Intensive Blood Pressure Treatment Research Articles

Comparison of intensive treatment versus standard treatment in lowering blood pressure and its association with cognitive decline and dementia: a systematic review and meta-analysis

Abstract Background The ideal blood pressure target level for preventing cognitive decline or dementia in patients with systemic arterial hypertension (SAH) remains unclear. Purpose This study aims to investigate whether intensive blood pressure reduction compared to standard treatment is associated with a reduced risk of cognitive decline or dementia in adults with SAH. Methods PubMed, Scopus and Cochrane databases were searched for randomized clinical trials (RCTs) comparing intensive treatment versus standard treatment for blood pressure reduction in patients with SAH. A random-effects model was used for analyzing the results, which were presented as relative risk (RR) with a 95% confidence interval (CI). Heterogeneity was examined using the I² statistic. Statistical analysis was performed using R software version 4.2.3. Results A total of 5 RCTs and 46,658 patients were included, of whom 23,726 (50,85%) underwent intensive therapy for SAH treatment. The mean age of participants ranged from 62.8 to 80.9 years in the intensive treatment group while it ranged from 63.3 to 80.3 years in the standard treatment group. Occurrence of dementia or probable dementia was significantly lower in the intensive treatment group (3.8% vs. 4,3%; RR 0.88; 95% CI: 0.80 - 0.96; p= 0.0049; I²=0%). Dementia or Cognitive decline (16.4% vs. 18.8%; RR 0.87; 95% CI 0.83 - 0.90; p < 0.000001; I²=0%), and cognitive decline (13.2% vs. 15.2%; RR 0.88; 95% CI 0.80 - 0.98; p= 0.014; I²=53%) also tended towards the intensive treatment group. Additionally, no significant association was found in mortality (6.4% vs. 7.3%; RR 0.87; 95% CI 0.75 - 1.02; p= 0.09; I²=28%) and serious adverse effects (34.4% vs. 35.5%; RR 0.99; 95% CI 0.92 - 1.06; p=0.73; I²=63%). Conclusion Our study shows that intensive blood pressure treatment is associated with a fewer occurrence of dementia, probable dementia and cognitive decline in comparison to the standard blood pressure target.General Analysis

Abstract P341: Orthostatic Hypertension Does Not Alter the Effect of Intensive Blood Pressure Treatment on Cardiovascular Disease and All-Cause Mortality: An Individual-Level Meta-analysis

Background: Orthostatic hypertension (OHTN) is common among adults with hypertension (HTN) and associated with cardiovascular disease (CVD). It is unclear whether HTN treatment reduces CVD outcomes similarly in adults with OHTN as adults without OHTN. Methods: We performed an individual-level meta-analysis, updating a previous systematic review of MEDLINE, EMBASE, and CENTRAL databases through November 13, 2023, which included randomized trials of blood pressure (BP) pharmacologic treatment (more intensive BP goal or active agent) on CVD or death. CVD events were adjudicated and included fatal and nonfatal coronary heart disease, stroke, and congestive heart failure. OHTN was defined as a rise in systolic BP ≥20 mmHg and/or diastolic BP ≥10 mmHg after changing positions from sitting to standing. Effects were examined overall and by trial type (BP goal or active agent), using Cox proportional hazard models adjusted for age and sex. Results: Of the 9 trials included, there were 29,235 participants followed for median of 4 years (mean age 69.5±10.9 years; 48.3% female; 21.0% with OHTN at baseline). Baseline OHTN was not associated with a higher risk of CVD or death (HR 1.03; 95% CI: 0.95, 1.13). More intensive BP treatment or active therapy lowered risk of CVD or death among those with OHTN at baseline (HR 0.80; 95% CI: 0.69, 0.93) and without OHTN at baseline (HR 0.81; 95% CI: 0.75, 0.87) with no difference between strata ( P -interaction 0.95) ( Figure ). Conclusion: While baseline OHTN was common among adults with HTN, it was not associated with CVD or death and did not alter the protective effect of more intensive treatment. More intensive treatment is an effective approach to prevent CVD events among adults with OHTN.

Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.

The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Intensive Blood Pressure Treatment and Subclinical Brain Infarcts: A Secondary Analysis of SPRINT (Systolic Pressure Intervention Trial).

Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment. In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment. Brain magnetic resonance images collected at baseline and follow-up were read for SBI. The occurrence of mild cognitive impairment (MCI) or probable dementia (PD) was evaluated. For 667 participants at baseline, SBI were identified in 75 (11%). At median 3.9 years follow-up, 12 of 457 had new SBI on magnetic resonance imaging (5 intensive, 7 standard), whereas 8 had clinical stroke (4 per group). Baseline SBI (subhazard ratio [sHR] = 3.90; 95% CI 1.49 to 10.24; p = 0.006), but not treatment group, was associated with new SBI or stroke. For participants with baseline SBI, intensive treatment reduced their risk for recurrent SBI or stroke (sHR = 0.050; 95% CI 0.0031 to 0.79; p = 0.033). Baseline SBI also increased risk for MCI or PD during follow-up (sHR = 2.38; 95% CI 1.23 to 4.61; p = 0.010). New cerebral ischemic events were infrequent, but intensive treatment mitigated the increased risk for participants with baseline SBI, indicating primary prevention SBP goals are still appropriate when SBI are present. ANN NEUROL 2024;95:866-875.

Blood Pressure Variability and Plasma Alzheimer's Disease Biomarkers in the SPRINT Trial.

Recent observational studies suggest higher blood pressure (BP) variability (BPV) is associated with Alzheimer's disease (AD) biomarkers amyloid-beta (Aβ) and tau. Less is known about relationships in interventional cohorts with strictly controlled mean BP levels. Investigate the longitudinal relationship between BPV and change in plasma AD biomarkers under standard versus intensive BP treatment. In this post hoc analysis of the SPRINT trial, 457 participants (n = 206 in standard group, n = 251 in intensive group) underwent repeated BP measurement between baseline and 12-months follow-up, and venipuncture at baseline and median (IQR) 3.5 (3.0-4.0) years later to determine plasma AD biomarkers total tau and Aβ1-42:Aβ1-40 ratio. BPV was calculated as tertiles of variability independent of mean. Linear mixed models investigated the effect of BPV×time on AD biomarker levels. Higher BPV was associated with increased levels of total tau in the standard group (β [95% CI] 1st versus 3rd tertiles of BPV: 0.21 [0.02, 0.41], p = 0.035), but not in the intensive group (β [95% CI] 1st versus 3rd tertiles of BPV: -0.02 [-0.19, 0.16], p = 0.843). BPV was not associated with Aβ 1-42:Aβ 1-40 ratio in either group. Mean BP was not associated with biomarkers. Higher BPV was associated with increased plasma total tau under standard BP treatment. Findings add new evidence to prior observational work linking BPV to AD pathophysiology and suggest that, despite strict control of mean BP, BPV remains a risk for pathophysiological change underlying risk for AD.

Orthostatic Hypotension in Adults With Hypertension: A Scientific Statement From the American Heart Association.

Although orthostatic hypotension (OH) has long been recognized as a manifestation of autonomic dysfunction, a growing body of literature has identified OH as a common comorbidity of hypertension. This connection is complex, related to pathophysiology in blood pressure regulation and the manner by which OH is derived as the difference between 2 blood pressure measurements. While traditional therapeutic approaches to OH among patients with neurodegenerative disorders focus on increasing upright blood pressure to prevent cerebral hypoperfusion, the management of OH among patients with hypertension is more nuanced; resting hypertension is itself associated with adverse outcomes among these patients. Although there is substantial evidence that intensive blood pressure treatment does not cause OH in the majority of patients with essential hypertension, some classes of antihypertensive agents may unmask OH in patients with an underlying autonomic impairment. Practical steps to manage OH among adults with hypertension start with (1) a thorough characterization of its patterns, triggers, and cause; (2) review and removal of aggravating factors (often pharmacological agents not related to hypertension treatment); (3) optimization of an antihypertensive regimen; and (4) adoption of a tailored treatment strategy that avoids exacerbating hypertension. These strategies include countermaneuvers and short-acting vasoactive agents (midodrine, droxidopa). Ultimately, further research is needed on the epidemiology of OH, the impact of hypertension treatment on OH, approaches to the screening and diagnosis of OH, and OH treatment among adults with hypertension to improve the care of these patients and their complex blood pressure pathophysiology.

Impact of Anemia on Cardiovascular Events and All-Cause Death Among Participants Who Received Intense Blood Pressure Treatment: A Secondary Analysis of SPRINT.

To investigate whether anemia is associated with incident cardiovascular events and all-cause death among participants who received intensive blood pressure (BP) treatment in the Systolic Blood Pressure Intervention Trial (SPRINT). A total of 4394 participants who received intensive BP control (systolic BP 120 mmHg) in SPRINT were included. Anemia status was self-reported. Our primary outcome was a composite of cardiovascular events, and the secondary outcome was all-cause death. Cox regression was used to compare the incidence of outcomes between participants with anemia and non-anemia. In order to balance the baseline characteristics between the 2 groups, inverse probability of treatment weighting (IPTW) was applied. Hazard ratios (HRs), along with 95% confidence intervals (CIs), were then calculated. There were 4394 participants who received intensive BP control (537 participants with anemia). Participants with anemia were older (mean age 68.86 versus 67.75, p = 0.01) and more likely to be female (64.8% versus 31.8%, p 0.001). The presence of anemia was strongly associated with composite cardiovascular events after adjusting for potential confounders (HR 1.66, 95% CI 1.18-2.34, p = 0.004). The association remained statistically significant even in the population after IPTW (HR 1.55, 95% CI 1.06-2.27, p = 0.024). The secondary outcome revealed that participants with anemia had a higher rate of all-cause death compared to those without anemia. The HR of all-cause death for participants with anemia was 1.61 (95% CI 1.00-2.57, p = 0.049) in the population after IPTW. Anemia appears to be an independent risk factor for composite cardiovascular events and all-cause death among participants who received intensive BP control in SPRINT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062. All SPRINT anonymized data can be found at the National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository (https://biolincc.nhlbi.nih.gov/home/).

Effect of Intensive Blood Pressure Control on Cardiovascular Outcomes in Cancer Survivors.

To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction=0.81) or diastolic BP (P for interaction=0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction=0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

Intensive blood pressure control on arterial stiffness among older patients with hypertension.

Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60-80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes. The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8-73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7-110.1 cm/s) in the standard treatment group ( P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s -1 ·year -1vs. 36.7 cm·s -1 ·year -1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70-80 years or with SBP <140 mmHg. Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension. http://www.clinicaltrials.gov ; No. NCT03015311.

Anti-Hypertensive Drugs Special References with Their Classification of Calcium Channel Blocker

Objective: Determine the distribution and longitudinal changes in antihypertensive medication regimens in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: We used antihypertensive medication data collected by pill bottle review at each visit to categorize antihypertensive regimens by medication class. Free text string variables of medication names were independently reviewed by two clinical pharmacists to create standardized generic medication names and classes. Results: Figure 1 illustrates longitudinal changes in class combinations and number of drugs at the randomization, 6, 12, and 18-month visits. Fifty-six percent of participants modified their initial regimen by the 6-month visits; 43% of participants made additional modifications to their regimens from the 6-month to the 18-month visit. The most common initial regimens, and least likely regimens to be changed over time, were combinations with an ACEI/ARB and diuretics ± other classes (42% of initial regimens). Participants in the intensive arm added a mean (standard deviation) of 0.6 (0.9) medications to their initial regimens in the first 18-months compared to -0.1 (0.9) in the standard arm. Conclusion: Intensive blood pressure treatment requires more medication complexity in terms of class and dose. Further study of distinct regimens may reveal if certain class and dose combinations provide better SBP control, safety, or patient satisfaction.

Abstract 14793: Relationship Between Self-Rated Health and Clinical Outcomes in Hypertension: A Secondary Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Background: Self-rated health (SRH) is a well-known independent predictor of mortality. However, the association of SRH with clinical outcomes in patients with hypertension remains uncertain. SPRINT investigated the benefit of intensive (vs. standard) blood pressure treatment in patients with high-risk hypertension. Objective: To examine the association between SRH and the primary SPRINT outcome, which was defined as the composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death. Methods: A trained study personnel administered a questionnaire to assess SRH. Each participant rated their overall health as excellent, very good, good, fair, or poor (E, VG, G, F, P). We categorized SRH into excellent, very good, good and fair/poor. Multivariate Cox regression was used to examine the association of SRH and clinical outcomes in SPRINT. Results: We included 9,319 participants (aged 67.9±9 years, 35.6% women, 57.6% White) who had available data on SRH. After a median follow-up of 3.8 years, 724 and 500 primary outcome and all-cause mortality events occurred, respectively. Relative to SRH of excellent, the risk of the primary outcome (HR 95% CI) associated with very good, good, and poor/fair SRH was 1.11 (0.78-1.56; p=0.555), 1.45 (1.03-2.05; p=0.036) and 1.87 (1.28-2.75; p=0.001), respectively. Similarly, relative to excellent, the risk of all-cause mortality (HR 95% CI) associated with very good, good, and poor/fair SRH was 1.13 (0.73-1.76; p=0.581), 1.72 (1.12-2.64; p=0.014) and 2.11 (1.32-3.38; p=0.002), respectively. Poorer SRH was also associated with a higher risk of each component of the primary outcome and adverse events ( Table). Conclusion: In the SPRINT cohort, SRH was independently associated with the risk of cardiovascular outcomes, mortality, and adverse events. Further studies are needed to explore the utility of incorporating SRH in the assessment of risk in patients with hypertension.

Examining the potential impacts of intensive blood pressure treatment on the socioeconomic inequity in hypertension prevalence in China: a nationally representative cross-sectional study.

Few studies focused on the equity of hypertension prevalence before and after the diagnostic threshold change. The study aimed to analyze the 130/80 mmHg hypertension diagnostic threshold on the equity of hypertension prevalence in China. The baseline survey data from the China Health and Retirement Longitudinal Study (CHARLS) conducted from 2011 to 2012 were utilized to evaluate the impact of the 130/80 mmHg diagnostic threshold on the equity of hypertension prevalence in China using the concentration index and its decomposition which was an index reflecting the health inequality caused by social and economic factors. The prevalence of hypertension was 41.56% and 57.33% under the diagnostic thresholds of 140/90 mmHg and 130/80 mmHg, respectively. The concentration index for hypertension prevalence in China was -0.017 (95%CI: -0.028, -0.006) under the 140/90 mmHg threshold and -0.010 (95%CI: -0.018, -0.002) under the 130/80 mmHg threshold. Concentration index decomposition analysis of hypertension prevalence diagnosed at both diagnostic thresholds showed that age, BMI, and economic status contributed more to the inequitable situation of hypertension prevalence. Higher age, higher BMI, and poorer economic status increased the inequity of hypertension prevalence. No significant difference in the increase in hypertension among individuals of different economic status after implementing the blood pressure control standard (130/80 mmHg), and the prevalence of hypertension in the region did not show a significant bias towards the low economic status population. Therefore, implementing this standard will not increase the risk of hypertension prevalence biased toward people of low economic status. Implementing the 130/80 mmHg diagnostic threshold will not increase the risk of hypertension prevalence biased towards people of low economic status.

Generalisability and potential deaths averted from intensive blood pressure treatment among the elderly population in the US and China: A nationally representative cross-sectional study.

The Systolic Blood Pressure Intervention Trial (SPRINT) from the US and the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial from China have consistently demonstrated clinical benefits from intensive blood pressure (BP) treatment among elderly adults with hypertension. However, we have little data on the generalisability and potential implications of a scale-up of intensive BP treatment to all eligible elderly in the US and China. We used two nationally representative data sets from China (Health and Retirement Longitudinal Study (CHALRS), 2011-2012) and the US (National Health and Nutrition Examination Survey (NHANES), 2007-2012) and linked them with CHARLS follow-up data (2013) and the National Death Index (1999-2015), respectively. We estimated the percentage, number, and characteristics of elderly (≥60 years old) meeting the STEP and SPRINT eligibility criteria, and deaths that would be prevented or postponed with the implementation of intensive BP treatment. Among the Chinese adults aged 60 years and over, 38.89% (95% confidence interval (CI) = 36.97-40.84) or 85.39 (95% CI = 81.14-89.64) million subjects met the STEP criteria, and 40.90 million (47.90%) adults were not taking antihypertensive medications. In the US, 23.77% (95% CI = 22.32%-25.28) or 12.46 (95% CI = 11.68-13.24) million elderly were eligible for the SPRINT, and 5.78 million (46.36%) were untreated. Overall, 0.07 (95% CI = 0.06-0.08) million deaths in the US and 0.31 (95% CI = 0.25-0.39) in China would be averted annually if intensive BP treatment was implemented, while 120 000 and 680 000 of hypotension cases would be identified yearly inthe US and China, respectively. A substantial percentage of Chinese and the US elderly meet the eligibility criteria for STEP and SPRINT. If intensive BP treatment was adopted, 70 000 and 310 000 deaths would be prevented or postponed yearly in the US and China, respectively.

Hypertension and small vessel disease: do the drugs work?

Associations of hypertension with ischaemic stroke and intracerebral haemorrhage, particularly when attributed to cerebral small vessel disease, are well established. While it seems plausible that treating hypertension should prevent small vessel disease from developing or progressing, there is limited evidence demonstrating this. This article critically appraises the evidence answering this clinical question. Hypertension is also closely associated with chronic kidney disease, with anatomical and functional similarities between the vasculature of the brain and kidneys leading to the hypothesis that shared multi-system pathophysiological processes may be involved. Therefore, the article also summarises data on prevention of progression of chronic kidney disease. Evidence supports a target blood pressure of <130/80 mmHg to optimally prevent progression of both small vessel disease and chronic kidney disease. However, future studies are needed to determine long-term effects of more intensive blood pressure treatment targets on small vessel disease progression and incident dementia.

Abstract 112: Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypertension: An Individual-level Meta-analysis

Background: Orthostatic hypertension (OHTN) is associated with cardiovascular disease (CVD). We previously demonstrated how more intensive blood pressure (BP) treatment reduced orthostatic hypotension (OH) via a net increase in BP upon standing. Whether this effect also increased OHTN was not examined. Methods: We used pooled data from an individual participant data meta-analysis of 9 randomized BP pharmacologic treatment trials with seated and standing BP (search conducted through May 13, 2022). OHTN was defined as an increase in SBP ≥20 or DBP ≥10 mm Hg after changing from sitting to standing. Effects were examined overall and by baseline characteristics. Results: Of 31,124 participants with 315,497 standing BP assessments, 9% had OH, and 20% had OHTN at baseline. Trial effects were similar ( I 2 = 38.0%). During follow-up, 17% of those assigned more intensive treatment had OHTN, while 19% of those assigned less intensive treatment had OHTN. Intensive BP treatment significantly lowered OHTN risk (OR 0.93; 95% CI: 0.90, 0.96) ( Figure ). Effects were significantly greater among non-Black adults (OR 0.86 vs 0.97, P -interaction =0.003) and adults without diabetes (OR 0.88 vs 0.96; P -interaction =0.047). Effects did not differ by age≥75 years, sex, baseline seated BP≥130/≥80 mm Hg, obesity, stage 3 kidney disease, stroke, cardiovascular disease, standing SBP ≥140 mm Hg, or pre-randomization OHTN ( P -interactions ≥0.05). Conclusion: In this pooled cohort of adults with hypertension or higher CVD risk, OHTN was more common than OH and more intensive BP treatment reduced OHTN risk. The relationship between this effect with respect to CVD should be a focus of subsequent research.

Targeting the Efficacy of Intensive Blood Pressure Treatment in Hypertensive Patients - An Exploratory Analysis of SPRINT.

Hypertensive patients show highly heterogeneous treatment effects (HTEs) and cardiovascular prognosis, and not all benefit from intensive blood pressure treatment. We used the causal forest model to identify potential HTEs of patients in the Systolic Blood Pressure Intervention Trial (SPRINT). Cox regression was performed to assess hazard ratios (HRs) for cardiovascular disease (CVD) outcomes and to compare the effects of intensive treatment among groups. The model revealed 3 representative covariates and patients were partitioned into 4 subgroups: Group 1 (baseline body mass index [BMI] ≤28.32 kg/m2and estimated glomerular filtration rate [eGFR] ≤69.53 mL/min/1.73 m2); Group 2 (baseline BMI ≤28.32 kg/m2and eGFR >69.53 mL/min/1.73 m2); Group 3 (baseline BMI >28.32 kg/m2and 10-year CVD risk ≤15.8%); Group 4 (baseline BMI >28.32 kg/m2and 10-year CVD risk >15.8%). Intensive treatment was shown to be beneficial only in Group 2 (HR 0.54, 95% confidence interval [CI] 0.35-0.82; P=0.004) and Group 4 (HR 0.69, 95% CI 0.52-0.91; P=0.009). Intensive treatment was effective for patients with high BMI and 10-year CVD risk, or low BMI and normal eGFR, but not for those with low BMI and eGFR, or high BMI and low 10-year CVD risk. Our study could facilitate the categorization of hypertensive patients, ensuring individualized therapy.

Association between physical activity and clinical outcomes in high-risk hypertension: Post-hoc analysis of SPRINT

ObjectiveEngaging in physical activity (PA) is recommended to reduce the risk of morbidity and mortality in patients with hypertension. However, the association between PA and clinical outcomes in individuals with high-risk hypertension is understudied. We examined the relationship between PA and clinical outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT investigated the benefit of intensive (vs. standard) blood pressure treatment in patients with high-risk hypertension. MethodsBaseline data on PA was self-reported. Vigorous-intensity PA (VPA) was categorized into 2 groups based on frequency of “Rarely or Never” and 1 or more sessions/month. Moderate-intensity PA (MPA) was also categorized into 2 groups based on average duration/day of <15 min and 15 or more minutes. Using multivariable Cox regression, we estimated the associations between PA the primary outcome which was a composite of cardiovascular events, and all-cause mortality. ResultsA total of 8,320 (age 67.8 ± 9.3, 34.9% women) of SPRINT participants with data on PA were included. During a median follow-up of 3.8 years, 619 primary outcome, and 419 all-cause mortality events occurred. Compared to not engaging in VPA, the risk of the primary outcome, myocardial infarction, and all-cause mortality (HR 95% CIs) associated with VPA of ≥1sessions/month was 0.79(0.65–0.94; p=0.009), 0.70(0.52–0.93; p=0.014) and 0.75(0.60–0.94; p=0.011), respectively. Similarly, the risk of the primary outcome and all-cause mortality (HR 95% CI) associated with engaging in MPA for ≥15 min/day, relative to <15 min/day was 0.76(0.63–0.93; p=0.008) and 0.80(0.62–1.02; p=0.066), respectively. ConclusionAmong individuals with hypertension from the SPRINT study, VPA and MPA at a threshold of ≥1sessions/month and MPA of ≥15 min/day respectively, were both associated with a lower risk for cardiovascular events, and VPA was also associated with a reduced risk for all-cause mortality. Further studies are required to identify the optimal volume and intensity of PA in high-risk hypertension.

Estimated Population Health Benefits of Intensive Systolic Blood Pressure Treatment Among SPRINT-Eligible US Adults.

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated an intensive (<120 mm Hg) vs. standard (<140 mm Hg) systolic blood pressure (SBP) goal lowered cardiovascular disease (CVD) risk. Estimating the effect of intensive SBP lowering among SPRINT-eligible adults most likely to benefit can guide implementation efforts. We studied SPRINT participants and SPRINT-eligible participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study and National Health and Nutrition Examination Surveys (NHANES). A published algorithm of predicted CVD benefit with intensive SBP treatment was used to categorize participants into low, medium, or high predicted benefit. CVD event rates were estimated with intensive and standard treatment. Median age was 67.0, 72.0, and 64.0 years in SPRINT, SPRINT-eligible REGARDS, and SPRINT-eligible NHANES participants, respectively. The proportion with high predicted benefit was 33.0% in SPRINT, 39.0% in SPRINT-eligible REGARDS, and 23.5% in SPRINT-eligible NHANES. The estimated difference in CVD event rate (standard minus intensive) was 7.0 (95% confidence interval [CI] 3.4-10.7), 8.4 (95% CI 8.2-8.5), and 6.1 (95% CI 5.9-6.3) per 1,000 person-years in SPRINT, SPRINT-eligible REGARDS participants, and SPRINT-eligible NHANES participants, respectively (median 3.2-year follow-up). Intensive SBP treatment could prevent 84,300 (95% CI 80,800-87,920) CVD events per year in 14.1 million SPRINT-eligible US adults; 29,400 and 28,600 would be in 7.0 million individuals with medium or high predicted benefit, respectively. Most of the population health benefit from intensive SBP goals could be achieved by treating those characterized by a previously published algorithm as having medium or high predicted benefit.

Acute Declines in Estimated GFR in Blood Pressure Target Trials and Risk of Adverse Outcomes

Acute decreases in glomerular filtration rate (GFR) occur commonly during intensive blood pressure (BP) lowering. Our objective was to determine the relationship between acute decreases in estimated GFR and patient outcomes. Retrospective observational study. Participants from 4 randomized controlled trials of intensive BP lowering in chronic kidney disease (Modification of Diet in Renal Disease study, African American Study of Kidney Disease and Hypertension, Systolic Blood Pressure Intervention Trial, and Action to Control Cardiovascular Risk in Diabetes trial). A 4-category exposure defined by the level of acute decrease in estimated GFR (defined as>15% vs≤15% between baseline and month 4) and the randomization to intensive versus usual BP control. Risk of kidney replacement therapy (primary outcome), defined as the need for dialysis or transplant except in the Action to Control Cardiovascular Risk in Diabetes trial, which defined its kidney outcome as a composite occurrence of serum creatinine concentration>3.3mg/dL, kidney failure, or kidney replacement therapy. Multivariable Cox models. We included 4,473 individuals randomly assigned to intensive versus usual BP control who had a total of 351 kidney outcomes and 304 deaths during median follow-up durations of 22 and 24 months, respectively. Approximately 14% of participants exhibited an acute decrease in eGFR, 11.0% in the usual BP treatment arm and 17.8% in the intensive BP treatment arm. In adjusted models, compared with a≤15% eGFR decrease in the usual BP arm, a≤15% eGFR decrease in the intensive BP control arm was associated with lower risk of the kidney outcome (HR, 0.75; 95% CI, 0.57-0.98). In contrast, a>15% decrease in eGFR was associated with a higher risk of the kidney outcome in the usual (HR, 2.47; 95% CI, 1.80-3.38) and intensive BP treatment arms (HR, 1.99; 95% CI, 1.45-2.73) compared with a≤15% decrease in the usual BP arm. Observational study, residual confounding. Decreases in eGFR of>15% in the usual and intensive BP treatment arms were associated with a higher risk of kidney outcomes compared with a≤15% decrease in the usual BP arm and may be a harbinger of adverse outcomes.