Impact of Model Choice When Studying the Relationship Between Blood Pressure Variability and Risk of Stroke Recurrence

Long-term blood pressure variability (BPV), an increasingly recognized vascular risk factor, is challenging to analyze. The objective was to assess the impact of BPV modeling on its estimated effect on the risk of stroke. We used data from a secondary stroke prevention trial, PROGRESS (Perindopril Protection Against Stroke Study), which included 6105 subjects. The median number of blood pressure (BP) measurements was 12 per patient and 727 patients experienced a first stroke recurrence over a mean follow-up of 4.3 years. Hazard ratios (HRs) of BPV were estimated from 6 proportional hazards models using different BPV modeling for comparison purposes. The 3 commonly used methods first derived SD of BP measures observed over a given period of follow-up and then used it as a fixed covariate in a Cox model. The 3 more advanced modeling accounted for changes in BP or BPV over time in a single-stage analysis. While the 3 commonly used methods produced contradictory results (for a 5 mmHg increase in BPV, HR=0.75 [95% CI, 0.68–0.82], HR=0.99 [0.91–1.08], HR=1.19 [1.10–1.30]), the 3 more advanced modeling resulted in a similar moderate positive association (HR=1.08 [95% CI, 0.99–1.17]), whether adjusted for BP at randomization or mean BP over the follow-up. The method used to assess BPV strongly affects its estimated effect on the risk of stroke, and should be chosen with caution. Further methodological developments are needed to account for the dynamics of both BP and BPV over time, to clarify the specific role of BPV.

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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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Impact of anxiety and depression on progression to glaucoma among glaucoma suspects

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316617 ◽

2020 ◽

pp. bjophthalmol-2020-316617

Author(s):

Samuel Berchuck ◽

Alessandro Jammal ◽

Sayan Mukherjee ◽

Tamara Somers ◽

Felipe A Medeiros

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Anxiety And Depression ◽

Pressure Measurements ◽

Health Records ◽

Cox Proportional Hazards Models ◽

History Of ◽

The Impact ◽

Over Time

AimsTo assess the impact of anxiety and depression in the risk of converting to glaucoma in a cohort of glaucoma suspects followed over time.MethodsThe study included a retrospective cohort of subjects with diagnosis of glaucoma suspect at baseline, extracted from the Duke Glaucoma Registry. The presence of anxiety and depression was defined based on electronic health records billing codes, medical history and problem list. Univariable and multivariable Cox proportional hazards models were used to obtain HRs for the risk of converting to glaucoma over time. Multivariable models were adjusted for age, gender, race, intraocular pressure measurements over time and disease severity at baseline.ResultsA total of 3259 glaucoma suspects followed for an average of 3.60 (2.05) years were included in our cohort, of which 911 (28%) were diagnosed with glaucoma during follow-up. Prevalence of anxiety and depression were 32% and 33%, respectively. Diagnoses of anxiety, or concomitant anxiety and depression were significantly associated with risk of converting to glaucoma over time, with adjusted HRs (95% CI) of 1.16 (1.01, 1.33) and 1.27 (1.07, 1.50), respectively.ConclusionA history of anxiety or both anxiety and depression in glaucoma suspects was associated with developing glaucoma during follow-up.

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Analysis of factors influencing outcome in patients with in transit malignant melanoma (MM) undergoing isolated limb perfusion (ILP) using standardized operative parameters with melphalan and biological agents

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.8006 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 8006-8006

Author(s):

P. A. Soriano ◽

S. K. Libutti ◽

J. F. Pingpank ◽

T. Beresenev ◽

S. M. Steinberg ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Model ◽

Univariate Analysis ◽

Female Gender ◽

Tumor Stage ◽

Cox Proportional Hazards ◽

Stage Iiia ◽

In Transit ◽

The Impact

8006 Background: In transit disease afflicts about 10% of MM patients and no single systemic or regional treatment has been widely accepted as most effective or appropriate. Previously, the impact of ILP on the natural history of MM patients has been difficult to gauge. We report long-term outcomes in MM patients undergoing hyperthermic ILP in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular follow-up. Methods: Between 5/1992 to 2/2005, 90 patients (median age: 57 y [range: 24–84]; F: 49, M: 41) with Stage IIIA or IIIAB MM underwent a 90 min hyperthermic (mean calf T: 39.3° C) ILP (melphalan: 10–13 mg/L limb volume, TNF: 3–6 mg [n=44], or IFN: 200 μg [n=38]) using uniform operative technique including intra-operative leak monitoring. There was 1 operative mortality (1/91, 1.1%). Patients were prospectively followed for response, in-field progression free (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by the Kaplan-Meier method with log rank tests, as well as by Cox proportional hazards models. Results: There were 61 complete responses (68%) and 23 partial responses (26%). At a median follow-up of 47 months, median in-field PFS was 12.4 months, and median OS was 47.4 months; 5 and 10-year actuarial OS were 43 and 34%, respectively. Female gender and low tumor burden (< 20 tumors) were associated with prolonged in-field PFS (M:F hazard ratio (HR): 2.07, CI:1.27–3.38; 21+ vs. ≤20 tumors HR: 2.29, CI: 1.21- 4.34; p<0.011 for both) in a Cox model, whereas TNF, IFN, perfusion pressure, and tumor stage were not. Female gender was associated with improved OS (p=0.027, M:F HR=1.82, 95% CI 1.07–3.09) and Stage IIIA marginally so, in univariate analysis, (p=0.065). Conclusions: ILP for MM patients is associated with noteworthy in-field PFS and prolonged OS. Neither use of TNF nor tumor stage were significantly associated with in-field PFS in Cox models, while female gender was associated with better outcomes. In appropriately selected patients using standardized technique, ILP has clinical benefit in this setting. No significant financial relationships to disclose.

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Abstract P440: Inpatient Blood Pressure Variability is Associated With Mortality and Poor Functional Outcome in Patients With Intracerebral Hemorrhage

Stroke ◽

10.1161/str.52.suppl_1.p440 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Evangelos Pavlos Myserlis ◽

Jessica R Abramson ◽

Haitham Alabsi ◽

Christopher D Anderson ◽

Alessandro Biffi ◽

...

Keyword(s):

Blood Pressure ◽

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Poor Functional Outcome ◽

Logistic Regression Models ◽

Established Risk Factor ◽

The Impact

Introduction: Although elevated blood pressure (BP) is an established risk factor for intracerebral hemorrhage (ICH), the impact of acute BP fluctuations on ICH outcomes remains unclear. In this study, we sought to investigate the effect of acute BP variability (BPV) on mortality and functional outcome in ICH survivors. Methods: Subjects were consecutive ICH patients ≥ 18 years with available inpatient BP data, who survived hospitalization. Four measures of systolic BPV were calculated: standard deviation (SD), coefficient of variation (CoV), average real variability (ARV), and successive variation (SV). Our outcomes were (1) death and (2) poor functional outcome, defined as a modified Rankin Score (mRS) of 3-6 in a period between 60-120 days after discharge. We assessed the effect of hyperacute (ICH event-72 hours) and acute/subacute (72 hours-discharge) BPV on outcomes. We constructed Cox proportional hazards and logistic regression models to investigate the associations of BPV (per 10 mmHg increase) with mortality and poor functional outcome, respectively, after adjustment for potential confounders. Results: We included 345 patients, 120 of whom had available mRS data. 151 (43.8%) patients were female and 280 (81.2%) were white; mean age was 71 (±13) years. SBP ARV and SBP SV were the strongest predictors of mortality (HR 2.53-2.91 per 10 mmHg increase), while SBP SD, CoV, and SV were the strongest predictors of poor functional outcome (OR 2.89-5.14 per 10 mmHg increase) (Table) . These associations remained significant when analyzing both hyperacute as well as acute/subacute BPV. Compared to hyperacute BPV, acute/subacute BPV was more strongly associated with both mortality and poor functional outcome. Conclusion: Inpatient blood pressure variability is an important determinant of mortality and poor functional outcome in ICH survivors. Further studies are needed to investigate the role of addressing BPV as a potential target for intervention.

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Abstract P160: Long-term Blood Pressure Variability And Cognitive Decline And Dementia Among Community-dwelling Elderly

Hypertension ◽

10.1161/hyp.76.suppl_1.p160 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Michael E Ernst ◽

Joanne Ryan ◽

Enayet K Chowdhury ◽

Anne M Murray ◽

Robyn L Woods ◽

...

Keyword(s):

Blood Pressure ◽

Cognitive Decline ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Immortal Time Bias ◽

Incident Dementia ◽

The Impact

Greater blood pressure variability (BPV) in midlife increases the risk of dementia, but the impact of BPV in cognitively intact older adults is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) study, a randomized primary prevention trial of daily low-dose aspirin in community-dwelling adults in Australia and the US aged 70 and older (65 if US minority), who were free of dementia or evidence of cognitive impairment at enrollment. The mean of three BPs using an automated cuff was recorded at baseline and annually; participants also underwent baseline and biennial standardized assessments of global cognition, delayed episodic memory, verbal fluency, processing speed and attention. Cognitive decline was pre-specified as a >1.5 standard deviation (SD) decline in score from baseline on any of the cognitive tests, while incident dementia was a pre-specified secondary endpoint of ASPREE which was adjudicated using DSM-IV criteria. BPV was estimated using within-individual SD of mean systolic BP across baseline and the first two annual visits, and participants with cognitive decline or incident dementia during this period were excluded from the analysis to avoid immortal time bias. After adjustment for key covariates, Cox proportional hazards regression revealed increased risks for dementia and cognitive decline during follow-up for individuals in the highest SD tertile of BPV (Table). Our findings suggest that high BPV in older ages should be considered a potential therapeutic target to preserve cognitive function.

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FC08-04 - Trajectories of depressive episodes and hypertension over 24 years: the whitehall II prospective cohort study

European Psychiatry ◽

10.1016/s0924-9338(11)73559-3 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1855-1855

Author(s):

H. Nabi ◽

J.-F. Chanstang ◽

T. Lefèvre ◽

A. Dugravot ◽

M. Melchior ◽

...

Keyword(s):

Blood Pressure ◽

General Health Questionnaire ◽

Antidepressant Medication ◽

Estimating Equation ◽

Depression Subscale ◽

Medical Examinations ◽

Depressive Episodes ◽

The Impact ◽

Over Time

IntroductionProspective data on depressive symptoms and blood pressure (BP) are scarce, and the impact of age on this association is poorly understood.ObjectivesThe present study examines longitudinal trajectories of depressive episodes and the probability of hypertension associated with these trajectories over time.MethodsParticipants were 6,889 men and 3,413 women London based civil servants followed for 24 years between 1985 and 2009. The age of participants over the follow-up ranged from 35 to 80 years. Depressive episode (defined as scoring 4 or more on the General Health Questionnaire-Depression subscale or using prescribed antidepressant medication) and hypertension (systolic/diastolic blood pressure ≥ 140/90 mm Hg or use of antihypertensive medication) were assessed concurrently at five medical examinations.ResultsIn longitudinal logistic regression analyses based on Generalized-Estimating-Equation using age as the time scale, participants with depression trajectory characterised by increasing depressive episodes overtime had a greater increase in the likelihood for hypertension with advancing age; an adjusted-excess increase of 7% (95% CI 3-12, p < 0.001) for each five-year increase in age compared to those with a low/stable depression trajectory. In a model adjusted for relevant confounders, a higher risk of hypertension in the first group of participants did not become evident before age 55. A similar pattern of association was observed in men and women although the association was stronger in men.ConclusionsThis study suggests that the risk of hypertension increases with repeated experience of depressive episodes over time and materializes in later adulthood.

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Blood pressure variability is related to faster cognitive decline in ischemic stroke patients: PICASSO subanalysis

Scientific Reports ◽

10.1038/s41598-021-83945-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yerim Kim ◽

Jae-Sung Lim ◽

Mi Sun Oh ◽

Kyung-Ho Yu ◽

Ji Sung Lee ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Cognitive Function ◽

Cognitive Decline ◽

Repeated Measures ◽

Blood Pressure Variability ◽

Cognitive Test ◽

Multiple Variables ◽

Over Time

AbstractBlood pressure variability (BPV) is associated with higher cardiovascular morbidity risks; however, its association with cognitive decline remains unclear. We investigated whether higher BPV is associated with faster declines in cognitive function in ischemic stroke (IS) patients. Cognitive function was evaluated between April 2010 and August 2015 using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment in 1,240 Korean PICASSO participants. Patients for whom baseline and follow-up cognitive test results and at least five valid BP readings were available were included. A restricted maximum likelihood–based Mixed Model for Repeated Measures was used to compare changes in cognitive function over time. Among a total of 746 participants (64.6 ± 10.8 years; 35.9% female). Baseline mean-MMSE score was 24.9 ± 4.7. The median number of BP readings was 11. During a mean follow-up of 2.6 years, mean baseline and last follow-up MMSE scores were 25.4 ± 4.8 vs. 27.8 ± 4.4 (the lowest BPV group) and 23.9 ± 5.2 vs. 23.2 ± 5.9 (the highest BPV group). After adjusting for multiple variables, higher BPV was independently associated with faster cognitive decline over time. However, no significant intergroup difference in cognitive changes associated with mean systolic BP was observed. Further research is needed to elucidate how BPV might affect cognitive function.

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0650 Impact of Upper Airway Stimulation Therapy on 24 Hour Ambulatory Blood Pressure Monitoring

SLEEP ◽

10.1093/sleep/zsaa056.646 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A248-A248

Author(s):

A De ◽

J Bena ◽

L Wang ◽

J Aylor ◽

R Bhambra ◽

...

Keyword(s):

Blood Pressure ◽

Ambulatory Blood Pressure ◽

Cleveland Clinic ◽

Upper Airway ◽

Repeated Measure ◽

Upper Airway Stimulation ◽

Obstructive Sleep ◽

The Impact ◽

Over Time

Abstract Introduction Upper airway stimulation (UAS) is recommended treatment for moderate to severe obstructive sleep apnea (OSA) in select patients. Existing data have not focused on gold standard 24 hour ambulatory blood pressure monitor (ABPM) to elucidate the impact of UAS. We hypothesize that UAS reduces ABPM indices characterized using objective sleep-wake from actigraphy data over 12-month follow-up period. Methods A prospective sub-study of the Inspire ® post-approval study at the Cleveland Clinic was designed to examine the effect of UAS on 24-hour ABPM measures post-implantation by examining blood pressure (BP) at baseline, and-2, 6, and 12 months follow-up. Actigraphy data was contemporaneously collected. Paired T-tests were used to evaluate BP changes over time. Repeated measure correlations measured within-patient associations between BP and actigraphy measures. Results Average age and BMI were 62.4 +/-12.9) years and 30.1 +/-3.3 kg/m2, 73.3% males and all Caucasian. The mean baseline systolic, diastolic and mean arterial pressure (MAP) were 119.7+/-12.9 mmHg, 74.3+/-7.4 mmHg and 89.3+/- 8.1 mmHg. There were no changes to number, type or dosage of BP medications. At 12 months, there were non-significant overall mean reduction in systolic [-0.55mmHg, p=0.75], diastolic [-0.73mmHg, p=0.63], and MAP [-0.55mmHg, p=0.71]. Mean sleeping systolic, diastolic and MAP changed by -4.36(p=0.34), -1.45 (p=0.57), -2.18 (p=0.50), respectively. Positive correlations above 0.25 (p<0.10) were observed between all dipping percentage measures and total sleep time. Negative correlations were seen between overall systolic, diastolic and MAP with sleep latency (-0.22, p=0.19, -0.35, p=0.031 and -0.29, p=0.075 respectively). No significant changes in BMI was observed, but average hours of usage decreased over time. Conclusion Although consistent reduction of BP measures were observed post-UAS implantation, findings were not statistically significant. It is unclear whether this is due to insufficient sample size or true lack of effect. Larger-scale clinical and mechanistic studies are needed to enhance understanding of UAS-related vascular influences. Support Funded: Inspire Medical Systems

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Preliminary Experiment on the Effect of 18% Substitute Salt on Home Blood Pressure Variability in Hypertensives

International Journal of Hypertension ◽

10.1155/2021/9993328 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Jing Li ◽

Lisha Mu ◽

Huakun Rao ◽

Yangfeng Wu ◽

Hao Wang ◽

...

Keyword(s):

Blood Pressure ◽

Clinical Trial ◽

Adverse Events ◽

Phase I ◽

Blood Pressure Variability ◽

Sodium Intake ◽

Home Blood Pressure ◽

Intervention Period ◽

Over Time

At present, the effect of substitute salt in reducing sodium intake and blood pressure is relatively clear. The present study is a phase I clinical trial involving 43 hypertensives in which the effect of 18% sodium substitute salt on the home blood pressure variability (BPV) was observed for 8 weeks with weekly follow-up. Finally, 4 patients were lost, and 39 patients completed the intervention and were included in the analysis. Daily home blood pressure and weekly adverse events were collected. The systolic blood pressure (SBP) in the morning (−10.0 mmHg, 95% CI: −16.5 to −3.5, P = 0.003), SBP at night (−10.2 mmHg, 95% CI: −16.1 to −4.3, P = 0.001), and diastolic blood pressure (DBP) at night (−4.0 mmHg, 95% CI: −7.1 to −0.8, P = 0.014) decreased significantly. Also, there was no statistically significant change in morning (F = 1.137, P = 0.352) and night diastolic (F = 0.344, P = 0.481) BPV and morning systolic BPV (F = 0.663, P = 0.930) over time during the intervention period, except for that night systolic BPV had a downward trend (F = 2.778, P = 0.016) and had decreased 2.04 mmHg (95% CI: 0.84 to 3.23, P = 0.001) after intervention. The use of 18% of the substitute salt did not increase BPV during the intervention and even may decrease it, which indicates its control effects on blood pressure. This study is the first one to observe the effect of 18% sodium substitute salt on the home blood pressure variability, providing a basis for further experiments.

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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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