Incidence and Outcomes of Acute Heart Failure With Preserved Versus Reduced Ejection Fraction in SPRINT.

BACKGROUND: In the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes. METHODS: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF <45%. RESULTS: Among the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF (P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission. CONCLUSIONS: In SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes.

BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. METHODS: In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.

Orthostatic Hypotension, Cardiovascular Outcomes, and Adverse Events: Results From SPRINT.

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg. OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mm Hg 1 minute after standing from a seated position. We used Cox models to examine the association of OH with cardiovascular disease or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1170 (5.7%) instances of OH among those assigned a standard BP goal and 1057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of cardiovascular disease events (primary outcome: hazard ratio 1.06 [95% CI, 0.78-1.44]). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (hazard ratio, 1.77 [95% CI, 1.11-2.82]) and bradycardia (hazard ratio, 1.94 [95% CI, 1.19-3.15]), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of cardiovascular disease events, and BP treatment goal had no effect on OH's association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

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

OBJECTIVE: 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. DESIGN: Randomized clinical trial. SETTING: Academic and private practices across the United States (N = 102). PARTICIPANTS: Adults aged 50 and older with a systolic blood pressure (SBP) of 130 to 180 mmHg 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 110 mmHg (N = 9,361). INTERVENTION: Treatment of SBP to a goal of less than 120 mmHg or 140 mmHg. MEASUREMENTS: Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were treatment assignment, demographic characteristics, comorbidities, baseline measurements, and baseline use of cardiovascular medications. RESULTS: 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. CONCLUSIONS: 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.

Gender, blood pressure, and cardiovascular and renal outcomes in adults with hypertension from the Systolic Blood Pressure Intervention Trial.

BACKGROUND: To determine if the effects of intensive lowering of systolic blood pressure (goal of less than 120 mmHg) versus standard lowering (goal of less than 140 mmHg) upon cardiovascular, renal, and safety outcomes differed by gender. METHODS: Nine thousand three hundred and sixty-one men and women aged 50 years or older with systolic blood pressure of 130 mmHg or greater, taking 0-4 antihypertensive medications, and with increased risk of cardiovascular disease, but free of diabetes, were randomly assigned to either a systolic blood pressure target of less than 120 mmHg (intensive treatment) or a target of less than 140 mmHg (standard treatment). The primary composite outcome encompassed incident myocardial infarction, heart failure, other acute coronary syndromes, stroke, or cardiovascular-related death. All-cause mortality, renal outcomes, and serious adverse events were also assessed. RESULTS: Compared with the standard treatment group, the primary composite outcome in the intensive treatment group was reduced by 16% [hazard ratio 0.84 (0.61-1.13)] in women, and by 27% in men [hazard ratio 0.73 (0.59-0.89), P value for interaction between treatment and gender is 0.45]. Similarly, the effect of the intensive treatment on individual components of the primary composite outcome, renal outcomes, and overall serious adverse events was not significantly different according to gender. CONCLUSION: In adults with hypertension but not with diabetes, treatment to a systolic blood pressure goal of less than 120 mmHg, compared with a goal of less than 140 mmHg, resulted in no heterogeneity of effect between men and women on cardiovascular or renal outcomes, or on rates of serious adverse events.ClinicalTrials.gov number, NCT01206062.

Influence of metabolic syndrome and race on the relationship between intensive blood pressure control and cardiovascular outcomes in the SPRINT cohort.

AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether the effects varied by race/ethnicity. METHODS: We performed post hoc analyses among non-Hispanic black, non-hispanic white and Hispanic participants, with and without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who were randomized to a systolic blood pressure (SBP) target of <120 mm Hg (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N = 4553). The median follow-up was 3.26 years. The primary outcome was the composite of the first occurrence of myocardial infarction, stroke, heart failure, non-myocardial infarction acute coronary syndrome or CV death. RESULTS: Overall, 3521/9097 participants (38.7%) met the criteria for MetS at baseline. Baseline characteristics were similar in the two SBP target groups within each MetS subgroup, except body mass index was slightly higher in the standard arm of the MetS subgroup (33.3 ± 5.6 vs 33.0 ± 5.3 kg/m2 ; P < .01), but were similar across treatment arms in the non-MetS subgroup. The hazard ratio for the primary outcome was similarly reduced in participants with or without baseline MetS: 0.75 (95% confidence interval [CI] 0.57, 0.96) and 0.71 (95% CI 0.57, 0.87), respectively (adjusted P value for treatment by subgroup interaction = .98). Similarly, there was no evidence of treatment × MetS subgroup interaction for all-cause mortality (adjusted interaction P value = .98). The findings were also similar across race/ethnic subgroups. CONCLUSIONS: In this analysis the CV benefit of intensive SBP control did not differ among participants by baseline MetS status, regardless of race/ethnicity.

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

OBJECTIVE: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSIONS: In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

Effect of Intensive Blood Pressure Treatment on Heart Failure Events in the Systolic Blood Pressure Reduction Intervention Trial.

BACKGROUND: Acute decompensated heart failure (ADHF) was a frequent common outcome in SPRINT (Systolic Blood Pressure Intervention Trial). We examined whether there was differential reduction in ADHF events from intensive blood pressure [BP] treatment among the 6 key, prespecified subgroups in SPRINT: age ≥75 years, prior cardiovascular disease, chronic kidney disease, women, black race, and 3 levels of baseline systolic BP (≤132 versus >132 to <145 versus ≥145 mm Hg). METHODS AND RESULTS: ADHF was defined as hospitalization for ADHF, confirmed and formally adjudicated by a blinded events committee using standardized protocols. At 3.29 years follow-up, there were 103 ADHF events (2.2%) among 4683 standard arm participants and 65 ADHF events (1.4%) among 4678 intensive arm participants (Cox proportional hazards ratio, 0.63; 95% confidence interval, 0.46-0.85; P value =0.003). In multivariable analyses, including treatment arm, baseline covariates that were significant predictors for ADHF included chronic kidney disease, cardiovascular disease, age≥75 years, body mass index, and higher systolic BP. The beneficial effect of the intervention on incident ADHF was consistent across all prespecified subgroups. Participants who had incident ADHF had markedly increased risk of subsequent cardiovascular events, including a 27-fold increase (P<0.001) in cardiovascular death. CONCLUSIONS: Targeting a systolic BP<120 mm Hg, compared with <140 mm Hg, significantly reduced ADHF events, and the benefit was similar across all key, prespecified subgroups. Participants who developed ADHF had markedly increased risk for subsequent cardiovascular events and death, highlighting the importance of strategies aimed at prevention of ADHF, especially intensive BP reduction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

The association between Self-Reported Medication Adherence scores and systolic blood pressure control: a SPRINT baseline data study.

We examined baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT) to investigate whether medication adherence, measured by the 8-item Morisky Medication Adherence Scale (MMAS-8), was associated with systolic blood pressure (SBP) and whether MMAS-8 score and number of antihypertensive medications interacted in influencing SBP. A total of 8435 SPRINT participants were included: 21.2% had low adherence (MMAS-8: <6); 40.0% had medium adherence (6 to <8); and 38.8% had high adherence (8). SBP was <140 mm Hg in 54.6%; 140-160 mm Hg in 36.6%; and >160 mm Hg in 8.8%. In multivariable regression, medium vs. low adherence weakly associated with lower SBP (odds ratio: 1.17; confidence interval: 1.04, 1.31). SPRINT eligibility criteria should be considered when interpreting results. Efforts to understand and enhance adherence are crucial to improve population health, and using self-report instruments might be considered for predicting treatment adherence and response in future efficacy trials and for identifying patients for adherence support in clinical practice.