Standard Blood Pressure Lowering Research Articles

#783 Individualized net benefit of intensive blood pressure lowering among older adults in SPRINT

Abstract Background and Aims The optimal blood pressure (BP) target for older adults remains controversial. This study aimed to determine whether results from the Systolic Blood Pressure Intervention Trial (SPRINT) could be tailored to individual trial participants using risk estimates and simulated preferences about the relative importance of multiple outcomes related to BP lowering. Method This analysis included 4,850 SPRINT participants age ≥65 years. Parsimonious Cox models were internally validated to predict the absolute difference in risk between intensive versus standard BP lowering in each SPRINT participant for all-cause death, cardiovascular outcomes, cognitive outcomes, and serious adverse events. Treatment effects were combined using simulated preference weights into an individualized net benefit, which represents the weighted sum of risk differences across outcomes. Individualized net benefits among older SPRINT participants were compared across categories of age (65-74 years vs. ≥ 75 years), frailty (fit, less fit, and frail), and polypharmacy status. Results When simulating preferences for older adults who view death, cardiovascular events, and cognitive impairment as much more important than the harms of BP lowering, the median (IQR) individualized net benefit was 5% (3%, 7%), and 100% had a net benefit that favoured intensive BP lowering. When simulating benefits and harms to have similar importance, the median (IQR) individualized net benefit was 2% (1%, 3%), and 95.4% had a positive net benefit. In subgroup analyses, the predicted net benefit of intensive BP lowering was significantly greater among those with advanced age, frailty, and polypharmacy compared with lower risk individuals (P<0.001 for all comparisons). Conclusion Almost all older participants in SPRINT had a predicted net benefit that favoured intensive BP control, but the degree of net benefit varied considerably. Personalizing BP targets for older adults according to each person's estimated risks and preferences may provide more refined BP target recommendations.

24-Hour Blood Pressure Variability Via Ambulatory Monitoring and Risk for Probable Dementia in the SPRINT Trial

BackgroundBlood pressure variability is an emerging risk factor for dementia, independent and oftentimes beyond mean blood pressure levels. Recent evidence from interventional cohorts with rigorously controlled mean blood pressure levels suggest blood pressure variability over months to years remains a risk for dementia, but no prior studies have investigated relationships with blood pressure variability over shorter time periods.ObjectivesTo investigate the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering.DesignPost hoc analysis of the randomized, controlled, open-label Systolic Blood Pressure Intervention Trial clinical trial.SettingMultisite Systolic Blood Pressure Intervention Trial.Participants793 participants at increased risk for cardiovascular disease and without history of dementia at study randomization.InterventionStandard (<140 mmHg systolic blood pressure target) vs intensive (<120 mmHg systolic blood pressure target) lowering of mean blood pressure.Measurements24-hour ambulatory blood pressure monitoring 27 months after treatment randomization (standard vs intensive) and follow-up cognitive testing. Intraindividual blood pressure variability was calculated as the average real variability over 24-hour, daytime, and nighttime periods. Participants were categorized into 3 adjudicated clinical outcomes: no cognitive impairment, mild cognitive impairment, probable dementia. Cox proportional hazards models examined the potential effect of ambulatory blood pressure variability on the rate of cognitive outcomes under intensive vs standard blood pressure lowering. Associations with mean blood pressure were also explored.ResultsHigher systolic 24-hour blood pressure variability was associated with increased risk for probable dementia in the standard group (adjusted hazard ratio [HR]: 2.56 [95% CI 1.16, 5.62], p = 0.019) but not in the intensive group (HR: 0.54 [95% CI 0.24, 1.23], p = 0.141). Similar findings were observed with daytime systolic blood pressure variability but not nighttime blood pressure variability. Mean blood pressure was not associated with cognitive outcomes.ConclusionsHigher systolic 24-hour and daytime blood pressure variability via ambulatory monitoring is associated with risk for dementia under standard blood pressure treatment. Findings support prior evidence that blood pressure variability remains a risk for dementia despite strict control of mean blood pressure levels.

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion &gt; 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p &gt;0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Abstract 17590: Association of Intensive vs Standard Blood Pressure Lowering With 1-year and 2-year Changes in Cardiac Biomarker Levels: Findings From SPRINT

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive systolic blood pressure (SBP) lowering was associated with marked reductions in cardiovascular disease (CVD) endpoints. We recently reported that intensive SBP lowering was also associated with a small increase in high-sensitivity cardiac troponin T (hs-cTnT) and a large decrease in N-terminal pro-B-type natiuretic peptide (NT-proBNP) over 1-year. However, data on longer term biomarker changes with intensive versus standard SBP lowering have not been previously reported. Methods: hs-cTnT and NT-proBNP were measured at baseline, 1 year, and 2 years from stored specimens in SPRINT participants. Changes in biomarkers were evaluated continuously on the log scale with interval censoring of participants with CVD events. The effect of intensive SBP lowering on biomarker changes was assessed using linear regression models with treatment effects reported as geometric mean ratios. Results: Of 9,361 SPRINT participants, hs-cTnT and NT-proBNP were measured in 8,828 (baseline), 7,887 (Year 1), and 7,463 (Year 2) free of CVD events. Intensive SBP lowering led to a 3% increase in log-transformed hs-cTnT from baseline to Year 1, but there was no significant change observed from baseline to Year 2. In contrast, intensive SBP lowering led to a consistent 10% decrease in NT-proBNP from baseline to Year 1 and to Year 2. NT-proBNP levels increased slightly from Year 1 to Year 2 in both treatment arms such that the 1-Year treatment effect for intensive SBP lowering was maintained to Year 2 (see Table). Conclusions: Intensive SBP lowering was associated with a transient, modest increase in hscTnT at Year 1 that was no longer present at Year 2. In contrast, intensive SBP lowering was associated with a persistent reduction in NT-proBNP at both 1 and 2 years follow-up. These findings highlight the complex responses of cardiac biomarkers to intensive SBP lowering.

36. Clinical Outcome of Intensive Blood Pressure Lowering in Diabetic Patients: A Systematic Review and Meta-analysis

Background: It remains controversial in defining the optimal blood pressure (BP) targets for diabetes mellitus (DM) patients. There were various data on intensive BP lowering management in DM population, particularly in reducing cardiovascular outcomes. Objective: This study was conducted to compare the clinical outcome of intensive and standard BP lowering management in DM patients. Methods: Randomized Controlled Trials (RCTs) from Pubmed, Proquest, Google Scholar and Cochrane Library databases which compare the clinical outcome between intensive and standard BP lowering therapy were analyzed. Meta-analysis was conducted with random effects and Mantel-Haenszel method. Results: 18723 patients with DM from 11 RCTs were included. Intensive BP lowering strategy gave less number of stroke events (RR: 0.55; 95%CI: 0.36 to 0.85; p: 0.007) compared with standard BP lowering management. Between the two groups, there was no significant difference in causing all-cause death (RR: 0.94; 95%CI: 0.83 to 1.08; p: 0.39), cardiovascular death (RR: 0.85; 95%CI: 0.52 to 1.39; p: 0.53), myocardial infarction (RR: 0.96; 95%CI: 0.85 to 1.09; p: 0.54), heart failure (RR: 0.96; 95%CI: 0.75 to 1.23; p: 0.73), microalbuminuria (RR: 0.96; 95%CI: 0.65 to 1.40; p: 0.82). In the subgroup analysis, SBP reduction to lower than 120 mmHg caused lower incidence of stroke events compared with BP target of lower than 130 mmHg (RR: 0.57; 95%CI: 0.35 to 0.93; p: 0.02). Conclusion: Intensive BP lowering strategy gave a better outcome in reducing stroke events in DM patients. Targeting SBP to below 120 mmHg showed more benefit compared with below 130 mmHg.

Rationale and design of the Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT): A multicenter open-label randomized controlled trial

Lowering blood pressure (BP) effectively reduces the risk of cardiovascular (CV) events in high CV risk individuals. The optimal target of BP lowering among high CV risk individuals remains unclear. The Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT) trial is a multi-center, open-label, randomized controlled trial to compare the efficacy and safety of intensive BP lowering strategy (Systolic BP target <120 mm Hg) and standard BP lowering strategy (Systolic BP target <140 mm Hg). Participants aged at least 50 years old with baseline systolic BP within 130 to 180 mm Hg at high CV risk, defined by established CV diseases or 2 major CV risk factors, were enrolled. The primary outcome is a composite CV outcome of myocardial infarction, coronary or non-coronary revascularization, hospitalization or emergency department visit from new-onset heart failure or acute decompensated heart failure, stroke, or death from CV diseases. Secondary outcomes include components of the primary composite outcome, all-cause death, a composite of the primary outcome or all-cause death, kidney outcomes, as well as cognitive outcomes. Despite of the interruption of COVID-19 outbreak, the ESPRIT trial successfully enrolled and randomized 11,255 participants from 116 hospitals or primary health care institutions. The mean age of the participants was 64.6 (standard deviation [SD], 7.1) years, 4,650 (41.3%) were women. Among them 28.9%, 26.9% and 38.7% had coronary heart disease, prior stroke and diabetes mellitus, respectively. COVID-19 outbreak affected the BP lowering titration process of the trial, and delayed the reach of BP target. The ESPRIT trial will address the important question on the optimal BP lowering target for individuals with high CV risk, and generate high quality evidence for treating millions of patients from East Asian countries.

Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial.

Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making. To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001). Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated. ClinicalTrials.gov Registration: NCT01206062.

161-LB: Intensive Blood Pressure Lowering and the Risk of New-Onset Diabetes in Patients with Hypertension—A Post Hoc Analysis of the STEP Randomized Trial

Background: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial reported the cardiovascular benefit of intensive blood pressure (BP) control. The objective of this analysis was to evaluate the effect of intensive BP lowering on the new-onset diabetes incidence. Methods: The patients of STEP who had a baseline fasting serum glucose (FSG) &amp;lt;7.0 mmol/L without diabetes history and hypoglycemic medication use were included in the main analysis. The primary outcome was the new-onset diabetes, defined as the time to first occurrence of a FSG ≥7.0 mmol/l. The secondary outcome was the new-onset impaired fasting glucose (IFG: FSG 5.6-6.9 mmol/l) among patients with normoglycemia. The competing risk proportional hazards regression model was used in the main analysis. Results: Over a median follow-up of 3.42 years, 273 (9.6%) in the intensive group and 262 (9.5%) in the standard group developed new-onset diabetes (adjusted HR 1.03; 95% CI 0.87-1.22) . The adjusted hazard ratio for the secondary outcome was 1.05 (95% CI 0.92-1.19) . The mean of the highest FSG was 5.82 mmol/l for intensive group and 5.84 mmol/l for standard group. The sensitivity analyses showed no significant difference with respect to the effect of the treatment arms. Conclusions: Intensive BP lowering (target, 110 to &amp;lt;130 mmHg) , as compared with standard BP lowering (target, 130 to &amp;lt;150 mmHg) , did not increase the risk of new-onset diabetes and IFG in patients with hypertension. Disclosure R. Yang: None. J. Cai: None.

BLOOD PRESSURE TARGETS AND MORTALITY IN HYPERTENSIVE PATIENTS WITH CHRONIC RENAL DISEASE. SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: To compare the effects of intensive vs standard blood pressure (BP) targets on the mortality of hypertensive patients with chronic renal disease. Design and method: A bibliographic search of all relevant databases was carried out without restriction by language, year of publication or publication status. We considered randomized controlled clinical trials on patients older than 18 years, diagnosed with hypertension and chronic renal disease who were allocated to either “intensive’’ BP target (less than or equal to 130/80 mmHg) or “standard’’ BP target (less than or equal to 140–160/90–100 mmHg). Additionally, trials should include more than 50 participants per group followed during at least one year. Trials were not limited by any concomitant disease or baseline cardiovascular risk. We contacted trials’ authors to obtain Individual Patient Data and, if necessary, extracted information from chronic renal patients. COVIDENCE software was used for screening, the Cochrane Review Manager (RevMan web) for data synthesis and analysis, and the Cochrane Risk of Bias Tool (ROB2) to assess the risk of bias for each trial. Results: A total of 2298 records were identified by the bibliographic search. We obtained the full text of 29 publications from the pre-selected studies. Of these, six studies met the inclusion criteria and we obtained Individual Patient Data for all of them (AASK, SPRINT, HOT, ACCORD BP, MDRD, SPS3). There was no statistically significant difference in total mortality between the intensive and standard blood pressure target groups (RR 0.92, 95%CI 0.75–1.13, p = 0.42, 6 studies, 7,348 participants). In absolute terms, there were 5 additional deaths per 1000 participants in the standard target group (95% CI: 6 fewer to 16 more deaths per 1000 participants). Overall deaths were 227/3352 (6.8%) in the intensive target group vs 285/3996 (7.9%) in the standard target group (Figure). The quality of evidence was moderate according to the GRADE assessment. Conclusions: Intensive blood pressure lowering targets in patients with arterial hypertension and chronic renal disease do not result in lower mortality compared to standard blood pressure lowering.

Time to Clinical Benefit of Intensive Blood Pressure Lowering in Patients 60 Years and Older With Hypertension

Recent guidelines recommend a systolic blood pressure (BP) goal of less than 150 mm Hg or even 130 mm Hg for adults aged 60 years or older. However, harms from intensive BP treatments occur immediately (eg, syncope, fall), and benefits for cardiovascular event reduction emerge over time. Therefore, harms with low chance of benefit need to be clearer, particularly for those with limited life expectancy. To estimate the time needed to potentially derive clinical benefit from intensive BP treatment in patients 60 years and older. This secondary analysis included individual patient data from published randomized clinical trials with 27 414 patients 60 years or older with hypertension. Patient-level survival data were reconstructed when the original data were not available. Published trials were identified by searching PubMed until October 15, 2021. Intensive BP lowering vs standard BP lowering with the treat-to-target design. Major adverse cardiovascular event (MACE) defined by each trial, which was broadly similar with all trials including myocardial infarction, stroke, and cardiovascular mortality. Six trials (original data from 2 trials and reconstructed data from 4 trials) with 27 414 participants (mean age, 70 years; 56.3% were women) were included in the analysis. Intensive BP treatment with a systolic BP target below 140 mm Hg was significantly associated with a 21% reduction in MACE (hazard ratio, 0.79; 95% CI, 0.71-0.88; P < .001). On average, 9.1 (95% CI, 4.0-20.6) months were needed to prevent 1 MACE per 500 patients with the intensive BP treatment (absolute risk reduction [ARR], 0.002). Likewise, 19.1 (95% CI, 10.9-34.2) and 34.4 (95% CI, 22.7-59.8) months were estimated to avoid 1 MACE per 200 (ARR, 0.005) and 100 (ARR, 0.01) patients, respectively. In this analysis, findings suggest that for patients 60 years and older with hypertension, intensive BP treatment may be appropriate for some adults with a life expectancy of greater than 3 years but may not be suitable for those with less than 1 year.

MO094: Intensive Blood Pressure Lowering and Myocardial Fibrosis Biomarkers in Individuals With and Without CKD: Results From the Systolic Blood Pressure Intervention Trial (Sprint)

Abstract BACKGROUND AND AIMS Circulating cardiac biomarkers implicated in the pathogenesis of heart disease may provide a non-invasive, more precise assessment of cardiovascular risk. In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive blood pressure lowering was associated with a 25% reduction in cardiovascular events and a 27% reduction in all-cause mortality. We sought to assess whether the beneficial effect of lowering systolic blood pressure on clinical outcomes was accompanied by a reduction in serum biomarkers of myocardial fibrosis. METHOD SPRINT, a multicenter randomized controlled trial conducted in the United States, enrolled participants aged ≥ 50 years, at increased risk for cardiovascular disease and randomized them to intensive systolic blood pressure lowering (target &amp;lt; 120 mmHg) or standard blood pressure lowering (target &amp;lt; 140 mmHg). In a randomly selected subgroup of SPRINT participants, myocardial fibrosis was assessed by two collagen-derived serum peptides, C-terminal propeptide of procollagen type I (CICP) and N-terminal propeptide of procollagen type 3 (P3NP) and Galectin 3 measured at study baseline and at 24 months follow-up. Chronic kidney disease was defined as eGFR &amp;lt; 60 mL/min/1.73 m2. Analyses were based on linear mixed models including clinic site as a random effect, with adjustments for treatment group and baseline level of each respective biomarker. RESULTS A total of 742 SPRINT participants with and without CKD with available measurements of myocardial fibrosis biomarkers at study baseline and 24 months were included in the study. The median (IQR) Galectin 3, CICP and P3NP levels at study baseline and 24 months follow-up in the intensive versus standard group are presented in the Table 1. Intensive blood pressure lowering was not associated with longitudinal changes in CICP or P3NP (Table 1 and Figure 1). Intensive blood pressure lowering was associated with a statistically significant increase in Galectin 3 level [between group mean difference 0.47 (IQR: 0.03–0.92) ng/mL, P = 0.04]. All of the findings were generally consistent across participants with and without CKD (Table 1). CONCLUSION In a random sample of SPRINT participants, intensive versus standard blood pressure lowering was not associated with a reduction in circulating myocardial fibrosis biomarkers overtime in hypertensive individuals with and without CKD.

Risk-Based Intensive Blood Pressure Lowering and Prevention of Heart Failure: A SPRINT Post Hoc Analysis.

[Figure: see text].

Association Between Baseline Diastolic Blood Pressure and the Efficacy of Intensive vs Standard Blood Pressure–Lowering Therapy

Low diastolic blood pressure (DBP) has been found to be associated with increased adverse cardiovascular events; however, it is unknown whether intensifying blood pressure therapy in patients with an already low DBP to achieve a lower systolic blood pressure (SBP) target is safe or effective. To evaluate whether there is an association of baseline DBP and intensification of blood pressure-lowering therapy with the outcomes of all-cause death and cardiovascular events. This cohort study analyzed patients who were randomized to intensive or standard BP control in the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial and Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from September 1999 to June 2009 (ACCORD-BP) and from October 2010 to August 2015 (SPRINT). Data were analyzed from December 2020 to June 2021. Baseline DBP as a continuous variable. All-cause death and a composite cardiovascular end point (CVE) that included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. A total of 14 094 patients (mean [SD] age, 66.2 [8.9] years; 8504 [60.4%] men) were included in this analysis. There were significant nonlinear associations between baseline DBP and all-cause death (eg, baseline DBP 50 vs 80 mm Hg: hazard ratio [HR], 1.48; 95% CI, 1.06-2.08; P = .02) and the composite CVE (eg, baseline DBP 50 vs 80 mm Hg: HR, 1.45; 95% CI, 1.27-3.04; P = .003) observed among all participants. Findings for the interaction between baseline DBP and treatment group assignment for all cause death did not reach statistical significance. For intensive vs standard therapy, the HR of death for a baseline DBP of 50 mm Hg was 1.80 (95% CI, 0.95-3.39; P = .07) and that for a baseline DBP of 80 mm Hg was 0.77 (95% CI, 0.59-1.01; P = .05). Overall, there was no interaction found between baseline DBP and treatment group assignment for the composite CVE. Over the range of baseline DBP values, significant reductions in the composite CVE for patients assigned to intensive vs standard therapy were found for baseline DBP values of 80 mm Hg (HR, 0.78; 95% CI, 0.62-0.98; P = .03) and 90 mm Hg (HR, 0.74; 95% CI, 0.55-0.98; P = .04). This pooled cohort study found no evidence of a significant interaction between baseline DBP and treatment intensity for all-cause death or for a composite CVE. These results are hypothesis generating and merit further study.

Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in individuals with and without CKD. Neuroimaging substudy of a randomized trial. A subset of participants in the Systolic Blood Pressure Intervention Trial (SPRINT) who underwent brain magnetic resonance imaging studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Participants were randomly assigned to intensive (systolic BP<120 mm Hg) versus standard (systolic BP<140 mm Hg) BP lowering. The magnetic resonance imaging outcome measures were the 4-year change in global cerebral blood flow (CBF), white matter lesion (WML) volume, and total brain volume (TBV). A total of 716 randomized participants with a mean age of 68 years were enrolled; follow-up imaging occurred after a median 3.9 years. Among participants with eGFR<60 mL/min/1.73 m2 (n= 234), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 3.38 (95% CI, 0.32 to 6.44) mL/100 g/min,-0.06 (95% CI,-0.16 to 0.04) cm3 (inverse hyperbolic sine-transformed), and-3.8 (95% CI,-8.3 to 0.7) cm3, respectively. Among participants with UACR >30 mg/g (n= 151), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 1.91 (95% CI,-3.01 to 6.82) mL/100 g/min, 0.003 (95% CI,-0.13 to 0.13) cm3 (inverse hyperbolic sine-transformed), and-7.0 (95% CI,-13.3 to-0.3) cm3, respectively. The overall treatment effects on CBF and TBV were not modified by baseline eGFR or UACR; however, the effect on WMLs was attenuated in participants with albuminuria (P= 0.04 for interaction). Measurement variability due to multisite design. Among adults with hypertension who have primarily early kidney disease, intensive versus standard BP treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive BP treatment targets on brain health in persons with early kidney disease. SPRINT was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. SPRINT was registered at ClinicalTrials.gov with study number NCT01206062.

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target.

We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90]) but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], Pinteraction = 0.05). Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01422616.

ASSOCIATION BETWEEN THE PRESENCE OF CORONARY ARTERY DISEASE AND INTENSIVE LOWERING BLOOD PRESSURE AT THE TIME OF CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY

Abstract Objective: Blood pressure (BP) lowering treatment should be an intensive BP control according to JSH2019 guideline. Coronary computed tomography angiography (CCTA) has become more widely available in many general hospitals and enables the accurate non-invasive assessment of coronary artery stenosis for screening. The presence or severity of coronary artery disease (CAD) in patients with intensive BP control at the time of CCTA were compared with those in patients without hypertension (HTN). Design and method: One thousand one hundred consecutive subjects (65 yrs., males 53%) who were clinically suspected of having CAD or who had at least one cardiac risk factor underwent CCTA. The patients were divided into 4 groups: the patients without HTN (non-HTN group), hypertensive patients with intensive BP lowering (Intensive group, &lt; 130/80 mmHg), standard BP lowering (Standard group, 130–139/80–89 mmHg) and uncontrolled BP (Uncontrolled group, 140/90 mmHg&lt;) groups. Results: % CAD in patients with HTN was significantly higher than that in patients without HTN. Interestingly, % CAD in the intensive group was also significantly higher than that in patients without HTN. The intensive group showed older, higher body mass index and the number of significantly stenosed coronary vessels, lower levels of high-density lipoprotein cholesterol in blood, higher rates of dyslipidemia, diabetes, anti-dyslipidemia and anti-diabetic medications. Conclusions: The hypertensive patients with intensive BP lowering showed older, higher rate of CAD and more severe coronary stenosis. Thus, it was suggested that the patients also need more rigorous management of other coronary risk factors, as well as intensive BP lowering, and the patients need to perform CCTA much earlier than we think.

Abstract 40: Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments

Background and Purpose: In present-day intracerebral hemorrhage (ICH) trials, hematoma expansion (HE) is often analyzed as a binary variable - present or absent. However, dichotomizing intrinsically wide-ranging variables discards substantial information reflective of treatment effect and can reduce the ability to detect relationships between the exposure and outcome of interest. We explored the concept of a “HE shift analysis” as a novel analytic mode for ICH treatment trials using previously published clinical trial data. Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, patients were stratified by treatment status (intensive vs. standard blood pressure lowering with IV nicardipine) and HE shift was evaluated by generating strata based on a) previously established HE definitions, b) quartiles of 24-hour total hematoma volume, and c) quartiles of 24-hour total hematoma volume (THV) change. The relationship between blood pressure treatment and hematoma expansion shift was explored using proportional odds models and adjusted Wilcoxon testing. Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no hematoma growth. Using a conventional threshold, significant intraparenchymal expansion (≥33%) was reduced by 5.8% in those assigned to the intensive therapy arm (aOR: 0.77 [95% CI: 0.60-0.99], Figure 1A). The stratified quartiles of 24-hour total hematoma volumes were associated with a 5% shift within the highest and lowest strata in the intensive arm, (aOR: 0.83 [0.66-1.05], Figure 1B). Intensive therapy was associated with a 5.2% reduction from &gt; 3 mL to 0.5-3 mL (aOR: 0.86 [0.68-1.09], Figure 1C). Conclusions: A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an alternate way to assess hemostatic agents in future hemorrhage trials.

Abstract MP37: Race/Ethnicity Differences in Response to Intensive Blood Pressure Treatment After Intracerebral Hemorrhage: Analysis of the Atach-2 Trial

Background: The main analysis of the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage-2) trial suggested no benefit from intensive blood pressure lowering (BPL) treatment after intracerebral hemorrhage (ICH). However, whether outcome and response to treatment differs according to race was not sufficiently studied. Methods: This is a post-hoc analysis of the ATACH-2 trial. The primary outcome was death or disability (90-day modified Rankin Scale [mRS] 4-6). Patients were divided according to race/ethnicity. Logistic regression was fit to assess the association between race and the primary outcome. In addition, we assessed the interaction between intensive BPL treatment and race. Results: A total of 939 patients (White=206, Asian=549, Black=111, Hispanic=73) were included. Death and disability occurred more frequently in White patients than other races (Figure). However, after adjusting for patient age, sex, baseline Glasgow Coma Scale, intracranial hemorrhage volume in mL, presence of intraventricular hemorrhage, deep vs. lobar, left vs. right hemisphere, intubation and ATACH treatment arm, Black patients had higher odds of the primary outcome (OR=1.98, P=0.02) compared to White patients. In contrast, Asian and Hispanic patients had non-statistically significant lower odds of the primary outcome (OR=0.68, P=0.09; OR= 0.97; P=0.95, respectively) compared to White patients. We did not observe treatment-by-race interaction. the p values for the interaction of intensive BPL treatment vs. standard BPL were 0.508 in Blacks, 0.336 in Hispanics and 0.190 in Asians, with Whites as the reference group. Conclusion: Black patients had higher odds of death or disability after non-traumatic supratentorial intracerebral hemorrhage compared to White patients.

Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis.

The effect of intensive versus standard blood pressure (BP) lowering on the risk of atrial fibrillation (AF) is uncertain. Intensive BP lowering is associated with a lower risk of AF among patients with hypertension. We searched PubMed, EMBASE, and CENTRAL (inception to June 5, 2020) for randomized controlled trials evaluating the effect of intensive versus standard (target systolic BP < 140 mmHg) BP lowering on incident AF. We assessed heterogeneity using the I2 statistic then used fixed-effects meta-analysis models to report pooled treatment effects and 95% confidence intervals. We also tested for publication bias by three funnel plot-based methods. The quality of each study was assessed with the Cochrane Risk of Bias tool. We assessed 16 candidate studies for eligibility from 2,312 published articles, but only three randomized clinical trials were eligible for inclusion and included a combined 12,219 participants with hypertension: Cardio-Sis (Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica), ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial), and SPRINT (Systolic Blood Pressure Intervention Trial). The target systolic BP in the intensive BP arm was <120 mmHg for participants in SPRINT and ACCORD-BP, but <130 mmHg for participants in Cardio-Sis. Participants randomized to intensive BP lowering had significantly lower risk of incident AF compared with those randomized to standard BP lowering (AF incidence 2.2% vs. 3.0%, respectively; pooled hazard ratio (95% confidence interval): 0.74 (0.59 - 0.93)). Intensive BP lowering is associated with a significantly lower risk of incident AF in patients with hypertension. These findings add to the current evidence supporting the benefits of intensive BP control.

Abstract 14191: Effect of Intensive Blood Pressure Lowering on Incident Atrial Fibrillation: A Systemic Review and Meta-analysis

Introduction: The effect of intensive versus standard blood pressure (BP) lowering on the risk of atrial fibrillation (AF) is uncertain. Hypothesis: Intensive BP lowering is associated with a lower risk of AF among patients with hypertension. Methods: We searched PubMed, EMBASE, and CENTRAL for trials published between inception and June 5, 2020 for randomized controlled trials evaluating the effect of intensive versus standard (target systolic BP &lt; 140 mmHg) BP lowering on incident AF. We assessed heterogeneity using the I 2 statistic then used fixed-effects meta-analysis models to report pooled treatment effects and 95% confidence intervals. We also tested for publication bias by three funnel plot-based methods. The quality of each study was assessed with the Cochrane Risk of Bias tool. Results: We assessed 16 candidate studies for eligibility from 2,312 published articles, but only three randomized clinical trials were eligible for inclusion and included a combined 12,219 participants with hypertension: Cardio-Sis (Studio Italiano Sugli Effetti Cardiovascolari del Controllo della Pressione Arteriosa Sistolica), ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial), and SPRINT (Systolic Blood Pressure Intervention Trial). The target systolic BP in the intensive BP arm was &lt;120 mmHg for participants in SPRINT and ACCORD-BP, but &lt;130 mmHg for participants in Cardio-Sis. Participants randomized to intensive BP lowering had significantly lower risk of incident AF compared with those randomized tostandard BP lowering (AF incidence 2.2% vs. 3.0%, respectively; pooled hazard ratio (95% confidence interval ): 0.74 (0.59 - 0.93)). Conclusions: Intensive BP lowering is associated with a significantly lower risk of incident AF in patients with hypertension. These findings add to the current evidence supporting the benefits of intensive BP control.