyze implementation. Study Reach included 94 older, racially diverse participants reflecting neighborhood characteristics. Effectiveness: change in systolic BP at Month 1 trended towards significance (-4 mmHg, p = 0.07); change in SMBP reached significance at Month 6 (-6.9 mmHg, p = 0.004). We leveraged existing community-academic partnerships, leading to Adoption at both target sites. The COVID pandemic interrupted Implementation and Maintenance and may have attenuated BP effectiveness. DASH meals served were largely aligned with planned menus. Meal attendance remained consistent; meal satisfaction was high. Food costs increased by 10%. This RE-AIM analysis highlights the acceptability, feasibility, and fidelity of this DASH/SMBP health intervention to lower BP at senior centers. It encourages future research and offers important lessons for organizations delivering services to older adults and addressing cardiovascular risk among vulnerable populations.

Effects of minimally and ultra-processed foods on blood pressure in Brazilian adults: a two-year follow up of the CUME Project.

To assess the association of food consumption according to degree of processing with changes in systolic (SBP) and diastolic (DBP) blood pressure in adult participants of a Brazilian cohort. Longitudinal study with 2496 adult participants of the Cohort of Universities of Minas Gerais (CUME Project). Food consumption was categorized by food groups according to degree of processing following the NOVA grading system: unprocessed/minimally processed foods/culinary ingredients (U/MPF&CI), processed foods (PFs) and ultra-processed foods (UPFs). unprocessed/minimally processed foods/culinary ingredients (U/MPF&CI), processed foods (PFs) and ultra-processed foods (UPFs). Changes in SBP and DBP were categorized (decreased, maintained, increased). Independent associations between exposure and outcomes were verified using multiple generalized ordered logistic models adjusted for potential confounders. After a two-year follow-up, the consumption of U/MPF&CI (% daily caloric intake) reduced the chance of increasing DBP (P for trend = 0.014), with a more evident effect among participants within the 5th quintile of this food group (odds ratio (OR) = 0.55; 95% confidence interval (CI): 0.34-0.97]. On the other hand, the consumption of UPFs (% daily caloric intake) raised the chance of increasing DBP (P for trend = 0.005) and was more evident among participants within the quintiles of higher consumption (4th quintile - OR = 1.97; 95% CI: 1.25-3.10; 5th quintile - OR = 1.79; 95% CI = 1.12-2.86). No associations were found between food consumption according to degree of processing and changes in SBP. Higher consumption of U/MPF&CI and UPFs were independently associated to lower and greater chances of increased DBP in adult participants from CUME Project.

Impact of intravenous calcium with diltiazem for atrial fibrillation/flutter in the emergency department

ObjectiveThe purpose of this study was to evaluate the effect of early intravenous (IV) calcium on systolic blood pressure (SBP) when administered with IV diltiazem in subjects with atrial fibrillation (AF) or flutter (AFL) with rapid ventricular response (RVR) in the Emergency Department (ED). MethodsThis was a multicenter, retrospective cohort study that evaluated adults admitted to the ED with documented AF or AFL, heart rate (HR) > 120 bpm, SBP 90 to 140 mmHg, and received treatment with IV diltiazem for rate control. The primary outcome was the change in SBP 60 min (+/− 30 min) after initial IV diltiazem administration. Secondary outcomes included time to initial rate control (HR < 100 bpm), time to sustained rate control (HR < 100 bpm for 3 h), change in HR, rates of hypotension, bradycardia, hypercalcemia, and line extravasation within 24 h of initial diltiazem administration. ResultsThere were 198 subjects in the diltiazem monotherapy group and 56 subjects in the diltiazem with calcium group meeting the inclusion criteria. The primary outcome, median change in SBP 60 min after initial IV diltiazem administration, was similar between groups (−2 mmHg vs −1.5 mmHg; p = 0.642), but this difference was not statistically significant. All secondary outcomes were found to be similar between groups. Although not statistically significant, hypotension occurred more often in the diltiazem with calcium group (20.2% vs 32.1%; p = 0.060) while bradycardia occurred more often in the diltiazem monotherapy group (4.5% vs 0%; p = 0.213). In terms of achieving rate control, the administration of calcium with diltiazem did not significantly change the time to initial rate control (1.4 h vs 1.8 h; p = 0.141) or time to sustained rate control (7.9 h vs 7.7 h; p = 0.570) compared to diltiazem alone. ConclusionsIn the setting of AF/AFL with RVR, administration of IV calcium with IV diltiazem did not show a significant impact on clinical or safety outcomes compared to IV diltiazem monotherapy.

Real-World Incidence and Management of Ibrutinib-Induced Hypertension in Patients with Chronic Lymphocytic Leukemia

Background: Clinical trials demonstrated that ibrutinib improves progression-free and overall survival in patients with chronic lymphocytic leukemia (CLL). After widespread use of ibrutinib in clinical practice, the incidence of ibrutinib-induced hypertension (HTN) has been more frequent than reported in the clinical trials, with an incidence between 35% and 72%. No guidelines exist for the management of ibrutinib-induced HTN. Methods: A single-center, retrospective cohort study was conducted in patients with CLL initiated on ibrutinib from April 2014 to May 2020. We identified patients at least 18 years old, prescribed ibrutinib for CLL at UNC Medical Center and affiliated centers, alive and not transitioned to hospice or discontinued from ibrutinib within two months of initiation. Patients were excluded if they had blood pressure (BP) measurements documented at less than 3 visits within 24 weeks of initiating ibrutinib. Co-primary study outcomes were overall incidence and severity of HTN within 24 weeks of ibrutinib initiation. Secondary study outcomes include change in systolic BP (SBP) and diastolic BP (DBP), and the probability of increasing the antihypertensive intensity (e.g., new agent or increased dose) adjusted for mean SBP. Incidence of HTN, including new onset (defined by ACC/AHA 2017 Guideline for High Blood Pressure in Adults) or worsening HTN (defined by change in version 5 of Common Terminology Criteria for Adverse Events [CTCAE v5.0] grade), was assessed by descriptive statistics. A linear mixed effects regression model, with random intercepts for patients, estimated mean SBP and DBP measurements at weeks 0, 4, 8, 12, 16, 20, and 24. A logistic mixed effects model was used to estimate the probability of antihypertensive therapy intensification, adjusting for SBP. Results: Among 37 patients (mean age 67.3 ± 10.6 years, 87% Caucasian, 65% male), mean baseline SBP and DBP were 134.0 ± 17.9 mmHg and 70.5 ± 9.87 mmHg, respectively, and 73% were on at least one antihypertensive agent prior to ibrutinib initiation. The prevalence of HTN at baseline was 54% (Stage 2, 38%). Over 24 weeks, the incidence of new onset HTN was 69% (Stage 2, 33%) and worsening HTN was 68% (Stage 2, 92%). At 24 weeks, 29% of BPs were defined as Grade 3 per CTCAE v5.0. Over 24 weeks, mean SBP increased 9.7 mmHg (95% CI 2.20, 16.50) and mean DBP increased 5.9-mmHg (95% CI 1.03, 9.13). On average, patients who had a SBP measurement less than 165 mmHg had a less than 5% chance of antihypertensive intensification. The chance of intensification for patients with a SBP measurement of 165-210 mmHg increased up to 15%. Conclusions: Following initiation of ibrutinib in CLL patients, the incidence of new onset and worsening HTN was higher than previously described. Over 24 weeks, a clinically meaningful increase in BP occurred. Regardless of BP severity, antihypertensive intensification was minimal.

Receiver Operating Characteristics of NT-Probnp in the Transfusion Associated Dyspnea: Prospective Observation & Laboratory Assessment (TADPOL) Study of Cardiorespiratory Versus Febrile Presentation Archetypes

BACKGROUND: B-type natriuretic peptide (BNP) is a hormone secreted in response to volume-related ventricular stretch, and as a biomarker is both diagnostic and prognostic in heart failure. Elevation in BNP or its equimolar N-terminal prohormone fragment (NT-proBNP, noteworthy for its longer half-life) qualifies as a criterion in ISBT-IHN-AABB guidelines for the diagnosis of transfusion-associated circulatory overload (TACO). However, real-life range comparisons in TACO vs. non-respiratory transfusion reactions (TR) are lacking. In the Transfusion Associated Dyspnea-Prospective Observation and Laboratory Assessment (TADPOL) study of acute TRs requiring laboratory investigation (cardiorespiratory events +/- fever [CRTR+/-F] vs. standalone high-risk fevers [HRFTR]), patients consented to NT-proBNP testing as part of a multi-dimensional assessment of presentation archetypes and final diagnoses (e.g., TACO, transfusion-associated dyspnea [TAD], febrile non-hemolytic TR [FNHTR]). METHODS: Blood samples were collected within 24h of reaction onset from patients enrolled across 6 centers in the study's first 134 weeks. NT-proBNP (ng/L) was quantified by chemiluminescence immunoassay (Roche Diagnostics) in real-time (3 sites) or by batched testing (3 sites); reference cut-off values to rule in a cardiac cause for dyspnea in the acute care setting were >450 (age <50y), >900 (age 50-75y), and >1800 (age >75y). Summary statistics are reported. Relationships to provisional reaction diagnosis and clinical features were also explored using appropriate tests (Student's t-test, Mann-Whitney U, Pearson's correlation, and/or Fisher's exact test). Discrimination between possible-to-definite TACO and doubtful or ruled-out TACO was assessed using receiver operating characteristic (ROC) curve analysis with logistic regression. RESULTS: At the study mid-point, 1180 TR (604 TADPOL-eligible) occurred, with NT-proBNP tested in 77/100 enrolled patients. NT-proBNP was significantly higher in patients enrolled in the CRTR arms compared to HRFTR (p=0.0009), with no difference between CRTR+F and CRTR-F (p=0.4). NT-proBNP was also significantly higher in patients with dyspnea in the TR (p=0.005). There was no correlation between NT-proBNP and systolic blood pressure change (p=0.1) or at baseline (p=0.1). Provisional reaction diagnoses were available for 55 patients including 32/39 in the CRTR arms: for possible-to-definite TACO (n=14) and TAD (n=19), vs. standalone FNHTR (n=38), the median NT-proBNP (IQR) was 3,439 (1,587-10,668) and 1,893 (674-5,361), vs. 710 (124-10,542), respectively. Transfusion-related acute lung injury was considered possible in 3 cases, all with TACO. Among CRTR, there was a trend towards higher NT-proBNP values in patients with TACO (p=0.05), with no difference in ages (p=0.8). Using the age-adjusted reference cut-off, the sensitivity of high NT-proBNP for TACO was 86%; specificity was 54% when differentiating TACO from all enrolled TR and 38% between TACO and non-TACO CRTR. In ROC curve analysis (Fig. 1), the area under the curve was 72% (95% CI 55-88%) and the threshold value for discriminating TACO from other TR was 1606 with 60% sensitivity and 65% specificity (Fig. 2). CONCLUSIONS: NT-proBNP is strongly correlated with dyspneic TRs compared to isolated febrile TRs. Elevations appeared more marked in TACO, with a sensitivity of 86% using existing laboratory reference values. However, specificity and discrimination within CRTR were poor. These results affirm that NT-proBNP is helpful in ruling out TACO, whereas ruling in TACO continues to demand a more integrated approach. Whether cardiac strain in unclassified CRTR and TAD is evidence of missed TACO or other insults remains to be determined. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 11861: Reach Out Behavioral Intervention for Hypertension Initiated in the Emergency Department Connecting Multiple Health Systems: A Randomized Control Trial

Introduction: Hypertension (HTN) is the most important modifiable risk factor for cardiovascular disease and disproportionally impacts Black and low-income people. The emergency department (ED) cares for medically underserved populations, many of whom have HTN. Mobile health (mHealth) strategies initiated in safety-net EDs may be one approach to control blood pressure (BP) in a medically underserved population. Hypothesis: A multicomponent, ED initiated multiphase optimization strategy would identify intervention components that reduce BP at 12 months. Methods: Reach Out is a health system focused, health theory based, mHealth 2x2x2 factorial behavioral trial to reduce BP among hypertensive patients evaluated in a safety-net ED. Intervention components included: 1) healthy behavior text messaging (yes vs. no), 2) prompted BP self-monitoring (SMBP) (weekly vs. daily), and 3) facilitated primary care provider (PCP) appointment scheduling and transportation (yes vs. no). The primary outcome was change in systolic BP (SBP) from baseline to 12 months. We fit linear regression models accounting for intervention components, age, sex, race and prior use of BP medications. Results: We randomized 488 participants to the intervention and 211 (43%) participants completed 12-month follow-up. The mean age was 45.5 years, 61% were women, 54% were Black people, 22% did not have a PCP, 10% were uninsured, 21% lacked transportation, 21% did not have a previous diagnosis of HTN and 51% were not taking BP medications. SBP declined in all 8 groups. Overall, across all groups, SBP declined (-9.2 mmHg, 95%CI, -12.2 to -6.3) after 6 months and (-6.6 mmHg, -9.3 to -3.8) after 12 months. In fully adjusted models, no intervention components were associated with a change in systolic BP at 12 months. Conclusions: Higher intensity of the intervention components were not associated with greater reduction in BP. Overall, participants receiving lower intensity levels of our intervention had reductions of BP that were clinically relevant. Future studies should focus on further tailoring intervention components to the needs of participants.

Abstract 14746: Pulse Pressure More Strongly Associates With Subclinical Myocardial Injury Than Do Systolic and Diastolic Blood Pressures

Introduction: Long-standing hypertension is associated with subclinical myocardial injury expressed as chronically elevated cardiac troponin concentrations. Subclinical myocardial injury and subsequent diffuse myocardial fibrosis may represent important intermediaries between hypertension and risk of heart failure and cardiovascular (CV) death. The relative strength of the associations between systolic blood pressure (BP), diastolic BP and pulse pressure and subclinical myocardial injury is unknown. Aim: To assess the relative impact of systolic BP, diastolic BP and pulse pressure on subclinical myocardial injury. Methods: Cardiac troponin I (cTnI) was measured by a high-sensitivity assay (Abbott Diagnostics) in 32,968 participants of the fourth wave of the Trøndelag Health Study (HUNT4) from 2017 to 2019. The longitudinal substudy included participants from HUNT4 who also had BP measurements from the third wave of HUNT (HUNT3) from 2006 to 2008. This included 18,681 study participants. All study participants with a history of CV disease were excluded prior to analysis. We defined subclinical myocardial injury as cTnI ≥4ng/L for women and ≥6ng/L for men, and used logistic regression models adjusted for established CV risk factors. Results: The mean age was 52 (SD±17) years, and 56.9% were female. Cross-sectionally, pulse pressure was more strongly associated with subclinical myocardial injury (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.06-1.10) compared to systolic BP (aOR 1.05, 95% CI 1.04-1.06) and diastolic BP (aOR 1.02, 95% CI 0.99-1.04). Longitudinally, change in diastolic BP was the only BP variable associated with subclinical myocardial injury (aOR 1.03, 95% CI 1.01-1.06), compared to change in systolic BP (aOR 1.01, 95% CI 0.99-1.02) and change in pulse pressure (aOR 0.99, 95% 0.97-1.01, p for all comparisons &lt; 0.05). Conclusions: At a given time, pulse pressure is the superior BP variable in predicting subclinical myocardial injury. Over time, only change in diastolic BP is associated with subclinical myocardial injury. High pulse pressure and longitudinal changes in diastolic BP could represent hypertension phenotypes at high risk for subclinical myocardial injury and subsequent increased CV risk.

Abstract 12898: Mobile Health Interventions and Remote Blood Pressure Monitoring in Underserved Populations: A Systematic Review and Meta-Analysis

Introduction: Disparities in blood pressure (BP) control persist in underserved communities. Although mobile health (mHealth) technologies have increased access to routine care for HTN, few studies have analyzed the effectiveness of mHealth interventions in populations experiencing HTN disparities. Methods: We conducted a systematic review of studies in seven databases published up to November 2021. The search used controlled vocabulary and keywords for HTN, mHealth interventions, and social determinants of health. We included papers that focused on mHealth interventions to manage HTN in underserved populations based on racial, ethnic, and socioeconomic factors. The primary outcome was change in systolic BP (SBP) and diastolic BP (DBP), and we assessed variations in the primary outcome by each study’s relative sociodemographic representation. Results: Among 2,644 unique studies identified, 24 studies (evaluating 7,960 participants in total) met our inclusion criteria. Demographic characteristics were similar between intervention and control groups (intervention: mean age 57.7 [SD 6.2] years; 59.8% women; 40.4% Black; 22.2% Hispanic). Among 18 studies that reported 6-month BP changes, reductions in SBP and DBP values in the intervention group were -7.03 mmHg (control: -2.71 mmHg) and -3.65 mmHg (control: -1.63 mmHg), respectively. Subgroup analysis showed that studies with a higher representation of Hispanic, low-income, and low-education level participants had less pronounced BP improvements than studies with a lower representation of these subgroups. Conclusion: This review provides evidence for the effectiveness of mHealth interventions for HTN management. Future studies and community-based initiatives are needed to further increase individuals’ access to these interventions and to ensure their effectiveness across all populations disproportionately impacted by HTN.

Abstract 13592: Gender Related Divergences in Cardiac and Vascular Function With Age

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a disease of advanced aging that disproportionately affects women. Diastolic function changes with age and it is unknown if gender-related differences in progression exist. Understanding ages at which parameters of vascular and diastolic function diverge may provide insight into the differential risk of HFpEF between genders. Methods: Sedentary but healthy non-obese subjects aged 20-90 (n=178, 58% female; avg age 56 ± 13 yrs) underwent measures of pulmonary capillary wedge pressure (PCWP; right heart catheterization), blood pressure and cardiac output (acetylene rebreathe). Diastolic function was assessed by Doppler echocardiogram. A generalized linear model was used to estimate effects of age for each measured hemodynamic parameter as a function of gender. Results: Across age, women had higher systolic blood pressure (SBP) (age*gender p=0.025, age p&lt;0.001) and total peripheral resistance (TPR) (age*gender p=0.053, age p&lt;0.001). Changes in TPR were apparent at age 26 while SBP diverged at age 55. (Figure) Women had slower early diastolic recoil (e’) (age*gender p&lt;0.001) starting at age 55. While E wave velocity was lower in women, age-related decline was similar to men. E/e’ was higher in women (age*gender p=0.007) and diverged at a young age (28). PCWP declined with age similarly in both men and women. Systolic velocity (s’) declined in early middle age (42) in women (age*gender p=0.007, age p=0.002). Conclusions: Women experience greater changes in cardiac and vascular function with age than men. The age at which these parameters diverge differs, with evidence for decline in vascular function and cardiac contractility occurring at young ages in women while changes in SBP and diastolic recoil occur after age 55. Understanding lifestyle and hormonal factors that influence these differences may help elucidate HFpEF risk factors that are modifiable and serve as a target for therapy.

Abstract 11963: Blood Level of Coffee-Eelated DNA Methylation and Long-Term Changes in Blood Pressure in Response to Weight-Loss Diet Interventions: The Pounds Lost Trial

Introduction: Coffee intake has been associated with a lower risk of hypertension. Recent epigenome-wide association studies linked DNA methylation (DNAm) at PHGDH (cg14476101) with coffee consumption and blood pressure, which may explain the mechanism underlying coffee intake and blood pressure. However, little is known about whether the coffee-related DNAm is associated with long-term changes in blood pressure in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying coffee-related DNAm levels may respond differently to dietary weight-loss interventions on long-term changes in blood pressure. Methods: The current study included 669 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at PHGDH was defined as the average methylation level over CpGs within ±250 bp of cg14476101. Two-year changes in blood pressure were calculated. Linear regression models were used to examine the associations between DNAm at PHDGH and 2-year changes in blood pressure in response to dietary weight-loss interventions, adjusting for age, race, sex, body mass index, anti-hypertensive medications, and concurrent weight loss. Results: Regional DNAm at PHDGH was not associated with 2-year changes in blood pressure in the total population. We found significant interactions between regional DNAm at PHDGH and dietary protein intake on 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p-interaction=0.018 and 0.005, respectively). Among participants assigned to an average-protein diet (15% of energy intake), higher baseline regional DNAm at PHDGH was associated with greater reductions in SBP (beta [SE]: -9.7 [3.4], p=0.005) and DBP (beta [SE]: -6.5 [2.4], p=0.007); while no association was observed among those assigned to a high-protein diet (25% of energy intake; p=0.40 for SBP, p=0.15 for BP). Conclusion: Our data indicate that participants with a higher regional DNAm level at PHDGH benefited more in long-term improvement in blood pressure when consuming an average-protein weight-loss diet.

Abstract 13183: Effectiveness of a Telehealth-Based Behavioral Lifestyle Program for Hypertension Control in African Americans: Results From Heals Med-Tech Randomized Controlled Study

Background: Hypertension (HTN) is a great concern because of its widespread prevalence, and associated racial health disparities. HTN is higher among African Americans (AAs) than whites. Among the many barriers to control HTN is poor adherence to needed lifestyle changes. The efficacy-tested HEALS Med-Tech behavioral lifestyle HTN control program may provide some solutions. We present the findings from the 1-year HEALS Med-Tech program in AAs. Methods: This is a randomized control community trial implemented in a primary care setting. HEALS Med-Tech program includes a) HEALS (Healthy Eating and Living Spiritually), a 12-month program modified from DASH and PREMIER programs; b) Med-component provides medications and social support; and c) Tech-component provides interactive telehealth contact. Primary outcomes of interest is change in systolic BP (SBP). Mixed Model repeated measure method was used for outcome analysis. Results: 61 participants (50 females, 11 males) were enrolled and randomized to either HEALS Med-Tech or standard care (control). Participants’ mean age is 62.8 ± 10.8 years, majority (90%) had a family history of CVD and 26.5% had diabetes. At the baseline, the SBP was 139.52 mmHg and 146 mmHg for the HEALS and control groups, respectively (Figure 1), which significantly reduced after 1 year (p=0.0134) in HEALS group. Similarly, the DBP was 82.78 mmHg and 84.32 mmHg for HEALS and control groups, respectively, at the baseline (not shown). For DBP and SBP, the results showed a significant difference between the HEALS and Control groups at 6 and 12 weeks. Conclusion: HEALS Med-Tech behavioral lifestyle program could serve as an effective and sustainable model for BP among marginalized AAs. There is a need for implementation studies of longer duration, such as HEALS Med-Tech, to address social determinants for the programs to be sustainable. Further research is needed to explore the potential implementation of HEALS Med-Tech program into clinical practice.

Abstract 11808: Association Between Weight Gain After Smoking Cessation and Future Hypertension

Introduction: While smoking cessation reduces the risk of ischemic heart disease and stroke, it may be associated with weight gain. However, literature on the association between weight gain after smoking cessation and future hypertension is scarce. Methods: Of the 234,596 individuals who visited our health checkup center, 1085 individuals (mean age 47.5 ± 10.6 years; 1005 men) with previous history of smoking and available data after 5 years of smoking cessation were included. We compared the relationship between weight gain after smoking cessation and future hypertension (changes in blood pressure [BP] from baseline to 5 years, following smoking cessation and prescription rate of antihypertensive drugs. Multiple regression analysis was performed to evaluate changes in systolic and diastolic blood pressures (SBP and DBP) using covariates affecting BP changes from baseline values, such as weight gain, age, baseline weight, sex, and habitual alcohol consumption. Results: Since a median weight gain of 1.7 kg was observed after 1 year of smoking cessation, we divided participants into two groups: high weight gain (547 individuals, ≥1.7 kg) and low weight gain (538 individuals, &lt;1.7 kg). There was no significant difference in the prescription rate of antihypertensive drugs between the two groups (high weight gain vs. low weight gain), at the baseline (10.6% vs. 10.4%; p = 0.92) and 5 years following smoking cessation (25.4% vs. 28.4%, p=0.26). Nevertheless, the changes in SBP (high weight gain vs. low weight gain: 7.9±15.4 vs 3.8±15.4 mmHg, p&lt;0.001) and DBP (high weight gain vs. low weight gain: 4.2±10.5 vs 1.1±10.8 mmHg, p&lt;0.001) from baseline to 5 years following smoking cessation were significantly higher in the high weight gain group. Additionally, multiple regression analysis showed that changes in SBP were influenced by high weight gain (β=-0.13, p&lt;0.001) and age (β=0.06, p&lt;0.05), while changes in DBP were influenced by high weight gain (β=-0.14, p&lt;0.001), age (β=-0.10, p&lt;0.001), and baseline weight (β=-0.10, p&lt;0.01). Conclusions: Our results suggest that weight gain following smoking cessation subsequently leads to hypertension, and weight loss guidance may be useful in such cases.

Beneficial effect of time-restricted eating on blood pressure: a systematic meta-analysis and meta-regression analysis

BackgroundAs a cardiometabolic disease, hypertension has shown an obvious upward trend, becoming a global epidemic chronic disease. Lifestyle intervention is a fundamental method for lowering blood pressure. This systematic review and meta-analysis aimed to evaluate the effects of time-restricted eating (TRE) on blood pressure.MethodsStudies were retrieved from the PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of TRE on blood pressure. The time frame of search was from the start of database construction until July 14, 2022.There were no language restrictions. Meta-analysis and meta-regression were performed using Stata version 16. The weighted mean difference with 95% CI was used to assess the effect of TRE on blood pressure, heart rate, weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. The main ending of this article were blood pressure and heart rate, while the secondary ending were weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides.ResultsTen randomized controlled trials involving 694 patients were identified. TRE significantly reduced systolic blood pressure (SBP) (mean difference = −4.15; 95% CI: −6.73, −2.30; P < 0.0001), but had no significant effect on diastolic blood pressure (DBP) (mean difference = −2.06; 95% CI: −4.16, 0.02; P = 0.053) and no beneficial effect on heart rate (mean difference = 0.36; 95% CI: −2.83, 3.54; P = 0.0825). TRE promoted weight loss (mean difference = −1.63; 95% CI: −2.61, −0.64; P = 0.001) and decreased blood glucose levels (mean difference = −2.80; 95% CI: −4.64, −0.96; P = 0.003), but had no significant effect on total cholesterol (mean difference = 0.03, 95% CI: −10.01, 10.08; P = 0.995), HDL-C (mean difference = 0.85, 95% CI: −1.80, 3.49; P = 0.531), LDL-C (mean difference = −0.86, 95% CI: −6.47, 4.76; P = 0.764), or triglycerides (mean difference = −3.524, 95% CI: −9.49, 2.45; P = 0.248). In a separate meta-regression analysis, the degree of SBP change was related to weight loss (P = 0.044) but not to glucose improvement (P = 0.867).ConclusionsThe present meta-analysis suggests that TRE significantly reduced SBP, while no effect of reducing DBP was seen. The observed lower blood pressure may be attributed to significant weight loss. The effects of TRE on heart rate and blood lipid levels were not apparent.

Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension

BackgroundAldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels.MethodsIn this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group.ResultsA total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of −20.3 mm Hg, −17.5 mm Hg, −12.1 mm Hg, and −9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was −11.0 mm Hg (95% confidence interval [CI], −16.4 to −5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was −8.1 mm Hg (95% CI, −13.5 to −2.8; P=0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug.ConclusionsPatients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.)

Estimating the sample size of sham-controlled randomized controlled trials using existing evidence.

Background: In randomized controlled trials (RCTs), the power is often 'reverse engineered' based on the number of participants that can realistically be achieved. An attractive alternative is planning a new trial conditional on the available evidence; a design of particular interest in RCTs that use a sham control arm (sham-RCTs). Methods: We explore the design of sham-RCTs, the role of sequential meta-analysis and conditional planning in a systematic review of renal sympathetic denervation for patients with arterial hypertension. The main efficacy endpoint was mean change in 24-hour systolic blood pressure. We performed sequential meta-analysis to identify the time point where the null hypothesis would be rejected in a prospective scenario. Evidence-based conditional sample size calculations were performed based on fixed-effect meta-analysis. Results: In total, six sham-RCTs (981 participants) were identified. The first RCT was considerably larger (535 participants) than those subsequently published (median sample size of 80). All trial sample sizes were calculated assuming an unrealistically large intervention effect which resulted in low power when each study is considered as a stand-alone experiment. Sequential meta-analysis provided firm evidence against the null hypothesis with the synthesis of the first four trials (755 patients, cumulative mean difference -2.75 (95%CI -4.93 to -0.58) favoring the active intervention)). Conditional planning resulted in much larger sample sizes compared to those in the original trials, due to overoptimistic expected effects made by the investigators in individual trials, and potentially a time-effect association. Conclusions: Sequential meta-analysis of sham-RCTs can reach conclusive findings earlier and hence avoid exposing patients to sham-related risks. Conditional planning of new sham-RCTs poses important challenges as many surgical/minimally invasive procedures improve over time, the intervention effect is expected to increase in new studies and this violates the underlying assumptions. Unless this is accounted for, conditional planning will not improve the design of sham-RCTs.

Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial

Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p<0·0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12·5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment. In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40. Idorsia Pharmaceuticals and Janssen Biotech.

Effects of Face Masks on Pulse Rate and Blood Pressure Components During Stairs Climbing.

The use of face masks has been associated with physiological changes in body. This study aims to know the changes in pulse rate and blood pressure components after wearing face masks during stairs climbing. An experimental study was conducted among 60 apparently healthy young adults between 18-35 years of age. The pulse rate and blood pressure of the participants were recorded during rest at ground floor and after climbing the stairs till 5th floor at brisk and regular pace without wearing the face masks. The uniform KN95 masks were distributed and proper coverage of nose, mouth and chin were ensured. After 5 minutes interval, the pulse rate and blood pressure were recorded again at rest in ground floor and after climbing stairs with use of KN95 masks. At rest, the difference in mean pulse rate was statistically significant after wearing masks in participants between 21-25 years of age (86.46±14.59 bpm, p=0.014). After climbing the stairs, the mean pulse rate (131.16±18.48 bpm), mean systolic blood pressure (137.67±16.13 mmHg) and mean rate pressure product (182.87±41.70) were higher in participants (age group: 26-30 years) wearing masks and the difference was statistically significant (p=0.001; 0.013; 0.001respectively). During stairs climbing, the change in mean systolic blood pressure (32.66±16.73 mmHg), mean pulse pressure (43.77±24.64 mmHg) and mean rate pressure product (96.58±37.23) were higher in participants (age group: 26-30 years) and the difference was statistically significant (p=0.036; 0.047 and 0.009 respectively). The changes in systolic blood pressure, pulse pressure and rate pressure product are found to increase after wearing face masks during stairs climbing. It can be suggestive of increase workload to the heart by wearing face masks in addition to climbing the stairs.