Intensive Systolic Blood Pressure Lowering Research Articles

Abstract MP12: Educational Attainment and the Effect of Intensive Blood Pressure Reduction: A Post-Hoc Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Introduction: Hypertension is a major risk factor for cardiovascular disease (CVD). The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that systolic blood pressure (SBP) <120 mm Hg reduced CVD risk and all-cause mortality among those with elevated SBP and high CVD risk. Educational attainment (EA) is associated with CV health, but whether EA modifies the effect of intensive SBP reduction remains unclear. Hypothesis: We predicted that SPRINT participants with lower EA would have greater CVD risk reduction with intensive SBP lowering than those with higher EA. Methods: We included 9,361 individuals recruited as part of the SPRINT study and categorized them by EA (<college, some college through college graduate, and >college degree). We examined the effect of intensive SBP lowering across EA strata in relation to the composite endpoint defined by SPRINT (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or CV death) in multivariable proportional hazards models. Results: The cohort was age 67.9±9.4 years, 35.6% female, and 57.8% White race. Those with high EA were more likely to be older, male, and White race. Higher EA was associated in a dose-response manner with a larger reduction in the risk of developing the composite endpoint after intensive SBP lowering [highest to lowest EA: adjusted HR 0.48 (95% CI: 0.34, 0.70); 0.81 (0.63, 1.03); 0.90 (0.70, 1.15); P , interaction=0.01] ( Table ). The interaction between intensive SBP lowering and EA was limited to non-Black individuals; among Black participants, the association of SBP lowering with the endpoint did not differ significantly by EA. Conclusion: In the SPRINT cohort, higher EA was associated with a larger improvement in CV outcomes after intensive SBP reduction, with differences by race or ethnicity. This post-hoc SPRINT analysis suggests that the benefit of intensive SBP lowering varies by EA, and highlights a need for tailored approaches to optimize hypertension management for individuals with different social backgrounds.

Intensive Blood Pressure Lowering and Renal Function in Ischemic Stroke Patients: Secondary Analysis of the ENCHANTED Trial

Introduction: 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). Methods: 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 ∆eGFR = 24 h – baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation), and magnitude of reduction within 24 h. Results: Of 2,151 participants (mean age 66.9 years; 38% female) included with the available baseline eGFR, there were significant differences in attained 144.3 ± 10.2 versus 149.8 ± 12.0 [Δ5.5 mm Hg]; p p p ∆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 imputations 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). Conclusion: 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.

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 analysed by the tertile of baseline RC (lowest, middle, and highest). We followed 8206 patients for 3.33 years (median). The adjusted hazard ratios (HRs) [95% confidence interval (CI)] 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 HRs (95% CI) 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.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP&lt;120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP&lt;140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP&lt;120 mm Hg compared to the SBP achieved by enhanced usual care (SBP = 135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP&lt;120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP&lt;140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP&lt;120 mm Hg compared to the SBP achieved by enhanced usual care (SBP≥135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

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 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 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.

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.

Intensive Blood Pressure Lowering Improves Left Ventricular Hypertrophy in Older Patients with Hypertension: The STEP Trial.

Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, its effect on cardiac remodeling remains not fully understood. This secondary analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients trial aims to determine the changes in left ventricular hypertrophy (LVH) that occur in the context of intensive SBP lowering. A total of 7141 older patients with hypertension were randomly assigned to intensive treatment (SBP target, 110-130 mm Hg) or standard treatment (130 to 150 mm Hg). LVH was defined according to the Peguero-Lo Presti criteria on a standard 12-lead ECG. At baseline, the prevalence of LVH (16.6% versus 16.5%) and the mean Peguero-Lo Presti value (1811 versus 1808 μV) were comparable between the treatment groups. During a median follow-up of 3.24 years, intensive SBP lowering was associated with a significantly lower risk of new LVH occurrence (hazard ratio, 0.76 [95% CI, 0.66-0.89]; P=0.001) and slower progression of the mean Peguero-Lo Presti index value by -23.47 μV/y (95% CI, -34.93 to -12.01; P=0.000). However, the rates of regression of baseline LVH did not differ significantly. Of note, the beneficial effect of intensive SBP lowering in terms of cardiovascular events (hazard ratio, 0.75 [95% CI, 0.59-0.97]) was not markedly attenuated after adjusting for LVH as a time-varying covariate (hazard ratio, 0.76 [95% CI, 0.59-0.97]). Intensive SBP lowering protects against LVH development in older hypertensive patients, however, this favorable effect could not explain most of the reduction in cardiovascular events associated 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.

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 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 low diastolic blood pressure with all-cause death among US adults with normal systolic blood pressure.

Although the effect of intensive systolic blood pressure lowering is widely recognized, treatment-related low diastolic blood pressure still worrisome. This was a prospective cohort study based on the National Health and Nutrition Examination Survey. Adults (≥20 years old) with guideline-recommended blood pressure were included and pregnant women were excluded. Survey-weighted logistic regression and cox models were used for analysis. A total of 25 858 participants were included in this study. After weighted, the overall mean age of the participants was 43.17 (16.03) years, including 53.7% women and 68.1% non-Hispanic white. Numerous factors were associated with low DBP (<60 mmHg), including advanced age, heart failure, myocardial infarction, and diabetes. The use of antihypertensive drugs was also associated with lower DBP (OR, 1.52; 95% CI, 1.26-1.83). DBP of less than 60 mmHg were associated with a higher risk of all-cause death (HR, 1.30; 95% CI, 1.12-1.51) and cardiovascular death (HR, 1.34; 95% CI, 1.00-1.79) compared to those with DBP between 70 and 80 mmHg. After regrouping, DBP <60 mmHg (no antihypertensive drugs) was associated with a higher risk of all-cause death (HR, 1.46; 95% CI, 1.21-1.75). DBP <60 mmHg after taking antihypertensive drugs was not associated with a higher risk of all-cause death (HR, 0.99; 95% CI, 0.73-1.36). Antihypertensive drug is an important factor contributing to DBP below 60 mmHg. But the pre-existing risk does not increase further with an additional reduction of DBP after antihypertensive drugs treatment.

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

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

Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT.

Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

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

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

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.

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

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

Does Post-Randomization Diuretics Use Account for the Cardiovascular Benefits of Intensive Systolic Blood Pressure Lowering in the Systolic Blood Pressure Intervention Trial (SPRINT)?

Does Post-Randomization Diuretics Use Account for the Cardiovascular Benefits of Intensive Systolic Blood Pressure Lowering in the Systolic Blood Pressure Intervention Trial (SPRINT)?