Baseline Blood Pressure Categories Research Articles

Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial.

Apparent treatment-resistant hypertension (aTRH) is prevalent and associated with adverse outcomes in heart failure with mildly reduced or preserved ejection fraction. Less is known about the potential role of sodium-glucose co-transporter 2 inhibition in this high-risk population. In this post hoc analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), we evaluated clinical profiles and treatment effects of dapagliflozin among participants with aTRH. DELIVER participants were categorized on the basis of baseline blood pressure (BP), with aTRH defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic. Nonresistant hypertension was defined as BP above threshold but not meeting aTRH criteria. Controlled BP was defined as BP under threshold. Incidence of the primary outcome (cardiovascular death or worsening heart failure event), key secondary outcomes, and safety events was assessed by baseline BP category. Among 6263 DELIVER participants, 3766 (60.1%) had controlled BP, 1779 (28.4%) had nonresistant hypertension, and 718 (11.5%) had aTRH at baseline. Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function. Rates of the primary outcome were 8.7 per 100 patient-years in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patient-years in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories (Pinteraction=0.114). Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years). Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up. Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time. aTRH was identified in >1 in 10 patients with heart failure and left ventricular ejection fraction >40% in DELIVER. Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with aTRH. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.

Sex-Specific Effects of Blood Pressure Lowering Pharmacotherapy for the Prevention of Cardiovascular Disease: An Individual Participant-Level Data Meta-Analysis.

Whether the relative effects of blood pressure (BP)-lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain. We conducted an individual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. We included data from 51 randomized controlled trials involving 358 636 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89-0.95] for women and 0.90 [0.88-0.93] for men; P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14). The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.

Blood pressure dynamics during home blood pressure monitoring with a digital blood pressure coach-a prospective analysis of individual user data.

Self-monitoring of blood pressure at home is a better predictor of prognosis and recommended in hypertension guidelines. However, the influence of baseline blood pressure category and measurement schedule on BP values during a period of home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application. We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach. Of 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, >90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%. The optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.

Evaluation of vascular risk in patients with migraine with and without aura treated with erenumab: Post hoc analysis of pooled long‐term clinical trial data

To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene-related peptide pathway in migraine management, particularly in a patient population with pre-existing CV risk factors. Data pooled from four double-blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10-year risk of cardiac, cerebrovascular, and peripheral artery disease as no-risk-factors, low-risk (>0% to ≤10%), moderate-risk (>10% to ≤20%), and high-risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). There was no apparent difference between placebo- (N=1032) and erenumab-treatment groups (70 mg, N=885; 140 mg, N=504) in clinical worsening of BP category from baseline to Months 1-3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long-term analysis. Erenumab-treated patients with high and moderate 10-year CV risk (N=107) did not experience any ICCAEs during the double-blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low-risk erenumab group (N=273). There were no increases in AEs during the long-term extensions of up to 5 years (N= 2499; 3482 patient-years of exposure to erenumab) with exposure-adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient-years) for no risk factor (N= 1805), low (N= 492), moderate (N= 121), and high (N= 81) 10-year CV risk groups, respectively. Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10-year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Abstract P394: Initial Antihypertensive Prescribing in Relation to Blood Pressure Among Medicaid and Medicare Recipients

Introduction: Early treatment for hypertension (HTN) portends better outcomes. However, few real-world studies have assessed initial antiHTN regimens and how they differ by baseline blood pressure (BP). We sought to compare initial treatment patterns, stratified by BP, between Medicaid and Medicare recipients. Methods: We performed a cross-sectional study of adults with newly-treated HTN in the One Florida+ Consortium(2012-2020) who had linked claims-EHR data from the treatment initiation visit. Eligible patients were Floridians with Medicaid or Medicare aged ≥18 years, with diagnosed HTN, who filled ≥1 first-line antiHTN class with no evidence of anti HTN fills during the year prior (in which continuous insurance enrollment was required). Baseline BP was categorized per current HTN guidelines, and logistic regression was used to estimate age-adjusted odds of combination vs. monotherapy, per 10 mmHg increase in systolic BP (SBP) or diastolic BP (DBP). Results: We included 2,902 patients (47% Medicaid, 53% Medicare); mean age was 44 (Medicaid) and 67 yrs(Medicare); 60% (64% and 56%, respectively) were women and 42% (57% and 29%, respectively) were Black. Initial antiHTN classes were similar comparing cohorts: ACEI, ARB and thiazide initiation varied little by BP category, in contrast to CCBs and β-blockers (Figure, panels A-B). In age-adjusted analyses, use of initial combination therapy was 40% more likely (OR, 1.40; 95% CI, 1.11, 1.76) among Medicare recipients and inversely related to BP category (panels C-D) among Medicare patients, in which each 10mmHg greater SBP (OR, 0.93; 95% CI, 0.88, 0.97) and DBP (OR 0.82; 95% CI, 0.75, 0.90) had lower odds of combination therapy. Among Medicaid recipients, only SBP associated with combination therapy (OR1.11; 95% CI, 1.03, 1.20). Conclusions: We observed similar initial class patterns among Medicaid &amp; Medicare recipients across baseline BP, but differential use of combination therapy was less likely at higher baseline BP in Medicare recipients, which contrasts current guidance.

Retinal Vascular Occlusion Risks in High Blood Pressure and the Benefits of Blood Pressure Control

This study aimed to evaluate the association of retinal vascular occlusion, including retinal vein occlusion (RVO) and retinal artery occlusion (RAO), with stages of hypertension. Nationwide, population-based retrospective cohort study. Based on baseline blood pressure (BP) as defined by the 2017 American College of Cardiology/American Heart Association guideline, participants were categorized into 4 BP groups. For the BP change measurement, BP groups were defined based on the combination of baseline and follow-up BP categories. The composite retinal vascular occlusion events and hazard ratios (HRs) of retinal vascular occlusion according to BP groups were estimated. With normal BP as the reference, multivariate-adjusted HRs for retinal vascular occlusion were significantly higher than in other BP groups, showing much higher HRs in stage 2 hypertension than in stage 1 (HR, 1.10 for elevated BP; 1.07 for stage 1 hypertension; and 1.32 for stage 2 hypertension). Individual disease analysis showed consistent statistical significance in RVO, whereas RAO showed nonsignificant results. Lowering BP significantly decreased the HRs of retinal vascular occlusion in both stage 1 and stage 2 hypertension (HR, 0.88 and 0.73, respectively). However, once hypertension was diagnosed, the risk of retinal vascular occlusion was higher compared to that in the normal BP groups. Elevated BP, stage 1 hypertension, and stage 2 hypertension were all associated with higher retinal vascular occlusion risks than was normal BP. Controlling hypertension appears to reduce the risk of subsequent retinal vascular occlusion; however, the incidence rate was still be significantly higher than that in persons who maintained a normal BP.

PS-BPC11-2: PEDIATRIC BLOOD PRESSURE CATEGORY PREDICTS LONGITUDINAL VARIABILITY IN BLOOD PRESSURE IN YOUTH

Objectives: In order to identify risk factors that cause elevated blood pressure during adolescence, we aimed to evaluate the predictive effect of childhood factors on longitudinal variability of individual blood pressure during youth. Methods: Childhood data were obtained from medical checkups of Japanese male and female junior high school students aged 12–13 years during the period from 2009 to 2010. Childhood measurements were height, body weight, body mass index (BMI), systolic and diastolic blood pressures, complete blood counts, uric acid, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Childhood blood pressure was categorized as normal, elevated blood pressure, or hypertension according to the American Academy of Pediatrics (AAP) clinical practice guideline. Linear mixed-effects models for repeated measures were used to estimate the effect of baseline childhood factors on longitudinal changes in systolic and diastolic blood pressures. Results: A total of 1304 participants were followed up to the 10th year. At baseline, the mean age was 12.6 years [SD, 0.3] and 26.2% were female. Among male participants, 6.3% were categorized as having elevated blood pressure and 8.8% were categorized as having hypertension, while among female participants 6.1% were categorized as having elevated blood pressure and 8.5% were categorized as having hypertension. Boys in the hypertension category had higher BMI, higher uric acid, and lower HDLC compared with those in the normal blood pressure category, but this trend was not statistically significant in girls. Of each childhood factor, the baseline blood pressure category according to AAP clinical practice guideline fit best with longitudinal changes in both systolic and diastolic blood pressure in the linear mixed-effects models. Conclusion: These results suggest that the AAP pediatric blood pressure category is the strongest predictor of longitudinal variability in individual blood pressure in youth.

Change in blood pressure status defined by 2017 ACC/AHA hypertension guideline and risk of cardiovascular disease: results of over a decade of follow-up of the Iranian population.

Hypertension (HTN) is known to be the leading cause of cardiovascular disease (CVD) and mortality. We aimed to assess the impact of changes in 3 years in different blood pressure (BP) categories on incident CVD. In this study, 3,685 Tehranians aged ≥30 years (42.2% men) free of prevalent CVD with BP level <140/90 mmHg and not on BP-lowering medications were enrolled. Participants were grouped according to baseline BP category using the 2017 ACC/AHA hypertension guideline definition: normal BP (<120/80 mmHg), elevated BP (120-129/<80), and stage 1 HTN (130-139 and/or 80-89). The hazard ratio of incident CVD by changes in the BP category was estimated after adjustment for traditional risk factors using Cox's proportional hazard model, with stable normotension as a reference. During a median follow-up of 11.7 years, 346 CVD events (men = 208) occurred. Compared to the reference group, among participants with normal BP at baseline, only those with BP rising to stage 1 HTN [1.47 (0.99-2.16)], and among those with stage 1 HTN at baseline, regression to elevated BP [1.80 (1.11-2.91)], remaining at stage 1 [1.80 (1.29-2.52)], and progression to stage 2 HTN [1.81 (1.25-2.61)] had a higher risk for CVD; however, regression to normal BP attenuated this risk [1.36 (0.88-2.12)]. Conversion from elevated BP to any other categories had no significant association with CVD risk. Generally, prevalent stage 1 HTN (regardless of changing category) and incident stage 1 HTN were significantly associated with a higher risk of CVD; even regression to elevated BP did not attenuate the risk. Accordingly, these populations are potential candidates for antihypertensive management.

Reduction in blood pressure for elevated blood pressure/stage 1 hypertension according to the American College of Cardiology/American Heart Association guideline and cardiovascular outcomes.

Few studies have examined the relationship of blood pressure (BP) change in adults with elevated BP or stage 1 hypertension according to the American College of Cardiology (ACC)/American Heart Association (AHA) guideline with cardiovascular outcomes. We sought to identify the effect of BP change among individuals with elevated BP or stage 1 hypertension on incident heart failure (HF) and other cardiovascular diseases (CVDs). We conducted a retrospective cohort study including 616 483 individuals (median age 46 years, 73.7% men) with elevated BP or stage 1 hypertension based on the ACC/AHA BP guideline. Participants were categorized using BP classification at one-year as normal BP (n = 173 558), elevated BP/stage 1 hypertension (n = 367 454), or stage 2 hypertension (n = 75 471). The primary outcome was HF, and the secondary outcomes included (separately) myocardial infarction (MI), angina pectoris (AP), and stroke. Over a mean follow-up of 1097 ± 908 days, 10 544 HFs, 1317 MIs, 11 070 APs, and 5198 strokes were recorded. Compared with elevated BP/stage 1 hypertension at one-year, normal BP at one-year was associated with a lower risk of developing HF [hazard ratio (HR): 0.89, 95% CI:0.85-0.94], whereas stage 2 hypertension at one-year was associated with an elevated risk of developing HF (HR:1.43, 95% CI:1.36-1.51). This association was also present in other cardiovascular outcomes including MI, AP, and stroke. The relationship was consistent in all subgroups stratified by age, sex, baseline BP category, and overweight/obesity. A one-year decline in BP was associated with the lower risk of HF, MI, AP, and stroke, suggesting the importance of lowering BP in individuals with elevated BP or stage 1 hypertension according to the ACC/AHA guideline to prevent the risk of developing CVD.

The 10-year incidence of hypertension across blood pressure categories in a population-based cohort in southwestern Sweden

BackgroundTo explore the determinants of incident hypertension, and especially the impact of baseline blood pressure categories, in a representative Swedish population.MethodsA 10-year longitudinal study of residents aged 30–74. Blood pressures were measured and categorized according to ESH guidelines with optimal blood pressure < 120/80 mmHg, normal 120–129/80–84 mmHg, and high normal 130–139/85–89 mmHg. Incident hypertension was defined as ongoing treatment or three consecutive blood pressure readings ≥ 140/ ≥ 90 mmHg (one or both) at follow-up, while those with ≥ 140 and/or ≥ 90 mmHg at only one or two visits were labelled as unstable. After excluding subjects with hypertension, ongoing blood pressure lowering medication or a previous CVD event at baseline, 1099 remained for further analyses.ResultsSixteen (2.6%) subjects with optimal baseline blood pressure had hypertension at follow up. Corresponding numbers for subjects with normal, high normal and unstable blood pressure were 55 (19.4%), 50 (39.1%) and 46 (74.2%), respectively. Compared with subjects in optimal group those in normal, high normal and unstable blood pressure categories had significantly higher risk to develop manifest hypertension with odds ratios OR and (95% CI) of 7.04 (3.89–12.7), 17.1 (8.88–33.0) and 84.2 (37.4–190), respectively, with adjustment for age, BMI and family history for hypertension. The progression to hypertension was also independently predicted by BMI (p < 0.001), however, not by age.ConclusionsSubjects with high normal or unstable blood pressure should be identified in clinical practice, evaluated for global hypertension risk and offered personalized advice on lifestyle modification for early prevention of manifest hypertension and cardiovascular disease.

Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

SummaryBackgroundThe effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.MethodsWe did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.FindingsWe included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group.InterpretationPharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines.FundingBritish Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Insulin resistance, metabolic syndrome, and blood pressure progression among Blacks: the Jackson Heart Study.

There is a paucity of data on the relations of insulin resistance with incident blood pressure (BP) changes among Blacks. We investigated the associations of insulin resistance and metabolic syndrome (MetS) with BP progression in a community-based sample of African Americans. We analyzed 1064 participants without hypertension at baseline (2000-2004) who attended at least one follow-up visit in 2005-2008 or 2009-2013. Four insulin resistance indices [fasting insulin, insulin-to-glucose ratio (IGR), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI)] and MetS (excluding hypertension in the definition) were assessed at baseline. Robust Poisson regression was used to generate risk ratios (RRs) and 95% confidence intervals (CI) for BP progression and incident hypertension. Over a median of 7 years, 69.6% progressed to a higher BP category and 62.7% developed hypertension. After multivariable adjustment, participants in the highest quartile of HOMA-IR had higher risks of BP progression [RR 1.25 (95% CI 1.09-1.43), Ptrend = 0.004] and hypertension [RR 1.35 (95% CI 1.16-1.58), Ptrend < 0.001] compared with those in the lowest quartile. A similar positive association of insulin resistance with BP outcomes was noted with insulin resistance assessed using IGR, fasting insulin, and QUICKI. MetS was associated with increased risks of BP progression [RR 1.15 (95% CI 1.02-1.30), P = 0.02] and incident hypertension [RR 1.23 [95% CI 1.08-1.41], P = 0.002]. These associations were present across baseline BP categories. Our findings support the notion that higher insulin resistance levels are associated with greater risks of BP progression and incident hypertension among Blacks.

Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study.

Hypertension has been suggested as a stronger risk factor for acute coronary syndromes (ACS) in women than men. Whether this also applies to stage 1 hypertension [blood pressure (BP) 130-139/80-89 mmHg] is not known. We tested associations of stage 1 hypertension with ACS in 12329 participants in the Hordaland Health Study (mean baseline age 41 years, 52% women). Participants were grouped by baseline BP category: Normotension (BP < 130/80 mmHg), stage 1 and stage 2 hypertension (BP ≥140/90 mmHg). ACS was defined as hospitalization or death due to myocardial infarction or unstable angina pectoris during 16 years of follow-up. At baseline, a lower proportion of women than men had stage 1 and 2 hypertension, respectively (25 vs. 35% and 14 vs. 31%, P < 0.001). During follow-up, 1.4% of women and 5.7% of men experienced incident ACS (P < 0.001). Adjusted for diabetes, smoking, body mass index, cholesterol, and physical activity, stage 1 hypertension was associated with higher risk of ACS in women [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.32-3.60], while the association was non-significant in men (HR 1.30, 95% CI 0.98-1.71). After additional adjustment for systolic and diastolic BP, respectively, stage 1 diastolic hypertension was associated with ACS in women (HR 2.79 [95% CI 1.62-4.82]), but not in men (HR 1.24 [95% CI 0.95-1.62]), while stage 1 systolic hypertension was not associated with ACS in either sex. Among subjects in their early 40s, stage 1 hypertension was a stronger risk factor for ACS during midlife in women than in men.

Abstract P169: Change In Blood Pressure Level And Its Association With Cardiovascular Events In The Healthy Elderly: Findings From The Aspirin In Reducing Events In The Elderly Trial

Blood pressure (BP) increases with age and is a major risk factor for cardiovascular disease (CVD). We examined change in BP level over a median of 4.7 years in ASPirin in Reducing Events in the Elderly trial participants, and its association with CVD events. Participants with baseline and at least one in-trial BP measurement were included. Since CVD event can affect BP (before and after), participants having a non-fatal CVD event in between in-trial BP records were excluded. Participants were classified according to baseline BP level, irrespective of antihypertensive use, into three groups (A) normal (SBP&lt;130 &amp; DBP&lt;80 mmHg), (B) elevated (SBP 130-139 and/or DBP 80-89) and (C) high (BP≥140/90). Thereafter, based on the average of their in-trial BP level, participants were again classified into three BP categories (i.e. normal /elevated /high). Cox proportional hazards regression was used to examine the association of CVD events with change in BP group in relation to their baseline. 17543 ASPREE participants were included in the analysis. At baseline, 26% had normal, 25% had elevated and 49% had high BP. Participants’ BP status during the trial period and its association with CVD events in relation to baseline BP category are summarized in the Figure. Among those with high BP at baseline, 60% remained with high BP, 28% moved down to elevated BP, and 11% moved to normal BP. Reduced CVD risk was observed among participants who reduced BP to elevated BP category from high BP during the trial period. However, no difference was observed in risk reduction among those achieving normal BP levels from baseline high BP. An increase in BP from normal category demonstrates a two times increase in CVD risk.

The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials.

It is unknown if the cardioprotective and renal effects of glucagon‐like peptide‐1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analysed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (P = .06 for MACE; P = .14 for nephropathy) or semaglutide (P = .40 for MACE; P = .27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP.

The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials

The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials

THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS LIRAGLUTIDE AND SEMAGLUTIDE IMPROVE CARDIOVASCULAR AND RENAL OUTCOMES ACROSS BASELINE BLOOD PRESSURE CATEGORIES: ANALYSIS OF LEADER AND SUSTAIN 6

High blood pressure (BP) is prevalent in patients with type 2 diabetes (T2D). This post hoc analysis evaluated major adverse cardiovascular (CV) events (MACE) and renal events in patients from LEADER and SUSTAIN 6 (CV outcome trials) with T2D and high CV risk who received liraglutide or semaglutide (vs placebo) according to BP categories: normal ( < 120/80 mmHg), elevated (systolic 120-129 mmHg and diastolic < 80 mmHg), stage 1 hypertension (systolic 130-139 mmHg or diastolic 80-89 mmHg), and stage 2 hypertension (systolic 140 mmHg or diastolic 90 mmHg). LEADER and SUSTAIN 6 were global randomized CV outcome trials of liraglutide and semaglutide, vs placebo, in 9340 and 3297 patients, respectively, with T2D and high CV risk. Primary outcome was MACE (CV death, non-fatal myocardial infarction, or non-fatal stroke), with secondary outcomes including nephropathy. We evaluated the cardiorenal effect of liraglutide and semaglutide on the primary and secondary renal endpoints by baseline BP categories using Cox proportional hazards, with treatment and risk group as factors, adjusted for baseline characteristics related to cardiorenal risk. In LEADER, 15%, 14%, 30%, and 41% of patients had normal BP, elevated BP, stage 1 or stage 2 hypertension, respectively; proportions for SUSTAIN 6 were 13%, 13%, 31%, and 43%, respectively. Within each BP category, baseline demographics were generally well balanced across trial groups. The effects of liraglutide and semaglutide on MACE and secondary nephropathy endpoints across BP categories are shown in the Figure. Liraglutide and semaglutide demonstrated consistent improvements in CV and renal outcomes across most baseline BP categories.

Blood Pressure and Memory: Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies.

Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory. We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates. Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory. By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives.

Effects of Blood Pressure Lowering on Clinical Outcomes According to Baseline Blood Pressure and Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus.

The optimal blood pressure (BP) goal in patients with diabetes mellitus remains controversial. We examined whether benefits and risks of intensified antihypertensive therapy in diabetes mellitus are influenced by either baseline BP or cardiovascular disease (CVD) risk. We studied 10 948 people with diabetes mellitus, at moderate-to-high risk, in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation). Cox models were used to determine whether baseline BP category or CVD risk modified the outcomes of combination perindopril-indapamide treatment, compared with placebo. During 4.3 years of follow-up, treatment with perindopril-indapamide versus placebo reduced mortality and major vascular (macrovascular or microvascular) events. There was no evidence of differences in these effects, regardless of baseline systolic BP (evaluated down to <120 mm Hg; P for heterogeneity, 0.85), diastolic BP (evaluated down to <70 mm Hg; P=0.49), or whether 10-year CVD risk was ≥20% or <20% ( P=0.08). The effects of randomized treatment on discontinuation of treatment because of cough or hypotension/dizziness were also statistically consistent across subgroups defined by baseline BP and CVD risk (all P ≥0.08). Adults with diabetes mellitus appear to benefit from more intensive BP treatment even at levels of BP and CVD risk that some guidelines do not currently recommend for intervention. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00751972.

Regression to the mean of repeated ambulatory blood pressure monitoring in five studies.

To estimate the size of regression to the mean with ambulatory blood pressure (ABP) measurement. Participants from five studies who had repeated blood pressure (BP) measurements using office and ambulatory devices were included. Regression to the mean was calculated following participants being grouped by baseline BP categories. Regression dilution ratio was calculated for groups defined by each baseline BP variable. High baseline ABP readings were substantially lower on long-term follow-up, and low baseline readings tended to be higher. Regression to the mean was observed for all ABP parameters; for systolic and diastolic measures; and for intervention and control groups. For example, among those with baseline 24-h SBP of at least 150 mmHg, mean baseline and follow-up BP was 156 and 141 mmHg, respectively; whereas those with baseline 24-h SBP of less than 120 mmHg, mean baseline and follow-up BP was 113 and 119 mmHg, respectively. Regression to the mean was the greatest for night-time ABP. Regression dilution ratios calculated from control groups were 0.52, 0.53, 0.38 and 0.60 for 24-h, daytime, night-time and office SBP, respectively. Similar results were seen for diastolic measures. ABP is subject to considerable regression to the mean, which has implications for diagnosis and practise; for example, after initiating treatment for hypertension some of the fall in ABP will be because of regression to the mean. Furthermore, associations of ABP with cardiovascular disease will be substantially underestimated if analyses are not adjusted for regression to the mean, especially for night-time ABP. Replication studies are needed to confirm these findings.