Intensive Blood Pressure Research Articles

Intensive Blood-Pressure Control in Patients with Type 2 Diabetes

Intensive Blood-Pressure Control in Patients with Type 2 Diabetes

NEJM at AHA — Intensive Blood-Pressure Control in Patients with Type 2 Diabetes

NEJM at AHA — Intensive Blood-Pressure Control in Patients with Type 2 Diabetes

Abstract 4138672: Blood Pressure and Cardiovascular Outcomes in Adults with Diabetes and Chronic Kidney Disease

Background: Most international guidelines recommend intensive blood pressure (BP) targets (e.g., <130/80 mm Hg) for patients with chronic kidney disease (CKD). However, the data supporting these recommendations are limited, particularly for those with concomitant diabetes. Hypothesis: Systolic BP (SBP) <130 mm Hg and diastolic BP (DBP) <80 mm Hg are associated with a reduced risk of cardiovascular disease (CVD) in adults with diabetes and CKD. Aims: To determine the association of BP with incident CVD risk among adults with diabetes and CKD. Methods: From a Korean nationwide health screening database, we identified 373,966 adults aged 20-79 with both diabetes and CKD who: (1) underwent baseline health examinations in 2009-2013; (2) had ≥3 BP measurements; and (3) did not have CVD at baseline. The associations of baseline average SBP and DBP with CVD risk were assessed using multivariable-adjusted cause-specific Cox models. The primary outcome was CVD event, defined as a composite of myocardial infarction, stroke, heart failure, or death from CVD. Results: The median (Q1-Q3) age of the participants was 62 (53-70) years; 40.8% were female. Over a median follow-up of 10.2 years, a total of 40,781 incident CVD events occurred. Compared with SBP 130 to <140 mm Hg as the referent group, the multivariable-adjusted HRs (95% CIs) for CVD event in the SBP ≥150 mm Hg, 140 to <150 mm Hg, 120 to <130 mm Hg, and <120 mm Hg groups were 1.34 (1.29-1.39), 1.11 (1.08-1.14), 0.89 (0.87-0.91), and 0.77 (0.74-0.80), respectively. Compared with DBP 80 to <90 mm Hg as the referent group, the HRs (95% CIs) in the DBP ≥100 mm Hg, 90 to <100 mm Hg, 70 to <80 mm Hg, and <70 mm Hg groups were 1.70 (1.56-1.85), 1.19 (1.15-1.24), 0.88 (0.86-0.90), and 0.83 (0.80-0.87), respectively (Figure A). SBP <130 mm Hg and DBP <80 mm Hg were each associated with a reduced CVD risk in a log-linear manner (Figure B, Figure C). The findings were consistent when examining kidney instead of cardiovascular outcomes. Conclusion: Among patients with diabetes and CKD, SBP below 130 mm Hg and DBP below 80 mm Hg were associated with a reduced risk of CVD.

Effect of Intensive Blood Pressure Lowering on the Risk of Incident Silent Myocardial Infarction: A Post Hoc Analysis of a Randomized Controlled Trial.

Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23). This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. ClinicalTrials.gov Identifier: NCT01206062.

Influence of orthostatic blood pressure changes on the effects of intensive blood pressure control in patients with type 2 diabetes

Abstract Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Intensive blood pressure lowering after endovascular thrombectomy in acute ischaemic stroke: an updated systematic review and meta-analysis of randomized controlled trials

Abstract Background Endovascular thrombectomy is an effective treatment in those with acute ischemic stroke. However, following successful reperfusion there are still many uncertainties as to the factors which influence patient outcome. Effective blood pressure management in this cohort has been elicited as one of these factors, with worse outcomes seen at both the high and low extremes. Purpose Pinpointing an optimal systolic blood pressure target after this procedure is still uncertain. We aimed to perform an updated meta-analysis of randomised controlled trials (RCTs) to evaluate the safety and efficacy of intensive blood pressure management as compared to conventional blood pressure management in this patient population. Methods We searched various electronic databases, including Embase, MEDLINE (via PubMed), and CENTRAL, to retrieve relevant RCTs evaluating a strategy of intensive blood pressure management after endovascular thrombectomy compared to conventional management. We pooled risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes, using RevMan 5.4. Results The meta-analysis included 4 RCTs with a total of 1560 patients. According to the analysis, intensive blood pressure management was associated with a statistically significant decrease in the number of patients showing functional independence (modified Rankin scale mRS score=0-2) at 90 days (RR 0.81; CI = 0.72-0.91; I2 = 12%). Regarding 90-day mortality, the pooled results from three RCTs showed no statistically significant difference between the intensive blood pressure management group and the conventional blood pressure management group (RR 1.17; CI = 0.90-1.52; I2 = 0%). There was no statistically significant difference between the two groups regarding the incidence of intracerebral haemorrhage (ICH) (RR 1.05; CI = 0.90-1.23; I2 = 0%) and the incidence of symptomatic intracerebral haemorrhage (sICH) (RR 1.10; CI = 0.76-1.60; I2 = 0%). Conclusion The meta-analysis showed no benefit of intensive lowering of blood pressure in terms of functional independence at 90 days, mortality rates, and incidence of ICH. Future large-scale trials should focus on other interventions to improve prognosis in these patients.Figure 1Figure 2

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 &amp;lt; 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

Differential impact of clinic BP target on the prevalence and predictors of the masked uncontrolled hypertension and white-coat uncontrolled hypertension

Abstract Background Although intensive blood pressure (BP) control have been advocated, major clinical practices guidelines still recommend clinic BP (cBP) &amp;lt; 149/90 mmHg as the target for antihypertensive therapy. But, cBP targets could influence the prevalence and predictors of any hypertension phenotype. We investigated how different cBP targets impacted on the prevalence and predictors of masked uncontrolled hypertension (MUCH) and white-coat uncontrolled hypertension (WUCH) using the Korean Ambulatory Blood Pressure (KorABP) registry. Methods A multicenter prospective longitudinal cohort study was performed in outpatients with hypertension. Among 5,965 patients enrolled in the KorABP registry, 1,601 patients on antihypertensive medications with a valid ambulatory BP monitoring record were included in this study. Two different cBP targets, &amp;lt;130/80mmHg (intensive) and &amp;lt;140/90 mmHg (conventional) were investigated. Results Controlled ambulatory BP (aBP; &amp;lt;130/80 mmHg) was observed in 472 patients (29.5%). Controlled cBP was shown in 348 patients (21.7%) with the intensive cBP target and in 697 patients (43.5%) with the conventional cBP target. Controlled hypertension, WUCH, MUCH and uncontrolled hypertension were found in 294, 174, 54, and 1,075 patients with the intensive target and in 378, 94, 319 and 810 patients with the conventional target, respectively. Among the patients with controlled cBP, the prevalence of MUCH markedly decreased with the intensive target (15.5%), compared to the conventional target (45.8%). In contrast, among the patients with uncontrolled cBP, the prevalence of WUCH had only 3.8% increase with the intensive target (10.4%), compared to the conventional target (14.2%) (Figure 1). With the conventional target, 75.9% of patients with MUCH had cBP between 130/80 mmHg and 139/89 mmHg. The concordance between the controlled aBP and controlled cBP was higher with the intensive target than with the conventional target (Cohen’s κ 0.62 [0.58-0.67] vs. 0.46 [0.41-0.50]). The logistic models for MUCH included the left ventricular mass index and underuse of antihypertensive drugs (&amp;lt;2 types of drugs) as the common predictors of the both targets. With the conventional target, clinic systolic BP and diastolic BP were the strongest predictors of MUCH, but the cBP was not a predictor of MUCH with the intensive target. The logistic models for WUCH included beta-blocker use, increased heart rate and lower waist circumference and clinic systolic BP as the common predictors of WUCH with the both target. The logistic model for MUCH performed better with the conventional target, whereas the logistic model for WUCH performed better with the intensive target (Figure 2). Conclusion The use of the intensive cBP target (&amp;lt;130/80 mmHg) could reduce the prevalence of MUCH with minimal increase in the prevalence of WUCH and would provide the better assessment for the BP control status than the use of the conventional cBP target (&amp;lt;140/90 mmHg).Figure 1Figure 2

Impact of appendicular skeletal muscle mass on effect of intensive blood pressure control

Abstract Background Appendicular skeletal muscle mass (ASM) is associated with cardiovascular diseases (CVDs) and chronic kidney diseases (CKDs). However, whether low ASM affects the efficacy of intensive systolic blood pressure control is currently uncertain. Purpose To examine the impact of low ASM on the effects of intensive SBP control on cardiovascular and kidney outcomes. Methods Data from the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trials was used. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. The prespecified incident CKD was defined as a &amp;gt;30% decrease in estimated glomerular filtration rate to a value &amp;lt;60 mL/min/1.73 m2. Results A total of 14,017 patients were included in this study, 2203 (15.7%) of whom had low ASM. Over a median follow-up of 3.26 years, 1,032 primary outcomes and 460 incident CKD were observed. Patients with low ASM had a significantly higher risk of primary outcome and CKD. Intensive SBP control effects on cardiovascular outcomes were not significantly different on a relative scale or absolute scale. But low ASM significantly amplified the increased risk of CKD associated with intensive SBP control, on an absolute scale (P for interaction = 0.04). Conclusions Low ASM is one of the markers of increased risk of CVD and CKD, and it did not affect the cardiovascular benefits of intensive treatment, but significantly amplified the increased risk of CKD associated with intensive SBP control.

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

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

A novel digital twin strategy to enable the translation of evidence from randomized control trials to new populations

Abstract Background Randomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. Between the SPRINT and ACCORD trials, only SPRINT found a significant reduction in major cardiovascular events (MACE) with intensive blood pressure control, but ACCORD did not, without clear evidence of whether this reflected differences in enrolled patients. Purpose To use a novel RCT digital twin-based approach to demonstrate the translation of an RCT to a different population, leveraging the differences in populations and treatment effects in SPRINT and ACCORD. Methods We developed a statistically informed Generative Adversarial Network (GAN) model that leverages relationships between covariates and outcomes using Directed Acyclic Graphs (DAGs). This model can generate a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population while maintaining these relationships (Fig A). Using this, we generated the (i) RCT-Twin of SPRINT, which was conditioned on the 10 most disparate covariates drawn from ACCORD, and (ii) an RCT-Twin of ACCORD conditioned on SPRINT. To demonstrate treatment effect estimates of each RCT conditioned on the other RCT’s patient population, we evaluated the cardiovascular event-free survival of 10 iterations of these cross-trained RCT-Twins against the original trials. Results Using 9361 SPRINT participants and conditioning on 4733 ACCORD participants, we generated 10 ACCORD-conditioned SPRINT-Twin datasets. We confirmed that the RCT-Twins were consistently balanced between treatment and controls across all measured covariates (mean absolute standardized mean difference (MASMD) 0.019, SD 0.018), as expected for real RCTs. We also confirmed that covariates of the ACCORD-conditioned SPRINT-Twins were closer to ACCORD than SPRINT (MASMD 0.0082 vs 0.46, SD 0.016 vs 0.20), suggestive of successful conditioning. Most importantly, across iterations, ACCORD-conditioned SPRINT-Twin datasets reproduced the overall non-significant effect size seen in ACCORD (5-year MACE hazard ratio (95% confidence interval) of 0.88 (0.73-1.06) in ACCORD vs median 0.87 (0.68-1.13) in the ACCORD-conditioned SPRINT-Twins, Fig B), while the SPRINT-conditioned ACCORD-Twin datasets reproduced the significant effect size seen in SPRINT (0.75 (0.64-0.89) vs median 0.79 (0.72-0.86) in the SPRINT-conditioned ACCORD-Twins, Fig C). Conclusions Our novel conditioned digital twin approach simulates RCT-derived effects in different patient populations by translating these effects to the covariate distributions of the patients. This key methodological advance may enable the direct translation of RCT-derived effects into disparate patient populations and may enable causal inference in real-world settings.

Intensive postpartum antihypertensive treatment (IPAT) and healthy lifestyle education: Study protocol for a pilot randomized controlled trial for patients with hypertensive disorders of pregnancy

BackgroundHypertensive disorders of pregnancy (HDP) complicate about 10 % of pregnancies and lead to postpartum hospital readmissions and cardiovascular complications. Following HDP, vascular dysfunction could persist and accelerate the trajectory of cardiovascular disease risk. The benefits of intensive blood pressure (BP) control following HDP have not been adequately investigated. Therefore, no standard guidelines exist to guide the management of mild-to-moderate hypertension in the postpartum period, leading to a wide variation in clinical practice. The present study will investigate the effect of intensive BP control and healthy lifestyle education on maternal cardiovascular health (CVH) and vascular function following HDP. MethodsThe Intensive Postpartum Antihypertensive Treatment (IPAT) study is a randomized controlled, two-arm, single-site, pilot trial where 60 postpartum HDP patients will be randomized 1:1 to one of two groups: 1) Intensive postpartum BP control – nifedipine initiation at BP ≥140/90 mmHg to maintain BP <140/90 mmHg; or 2) Less intensive postpartum BP control – nifedipine initiation at BP ≥150/100 mmHg to maintain BP <150/100 mmHg. All participants will also undergo vascular function assessments and receive healthy lifestyle education. The study will primarily test feasibility of all study procedures. It will secondarily examine changes in BP and CVH scores from baseline to 12 months postpartum. ConclusionThis pilot trial will study whether the BP threshold of 140/90 is superior to 150/100 for initiation of pharmacotherapy and evaluate feasibility to ultimately conduct a trial capable of generating robust evidence to standardize clinical practice and guidelines in postpartum HDP management.Trial registration number: NCT05687344

Intensive Home Blood Pressure Lowering in Patients with Advanced CKD

Optimal blood pressure (BP) targets in advanced CKD are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and ESKD. We aimed to conduct a pilot trial of intensive BP control to determine if lower SBP targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP. Non-blinded randomized controlled trial. 108 patients with advanced CKD (eGFR ≤30 mL/min/1.73 m2) and hypertension. Participants were randomized either to a target home SBP goal of <120 mmHg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time. The primary efficacy outcome was the difference in achieved clinic SBP between the two study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation. The mean clinic SBP at month 12 was 124.7 mmHg in the intensive SBP group vs. 138.2 mmHg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7 mmHg (95% CI 7.5 to 16 mmHg, p<0.001) lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the two arms (all p>0.05). Small sample size which may limit our ability to detect clinically significant differences in rates of adverse outcomes; single-center design. A clinic SBP goal of <120 mmHg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted.

Optimal blood pressure control with fewer antihypertensive medications: Achieved mostly in low-risk hypertensive patients.

Recent studies indicate that intensive blood pressure (BP) targets can be reached with less than two medications. This cross-sectional study, involving 4991 individuals from the Majiapu community, assessed the correlation between BP control and the burden of antihypertensive drugs. Participants on medication were categorized into controlled (BP<140/90mm Hg) and uncontrolled (BP≥140/90mm Hg) groups, with the former further divided into optimal (BP<130/80mm Hg) and good control (BP<140/90 but >130/80mm Hg) subgroups. Multivariate logistic regression analyzed factors affecting hypertension control across these BP categories. The study found that, 54% of participants had hypertension. Of those treated (62.5%), 55.7% achieved BP control, including 23.15% maintaining BP below 130/80mm Hg. The average number of antihypertensive medications was 1.61 for the controlled group (with an average BP of 126.6/76mm Hg) and 1.75 for the uncontrolled group (with an average BP of 150.6/84.0mm Hg). Additionally, the average number of antihypertensive medications was 1.66 in the good control group and 1.55 in the optimal control group. The uncontrolled group had a higher mean systematic coronary risk estimation (SCORE) of 5.59, against 3.97 and 2.5 in the good and optimal control groups, respectively. Key factors linked to poor BP control included age over 65, male sex, obesity, and former smoking, whereas lipid-lowering medication use was associated with better control. In conclusions, patients needing fewer antihypertensive drugs to achieve stricter targets may have a lower risk profile. Notably, only a small proportion of treated patients are low-risk individuals who can easily achieve BP levels below 130/80mm Hg.

Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

Glomerular Hematuria as a Predictor of Renal Prognosis in Malignant Hypertension Patients with Thrombotic Microangiopathy: A Propensity Score-Matched Analysis of a Biopsy-Based Cohort Study

Introduction: Malignant hypertension (mHTN) is a hypertensive emergency. Thrombotic microangiopathy (TMA) is a widespread complication of mHTN. Few studies have evaluated whether glomerular hematuria provides prognostic information for renal dysfunction in patients with mHTN-associated TMA. Methods: This observational cohort study included 292 patients with mHTN-associated TMA based on renal biopsy. Propensity-score matching (PSM) analysis was conducted to adjust for clinical characteristics in a comparison between with and without glomerular hematuria. Cox regression was employed to identify risk factors for renal prognosis. Results: A total of 70 patients with glomerular hematuria were compared to 222 patients with non-glomerular hematuria. After PSM, 67 pairs of patients with mHTN-associated TMA were matched. Patients with glomerular hematuria exhibited lower serum albumin levels, higher 24-h proteinuria, and a higher prevalence of glomerular sclerosis than those with non-glomerular hematuria. Glomerular hematuria was independently associated with deteriorated renal function compared with non-glomerular hematuria (HR: 0.51; 95% CI: 0.29–0.89, p = 0.019). This association remained significant after PSM (HR: 0.51; 95% CI: 0.28–0.91, p = 0.022). Additionally, glomerular hematuria was independently associated with renal replacement therapy (RRT) (HR: 3.14; 95% CI: 2.06–5.66, p < 0.001). This difference remained significant after PSM comparison (HR: 2.41; 95% CI: 1.34–4.33, p = 0.003). Furthermore, despite intensive blood pressure control, patients with glomerular hematuria experienced a higher incidence of RRT and a poorer recovery in renal function, specifically a 25% reduction of creatinine levels, compared to patients with non-glomerular hematuria. Conclusion: Glomerular hematuria is significantly associated with an increased risk of adverse renal outcomes in patients with mHTN-associated TMA.

Evaluation of self-monitoring of blood pressure in the PERHIT study and the impact on glomerular function

Background Although intensive blood pressure (BP) control has not been shown to slow the progression of chronic kidney disease (CKD), intensive BP control has been shown to reduce the risk for adverse cardiovascular outcomes in the CKD population. The aim of this post-hoc study was to study the interplay between a self-monitoring BP system and glomerular function. Methods In all, 949 participants with hypertension underwent visits at baseline, after eight weeks and 12 months. Half of the participants received a BP monitor and installed a program on their mobile phone. During eight weeks, they measured daily and reported their BP values. Results Within the intervention group, BP and systolic BP (SBP) decreased from baseline to eight weeks and 12 months (p < .001). Pulse pressure (PP) and mean arterial blood pressure (MAP) decreased from baseline to eight weeks (p = .021 and p = .004) vs 12 months (p = .035 and p = .008). Within the control group, a decrease was observed from baseline to 12 months for SBP, diastolic BP (DBP) and PP (p = .025, p = .023 and p = .036). In the intervention group, we observed an association between a decrease in SBP, DBP, PP and MAP and a decrease in eGFR (estimated glomerular filtration rate), (p < .001, p < .001, p = .013 and p < .001). In the control group, similar results were observed for PP only (p = .027). Within the intervention group, eGFR decreased (p < .001) but within the control group, the decrease was non-significant (p = .051). Conclusion We observed an association between a decrease in all BP components and eGFR decline within the normal range in the intervention group but not in the controls. Trial registration The study was registered with ClinicalTrials.gov [NCT03554382].

Protocol for a randomized controlled trial of intensive blood pressure control on cardiovascular risk reduction in patients with atrial fibrillation: Rationale and design of the CRAFT trial

BackgroundCo-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. MethodsThe Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study. ConclusionsThis clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF. Trial registrationThe trial is registered at ClinicalTrials.gov (NCT04347330)

Process Evaluation of an Ambulance-Delivered Early Intensive Blood Pressure-Lowering Stroke Trial: Design, Rationale, and Reflection

Introduction: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of prehospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. Methods: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of prehospital early intensive BP-lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. Conclusion: The process evaluation of INTERACT4 will provide insights for the implementation of prehospital early intensive BP-lowering intervention in different health systems and help better explain the trial results for further scale up.

Abstract 24: Effects Of Intensive Blood Pressure Lowering on Brain Tissue Pulsatility in Hypertensive Patients

Recent studies have shown an association between blood pressure (BP), particularly pulse pressure (PP), in increasing brain tissue pulsatility. However, these studies were conducted in a phantom model or in healthy normotensive adults. Effects of intensive BP lowering on brain tissue pulsatility in hypertensive patients remain unknown. Accordingly, we performed a randomized clinical trial to compare effects of intensive BP lowering to target 24-h ambulatory BP &lt;120/70 mmHg (n=26) vs. target of &lt;130/80 mmHg in the control arm (n =19) in hypertensive patients aged 55-79 with normal cognitive function. The brain tissue pulsatility was assessed by the total tissue motion over one cardiac cycle, using CINE phase contrast MRI, with the velocity encoded in all three directions. In each cardiac cycle, the velocity of the tissue was measured at 16 time points. Brain tissue pulsatility was assessed at baseline and after 1 year of follow up. We found that 24-h ambulatory systolic BP (SBP) was reduced from 134.3±9.8 to 112.1±7.2 mmHg in the intensive arm and from 138.5±11.3 to 122.4±7.8 mmHg in the control arm (both p&lt;0.01). The magnitude of 24-h SBP reduction from baseline was greater in the intensive arm than control arm (23.6 vs. 13.1 mmHg, p=0.052) while 24-h diastolic BP was reduced similarly in both groups (11.6 vs. 9.6 mmHg, p=0.8). Similarly, PP based on 24-h BP was reduced from 57.5±11.7 to 45.1±12.1 mmHg in the intensive BP arm and from 62.2±10.6 to 55.4±10.5 mmHg in the control arm (both p&lt;0.01). The magnitude of PP reduction appeared greater in the intensive compared to control arm but was not statistically different (12.4 vs. 6.8 mmHg, p=0.08). We found that the overall gray-white matter tissue pulsatility per cardiac cycle remained unchanged after 12 months in the intensive arm (0.98±0.18 mm to 0.95±0.17 mm) while the brain pulsatility tended to increase in the control arm (0.85±0.17 mm to 0.92±0.16 mm, p=0.09 for treatment group, interaction-p=0.04). Similarly, the white matter (WM) tissue motion remained unchanged in the intensive arm (0.91±0.16 mm to 0.88±0.15 mm) while the WM pulsatility tended to increase in the control arm (from 0.77±0.14 mm to 0.84±0.15 mm, p=0.06 for group, interaction p=0.03). In conclusion, our data suggested a novel effect of intensive BP lowering in preventing the rise in brain tissue pulsatility in hypertensive patients, which may have an implication in the prevention of an accelerated brain injury related to hypertension.