Systolic Blood Pressure Intervention Research Articles

Association of Total Medication Burden With Intensive and Standard Blood Pressure Control and Clinical Outcomes: A Secondary Analysis of SPRINT.

differences in SBP. 8-item Morisky Medication Adherence Scale and modified Treatment Satisfaction Questionnaire for Medications measured at baseline and 12 months and incident cardiovascular disease events and serious adverse events throughout the trial. Participants in the intensive group with high versus low medication burden were less likely to achieve their SBP goal at 12 months (risk ratio, 0.91; 95% CI, 0.85-0.97) but not in the standard group (risk ratio, 0.98; 95% CI, 0.93-1.03; Pinteraction<0.001). High medication burden was associated with increased cardiovascular disease events (hazard ratio, 1.39; 95% CI, 1.14-1.70) and serious adverse events (hazard ratio, 1.34; 95% CI, 1.24-1.45), but the effect of intensive versus standard treatment did not vary between medication burden groups (Pinteraction>0.5). Medication burden had minimal association with adherence or satisfaction. High baseline medication burden was associated with worse intensive SBP control and higher rates of cardiovascular disease events and serious adverse events. The relative benefits and risks of intensive SBP goals were similar regardless of medication burden. http://www. gov. Unique identifier: NCT01206062.

Abstract P197: Factors Contributing to the Success of a Multicomponent Intervention for Blood Pressure Control in Argentina: A Mediation Analysis

Introduction: The Hypertension Control Program in Argentina (HCPIA), a cluster-randomized trial of a community health worker-led multicomponent intervention on blood pressure (BP) control in low-income patients in Argentina, previously reported a significant reduction in systolic BP in the intervention compared to the control group over 18 months (6.6 mm Hg net difference; p&lt;0.001). Understanding which elements of a multicomponent intervention are important contributors to its success is critical for future BP control efforts. We conducted a mediation analysis to determine the contributions of seven measured intervention targets to the systolic BP intervention effect. Methods: HCPIA randomized 18 primary healthcare clinics treating uninsured patients to either a multicomponent intervention, consisting of health coaching, home blood pressure monitoring, blood pressure audit and feedback, physician education, and a mobile health intervention, or usual care. A total of 1,357 hypertensive participants completed the trial and are included in the mediation analyses. Changes in seven potential mediators over the 18-month intervention were assessed: medication adherence score, medication adjustments (addition of new medication or dose titration), waist circumference, physical activity, fruit and vegetable consumption, sodium consumption, and alcohol consumption. Generalized estimating equations were used to compare changes in potential mediators between intervention groups. Path analytic models were used to test single-mediator and multiple mediator indirect intervention effects using the Lavaan package in R statistical software. Mediation was considered significant at p&lt;0.10. Results: All potential mediators were significantly improved in the intervention group compared to the control group. Fruit and vegetable consumption, medication adherence, physical activity, and salt consumption are each significant mediators accounting for 4.3, 3.8, 3.3, and 3.2%, respectively, of the intervention effect in single-mediator models. The multiple mediation model explained 15.5% (1.3 mm Hg) of the total intervention effect. Changes in fruit and vegetable consumption and medication adherence remained significant mediators in multiple mediation analysis, responsible for 3.8% and 4.3% of the net reduction in systolic BP, respectively. Other potential mediators did not account for a significant proportion of the intervention effect. Conclusions: Increases in medication adherence and fruit and vegetable consumption were responsible for the largest proportions of the explained intervention effect.

Abstract P366: Pooled Cohort Equation Performance in Primary and Secondary Prevention Subgroups of the SystolicBlood Pressure Intervention Trial (SPRINT)

Background: The Pooled Cohort Equation (PCE) estimates 10-y atherosclerotic cardiovascular disease (ASCVD) risk among adults aged 40-79 years without CVD. Recent studies applied the PCE to mixed primary (1°) and secondary (2°) prevention populations to predict risk of future CVD events. However, the PCE is not validated in 2° prevention populations. We studied the impact of prior CVD on PCE performance in a 2° prevention population of the SPRINT trial. Methods: SPRINT randomized 9,361 adults with hypertension and ≥1 CVD risk factor or prior ASCVD to standard or intensive BP control. Excluding those age &gt;79 years (n=1,158) or missing PCE covariates (n=52), we calculated 10-year ASCVD risk at baseline using the PCE. We assessed PCE discrimination with the C-statistic among all SPRINT participants and among 1° and 2° prevention subgroups. We estimated the hazard ratio (HR) for incident ASCVD events comparing the 2° to the 1° prevention group, controlling for baseline PCE-predicted 10-y risk. Results: Of the 8,151 included participants, 6,874 (84%) and 1,277 (16%) were in the 1° and 2° prevention groups, respectively. Mean (SD) age was 66 (8) years, 35% were female, 34% were black. Median (IQR) baseline predicted 10-year ASCVD risk in the 1° prevention group was lower than the 2° prevention group (P&lt;0.001; Table ). In the 3.3 years of follow-up, ASCVD events occurred more frequently in the 2° prevention group than the 1° prevention group (P&lt;0.001). The C-statistic was 0.618 (95% CI 0.589, 0.646) in the entire analytic population, and was non-significantly higher among the 1° prevention subgroup. Comparing the 2° to 1° prevention population, HR for incident ASCVD events was 2.6 (95% CI 2.1, 3.3) when controlling for baseline PCE-estimated 10-y risk. Conclusions: Adults with prior ASCVD events have a nearly 3-fold higher risk of subsequent events. This study demonstrates that the PCE underestimates risk of recurrent events in 2° prevention populations and use in mixed populations should be avoided.

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.

A1177 Effect of Intensive versus Standard Blood Pressure Treatment According to Baseline Systolic Blood Pressure

Objectives: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with different baseline SBP in SPRINT. Methods: De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥140 mmHg) group versus those with low-SBP (<140 mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, injurious falls, electrolyte abnormalities, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups. Results: Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 4,964 and 4,397 had baseline low-SBP (<140 mmHg) and high-SBP (≥140 mmHg), respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those with low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for low-SBP group and 1.80 (95% CI 1.32, 2.47) for high-SBP group (P value for interaction 0.28). Conclusion: In SPRINT, the beneficial effects of intensive SBP treatment might be taken away among those with high baseline SBP level.

Influence of baseline systolic blood pressure on the relationship between intensive blood pressure control and cardiovascular outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT).

To determine whether the effects of intensive (< 120mmHg) compared with standard (< 140mmHg) systolic blood pressure (SBP) treatments are different among those with different baseline SBP. De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥ 140mmHg) group versus the low-SBP (< 140mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups. Among 9361 participants randomized (age 67.9 ± 9.4years; 35.5% female), 4964 and 4397 had baseline low SBP (< 140mmHg) and high SBP (≥ 140mmHg), respectively. After a median follow-up of 3.26years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those in the low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for the low-SBP group and 1.80 (95% CI 1.32, 2.47) for the high-SBP group (P value for interaction 0.28). Hypertensive patients with low baseline SBP may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with high baseline SBP.

Estimating the Association of the 2017 and 2014 Hypertension Guidelines With Cardiovascular Events and Deaths in US Adults

The 2017 American College of Cardiology/American Heart Association hypertension guideline recommends lower blood pressure (BP) thresholds for initiating antihypertensive medication and treatment goals than the 2014 evidence-based hypertension guideline. To estimate the potential association of the 2017 and 2014 hypertension guidelines with the proportion of US adults defined as being hypertensive or recommended for antihypertensive treatment and with risk reduction of major cardiovascular disease (CVD) and all-cause mortality. Using data from the National Health and Nutrition Examination Survey 2013 to 2016, we estimated the proportions of US adults with hypertension or recommended for antihypertensive treatment according to the 2017 and 2014 hypertension guidelines. Using data from the National Health and Nutrition Examination Survey, antihypertensive clinical trials, and population-based cohort studies, we estimated risk reductions of CVD and all-cause mortality assuming the entire US adult population achieved guideline-recommended systolic BP (SBP) treatment goals. Data were analyzed between October 2017 and March 2018. Proportions and numbers of individuals with hypertension or recommended for antihypertensive treatment and numbers of CVD and all-cause mortality reduction. According to the 2017 hypertension guideline, the prevalence of hypertension (BP level ≥130/80 mm Hg) was 45.4% (95% CI, 43.9%-46.9%), representing 105.3 (95% CI, 101.9-108.8) million US adults, which was significantly higher than estimates per the 2014 hypertension guideline (BP level ≥140/90 mm Hg): 32.0% (95% CI, 30.3%-33.6%) or 74.1 (95% CI, 70.3-77.9) million individuals, respectively. Additionally, the proportion of individuals recommended for antihypertensive treatment was significantly higher according to the 2017 hypertension guideline (35.9%; 95% CI, 34.2%-37.5%) compared with the 2014 hypertension guideline (31.1%; 95% CI, 29.6%-32.7%). Achieving the 2017 hypertension guideline SBP treatment goals is estimated to reduce 610 000 (95% CI, 496 000-734 000) CVD events and 334 000 (95% CI, 245 000-434 000) total deaths in US adults 40 years and older. Corresponding estimates after achieving the 2014 hypertension guideline SBP treatment goals were 270 000 (95% CI, 202 000-349 000) and 177 000 (95% CI, 123 000-241 000), respectively. Implementing the 2017 hypertension guideline is estimated to increase 62 000 hypotension and 79 000 acute kidney injury or failure events. Compared with the 2014 hypertension guideline, the 2017 hypertension guideline was associated with an increase in the proportion of adults recommended for antihypertensive treatment and a further reduction in major CVD events and all-cause mortality, but a possible increase in the number of adverse events in the United States.

Impact of Intensive Versus Standard Blood Pressure Management by Tertiles of Blood Pressure in SPRINT (Systolic Blood Pressure Intervention Trial).

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.

Syncope, Hypotension, and Falls in the Treatment of Hypertension: Results from the Randomized Clinical Systolic Blood Pressure Intervention Trial.

To determine predictors of serious adverse events (SAEs) involving syncope, hypotension, and falls, with particular attention to age, in the Systolic Blood Pressure Intervention Trial. Randomized clinical trial. Academic and private practices across the United States (N=102). Adults aged 50 and older with a systolic blood pressure (SBP) of 130 to 180mmHg at high risk of cardiovascular disease events, but without diabetes, history of stroke, symptomatic heart failure or ejection fraction less than 35%, dementia, or standing SBP less than 110mmHg (N=9,361). Treatment of SBP to a goal of less than 120mmHg or 140mmHg. Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were treatment assignment, demographic characteristics, comorbidities, baseline measurements, and baseline use of cardiovascular medications. One hundred seventy-two (1.8%) participants had SAEs involving syncope, 155 (1.6%) hypotension, and 203 (2.2%) falls. Randomization to intensive SBP control was associated with greater risk of an SAE involving hypotension (hazard ratio (HR)=1.67, 95% confidence interval (CI)=1.21-2.32, P=.002), and possibly syncope (HR=1.32, 95% CI=0.98-1.79, P=.07), but not falls (HR=0.98, 95% CI=0.75-1.29, P=.90). Risk of all three outcomes was higher for participants with chronic kidney disease or frailty. Older age was also associated with greater risk of syncope, hypotension, and falls, but there was no age-by-treatment interaction for any of the SAE outcomes. Participants randomized to intensive SBP control had greater risk of hypotension and possibly syncope, but not falls. The greater risk of developing these events associated with intensive treatment did not vary according to age.

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction

Lower systolic blood pressure (SBP) levels are associated with poor outcomes in patients with heart failure. Less is known about this association in heart failure with preserved ejection fraction (HFpEF). To determine the associations of SBP levels with mortality and other outcomes in HFpEF. A propensity score-matched observational study of the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 25 354 patients who were discharged alive; 8873 (35.0%) had an ejection fraction of at least 50%, and of these, 3915 (44.1%) had stable SBP levels (≤20 mm Hg admission to discharge variation). Data were collected from 259 hospitals in 48 states between March 1, 2003, and December 31, 2004. Data were analyzed from March 1, 2003, to December 31, 2008. Discharge SBP levels less than 120 mm Hg. A total of 1076 of 3915 (27.5%) had SBP levels less than 120 mm Hg, of whom 901 (83.7%) were matched by propensity scores with 901 patients with SBP levels of 120 mm Hg or greater who were balanced on 58 baseline characteristics. Thirty-day, 1-year, and overall all-cause mortality and heart failure readmission through December 31, 2008. The 1802 matched patients had a mean (SD) age of 79 (10) years; 1147 (63.7%) were women, and 134 (7.4%) were African American. Thirty-day all-cause mortality occurred in 91 (10%) and 45 (5%) of matched patients with discharge SBP of less than 120 mm Hg vs 120 mm Hg or greater, respectively (hazard ratio [HR], 2.07; 95% CI, 1.45-2.95; P < .001). Systolic blood pressure level less than 120 mm Hg was also associated with a higher risk of mortality at 1 year (39% vs 31%; HR, 1.36; 95% CI, 1.16-1.59; P < .001) and during a median follow-up of 2.1 (overall 6) years (HR, 1.17; 95% CI, 1.05-1.30; P = .005). Systolic blood pressure level less than 120 mm Hg was associated with a higher risk of heart failure readmission at 30 days (HR, 1.47; 95% CI, 1.08-2.01; P = .02) but not at 1 or 6 years. Hazard ratios for the combined end point of heart failure readmission or all-cause mortality associated with SBP level less than 120 mm at 30 days, 1 year, and overall were 1.71 (95% CI, 1.34-2.18; P < .001), 1.21 (95% CI, 1.07-1.38; P = .004), and 1.12 (95% CI, 1.01-1.24; P = .03), respectively. Among hospitalized patients with HFpEF, an SBP level less than 120 mm Hg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in patients with HFpEF.

Do We Need a Patient-Centered Target for Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes Mellitus?

The current trend on diabetes mellitus management advocates replacing the paradigm from a uniform to an individualized patient-centered systolic blood pressure (SBP), but there is no consensus on the achieved treatment goals of SBP level. The study aimed at evaluating the association between SBP and the risk of cardiovascular diseases (CVD) and all-cause mortality for diabetic patients to identify patient-centered treatment targets. A retrospective study was conducted on 95 086 Chinese adult primary care patients with type 2 diabetes mellitus and hypertension. Using the average of the annual SBP records (updated SBP) over a median follow-up of 5.9 years, the risks of overall CVD, all-cause mortality, and their composite associated with SBP were evaluated using Cox proportional hazards regression. Subgroup analysis was performed on the incidence of CVD by stratifying patient's baseline characteristics. The SBP range for the lowest risk of CVD and all-cause mortality was 130 to 134 mm Hg among type 2 diabetes mellitus population. A J-shaped curvilinear relationship was identified between SBP and risk of CVD and all-cause mortality, irrespective of patients' characteristics. The findings showed that all patients with SBP <125 mm Hg or ≥140 mm Hg had an increased risk of CVD and mortality. This large territory-wide study showed the level of achieved SBP of 125 to 139 mm Hg in pharmacological therapy, irrespective of patients' characteristics, suggested that the SBP treatment goal of <140 mm Hg and individualized SBP target may not be necessary in diabetic management.

Abstract P376: Impact of Selected Differences Between Automated versus Conventional Office Blood Pressure and Adherence on the Prevalence of SPRINT Eligibility in Korean Population

Background: For the applicability of Systolic Blood Pressure (BP) Intervention Trial (SPRINT) is controversial due to regional cardiovascular (CV) risk stratification system, AHM adherence, and the automated office BP (AOBP) methodology. Method: General population aged 30 or more (n=205282) and 55208 hypertension subject in Korean National Health Insurance Service - National Sample Cohort (NHIS-NSC) 2010 data were analyzed. Three BP criteria 1, 2, and 3 according to the selected difference between office BP and AOBP of 0 mmHg, 5 mmHg, and 10 mmHg, respectively. Also according to the risk groups and adherence status, prevalence of SPRINT eligible subjects were investigated. Results: SPRINT eligibility subjects were observed in 6.5[6.4~6.7]% vs 5.6[5.5~5.7]% in the general population 15.9[15.7~16.0]% vs 14.8[14.7~15.0]% in hypertension patients by KSH vs. FRS, respectively ([ ], 95% confidence interval). According to BP criteria 1 to 3, SPRINT eligibilities by KSH were different significantly in the general population (6.5[6.4~6.7]%, 4.0[3.9~4.1]%, and 2.7[2.6~2.7]%, respectively) and in hypertension patients (15.9[15.7~16.0]%, 11.8[11.7~12.0]%, and 9.9[9.8~10.0]%, respectively). When the SPRINT eligibility was allowed only in PDC &gt;= 300 days per year in hypertension patients, the prevalence according to the BP criteria 1 to 3 were 8.0[7.7~8.2]%, 5.4[4.3~4.7]%, and 4.1[3.9~4.2]%, respectively by KSH and 8.1[7.8~8.3]%, 5.7[5.5~5.9]%, and 4.4[4.3~4.6]%, respectively by FRS. Conclusion: SPRINT eligibility can be markedly differed not by the risk stratification systems but by the application of AOBP to conventional office BP and adherence.

Abstract 113: Beneficial or Harmful? The Role of Intensive Anti-hypertensive Treatment in the Development of Chronic Kidney Disease

Hypertension is the leading cause of end-stage renal disease, and one of the goals of anti-hypertensive treatment is to protect the kidney. However, it is unknown how low of blood pressure as the treatment target should be so that anti-hypertensive therapy would not bring harm to patients especially for those already suffer from chronic kidney disease (CKD). Thus, we used the data set from The Systolic Blood Pressure Intervention Trial (SPRINT) to study the effect of lowering systolic blood pressure on renal disease development. The SPRINT data randomly assigned patients with a systolic blood pressure (SBP) of 130 mm Hg or higher to a SBP treatment target of less than 120 mm Hg (intensive treatment, n=4678) or a treatment target of less than 140 mm Hg (standard treatment, n=4683). We examined the effect of intensive treatment on six renal outcomes: 1) CKD composite, 2)50 percent reduction in eGFR, 3) dialysis 4) albuminuria, 5) 30 percent reduction in eGFR for patients with CKD at baseline (n=2646) and 6) albuminuria for patients without CKD at baseline (n=6715). Generalized Estimating Equation is used to account the correlation of blood pressure levels over time. At the end of year 1, the mean SBP was 121.4± 0.21 mm Hg in the intensive treatment group and 136.2± 0.21 mm Hg in the standard treatment group. The patients in intensive group were found to have a higher chance of 30% reduction of eGFR (OR=3.684, 95% CI= 2.51-5.40) than in standard treatment group. There was no difference between intensive and standard treatment groups for other 5 outcomes. In addition, 1 mm Hg elevation in SBP in patients with CDK at baseline significantly increased the chance of CKD composite (OR=1.03, 95% CI=1.01-1.04), the chance of 50 percent reduction in eGFR (OR=1.02, 95% CI=1.01-1.05), and chance of 30 percent reduction in eGFR (OR=1.02, 95% CI=1.01-1.02). Thus, SBP significantly correlated with renal outcomes in CKD patients. Our data show that five renal outcomes examined using SPRINT data set are not improved by intensive management of SBP in CKD patients, rather, patients received intensive management have a higher risk of eGFR reduction by 30%, which could be detrimental. Our study indicated that intensive SBP management should not be recommended to CKD patients.

Association of JNC-8 and SPRINT Systolic Blood Pressure Levels With Cognitive Function and Related Racial Disparity

ImportanceThe Eighth Joint National Committee (JNC-8) recommended treating systolic blood pressure (SBP) to a target below 150 mm Hg in older adults, whereas data from the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that a SBP level of lower than 120 mm Hg decreases cardiovascular event rates. Target SBP guidelines have not addressed the potential that black patients may have greater morbidity and mortality from hypertension, especially with regard to cognitive outcomes. The association of these discordant SBP targets with cognition and differences by race have not been systematically evaluated in the same population.ObjectivesTo assess the long-term outcomes of the various recommended SBP levels and to determine if racial differences exist based on long-term cognitive trajectories.Design, Setting, and ParticipantsA total of 1657 cognitively intact older adults receiving treatment for hypertension were studied from 1997 to 2007 in the Health Aging and Body Composition study. Data analysis was conducted from October 1, 2016, to January 1, 2017.Main Outcomes and MeasuresCognition was assessed using the Modified Mini-Mental State Examination (3MSE) 4 times and the Digit Symbol Substitution Test (DSST) 5 times. At each visit, participants were classified as having an SBP level of 120 mm Hg or lower, 121 to 139 mm Hg, 140 to 149 mm Hg, or 150 mm Hg or higher based on the mean SBP level of 2 seated readings. Mixed models assessed the association of SBP levels with 10-year cognitive trajectories. The impact of race was tested using a race interaction term.ResultsDuring the 10-year study period, among the 1657 individuals (908 women and 784 black patients; mean [SE] age, 73.7 [0.1] years), there was a differential decrease in 3MSE and DSST scores by the SBP levels, with the greatest decrease in the group with SBP levels of 150 mm Hg or higher (adjusted decrease was 3.7 for 3MSE and 6.2 for DSST) and the lowest decrease in the group with SBP levels of 120 mm Hg or lower (adjusted decrease was 3.0 for 3MSE and 5.0 for DSST) (P < .001 for both). Compared with white patients, black patients had a greater difference between the higher and lower SBP levels in the decrease in cognition; adjusted differences between the group with SBP levels of 150 mm Hg or higher and the group with SBP levels of 120 mm Hg or lower were –0.05 in white patients and –0.08 in black patients for 3MSE (P = .03) and –0.07 in white patients and –0.13 in black patients for DSST (P = .05).Conclusions and RelevanceFor patients 70 years of age or older receiving treatment for hypertension, a SPRINT SBP level of 120 mm Hg or lower was not associated with worsening cognitive outcome and may be superior to the JNC-8 target for cognition. Lower SBP treatment levels may result in improved cognition in black patients.

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age: Cohort Study Using Electronic Health Records.

Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Abstract P178: Cost-Effectiveness of Intensive versus Standard Blood Pressure Goals by Baseline Systolic Blood Pressure Levels in SPRINT-Eligible US Adults

Background: In high-risk adults, intensive systolic blood pressure (SBP) goals (&lt;120 mmHg) reduced cardiovascular disease (CVD) events and mortality, when compared to standard SBP goals (&lt;140 mmHg), in the Systolic Blood Pressure Intervention Trial (SPRINT). While average benefit of reduced CVD risk with intensive SBP goals outweighs the average risk of serious adverse events (SAEs) and treatment costs, net intensive SBP goal benefits may vary by baseline SBP. We hypothesized that intensive SBP goals would be cost-effective vs. standard SBP goals when stratified by baseline SBP level in SPRINT-eligible US adults from the payer’s perspective. Methods: Using CVD event, death, and SAE risks, a microsimulation model compared direct healthcare costs and quality-adjusted life-years (QALYs) in the SPRINT intensive and standard SBP goal arms over patients’ remaining lifetimes. Published literature and national estimates were used for model parameters. The model assumed that, after the planned duration of SPRINT, adherence to treatment goals decayed over time. To estimate the effect of baseline SBP on the cost-effectiveness of intensive SBP goals, baseline SBP was stratified into the following groups: 130-139 mmHg, 140-149 mmHg, 150-159 mmHg, 160-169 mmHg, and 170-180 mmHg. Results: With higher baseline SBP, patients in both arms experienced higher rates of CVD events or CVD deaths and accrued higher costs compared with patients starting with lower baseline SBP. However, with higher baseline SBP, there were slightly more incremental QALYs gained with intensive SBP treatment, from 0.29 to 0.31. This led to a modestly better incremental cost-effectiveness ratio (ICER) for intensive vs. standard SBP goals, decreasing from approximately $50,000 to $43,000 per QALY gained as baseline SBP increased. If SPRINT treatment effects and in-trial adherence persisted for the remaining lifetime, the ICER for intensive SBP goals decreased to approximately $25,000-$26,000 per QALY gained across baseline SBP groups. Conclusions: Treatment of all SPRINT-eligible patients led to lifetime cost-effectiveness below accepted willingness-to-pay thresholds and lifetime net benefit and cost-effectiveness varied only modestly by baseline SBP. However, this analysis was based on summary data and did not account for individual patient risks. Multiple predictors, in addition to baseline SBP, may be needed to identify which SPRINT-eligible patients derive maximal benefit from intensive SBP treatment.

Abstract P176: Impact of Serious Adverse Event Risks on the Cost-effectiveness of Intensive Blood Pressure Goals in Patients Aged ≥75 Years

Background: Compared to the overall Systolic Blood Pressure Intervention Trial (SPRINT) results, patients aged ≥75 years at baseline had a greater reduction in cardiovascular disease (CVD) events and all-cause mortality with an intensive systolic blood pressure (SBP) goal (&lt;120 mmHg) compared to a standard SBP goal (&lt;140 mmHg). Applying an intensive SBP goal in high-risk older patients represents a major shift in clinical practice and may increase concern for medication-related severe adverse events (SAEs). We hypothesized that the benefits of reduced CVD risk would outweigh the increased costs and SAE risk of intensive vs. standard SBP goals in SPRINT-eligible patients aged ≥75 years even when considering variable SAE risks. Methods: A microsimulation health-state transition model of 10,000 patients was created to estimate the CVD events, SAEs, quality-adjusted life years (QALYs), and direct healthcare costs of intensive vs. standard SBP goals. The model assumed patients were adherent to treatment during the median SPRINT follow-up, but that all patients would become non-adherent over 5 years. While adherent, CVD and SAE risks were derived from published SPRINT effect estimates for the ≥75 subgroup. Due to uncertainty in the SAE risk associated with intensive SBP goals in older adults, the intensive arm SAE risk was varied to determine the point at which treatment costs and harms outweighed CVD benefits at accepted willingness-to-pay thresholds. Healthcare costs and health state utilities were derived from national sources and other published estimates. Results: If SAE risk was equal to the observed rates in SPRINT, mean lifetime costs and QALYs were $268,000 and 7.85 for the intensive arm, and $262,000 and 7.60 for the standard arm. The resulting incremental cost-effectiveness ratio (ICER) was about $26,000 per QALY gained. However, as SAE risk in the intensive arm increased by 1.5, 2, and 2.5 times, the ICER increased to $33,000, $43,000, and $55,000 per QALY gained, respectively. Conclusion: Intensive SBP goals may be a cost-effective way to reduce CVD events and improve survival in patients aged ≥75 years, but safety and cost-effectiveness depend on medication-related SAE risk. However, these results are based on summary data and do not account for clustering of risks at the individual patient level. Thus, more precise prediction of risks and benefits is needed to guide selection of older patients for intensive SBP treatment goals.

Proportion and Characteristics of US Adults Who May Be Eligible From Additional Blood Pressure Lowering Based on Absolute Risk.

The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood pressure (BP) lowering to reduce cardiovascular events in intermediate to high cardiovascular risk adults. However, the population impact of an absolute risk-based strategy for BP lowering remains unclear. We examined 3 treatment thresholds using the National Health and Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment goals. Second, adults with a systolic BP (SBP) of 130 mm Hg and high cardiovascular risk (based on eligibility for SPRINT) were considered eligible for additional BP lowering. Finally, we combined the treatment threshold for high-risk adults with an SBP treatment threshold of 140 mm Hg for intermediate-risk adults that met the eligibility criteria for HOPE-3. Under the JNC8 guideline, 78.0% of adults ≥50 years were at target while 22.0% were eligible for additional BP lowering. If an SBP treatment threshold of 130 mm Hg was used for adults at high cardiovascular risk, 31.1% would be eligible for additional BP lowering (an increase of 8.1 million). If an SBP threshold of 140 mm Hg was additionally used for adults at intermediate risk, 31.4% of adults would be eligible for BP lowering (an increase of 8.3 million). The proportion of adults eligible for BP lowering with established coronary artery disease decreased with the risk-based strategies. An absolute risk treatment strategy would modestly increase the proportion of adults eligible for BP lowering.