Systolic Blood Pressure Intervention Trial Research Articles

Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta Analysis.

Lowering blood pressure (BP) in persons with low diastolic BP could be harmful. Hence, we examined whether baseline diastolic BP modifies the effects of BP lowering on clinical outcomes in a meta-analysis of five large BP lowering trials. In a study-level meta-analysis based on individual participant data of the Systolic Blood Pressure Intervention Trial (N = 9361), the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (N = 2362), the Secondary Prevention of Small Subcortical Strokes (N = 3020), the African American Study of Kidney Disease and Hypertension (N = 1094) and the Modification of Diet in Renal Disease (N = 840) studies, we used DerSimonian-Laird random-effects models to examine the dependence of the effect of the BP lowering intervention on baseline diastolic BP for cardiovascular, all-cause mortality and kidney outcomes. Mean baseline age was 65 ± 10 years old. Mean baseline systolic and diastolic BP were 141 ± 17 and 79 ± 12 mm Hg, respectively. More intensive BP control resulted in lower risk of composite cardiovascular outcome (HR 0.79, 95% CI 0.72, 0.87) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.99) without evidence that the BP intervention effects differed by level of baseline diastolic BP (interaction p = 0.76 for cardiovascular composite and 0.85 for all-cause mortality). The mean baseline diastolic BP in the lowest and the upper three quartiles of baseline diastolic BP were 65 ± 6 mm Hg and 84 ± 9 mm Hg, respectively but the effects of the BP interventions on the outcomes were similar in both groups. Furthermore, there was no evidence of interaction of the BP intervention and baseline diastolic BP for kidney outcomes. Within the included diastolic BP range, there was no evidence that baseline diastolic BP modified the beneficial effects of intensive BP lowering.

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.

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 (&amp;lt;120 mm Hg) and standard (&amp;lt;140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP &amp;lt;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 (&amp;gt;-4 mm Hg to &amp;lt;6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of &amp;gt;-4 mm Hg to &amp;lt;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

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend &amp;lt;0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend &amp;lt;0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

Association of different timepoint and threshold of time-in-target-range and MACEs: insight from the SPRINT study

Abstract Objective To evaluate the prognostic value of different timepoint and threshold of systolic blood pressure (SBP) Time in Target Rang (TTR) in Major Adverse Cardiovascular Events (MACEs). Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 2-years follow-up were enrolled. Different SBP TTR indexes was calculated by different timepoint (3 month,12 month,24 month) and threshold (110-130mmHg;110-140mmHg;110-130mmHg for intensive treatment group and 120-140mmHg for standard treatment group) (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs) occurred 2 years later, defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Results A total of 7134 participants in SPIRNT were enrolled in this study. Those SBP TTR indicators with independent predictive value of MACEs were selected by a multivariable COX model adjusted for traditional cardiovascular risk factors (Fig 2). SBP TTR calculated with 110-140mmHg window in 3 months (3month SBP TTR110-140) was considered to be the best predictor of MACEs occurred 2 years later among selected SBP TTR indexes according to c statistics and relative informativeness (Table1). The restricted cubic spline plot was used to evaluate the nonlinear trend of the TTR indicator. In addition, we obtain the cut-off value by looking for the point in the RCS curve with the largest slope change. 0.65 was considered to be the best truncation for 3month SBP TTR110-140(Fig 3). Patients with 3month TTR110-140 greater than 0.65 had 23.9% lower incidence of MACEs than patients with TTR less than or equal to 0.65 (HR 0.761[0.592-0978], P=0.033).(Table 2) In addition, for patients with early SBP control (3month SBP TTR110-140 &amp;gt;0.65), there was no significant difference in mean SBP between 110-130 mmHg and 130-140 mmHg (Fig4 Group1 Vs Group2). Lasso regression also suggests that TTR110-140 has more informatics advantages than TTR110-130 in cox model at different timepoints (Fig5). Conclusions 3month SBP TTR110-140 was considered to be the best predictor of MACEs occurred 2 years later in different SBP TTR indexes, which indicated the importance of early SBP control. This study also proposed 0.65 as the critical value of 3-month SBP TTR110-140 for prevention of the incident of MACEs. In the future, more cohort studies are needed to expend these findings.

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

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

Soluble Klotho and Baseline Clinical Characteristics in the Systolic Blood Pressure Intervention Trial

Soluble Klotho and Baseline Clinical Characteristics in the Systolic Blood Pressure Intervention Trial

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

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

A Novel Digital Twin Strategy to Examine the Implications of Randomized Clinical Trials for Real-World Populations.

Randomized clinical trials (RCTs) are essential to guide medical practice; however, their generalizability to a given population is often uncertain. We developed a statistically informed Generative Adversarial Network (GAN) model, RCT-Twin-GAN, that leverages relationships between covariates and outcomes and generates a digital twin of an RCT (RCT-Twin) conditioned on covariate distributions from a second patient population. We used RCT-Twin-GAN to reproduce treatment effect outcomes of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial, which tested the same intervention but found different treatment effects. To demonstrate treatment effect estimates of each RCT conditioned on the other RCT's patient population, we evaluated the cardiovascular event-free survival of SPRINT digital twins conditioned on the ACCORD cohort and vice versa (ACCORD twins conditioned on SPRINT). The conditioned digital twins were balanced across intervention and control arms (mean absolute standardized mean difference (MASMD) of covariates between treatment arms 0.019 (SD 0.018), and the conditioned covariates of the SPRINT-Twin on ACCORD were more similar to ACCORD than SPRINT (MASMD 0.0082 SD 0.016 vs. 0.46 SD 0.20). Notably, across iterations, SPRINT conditioned ACCORD-Twin datasets reproduced the overall non-significant effect size seen in ACCORD (5-year cardiovascular outcome hazard ratio (95% confidence interval) of 0.88 (0.73-1.06) in ACCORD vs. median 0.87 (0.68-1.13) in the SPRINT conditioned ACCORD-Twin), while the ACCORD conditioned SPRINT-Twins reproduced the significant effect size seen in SPRINT (0.75 (0.64-0.89) vs. median 0.79 (0.72-0.86)) in the ACCORD conditioned SPRINT-Twin). Finally, we demonstrate the translation of this approach to real-world populations by conditioning the trials on an electronic health record population. Therefore, RCT-Twin-GAN simulates the direct translation of RCT-derived treatment effects across various patient populations.

P070 ROLE OF NOVEL BLOOD PRESSURE METRICS IN EARLY BLOOD PRESSURE CONTROL ASSESSMENT: INSIGHTS FROM THE SPRINT TRIAL

Objective: Innovative blood pressure (BP) metrics is pivotal to expedite the BP management among individuals with hypertension. Methods and Findings: This is a post-hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial). A total of 8369 participants, who had comprehensive BP records and experienced no adverse events during the initial 90-day follow-up, were included. Two novel BP metrics, systolic blood pressure (SBP) burden and Time-in-Target-Range (TTR), were calculated by employing three-month SBP recordings from follow-up data. SBP Burden were derived as the proportion of area under curve (AUC) over a specific SBP threshold (SBP values &gt;130 mmHg) in a short-term exposure period (from the first month to third month). SBP TTR was estimated by the proportion of time in a specified SBP target range (110 to 140mmHg) in the same exposure period. Major adverse cardiovascular events (MACE), as the primary outcome of this analysis, was a composite endpoint including myocardial infarction, stroke, heart failure, and cardiovascular death. Secondary outcomes included individual components of the primary outcome, as well as all-cause mortality. The relationship of novel BP metrics and study endpoints was accessed by using adjusted Cox proportional hazards regression models. Over a median follow-up period of 3.90 [3.88-3.94] years, 559 MACEs occurred. Both SBP burden (Hazard Ratio [HR]: 1.126 [1.039-1.221]) and SBP TTR (HR: 0.862[0.783-0.949]) were independently correlated with MACEs according to adjusted Cox models. Evaluation using C-statistic and Net Reclassification Indexes (NRI) revealed that both two novel SBP metrics outperformed mean SBP and SBP standard deviation (SD) in predicting MACEs. Furthermore, the predictive value of SBP burden and TTR was consistent across MACE(P=0.383) and secondary endpoints (all P value &gt; 0.05) in this analysis. Conclusions: Among non-diabetic patients with hypertension, both the cumulative SBP burden and TTR independently predict MACEs, surpassing the predictive power of mean SBP and SBP SD. This study substantiates the application of innovative BP measurements for early-stage assessment of BP control.

Incorporating Individual-Level Treatment Effects and Outcome Preferences Into Personalized Blood Pressure Target Recommendations.

There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences. Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs). Individual treatment effects were combined using simulated preference weights into a net benefit, which represents a weighted sum of risk differences across outcomes. Net benefits were compared among those above versus below the median AE risk. In simulations for which cardiovascular, cognitive, and death events had much greater weight than the AEs of BP lowering, the median net benefit was 3.3 percentage points (interquartile range [IQR], 2.0-5.7), and 100% of participants had a net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar weights, the median net benefit was 0.8 percentage points (IQR, 0.2-2.2), and 87% had a positive net benefit. Compared with participants at lower risk of AEs from BP lowering, those at higher risk had a greater net benefit from intensive BP lowering despite experiencing more AEs (P<0.001 in both simulations). Most SPRINT participants had a predicted net benefit that favored intensive BP lowering, but the degree of net benefit varied considerably. Tailoring BP targets using each patient's risks and preferences may provide more refined BP target recommendations.

Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Associations of Urine Epidermal Growth Factor With Kidney and Cardiovascular Outcomes in Individuals With CKD in SPRINT

IntroductionUrine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, while its associations with cardiovascular disease (CVD) and mortality have not been studied. MethodsWe measured baseline uEGF levels among 2,346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an eGFR<60 ml/min/1.73m2. A linear mixed-effects model was used to investigate the associations of uEGF with the annual eGFR change, Cox proportional hazards regression models were used to analyze its associations with the ≥30% eGFR decline, CVD, and all-cause mortality outcomes. To account for the competing risk of death, the Fine and Gray method was utilized for acute kidney injury (AKI) and end-stage kidney disease (ESKD) outcomes. ResultsAt baseline, study participants had mean age of 73±9 years, mean eGFR of 46±11 ml/min/1.73m2, and median urine albumin-to-creatinine ratio of 15 mg/g (interquartile range: 7-49). In the multivariable-adjusted analysis including baseline urine albumin and eGFR, each 50% lower uEGF concentration was associated with 0.74% (95% confidence interval: 0.29, 1.19) per year faster decline in eGFR and 1.17 times higher risk of ≥30% eGFR decline (95% confidence interval: 1.00, 1.36). Lower uEGF concentrations were found to be associated with increased risks of ESKD, AKI, CVD, and all-cause mortality; however, these associations did not reach statistical significance when models were controlled for baseline urine albumin and eGFR. ConclusionAmong hypertensive adults with CKD, lower baseline uEGF concentration was associated with faster eGFR decline independent of baseline albuminuria and eGFR; but not with ESKD, AKI, CVD, and all-cause mortality.

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.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets. In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.

A study of baseline data from SPRINT: Exploring lipid profile changes in middle-aged and elderly patients.

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.

Electrocardiographic tracking of left ventricular hypertrophy in hypertension: incidence and prognostic outcomes from the SPRINT trial

BackgroundThis study explores the impact of intensive blood pressure (BP) control on left ventricular hypertrophy (LVH) incidence and evaluates the prognostic implications of LVH status (pre-existing/new-onset/persistent/regression) using Systolic Blood Pressure Intervention Trial (SPRINT) Electrocardiogram Data.MethodsPoisson regression was used to assess new-onset LVH and LVH regression rates. Multivariable-adjusted Cox proportional hazard models determined the risk of adverse cardiovascular events (ACE), a composite of myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or cardiovascular death, alongside safety adverse events.ResultsIn 8,016 participants, intensive BP control significantly reduced new-onset LVH (8.27 vs. 14.79 per 1000-person years; adjusted p<0.001) and increased LVH regression (14.89 vs. 11.89 per 1000-person years; adjusted p<0.001). Elevated ACE risk was notable in participants with pre-existing LVH [adjusted HR: 1.94 (95% CI: 1.25–2.99); p = 0.003], new-onset LVH [adjusted 1.74 (95% CI: 1.16–2.60); p = 0.007], and persistent LVH[adjusted HR: 1.96 (95% CI: 1.11–3.46); p = 0.020], compared to those without LVH. Intriguingly, LVH regression attenuated this risk increment [adjusted HR: 1.57 (95% CI: 0.98–2.53); p = 0.062]. Achieving a BP target of < 120/80 mmHg nullified the increased ACE risk in those with pre-existing LVH.ConclusionsIntensive BP control is instrumental in both reducing the emergence of LVH and fostering its regression. Pre-existing, new-onset LVH and persistent LV remain a predictor of adverse cardiovascular prognosis, whereas LVH regression and achieving on-treatment BP < 120/80 mmHg in pre-existing LVH individuals may further mitigate residual cardiovascular risk.Clinical trial registrationURL: ClinicalTrials.gov Unique Identifier: NCT01206062.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

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

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

Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial

Rationale & ObjectiveThe risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) CKD classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Study DesignProspective cohort. Settings & Participants2509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). ExposuresKDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. OutcomesPrimary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical ApproachMultivariable Cox proportional hazard models. ResultsMean age was 79.8 years, 37.4% were female, mean eGFR was 64.0 ml/min/1.73 m2, and median UACR 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥60 ml/min/1.73 m2 and UACR <30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 ml/min/1.73 m2 and UACR <30 mg/g. However, those with eGFR 45-59 or 15-44 ml/min/1.73 m2 and UACR ≥30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27, 3.04] and 3.32 [2.23, 4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 ml/min/1.73 m2 and UACR ≥30 mg/g (3.34 [2.05, 5.44]). LimitationsIndividuals with diabetes and urine protein >1 g/day were excluded from SPRINT. ConclusionAmong older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted CKD stage-based risk stratification for older adults.