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

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).

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Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽

10.1161/str.51.suppl_1.wp218 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Adam H de Havenon ◽

Ka-Ho Wong ◽

Eva Mistry ◽

Mohammad Anadani ◽

Shadi Yaghi ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Adjusted Risk ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

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Hypertension Subtype Defined by the 2017 ACC/AHA Blood Pressure Guidelines and Risk of Cardiovascular Disease: A Large Prospective Cohort Study

10.1101/2020.04.19.20071530 ◽

2020 ◽

Author(s):

Fu-Rong Li ◽

Xian-Bo Wu

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Cohort Study ◽

Proportional Hazards ◽

Blood Pressure Level ◽

Cox Proportional Hazards ◽

Cvd Risk ◽

Increased Risk ◽

Diastolic Hypertension ◽

The Uk

AbstractBackgroundThe 2017 American College of Cardiology/American Heart Association (ACC/ AHA) blood pressure (BP) guideline lowered the hypertension threshold from a systolic blood pressure/diastolic blood pressure level of ≥140/90 mm Hg to ≥130/80 mm Hg. The significance of hypertension subtype under the new definition has not been fully explored.ObjectiveTo examine the associations of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) by the 2017 ACC/AHA guidelines with risk of cardiovascular disease (CVD) among the UK population.DesignProspective population-based cohort studySettingUK BiobankParticipants and MethodsWe included 470,625 participants who were free of CVD at baseline and had available data on BP measures. Of these, 13,157 CVD events were recorded (median follow-up 8.1 years), including 6,865 nonfatal myocardial infarctions (MI), 3,415 nonfatal ischemic strokes (ISs), 1,118 nonfatal hemorrhagic strokes (HSs), and 2,971 CVD deaths. Participants were categorized into 5 groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension (SDH). The associations of each type of hypertension for the risk of CVD were estimated using a Cox proportional hazards regression model with adjustment for potential confounding factors.ResultsAccording to the hypertension threshold of ≥130/80 mm Hg by ACC/AHA guideline, both ISH (HR 1.35, 95% CI 1.24-1.46) and IDH (HR 1.22, 95% CI 1.11-1.36) were significantly associated with higher risk of overall CVD risk, compared with those with normal BP. ISH was predictive of most CVD risk, except for IS; while the excess CVD risk associated with IDH appeared to be driven mainly by MI. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with the associations stronger in women and younger adults (age < 60 years) and null in men and older adults (age ≥60 years).ConclusionsISH and IDH by the ACC/AHA BP guideline were both associated with increased risk of CVD, highlighting the justification to lower the criteria of hypertension definition in the UK. Further research is needed to identify participants with IDH who are at especially greater risk for developing CVD.

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Association between Stage 1 Hypertension Defined by the 2017 ACC/AHA Hypertension Guideline and Cardiovascular Risk: A Large Cohort Study from the UK

10.1101/2020.04.19.20071514 ◽

2020 ◽

Author(s):

Fu-Rong Li ◽

Xian-Bo Wu

Keyword(s):

Blood Pressure ◽

Cohort Study ◽

Cox Proportional Hazards ◽

Uk Biobank ◽

Cvd Risk ◽

Increased Risk ◽

National Cohort ◽

The Uk ◽

Stage 1 ◽

The Impact

ABSTRACTImportanceThe 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension (HTN) guideline lowered the threshold for HTN from 140/90 mmHg to 130/80 mmHg for systolic/diastolic blood pressure (SBP/DBP), resulting in a newly defined stage 1 HTN with an SBP/DBP reading of 130–139/80–89 mmHg. Few studies have assessed the impact of the redefined HTN on cardiovascular outcomes among UK population.ObjectiveTo examine the effects of the revised ACC/AHA stage 1 HTN blood pressure parameters on the prevalence of HTN and related cardiovascular disease (CVD) risk in a large UK population.DesignAdult men and women from a national cohort study in the UK.SettingThe UK Biobank Study.ParticipantsA total of 470,625 adults (mean age 56 years) with available data on blood pressure (BP) and without history of CVDs at baseline.Main outcome measuresPrevalence of HTN and incident composite CVD outcomes.MethodsProspective CVD events were analysed for survival in relation to BP measures using Cox proportional hazards regression models, adjusting for potential confounders. The associations are described by hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsBy adopting the 2017 ACC/AHA HTN guideline, an additional 24.7% of the participants were classified as having ACC/AHA stage 1 HTN, which resulted in a prevalence of HTN of 75.1% at baseline. During a mean follow-up period of 8.1 years, ACC/AHA stage 1 HTN (130–139/80–89 mmHg) was associated with a significantly increased risk of CVD (HR 1.20; 95% CI 1.10–1.30) compared to the risk associated with a normal BP (<120/80 mmHg). The excess risk of CVD associated with ACC/AHA stage 1 HTN was mainly driven by myocardial infarction (HR 1.19; 95% CI 1.05-1.36) and haemorrhagic stroke (HR 1.40; 95% CI 1.08-1.81), rather than ischaemic stroke (HR 1.02; 95% CI 0.87-1.19) and CVD death (HR 1.07; 95% CI 0.90-1.26).ConclusionsThe adoption of the 2017 ACC/AHA guideline would lead to a dramatic increase in the prevalence of HTN in the UK Biobank cohort study. Evidence from the present national cohort study may support lowering the threshold for HTN from 140/90 mmHg to 130/80 mmHg in the UK.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02164-9 ◽

2021 ◽

Author(s):

Cilie C. van ’t Klooster ◽

◽

Yolanda van der Graaf ◽

Hendrik M. Nathoe ◽

Michiel L. Bots ◽

...

Keyword(s):

Cardiovascular Disease ◽

Heart Valve ◽

Cardiovascular Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Added Value ◽

Cvd Risk ◽

Major Cardiovascular Events ◽

Cox Proportional Hazards Models ◽

Cardiovascular Interventions

AbstractThe purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

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Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

The Journals of Gerontology Series A ◽

10.1093/gerona/glab272 ◽

2021 ◽

Author(s):

Ma Cherrysse Ulsa ◽

Xi Zheng ◽

Peng Li ◽

Arlen Gaba ◽

Patricia M Wong ◽

...

Keyword(s):

Sleep Disturbances ◽

Proportional Hazards ◽

Time Lag ◽

Cox Proportional Hazards ◽

Poor Sleep ◽

Cardiovascular Risks ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

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Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Frontiers in Medicine ◽

10.3389/fmed.2021.639970 ◽

2021 ◽

Vol 8 ◽

Author(s):

Augusto Di Castelnuovo ◽

Simona Costanzo ◽

Andrea Antinori ◽

Nausicaa Berselli ◽

Lorenzo Blandi ◽

...

Keyword(s):

Observational Study ◽

Propensity Scores ◽

Proportional Hazards ◽

Real Life ◽

Cox Proportional Hazards ◽

Event Analysis ◽

Multicenter Observational Study ◽

Protein Levels ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

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Association of Blood Pressure Classification Using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline with Risk of Heart Failure and Atrial Fibrillation

Circulation ◽

10.1161/circulationaha.120.052624 ◽

2021 ◽

Author(s):

Hidehiro Kaneko ◽

Yuichiro Yano ◽

Hidetaka Itoh ◽

Kojiro Morita ◽

Hiroyuki Kiriyama ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Blood Pressure ◽

American Heart Association ◽

American Heart ◽

Heart Association ◽

Cox Proportional Hazards ◽

Health Claims ◽

Claims Database ◽

Stage 1

Background: Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) blood pressure (BP) guidelines is associated with incident HF and AF. Methods: Analyses were conducted using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2,196,437; mean age, 44.0±10.9 years; 584% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP [SBP]<120 mm Hg and diastolic BP [DBP]<80 mm Hg; n=1,155,885); elevated BP (SBP 120-129 mm Hg and DBP<80 mm Hg; n=337,390); stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg; n=459,820); or stage 2 hypertension (SBP≥140 mm Hg or DBP≥90 mm Hg; n=243,342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions (PAFs) to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP. Results: Over a mean follow-up of 1,112±854 days, 28,056 incident HF and 7,774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% Confidence interval [CI], 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension vs normal BP. PAFs for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The PAFs for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively. Conclusions: Both stage 1 and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The ACC/AHA BP classification system may help identify adults at higher risk for HF and AF events.

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Abstract 16476: Visit-to-Visit Blood Pressure Variability is Associated With Incident Frailty: The Multidomain Alzheimer Preventive Trial (MAPT)

Circulation ◽

10.1161/circ.142.suppl_3.16476 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Laure Rouch ◽

Philipe de Souto Barreto ◽

Olivier Hanon ◽

Jacques Amar ◽

Yves Rolland ◽

...

Keyword(s):

Blood Pressure ◽

Standard Deviation ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Antihypertensive Drugs ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Clinical Predictors ◽

Increased Risk ◽

Preventive Trial

Introduction: Visit-to-visit blood pressure variability (BPV) has been associated with greater cardiovascular and all-cause mortality, cognitive impairment, and incident dementia. It may also represent a decline in homeostatic mechanisms in blood pressure (BP) regulation associated with frailty, one of the most problematic expression of population aging. Hypothesis: We hypothesized that visit-to-visit systolic (SBPV), diastolic (DBPV), mean arterial (MAPV) and pulse pressure (PPV) variability are associated with greater incident frailty. Methods: We included 1,394 non-frail community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations over a 5-year follow-up period. SBPV, DBPV, MAPV and PPV were evaluated using standard deviation, coefficient of variation (CV), average real variability, successive variation, variation independent of mean and residual standard deviation. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Results: Higher SBPV was significantly associated with increased risk of incident frailty (1-sd increase of CV: HR = 1.18, 95% CI [1.02-1.37], p=0.03) after adjustment for demographics, body mass index, stroke, ischemic heart disease, diabetes, heart failure, antihypertensive drugs, systolic BP, MAPT intervention groups and baseline pre-frail status. Similar results were observed with all indicators of variability. DBPV and MAPV were not associated with incident frailty (p=0.6 and p=0.2, respectively). Interestingly, higher PPV was also associated with a greater risk of developing frailty over time (1-sd increase of CV: HR = 1.17, 95% CI [1.01-1.35], p=0.03). Conclusion: Independently of BP, higher SBPV and PPV are major clinical predictors of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that controlling BP instability could be a promising interventional target in preventing frailty.

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