Systolic Blood Pressure Intervention Research Articles

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.

Abstract 13622: Association Between Self-Reported Medication Adherence and Therapeutic Inertia in Hypertension: A Secondary Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Introduction: Therapeutic inertia (TI), the failure to intensify antihypertensive medication when blood pressure (BP) is above goal, remains highly prevalent in hypertension management. The degree to which self-reported antihypertensive adherence is associated with TI when targeting intensive BP goals remains unclear. Methods: Cross-sectional analysis of the 12-month visit of participants randomized to the intensive systolic BP (SBP) arm of the SBP Intervention Trial (SPRINT), which randomized adults at high cardiovascular disease risk to an intensive (&lt;120 mm Hg) vs. standard (&lt;140 mm Hg) SBP treatment group. TI was defined as no change in the antihypertensive medication regimen intensity score, which incorporates the medication number and dose, when the SBP &gt;120 mm Hg. Self-reported medication adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (&lt;6), medium (6 to &lt;8), and high (8). Poisson regression models with robust error variance estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for TI associated with MMAS-8 category. Results: Among 1,009 intensive arm participants with SBP &gt;120 mm Hg at the 12-month visit (mean age 69.6 years, 35.2% female, 28.8% non-Hispanic Black), TI occurred in 50.8% of participants. Participants with low self-reported adherence (vs. high) were younger and more likely to be non-Hispanic Black or current smokers. The prevalence of TI among low, medium, and high adherence was 45.0%, 53.5%, and 50.4%, respectively. After adjustment, neither low nor medium adherence (vs. high) were associated with TI (PR 1.11; 95% CI 0.87,1.42, PR 1.08; 95% CI 0.84,1.38, respectively). Conclusion: Although clinician uncertainty about medication adherence is often cited as a reason for why antihypertensive intensification is withheld when the BP is above goal, we observed no evidence of an association between self-reported adherence to antihypertensive medication and TI.

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.

THE INFLUENCE OF BASELINE DIASTOLIC BLOOD PRESSURE ON THE EFFECTS OF INTENSIVE BLOOD PRESSURE LOWERING: RESULTS FROM THE STEP RANDOMIZED TRIAL

Objective: The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial reported cardiovascular benefits of intensive systolic blood pressure (SBP) lowering. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive SBP lowering on cardiovascular outcomes has not been fully elucidated. Design and method: In this post hoc analysis of the STEP trial, participants were randomly assigned to receive intensive (110 to &lt;130 mmHg) or standard SBP treatment (130 to &lt;150 mmHg) and categorized by baseline DBP into subgroups: &lt;70, 70 - 79, and &gt; = 80 mmHg. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. A competing risk proportional hazards regression model was used in the analysis. We compared results across subgroups stratified by baseline DBP levels by including a multiplicative interaction term between SBP treatment arms and subgroups (treatment arm* subgroup). Results: Of the 8,511 participants, 960, 2,474, and 5,077 had baseline DBP divided in intervals of &lt;70, 70 - 79, and &gt; = 80 mmHg, respectively. A reduction in the primary outcome was observed among those randomized to intensive SBP lowering in each DBP subgroup but was significant only in the subset of participants with baseline DBP &gt; = 80 mmHg (&lt;70 mmHg: adjusted hazard ratio, 0.81 [95% confidence interval, 0.43 - 1.51]; 70 - 79 mmHg: 0.80 [0.55 - 1.15]; &gt; = 80 mmHg: 0.73 [0.54 - 0.97]). There were no significant interactions between SBP treatment and baseline DBP subgroups for the primary and secondary outcomes (all P for interaction &gt;0.05). The sensitivity analyses showed consistent results with the main analysis. Conclusions: Baseline DBP levels did not modify the beneficial effects of intensive SBP lowering on cardiovascular outcomes.

REMNANT CHOLESTEROL AND INTENSIVE BLOOD PRESSURE CONTROL IN OLDER PATIENTS WITH HYPERTENSION: A POST HOC ANALYSIS OF THE STEP RANDOMIZED TRIAL

Objective: Emerging evidence shows the close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effect of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. We aimed to determine the influence of baseline RC on the effect of intensive SBP lowering in hypertensive patients. Design and method: We performed a post-hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants were randomly allocated to intensive SBP treatment (110 to &lt;130 mmHg) or standard SBP treatment (130 to &lt;150 mmHg). RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. The median RC concentration was used to categorize participants into low and high RC groups. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. Results: Of the 8,511 participants in the STEP trial, 8,276 participants had available baseline RC concentrations (low RC group: n = 4,200; high RC group: n = 4,076). After a median follow-up of 3.33 years, a reduction in the primary outcome was observed in participants allocated to receive intensive SBP lowering in both groups; however, the reduction was only significant in the high RC group (high RC group: adjusted hazard ratio [aHR] 0.62; 95% confidence interval [CI] 0.45–0.84; low RC group: 0.91 [0.67–1.24]; P for interaction = 0.09). Intensive SBP treatment decreased all-cause mortality in the high RC group (aHR 0.48; 95% CI 0.28 – 0.81) but increased it in the low RC group (aHR 2.51; 95% CI 1.47 – 4.28; P for interaction &lt;0.001). Among the adverse events, only hypotension was slightly increased in the high RC group (adjusted relative risk 1.48; 95% CI 1.02 – 2.16). Conclusions: Patients with high RC experienced greater cardiovascular benefits with intensive SBP lowering.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit

Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. ClinicalTrials.gov Identifier: NCT01206062.

Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT MIND Trial.

The prognostic value of systolic blood pressure (SBP) time in target range (TTR) on cognitive outcomes among adults with hypertension remains unclear. We performed secondary analysis of SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension), which compared intensive (<120 mm Hg) versus standard (<140 mm Hg) SBP intervention in hypertensive individuals. TTR was calculated from baseline to month 3 using 110 to 130 mm Hg and 120 to 140 mm Hg as target range for the intensive and standard groups, respectively. Cognitive outcomes included probable dementia, mild cognitive impairment, and the composite of probable dementia or mild cognitive impairment. Cox regression models were used to evaluate the relationship between SBP-TTR and cognitive outcomes. A total of 8298 patients were included. Participants with higher TTR were younger and less likely to be women or to have a history of cardiovascular disease. After adjustment of baseline demographics, medical history, and mean SBP, a 1-SD (31.5%) increase in TTR was independently associated with a 14% lower risk of probable dementia (hazard ratio, 0.86 [95% CI, 0.76-0.98]; P=0.023). Sensitivity analysis showed consistent results when combining target range as 110 to 140 mm Hg. However, there was no significant association between SBP-TTR and mild cognitive impairment. In this post hoc analysis of SPRINT MIND, SBP-TTR was an independent predictor of probable dementia beyond mean SBP. Maintaining SBP within 110 to 140 mm Hg over time may be beneficial for dementia prevention. URL: https://www. gov; Unique identifier: NCT01206062.

The Influence of baseline glycemic status on the effects of intensive blood pressure lowering: Results from the STEP randomized trial

BackgroundIntensive systolic blood pressure (SBP) lowering showed cardiovascular benefits in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. We investigated whether baseline glycemic status influences the effects of intensive SBP lowering on cardiovascular outcomes. MethodsIn this post hoc analysis of the STEP trial, participants were randomly assigned to receive intensive (110 to <130 mmHg) or standard SBP treatment (130 to <150 mmHg) and categorized by baseline glycemic status into three subgroups: normoglycemia, prediabetes, and diabetes. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. A competing risk proportional hazards regression model was used in the analysis. ResultsOf the 8,318 participants, 3,275, 2,769, and 2,274 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 3.33 years, intensive SBP lowering significantly reduced the risk of the primary outcome (adjusted hazard ratio 0.73, 95% confidence interval [CI] 0.59–0.91). The adjusted hazard ratios for the primary outcome in the normoglycemia, prediabetes, and diabetes subgroups were 0.72 (95% CI 0.49–1.04), 0.69 (95% CI 0.46–1.02), and 0.80 (95% CI 0.56–1.15), respectively. The intensive SBP lowering strategy resulted in similar effects among participants in the three subgroups (all interaction P >0.05). The sensitivity analyses showed consistent results with the main analysis. ConclusionThe effects of intensive SBP lowering on cardiovascular outcomes were consistent among participants with normoglycemia, prediabetes, and diabetes.

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.

Effects of intensive vs. standard blood pressure control on cognitive function: Post-hoc analysis of the STEP randomized controlled trial.

The STEP (Strategy of Blood Pressure Intervention in the older Hypertensive Patients) trial showed that intensive systolic blood pressure (SBP) control resulted in a lower incidence of cardiovascular events than standard treatment. This study analyzed the effects of intensive SBP lowering on cognitive function. STEP was a multicenter, randomized controlled trial of hypertensive patients aged 60-80 years. Participants were randomly assigned (1:1) to SBP goals of 110-130 mmHg (intensive treatment) or 130-150 mmHg (standard treatment). Each individual was asked to complete a cognitive function test (Mini-Mental State Examination; MMSE) at baseline and during follow-up. The primary outcome for this study was the annual change in MMSE score. Subjects with a score less than education-specific cutoff point were categorized as cognitive decline. The analysis enrolled 6,501 participants (3,270 participants in the intensive-treatment and 3,231 participants in the standard-treatment groups). Median follow-up was 3.34 years. There was a minor change in MMSE score, with an annual change of -0.001 [95% confidence interval [CI] -0.020, 0.018] and 0.030 (95% CI 0.011, 0.049) in the intensive- and standard-treatment groups, respectively (p = 0.052). Cognitive decline occurred in 46/3,270 patients (1.4%) in the intensive-treatment group and 42/3,231 (1.3%) in the standard-treatment group (hazard ratio 0.005, 95% CI 0.654, 1.543, p = 0.983). Compared with standard treatment, intensive SBP treatment did not result in a significant change in cognitive function test score. The impact of intensive blood pressure lowering was not evident using this global cognitive function test. ClinicalTrials.gov. Unique identifier: NCT03015311.

Association of serum uric acid with benefits of intensive blood pressure control

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Intensive systolic blood pressure treatment remodels brain perivascular spaces: A secondary analysis of the Systolic Pressure Intervention Trial (SPRINT)

BackgroundBrain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. MethodsThis is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130–180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). ResultsFor 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: −0.029 [−0.055 to −0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB). ConclusionsPVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance.Clincaltrials.gov: NCT01206062.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes. We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n=1627 and n=2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings. A total of 3989 patients were randomized to undergo intensive (n=1984) or standard SBP treatment (n=2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses. An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Abstract 9705: Diastolic Blood Pressure and Intensive Blood Pressure Control on Cognitive Outcomes: Insights From the SPRINT Trial

Introduction: The potential benefits or harms of intensive systolic blood pressure (SBP) lowering on cognitive function in individuals with low diastolic blood pressure (DBP) remain unclear. Hypothesis: The effects of intensive SBP lowering on cognitive outcomes were consistent across baseline DBP levels. Methods: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 8563 participants with at least one follow-up cognitive assessment were included. Cognitive outcomes were the occurrence of probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models and likelihood ratio tests were used to assess the interaction between DBP quartiles and intensive SBP control on cognitive outcomes. Results: The incidence rates of cognitive outcomes among participants in the lowest DBP quartile were higher than those in the other three DBP quartiles (Figure 1). However, participants in the intensive group had a lower incidence rate of probable dementia or MCI than those in the standard group, regardless of DBP quartiles. There were no significant interactions between SBP intervention and DBP quartiles for probable dementia ( P for interaction =0.06), MCI ( P for interaction =0.80), or a composite of probable dementia or MCI ( P for interaction =0.24) (Figure 2). Conclusions: In this post hoc analysis of the SPRINT study, patients with lower DBP had a higher incidence of cognitive impairment. However, the effects of intensive SBP lowering on cognitive outcomes were consistent across different DBP groups.

Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.

Lowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition. This is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms. Mean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention. Intensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP.

Safety and efficacy of intensive systolic blood pressure lowering after successful endovascular therapy: a post hoc analysis of the BP TARGET trial

BackgroundThe Safety and Efficacy of Intensive Blood Pressure Lowering after Successful Endovascular Therapy in Acute Ischaemic Stroke (BP TARGET) trial demonstrated no benefit from intensive systolic blood pressure (SBP) treatment...

The relationship between achieved blood pressure values and cardiovascular risk in women and men during antihypertensive treatment

Abstract Introduction There is limited knowledge about sex differences in effect from clinical studies of blood pressure (BP) reduction. Purpose To evaluate the associations between achieved BP and outcome in the Systolic BP Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD BP) trials in sex-specific analyses. Methods Data of 9361 SPRINT and 4773 ACCORD BP trials participants were analysed separately. In both trials participants were randomly assigned 1:1 to the treatment goal (SBP &amp;lt;120 vs &amp;lt;140 mm Hg). SPRINT was performed in subjects without diabetes mellitus type 2 (DM2) while all ACCORD BP participants had DM2. In-trial SBP and DBP were computed as mean of all measurements obtained during the trials. The composite clinical endpoint (CE) was defined as combined myocardial infarction, stroke, hospitalization due to heart failure and death from cardiovascular disease (CVD). Cox proportional hazard risk models were used to evaluate the relationship between CE risk and SBP and DBP, respectively, adjusting for age, ethnicity, current smoking, body mass index, total serum cholesterol and glucose separately for each sex. Results Females (N=3332) enrolled in SPRINT were older than men (68.5±9.5 vs 67.6±9.3 years, p&amp;lt;0.001), and had higher SBP (141.2±16.8 vs 138.8±14.8 mm Hg, p&amp;lt;0.001) and lower DBP (77.6±12.1 vs 78.4±11.8 mm Hg, p=0.004) at baseline, and less often known CVD (15.3% vs 22.7%, p&amp;lt;0.001), but more often reported chronic kidney disease (CKD) (31.8% vs 26.3%, p&amp;lt;0.001), while smoking did not differ. Females obtained higher in-trial SBP and lower in-trial DBP than males (129.9±10.5 vs 129.2±9.5, p=0.0012, and 71.9±9.1 vs 72.3±9.4 mm Hg, p=0.038), respectively. Compared to males, females (N=2258) participating in ACCORD BP less often had known CVD (25.8% vs 40.8%, p&amp;lt;0.001) or CKD (34.4% vs 38.4%, p&amp;lt;0.001), less frequently smoked (9.8% vs 13.2%, p&amp;lt;0.001), had higher SBP (140.1±16.7 vs 138.4±14.9 mm Hg, p&amp;lt;0.001) and similar DBP (76.1±10.3 vs 75.9±10.5 mm Hg, p=0.51) at baseline, while age did not differ (62.8±6.4 vs 62.7±6.9 years, p=0.829). In-trial SBP and DBP were higher among females (128.5±11.8 vs 127.6±10.3 mm Hg, p=0.006, and 69.5±7.9 vs 68.8±8.2 mm Hg, p=0.001), respectively. Both in SPRINT and ACCORD BP trials female sex was associated with lower CE rate (hazard ratio for CE in SPRINT 0.72, 95% CI 0.60–0.86, p&amp;lt;0.001 and in ACCORD BP 0.74, 95% CI 0.62–0.87, p&amp;lt;0.001; respectively). The relationship between in-trial SBP and CE among SPRINT participants is presented in Figure 1. In ACCORD BP a stronger relationship between in-trial SBP and CE was found in females than in males (Figure 2). Conclusions The characteristics of females enrolled in clinical studies in hypertension are different from that of males. Better outcome was observed in females. Achieved SBP was stronger associated with outcome in women than in men only when DM2 comorbidity was present. Funding Acknowledgement Type of funding sources: None.

Considerations for Optimal Blood Pressure Target of Hypertension

Hypertension is a major risk factor for cardiovascular morbidity and mortality that has led to a huge public health burden. The optimal target of blood pressure (BP) to prevent cardiovascular complications remains unclear. Based on the results of the Systolic BP Intervention Trial (SPRINT) in 2015, the 2017 American College of Cardiology/American Heart Association guidelines for diagnosis and management of high BP in adults has changed the diagnostic threshold from 140/90 to 130/80 mmHg, and the target BP to 130/80 mmHg for nearly all hypertensive patients diagnosed using the new criteria. However, the findings from the SPRINT trial were to an extent contrasting with the results of previous large randomized controlled trials, namely Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Secondary Prevention of Small Subcortical Strokes (SPS3). Besides, the 2018 European Society of Cardiology/European Society of Hypertension guidelines and the 2018 Chinese guidelines have maintained the conventional threshold and recommended target of 140/90 mmHg for most hypertensive patients. Given the special measurement of BP in the SPRINT trial and using an automated measurement system, the intensive systolic BP target of 120 mmHg provided by the SPRINT trial was not widely adopted. Most recently, the Strategy of BP Intervention in the Elderly Hypertensive Patients (STEP) trial, with a higher systolic BP target of 110 to 130 mmHg in the intensive group, confirmed the benefit and safety of intensive BP control in patients with hypertension, in accordance with the SPRINT trial. Here, the results from randomized controlled trials, meta-analyses, and other observational research studies, have been reviewed to evaluate the optimal target of BP treatment and the threshold of diagnostic criteria for hypertension.