Standard Systolic Blood Pressure Research Articles

Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial

Abstract Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP <110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (>-4 mm Hg to <6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >-4 mm Hg to <6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

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.

Blood pressure control in diabetic kidney disease: a post-hoc analysis of the FANTASTIC trial

BackgroundThe target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or ‘on treatment’ BP on clinical outcomes in patients with DKD.MethodsA post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels.ResultsA total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60–2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130–139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03–0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits.ConclusionIn patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130–139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD.Trial registrationClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015.(https://clinicaltrials.gov/study/NCT02620306).

The Legacy Effect of Intensive versus Standard BP Control on the Incidence of Needing Dialysis or Kidney Transplantation.

The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure. Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020. Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30). Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

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

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

Systolic blood pressure reduction strategies in acute ischemic stroke patients following endovascular thrombectomy: a systematic review and meta-analysis

Background and AimsThere is no clear consensus on ideal systolic blood pressure (SBP) target post-endovascular thrombectomy (EVT) in patients with acute ischemic stroke. This study intends to investigate the relationship between reducing SBP and clinical outcomes and to determine the therapeutic efficacy of moderate and intensive SBP reduction post EVT. MethodsA comprehensive search was conducted across five electronic databases to identify studies relevant to our analysis. Data from these studies were then analyzed using pooled relative risk (RR) along with their corresponding 95 % confidence intervals (CI) for our categorical outcomes. functional independence at 90 days post-EVT was defined as a modified Rankin score (mRS) 0-2. ResultsOur meta-analysis included eight studies with 2922 patients: 1376 patients were treated with intensive SBP reduction, 306 with moderate SBP reduction, and 1243 with standard SBP reduction. There was no difference in the risk of functional independence at 90 days post-EVT with both intensive-SBP reduction (target 120-140 mmHg, relative risk (RR) =1.05, 95 % CI 0.82, 1.34, p = 0.72) and moderate-SBP reduction (>160 mm Hg) (RR= 0.95, 95 % CI 0.69, 1.31, p = 0.76) compared with standard SBP reduction (>180 mm Hg). The risk of symptomatic intracranial hemorrhage (sICH) did not significantly differ between standard-SBP reduction and intensive-SBP reduction (RR = 0.93, 95 % CI 0.66, 1.31, p = 0.36) or moderate-SBP reduction (0.72 (95 % CI [0.28, 1.87], p = 0.50) groups, respectively. Intensive-SBP reduction significantly decreased the risk of hemicraniectomy. ConclusionsWe did not identify any difference in functional independence at 90 days in acute ischemic stroke patients with either intensive-SBP reduction or moderate-SBP reduction compared with standard SBP reduction post-EVT.

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

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

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.

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.

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.

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.

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

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

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.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit

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

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

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

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

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

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

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

Effect of Decompressive Craniectomy with Stepwise Decompression of the Intracranial Compartment on Postoperative Neurologic Function, Hemodynamics, and Glasgow Outcome Scale Score of Patients with Severe Traumatic Brain Injury.

We assess the effects of standard decompressive craniectomy with stepwise decompression of the intracranial compartment on the postoperative neurologic function, hemodynamics, and Glasgow Outcome Scale (GOS) score of patients with severe traumatic brain injury (sTBI). One hundred sTBI patients admitted from July 2017 to February 2019 were enrolled and randomly divided into step and standard groups (n = 50) using a random number table. The standard group received traditional standard decompression during surgery, while the step group underwent multistep decompression during surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured immediately after surgery (T0), 3 hours after surgery (T1), 6 hours after surgery (T2), and 12 hours after surgery (T3). The postoperative Glasgow Coma Scale (GCS) score, neurologic function deficit score, and GOS score were evaluated. After treatment, the excellent/good rate of neurologic function improvement and GCS and GOS scores of the step group significantly exceeded those of the standard group (p < 0.05). Compared with the standard group, the HR, SBP, DBP, and MAP decreased significantly in the step group at T1, T2, and T3 (p < 0.05). Standard decompressive craniectomy under multistep decompression can markedly improve the neurologic function, hemodynamics, and prognosis of patients.