Abstract P179: The Magnitude, And Not Direction, Of Blood Pressure Change Influences The Risk Of Serious Adverse Events In SPRINT

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Michael Buhnerkempe ◽  
Vivek Prakash ◽  
Albert Botchway ◽  
Oritsegbubemi Adekola ◽  
John M Flack
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Proportional Hazards ◽  
Pressure Change ◽  
Cox Proportional Hazards ◽  
Intensive Treatment ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Ascvd Risk

Background: The landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that more intensive systolic blood pressure treatment (SBP < 120 mm Hg) was associated with lower risk for cardiovascular events and mortality but higher risk for serious adverse events (SAEs). However, it is unclear if the magnitude and/or the direction of the BP change determines SAE risk. In this study, we aim to determine how the magnitude and direction of BP change impacts SAE risk. Methods: This is a secondary analysis of 7922 participants in SPRINT. Time-varying Cox proportional hazards models were used to explore the relationship between visit-to-visit BP change and SAE risk. BP change was categorized using five intervals: 1) decreases ≥30 mm Hg, 2) decreases 10-29 mm Hg, 3) increases or decreases <10 mm Hg (reference category), 4) increases 10-29 mm Hg, and 5) increases ≥30 mm Hg. Additional variables adjusted for in the model included: age, gender, race, estimated glomerular filtration rate, treatment group, and baseline atherosclerotic cardiovascular disease (ASCVD) risk. Hypotension was excluded as an SAE to prevent bias in SAE risk in the large BP decrease category. Results: The hazard ratio (HR) for SAEs compared to the minimal BP change category was greatest for BP increases above 30 mm Hg (HR = 1.62, 95% confidence interval [1.30, 2.01]). However, the HR was similar for sharp BP decreases over 30 mm Hg (HR = 1.52 [1.23, 1.87]). Milder BP increases and decreases were associated with lower SAE risk (HR = 1.18 [1.06, 1.32] and HR = 1.10 [0.98, 1.22] for BP changes 10 to 30 mm Hg and -30 to -10 mm Hg, respectively). There were no significant interactions between BP change, intensive treatment, and baseline ASCVD risk. Conclusions: SAE risk was similar for similarly sized increases and decreases in BP between visits, with higher magnitude changes associated with higher SAE risk. When accounting for the magnitude of BP change, no significant effect of intensive treatment or baseline ASCVD risk was found.

Risk-Based Intensive Blood Pressure Lowering and Prevention of Heart Failure: A SPRINT Post Hoc Analysis

Hypertension ◽  
2021 ◽  
Author(s):  
Rebecca J. Molsberry ◽  
Leah Rethy ◽  
Michael C. Wang ◽  
Rupal C. Mehta ◽  
Donald M. Lloyd-Jones ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Adverse Events ◽  
Proportional Hazards ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Risk Category ◽  
Serious Adverse Events ◽  
Intensive Blood Pressure

The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated that intensive blood pressure (BP) lowering (target<120 mm Hg) was more effective in preventing heart failure (HF) compared with standard BP goals (target<140 mm Hg). However, intensive BP lowering also led to an increase in serious adverse events. We aimed to identify a subset of the clinical trial population who might derive the greatest benefit from intensive BP lowering for prevention of HF using a previously validated HF risk prediction model. SPRINT participants without prevalent cardiovascular disease were stratified into HF risk tertiles based on predicted HF risk. We performed Kaplan-Meier Survival analysis and multivariable Cox proportional hazards models to test the effect of intensive versus standard BP lowering on incident HF in each tertile of predicted HF risk. A total of 6911 individuals were included and 77 incident HF events occurred over a median follow-up time of 3.3 (interquartile range, 2.9–3.8) years. A reduction in risk of HF was observed among those randomized to intensive BP lowering in each risk tertile but was significant only in the highest HF risk category (risk tertile 1: hazard ratio, 0.86 [95% CI, 0.29–2.56]; risk tertile 2: 0.54 [0.23–1.30]; risk tertile 3: 0.46 [0.24–0.88]). Serious adverse events were frequent in all groups. While the short follow-up may lead to an underestimation of benefit in the lower predicted risk groups, prioritizing intensive BP lowering in those at highest predicted HF risk may help to reduce the high burden of HF in the United States.

Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wei Zhang ◽  
Jaime L Speiser ◽  
Miguel Cainzos Achirica ◽  
Khurram Nasir ◽  
Michael Tsai ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
High Sensitivity ◽  
Chinese Americans ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
C Reactive Protein ◽  
Lipoprotein A ◽  
Reactive Protein ◽  
Ascvd Risk

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

scholarly journals Blood Pressure Change from Normal to 2017 ACC/AHA Defined Stage 1 Hypertension and Cardiovascular Risk

2019 ◽  
Vol 8 (6) ◽  
pp. 820 ◽  
Author(s):  
Joung Sik Son ◽  
Seulggie Choi ◽  
Gyeongsil Lee ◽  
Su-Min Jeong ◽  
Sung Min Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Proportional Hazards ◽  
Heart Association ◽  
Pressure Change ◽  
Cox Proportional Hazards ◽  
Cvd Risk ◽  
Cox Proportional Hazards Models ◽  
Increased Risk ◽  
Stage 1 ◽  
Second Period

The purpose of this study was to investigate the clinical significance of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) defined stage 1 hypertension (systolic blood pressure (SBP) 130–139 mmHg or diastolic blood pressure (DBP) 80–89 mmHg), and increase in BP from previously normal BP in Korean adults. We conducted a retrospective analysis of 60,866 participants from a nationally representative claims database. Study subjects had normal BP (SBP < 120 mmHg and DBP < 80 mmHg), no history of anti-hypertensive medication, and cardiovascular disease (CVD) in the first period (2002–2003). The BP change was defined according to the BP difference between the first and second period (2004–2005). We used time-dependent Cox proportional hazards models in order to evaluate the effect of BP elevation on mortality and CVD with a mean follow-up of 7.8 years. Compared to those who maintained normal BP during the second period, participants with BP elevation from normal BP to stage 1 hypertension had a higher risk for CVD (adjusted hazard ratio (aHR) 1.23; 95% confidence interval (CI), 1.08–1.40), and ischemic stroke (aHR 1.32; 95% CI, 1.06–1.64). BP elevation to 2017 ACC/AHA defined elevated BP (SBP 120–129 mmHg and DBP < 80 mmHg) was associated with an increased risk of CVD (aHR 1.26; 95% CI, 1.06–1.50), but stage 1 isolated diastolic hypertension (SBP < 130 and DBP 80–89 mmHg) was not significantly related with CVD risk (aHR 1.12; 95% CI, 0.95–1.31).

P57262018 ESC/ESH guideline-recommended age categories and intensive blood pressure management in high-risk adults: insights from SPRINT

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Pareek ◽  
T Biering-Sorensen ◽  
M Vaduganathan ◽  
C Byrne ◽  
A Qamar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
European Society ◽  
Proportional Hazards ◽  
Controlled Trial ◽  
Cox Proportional Hazards ◽  
Standard Group ◽  
Primary Efficacy ◽  
Serious Adverse Events ◽  
Similar Treatment

Abstract Background The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for arterial hypertension propose different intensities of blood pressure (BP) lowering in patients <65 years, 65–79 years, and ≥80 years of age. However, it is unclear whether intensive BP management is well-tolerated and modifies risk uniformly across this age spectrum. Purpose To assess the relationship between age, treatment response to intensive BP lowering, and cardiovascular (CV) outcomes. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high CV risk but without diabetes who had a systolic BP (SBP) 130–180 mmHg, were randomized to intensive (target SBP <120mmHg) or standard antihypertensive treatment (target SBP <140mmHg). The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from CV causes. The primary safety endpoint was the composite of serious adverse events (SAE). We examined the prognostic implications of age, using Cox proportional-hazards regression models adjusted for demographic, clinical, and laboratory variables. Whether a linear association was present between age and clinical endpoints was evaluated using restricted cubic splines. We further explored the effects of intensive BP lowering across the age spectrum using interaction analyses. Results Age was noted for all individuals, and 3,805 (41%), 4,390 (47%), and 1,166 (12%) were <65 years, 65–79 years, and ≥80 years, respectively. Mean age was similar between the two study groups (intensive group 67.9 years vs. standard group 67.9 years; P=0.94). Median follow-up was 3.3 years (range 0–4.8), with 562 primary efficacy events (6%) and 3,529 primary safety events (38%) recorded during the study period. Age was linearly associated with the risk of stroke (test for overall trend, P<0.001) and non-linearly associated with the risk of primary efficacy events, death from CV causes, death from any cause, heart failure, and SAE (test for non-linearity, P<0.05; test for overall trend, P<0.001). Age remained significantly associated with all tested endpoints after multivariable adjustment (P<0.001). Furthermore, the risk of primary events increased over guideline-recommended age-categories (65–79 years vs. <65 years; adj. HR 1.65, 95% CI 1.34–2.04; P<0.001 and ≥80 years vs. 65–79 years; adj. HR 1.92, 95% CI 1.54–2.40; P<0.001), as did the risk of SAE (P<0.001). The safety and efficacy of intensive BP lowering was not modified by age whether tested continuously or categorically (P>0.05). The Figure shows similar treatment effects (hazard ratios) across the spectrum of age. P-values are for the interaction between age and treatment effect for each endpoint. Figure 1 Conclusions In SPRINT, higher age was associated with a greater risk of both CV events and SAE. However, intensive BP lowering appeared to be associated with similar risks and benefits across the age spectrum.

Abstract P021: Association Of Resting Heart Rate With All-cause And Cardiovascular Mortality: Sprint

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Steven J Mould ◽  
Elsayed Z Soliman ◽  
Yashashwi Pokharel ◽  
Elijah Beaty ◽  
Prashant Bhave ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Cardiovascular Mortality ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Channel Blockers ◽  
Resting Heart Rate ◽  
Autonomic Tone

Introduction: Elevated resting heart rate (RHR) has been shown to be associated with both all-cause and cardiovascular mortality. Prior studies have provided conflicting estimates of the strength of each association. To explore the relationship between RHR and competing mortality risks, we sought to compare the association between RHR and cardiovascular and non-cardiovascular mortality among participants in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: Eligible SPRINT participants had baseline RHR, longitudinal follow-up, and were not using beta blockers or non-dihydropyridine calcium channel blockers. Mortality was classified by a treatment-blinded adjudication committee as cardiovascular if secondary to coronary heart disease, stroke, sudden cardiac death, or congestive heart failure. Multivariable Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for cardiovascular and non-cardiovascular mortality, separately, associated with a 10 beats per minute increase in RHR. Results: Among 5,571 eligible SPRINT participants (67.1 ± 9.4 years, 33.8% female, 63.8% white, mean RHR 70.4±11.8 beats per minute) over a median 3.8 years of follow-up, there were 56 cardiovascular deaths and 176 non-cardiovascular deaths. In models adjusted for age, sex, race, prior cardiovascular disease, smoking, systolic blood pressure, creatinine, total cholesterol, high-density lipoprotein cholesterol, and trial treatment assignment, higher RHR (per ten beat-per-minute increase) was associated with both cardiovascular (HR 1.17, 95% CI 1.02-1.35) and non-cardiovascular mortality (HR 1.27, 95% CI 1.13-1.43). Conclusions: Elevated RHR was associated with both cardiovascular and non-cardiovascular mortality, suggesting that RHR may serve as a marker of both global health rather and cardiovascular health. Higher RHR may reflect imbalance in autonomic tone and further studies are needed to explore the mechanisms of these associations.4

scholarly journals Intensive blood pressure lowering in different age categories: insights from the Systolic Blood Pressure Intervention Trial

2019 ◽  
Vol 6 (6) ◽  
pp. 356-363 ◽  
Author(s):  
Christina Byrne ◽  
Manan Pareek ◽  
Muthiah Vaduganathan ◽  
Tor Biering-Sørensen ◽  
Arman Qamar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Primary Efficacy ◽  
Intervention Trial ◽  
Blood Pressure Lowering ◽  
Serious Adverse Events ◽  
Pressure Lowering ◽  
Intensive Blood Pressure

Abstract Aims The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are &lt;65, 65–79, and ≥80 years of age. However, it is unclear whether intensive blood pressure lowering is well-tolerated and modifies risk uniformly across the age spectrum. Methods and results SPRINT randomized 9361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130–180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive vs. standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3805 (41%), 4390 (47%), and 1166 (12%) were &lt;65, 65–79, and ≥80 years. Mean age was similar between the two study groups (intensive group 67.9 ± 9.4 years vs. standard group 67.9 ± 9.5 years; P = 0.94). Median follow-up was 3.3 years. In multivariable models, age was linearly associated with the risk of stroke (P &lt; 0.001) and non-linearly associated with the risk of primary efficacy events, death from cardiovascular causes, death from any cause, heart failure, and serious adverse events (P &lt; 0.001). The safety and efficacy of intensive blood pressure lowering were not modified by age, whether tested continuously or categorically (P &gt; 0.05). Conclusion In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension. Trial Registration SPRINT (Systolic Blood Pressure Intervention Trial); ClinicalTrials.gov Identifier: NCT01206062, https://clinicaltrials.gov/ct2/show/NCT01206062.

Intensive antihypertensive treatment and serious adverse events in older people

2018 ◽  
Vol 56 (12) ◽  
pp. 143-143
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Older People ◽  
Systolic Blood Pressure ◽  
Antihypertensive Treatment ◽  
Intervention Trial ◽  
Serious Adverse Events ◽  
Treatment Of Hypertension

Review of: Sink KM, et al. Syncope, hypotension and falls in the treatment of hypertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Ger Soc 2018;66:679–86.

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