Intensive Systolic Blood Pressure Research Articles

Effects of Achieving Rapid, Intensive, and Sustained Blood Pressure Reduction in Intracerebral Hemorrhage Expansion and Functional Outcome.

The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP ≥150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement ≤60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement ≤60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score ≥4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. We included 312 patients (mean age 70.2 ± 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement ≤60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 ± 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. This study provides Class III evidence that in adults with spontaneous ICH and initial SBP ≥150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial.

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03-2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20-3.18) and the intensive group (HR, 1.10; 95% CI, 0.57-2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19-0.95) and the low burden group (HR, 0.79; 95% CI, 0.63-0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89-0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

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.

Abstract WP210: Intensive vs. Conventional Blood Pressure Management After Thrombectomy for Acute Ischemic Stroke: Systemic Review and Meta-Analysis of Randomized Controlled Trials

Background: Optimal Blood pressure management after thrombectomy for acute ischemic stroke and its association with clinical outcomes remains unclear. We performed this study to compare clinical outcomes between intensive systolic blood pressure (SBP) control (&lt;120-140mmHg) and conventional SBP control (&lt; 180mmHg). Methods: In September 2023, this registered systematic review (CRD42023464176) was performed using multiple databases for the following keywords: stroke, thrombectomy, and Blood Pressure from 2010 to present. Randomized control studies were included if they had the reported the outcome for adults aged &gt;18 who underwent successful thrombectomy (defined as mTICI 2b or higher) for acute ischemic stroke. The primary outcome of interest was the rate of functional independence, defined as a modified Rankin scale of 0-2 at 90 days. The secondary outcomes of interest included rates of mortality, and symptomatic intracranial hemorrhage (sICH). For all outcome events, corresponding odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects meta-analysis model. Results: Four studies comprising 1497 patients were included. Compared to conventional SBP control, intensive SBP control was associated with lower rates of functional independence (OR 0.67, 95% CI 0.51- 0.88 p=0.0). There were comparable rates of sICH (OR 1.12, 95% CI 0.75-1.67; p = 0.56) and mortality (OR 1.21, 95% CI 0.90-1.64; p = 0.19) between intensive and conventional SBP control groups. Conclusions: Our findings suggest that intensive blood pressure control does not improve clinical outcomes. More robust data is needed to draw definite conclusions.

Intensive blood pressure lowering and renal function in ischemic stroke patients: secondary analysis of ENCHANTED trial.

Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is early change in renal function, defined by a difference in estimated glomerular filtration rate (∆eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation [SD]) and magnitude of reduction within 24 h. Of 2151 participants (mean age 66.9 years; 38% female) included with available baseline eGFR, there were significant differences in attained 144.3±10.2 vs 149.8±12.0 [5.5 mm Hg]; P<0.0001), variation (15.1±5.4 vs 14.0±5.6 mm Hg; P<0.0001) and magnitude of reduction (44.6±16.2 vs 38.7±17.6 mm Hg; P<0.0001) in SBP within 24 hours. 1718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in ∆eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; P=0.29) between the intensive and guideline groups, respectively. The neutral effect on ∆eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputation for missing follow-up eGFR. SBP variability was significantly associated with decreasing ∆eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95%CI -2.43 to -0.28; P for trend=0.01). Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR. ENCHANTED is registered at ClinicalTrials.gov (NCT01422616).

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: ASimulation Study.

Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Remnant Cholesterol and Intensive Blood Pressure Control in Older Patients with Hypertension: A Post hoc Analysis of the STEP Randomized Trial.

Emerging evidence shows a close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. 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 (110 to <130 mmHg) or standard (130 to <150 mmHg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation or cardiovascular death), the components thereof and all-cause mortality were analyzed by tertile of baseline RC (lowest, middle, highest). We followed 8,206 patients for 3.33 years (median). The adjusted hazard ratios (95% confidence interval) for the primary outcome were 1.06 (0.73-1.56), 0.58 (0.38-0.87) and 0.67 (0.46-0.96) in the lowest, middle and highest RC tertiles, respectively (P for interaction = 0.11). However, significant heterogeneity in the treatment effects was observed when comparing the upper two tertiles with the lowest tertile (P for interaction = 0.033). For all-cause mortality, the adjusted hazard ratios (95% confidence interval) were 2.48 (1.30-4.73), 1.37 (0.71-2.65) and 0.42 (0.22-0.80) in the lowest, middle and highest RC tertiles, respectively (P for interaction < 0.0001). Baseline RC concentrations were associated with the effects of intensive SBP lowering on the primary composite cardiovascular outcome and all-cause mortality in hypertensive patients. These results are hypothesis-generating and merit further study. STEP ClinicalTrials.gov number, NCT03015311.

Medication Regimens against Hypertension Utilized in the Systolic Blood Pressure Intervention Stud

Context: Standard and intensive Systolic Blood Pressure (SBP) interventions would be contextualized by describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial). This information may also help future implementation efforts to meet population-wide intensive SBP goals. Methods: At the rerandomization and 12-month visits, we provided SPRINT participants with comprehensive medication data. The class of antihypertensive medications was used to categorize regimens. The analyses were divided into groups based on the kind of treatment (intensive target SBP &lt;120 mm Hg versus standard goal SBP &lt;140 mm Hg) Findings: The median number of classes used at the rerandomization visit was 2.0 for 7860 individuals (83.7% of 9361 randomized), and 2.0 for the standard and intensive groups (P=0.559). After a year, the intensive and conventional groups used a median of 3.0 and 2.0 classes, respectively (P&lt;0.001). In the intensive and standard groups, the most common regimens were rerandomization, Angiotensin-Converting Enzyme inhibitor (ACE), or Angiotensin-II Receptor Blocker (ARB) monotherapy (12.6% versus 12.2%). After a year, 5.3% of participants in the intense group and 14.7% of participants in the normal group still used ACE/ARB monotherapy. The following multidrug regimens were utilized at 12 months by both the intensive and regular participants: a calcium channel blocker and thiazide (12.2% and 7.9%) combined in an ACE/ARB thiazide, and calcium channel blocker (11.4% and 4.3%); an ACE/ARB, thiazide, calcium channel blocker, and beta-blocker (6.5% and 1.2%); and 6.2% and 6.8% of each category. Conclusions: Compared to ACE/ARB monotherapy, SPRINT investigators preferred combining ACEs or ARBs, thiazide diuretics, and calcium channel blockers to aim SBP &lt;120 mm Hg.

Effect of Age Range on Power for a Clinical Trial Investigating the Effect of Intensive Systolic Blood Pressure Control on White Matter Hyperintensity Volume Accumulation

AbstractBackgroundEpidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (&lt;120 mm Hg) in midlife to lower future ADRD risk has ever been attempted. Clinical outcomes are not practical in the age range of interest (45‐65 or 45‐70) during an initial trial period of 5 years however robust evidence demonstrates white matter hyperintensity volume (WMHV) as an MRI finding associated with and predictive of incident ADRD.MethodWe used four data sets (SPRINT, Wisconsin Registry for Alzheimer’s Prevention, Framingham, and UK Biobank) with longitudinal MRI data to examine the effect of age range on power for a clinical trial proposal investigating the effect of intensive SBP control on annualized rates of WMHV accumulation in persons starting in middle age. Analyses were conducted separately in each data set. We calculated mean, standard deviations, and annualized rates of WMHV accumulation (derived from T2 FLAIR MRI), using the linear rate of change for accumulation rate, first stratifying by SBP ( = 132 mm Hg vs &lt;132mm Hg except in SPRINT where groups were stratified by goal SBP group) and then by various age ranges. Next, we examined the effect of age range on necessary sample size with 80% power and two‐tailed alpha of 0.05 for a prospective clinical trial.ResultAs expected, annualized WMHV accumulation rate is lower with younger age in all data sets. However, variability decreased (all four data sets) and the percent reduction achieved at lower SBPs is higher at younger ages (3/4 data sets), thus increasing power when excluding older individuals (e.g., &gt;65 years old, Table 1).ConclusionRestricting age to individuals to = 65 years‐old may unexpectedly increase power in a clinical trial designed to investigate the effect of goal SBP&lt;120 mm Hg on annualized WMHV accumulation rate. 45‐65 years‐old is a practical age range for the first ever clinical trial intended to investigate the effects of a lower SBP goal in middle age to reduce future ADRD risk.

Effect of Age Range on Power for a Clinical Trial Investigating the Effect of Intensive Systolic Blood Pressure Control on White Matter Hyperintensity Volume Accumulation

AbstractBackgroundEpidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (&lt;120 mm Hg) in midlife to lower future ADRD risk has ever been attempted. Clinical outcomes are not practical in the age range of interest (45‐65 or 45‐70) during an initial trial period of 5 years however robust evidence demonstrates white matter hyperintensity volume (WMHV) as an MRI finding associated with and predictive of incident ADRD.MethodWe used four data sets (SPRINT, Wisconsin Registry for Alzheimer’s Prevention, Framingham, and UK Biobank) with longitudinal MRI data to examine the effect of age range on power for a clinical trial proposal investigating the effect of intensive SBP control on annualized rates of WMHV accumulation in persons starting in middle age. Analyses were conducted separately in each data set. We calculated mean, standard deviations, and annualized rates of WMHV accumulation (derived from T2 FLAIR MRI), using the linear rate of change for accumulation rate, first stratifying by SBP (≥132 mm Hg vs &lt;132mm Hg except in SPRINT where groups were stratified by goal SBP group) and then by various age ranges. Next, we examined the effect of age range on necessary sample size with 80% power and two‐tailed alpha of 0.05 for a prospective clinical trial.ResultAs expected, annualized WMHV accumulation rate is lower with younger age in all data sets. However, variability decreased (all four data sets) and the percent reduction achieved at lower SBPs is higher at younger ages (3/4 data sets), thus increasing power when excluding older individuals (e.g., &gt;65 years old, Table 1).ConclusionRestricting age to individuals to ≤65 years‐old may unexpectedly increase power in a clinical trial designed to investigate the effect of goal SBP&lt;120 mm Hg on annualized WMHV accumulation rate. 45‐65 years‐old is a practical age range for the first ever clinical trial intended to investigate the effects of a lower SBP goal in middle age to reduce future ADRD risk.

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.

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.

Abstract 15307: Sex-Specific Cognitive Effects of Intensive Systolic Blood Pressure Lowering in Patients With and Without Diabetes Mellitus

Background: The SPRINT trial demonstrated that intensive systolic blood pressure (SBP) lowering (&lt;120 mm Hg) reduced risk of mild cognitive impairment compared to standard SBP control (&lt;140 mm Hg). However, the ACCORD-BP trial did not show the same effect in patients with diabetes. Aims: This study aimed to 1) determine the impact of intensive SBP on cognitive impairment in patients with and without diabetes by analyzing individual patient data of ACCORD-BP and SPRINT, using three cognitive domains and the same follow-up durations, and 2) assess potential sex differences in the effect of intensive SBP lowering on cognitive function in patients with and without diabetes. Methods/Approach: We pooled individual patient data from the SPRINT and ACCORD-BP and standardized cognitive outcomes at baseline, 20-24 months, and 40-48 months post-randomization. Both studies randomized hypertensive patients to intensive SBP control or standard SBP control. Cognitive outcomes included general cognitive function, cognitive processing speed, and memory. Linear mixed models were employed, adjusting for covariates such as age, baseline BMI, SBP, eGFR and LDL. Analyses were repeated separately for patients with and without diabetes and for men and women. Results: The study cohort comprised of 10,800 patients (mean age 67.2 ±9.1 years; mean baseline SBP:139.6 ± 15.6 mmHg, with 14.7% having diabetes and 61.8% being women. Patients without diabetes in the intensive SBP control group had an accelerated decline in processing speed decline compared to the standard control group (P time*treatment interaction=0.02). Patients with diabetes exhibited similar rates of decline in all cognitive outcomes across treatment groups. Stratifying by sex, intensive SBP control was associated with improved memory in female patients (estimated sd=0.07 (0.03), p=0.06), and faster decline in processing speed in male patients. (p=0.03). Conclusions: The effects of intensive SBP control on general cognitive function were comparable between patients with and without diabetes and between men and women. While intensive SBP control was associated with accelerated decline in cognitive processing speed in patients without diabetes, it was linked to improved memory in female patients.

Abstract 18264: Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Cognitive Outcomes in SPRINT

Background: Subclinical elevations in high sensitivity cardiac troponin T (hsc-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) identifies a high-risk subgroup with reduction in cardiovascular disease in response to intensive systolic blood pressure (SBP) lowering. However, it remains unknown if these markers also identify subgroups with greater improvement in cognitive outcomes from intensive SBP lowering. Methods: We measured hs-cTnT and NT-proBNP at baseline in Systolic Blood Pressure Intervention Trial (SPRINT). Adjudicated cognitive outcomes were classified as probable dementia (PD) and mild cognitive impairment (MCI). Combined cardiac biomarker categories were defined as elevated, intermediate, and non-elevated. The association of combined biomarker categories with risk of cognitive outcomes was assessed using multivariable Cox proportional hazards models. Heterogeneity in the effect of intensive versus standard SBP lowering on the risk of cognitive outcomes across combined biomarker categories was determined. Results: Of 8,111 SPRINT participants with measured biomarkers and at least one follow-up cognitive assessment, 830 (10.2%) experienced the composite outcome of PD or MCI. After multivariable adjustment, elevated vs. non-elevated cardiac biomarker levels were independently associated with increased risk of composite outcome [HR 95% CI: 1.56 (1.26 - 1.92)]. The effect of intensive SBP lowering on the composite outcome was strongest among participants with non-elevated cardiac biomarkers (see Table). Conclusion: Elevated cardiac biomarkers were associated with higher risk for cognitive impairment. The effect of intensive SBP lowering on preventing cognitive impairment was strongest among patients with non-elevated cardiac biomarkers. This suggests that intensive SBP lowering may be more effective in preventing cognitive impairment in individuals with favorable cardiac biomarker profiles.

Association of baseline serum cholesterol with benefits of intensive blood pressure control.

Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. ClinicalTrials.gov, NCT03015311.

Associations of Hyponatremia with Cognition Function and All-Cause Mortality: Post Hoc Analysis of the Systolic BP Intervention Trial.

Acute neurological effects of severe hyponatremia are well known. However, the long-term association of hyponatremia with cognitive impairment are unclear. In this post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), we examined whether incident hyponatremia is a risk factor for mild cognitive impairment (MCI) or probable dementia (PD). In those with baseline serum sodium ≥ 130 mmol/L, we defined incident hyponatremia in the first 6 months as a SPRINT safety alert for serum sodium < 130 mmol/L from randomization to the 6-month visit. In multivariate, Cox regression models adjusted for baseline cognitive function and other variables, we related incident hyponatremia in the first 6 months with subsequent MCI or PD in 8,540 participants with cognitive outcomes data and with all-cause mortality (ACM) in 9,135 participants with mortality data. Incident hyponatremia in the first 6 months was noted in 116 (1.4%) participants. Older age, female sex, non-African American race, lower body mass index and randomization to intensive systolic blood pressure control were associated with incident hyponatremia. Compared to those without hyponatremia, those with incident hyponatremia had higher risk of PD (2.1 versus 0.9 events/ 100 person years, HR 3.08, 95% CI 1.48 to 6.41) but not MCI (3.1 versus 3.6 events/ 100 person years, HR 0.95, 95% CI 0.54 to 1.68) and the composite of MCI/ PD (5.0 versus 4.2 events/ 100 person years, HR 1.28, 95% CI 0.82 to 2.0). There were no significant differences in ACM (HR 1.84, 95% CI 0.90 to 3.73). Biological plausibility for the association of incident hyponatremia with PD but not MCI or death is unclear. The association of incident hyponatremia with PD could reflect a chance finding or non-causal biological association or causal relationship.

[Study on the associations of meeting intensive systolic blood pressure control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China].

Objective: To evaluate the associations of meeting intensive systolic blood pressure (SBP) control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China. Methods: We used data from adult hypertensive patients from the China Kadoorie Biobank. logistic regression models evaluated the influencing factors of meeting intensive and standard SBP control goals. Cox proportional hazard models evaluated the associations between meeting intensive vs. standard SBP control goals and risk for incident cardiovascular and cerebrovascular diseases. Results: A total of 3 628 hypertensive patients who reported continuous medication use were included in this study, of which 5.0% of the participants met the goals of intensive SBP control (≤130 mmHg). Participants with higher educational attainment (OR=2.36,95%CI: 1.32-4.04), healthier diet (OR=2.09,95%CI: 1.45-2.96), daily intake of fresh fruit (OR=1.67,95%CI: 1.17-2.36) and combination treatment (OR=1.82,95%CI: 1.03-3.09) were more likely to meet intensive SBP control goal after adjustment of age, sex and urban/rural areas. During an average follow-up of (10.0±3.7) years, 1 278 cases of composite cardiovascular outcome were recorded. This study did not find a statistical correlation between achieving the goal of enhanced SBP control and the occurrence of composite cardiovascular and cerebrovascular outcomes (HR=0.89, 95%CI: 0.63-1.25). For major adverse cardiovascular events (MACE), cerebrovascular diseases, stroke, and ischemic stroke, we observed a trend of decrease in risk of outcomes with more intensive SBP control (trend test P<0.05). Conclusions: We observed decreased risk for MACE and cerebrovascular diseases with more intensive SBP control. However, there was no significant risk reduction for cardiovascular and cerebrovascular diseases when meeting the intensive SBP control goal, compared to the standard SBP control goal.

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.

CO140 Usual Care and Team-Based Care Vs. Trial Protocols for Hypertension Management in Sprint-Eligible US Adults: A Simulation Study

Despite reducing cardiovascular disease (CVD) events and mortality in the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic blood pressure (SBP) goals are not readily used in the US. This analysis projected long-term SBP and CVD outcomes of hypertensive treatment strategies in SPRINT-eligible US adults.

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.