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

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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Visit-to-visit blood pressure variability and incident frailty in older adults

The Journals of Gerontology Series A ◽

10.1093/gerona/glab112 ◽

2021 ◽

Author(s):

Laure Rouch ◽

Philipe De Souto Barreto ◽

Olivier Hanon ◽

Jean-Sébastien Vidal ◽

Jacques Amar ◽

...

Keyword(s):

Blood Pressure ◽

Standard Deviation ◽

Proportional Hazards ◽

Antihypertensive Drugs ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Frailty Status ◽

Physiological Dysregulation ◽

Cox Proportional Hazards Models ◽

Deviation Coefficient

Abstract To determine whether visit-to-visit blood pressure (BP) variability (BPV) is associated with incident frailty. We included 1,394 non-frail community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations, including BP and frailty, over a 5-year follow-up period. Systolic BPV (SBPV), diastolic BPV (DBPV), mean arterial pressure variability (MAPV) and pulse pressure variability (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. Higher SBPV was significantly associated with greater risk of frailty (1-sd increase of CV: HR = 1.18, 95% CI [1.02-1.36]) after adjustment for demographics, systolic BP, antihypertensive drugs, body mass index, diabetes, ischemic heart disease, congestive heart failure, stroke, atrial fibrillation, MAPT randomization group and frailty status. Similar results were observed with all indicators of variability. Higher PPV was associated with a greater risk of developing frailty over time (1-sd increase of CV: HR = 1.17, 95% CI [1.01-1.35]). DBPV and MAPV were not significantly associated with incident frailty. Higher SBPV and PPV were associated with greater risk of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that BP instability could be an early marker of frailty.

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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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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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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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The Joint Effects of Loneliness and Depression on Mortality: Does Gender Matter?

Innovation in Aging ◽

10.1093/geroni/igaa057.1034 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 323-323

Author(s):

Ted Kheng Siang Ng ◽

Abhijit Visaria ◽

Angelique W M Chan ◽

Kheng Siang Ted Ng

Keyword(s):

Los Angeles ◽

Mortality Risk ◽

Proportional Hazards ◽

Depression Scale ◽

Well Being ◽

Joint Effect ◽

Epidemiologic Studies ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Increased Risk

Abstract Loneliness and depression are both associated with an increased risk of all-cause mortality among older adults. However, the evidence on the joint effect of loneliness and depression is scarce. Furthermore, previous research has rarely examined the modifying effects of gender. We investigated these questions using the Panel on Health and Aging of Singaporean Elderly, a nationally-representative cohort study of community-dwelling older Singaporean adults aged 60 and above, conducted in 2009 with two follow-up waves in 2011 and 2015 (N=4536). We operationalized six groups based on three categories of loneliness measured using the 3-item University of California, Los Angeles (UCLA) loneliness scale: always lonely, sometimes lonely, and never lonely; Two categories of depressive symptom scores were measured using the 11-item Center for Epidemiologic Studies Depression Scale (CES-D) scale: depressed and not depressed. Cox proportional hazards models were employed to estimate the mortality risks for each group, with an extensive set of covariates. Due to significant differences in the prevalence of loneliness and depression in different genders, we conducted gender-stratified analyses. Compared to being not depressed and never lonely, women who were depressed and sometimes lonely and who were not depressed but always lonely had a higher mortality risk. Men who were not depressed but sometimes lonely had a higher mortality risk. We conclude that loneliness appears to be the predominant construct in conferring excess mortality risk. Health policies and interventions addressing the factors common and unique to each gender may improve psychological well-being at older ages, thereby extending the lifespan.

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Diet Inflammatory Index and Dementia Incidence: A Population-Based Study

Neurology ◽

10.1212/wnl.0000000000012973 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012973

Author(s):

Sokratis Charisis ◽

Eva Ntanasi ◽

Mary Yannakoulia ◽

Costas A Anastasiou ◽

Mary H Kosmidis ◽

...

Keyword(s):

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Dietary Interventions ◽

Clinical Criteria ◽

Inflammatory Index ◽

Incident Dementia ◽

Dementia Incidence ◽

Increased Risk

Background and objectives:Aging is characterized by a functional shift of the immune system towards a proinflammatory phenotype. This derangement has been associated with cognitive decline and has been implicated in the pathogenesis of dementia. Diet can modulate systemic inflammation; thus, it may be a valuable tool to counteract the associated risks for cognitive impairment and dementia. The present study aimed to explore the associations between the inflammatory potential of diet, assessed using an easily applicable, population-based, biomarker-validated diet inflammatory index (DII), and the risk for dementia in community-dwelling older adults.Methods:Individuals from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present cohort study. Participants were recruited through random population sampling, and were followed for a mean of 3.05 (SD=0.85) years. Dementia diagnosis was based on standard clinical criteria. Those with baseline dementia and/or missing cognitive follow-up data were excluded from the analyses. The inflammatory potential of diet was assessed through a DII score which considers literature-derived associations of 45 food parameters with levels of pro- and anti-inflammatory cytokines in the blood; higher values indicated a more pro-inflammatory diet. Consumption frequencies were derived from a detailed food frequency questionnaire, and were standardized to representative dietary intake normative data from 11 different countries. Analysis of dementia incidence as a function of baseline DII scores was performed by Cox proportional hazards models.Results:Analyses included 1059 individuals (mean age=73.1 years; 40.3% males; mean education=8.2 years), 62 of whom developed incident dementia. Each additional unit of DII was associated with a 21% increase in the risk for dementia incidence [HR=1.21 (1.03 – 1.42); p=0.023]. Compared to participants in the lowest DII tertile, participants in the highest one (maximal pro-inflammatory diet potential) were 3 [(1.2 – 7.3); p=0.014] times more likely to develop incident dementia. The test for trend was also significant, indicating a potential dose-response relationship (p=0.014).Conclusions:In the present study, higher DII scores (indicating greater pro-inflammatory diet potential) were associated with an increased risk for incident dementia. These findings might avail the development of primary dementia preventive strategies through tailored and precise dietary interventions.

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Abstract MP33: Association Between Neurologic Outcomes and Temporal Profile of Systolic Blood Pressure Variability After Endovascular Thrombectomy

Stroke ◽

10.1161/str.52.suppl_1.mp33 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Ayush Prasad ◽

Jessica Kobsa ◽

Sreeja Kodali ◽

Cindy Khanh Nguyen ◽

Darko Quispe Orozco ◽

...

Keyword(s):

Blood Pressure ◽

Standard Deviation ◽

Systolic Blood Pressure ◽

Functional Outcome ◽

Blood Pressure Variability ◽

Treatment Strategies ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Increased Risk ◽

Systolic Blood Pressure Variability

Introduction: Higher systolic blood pressure variability (BPV) after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and worse functional outcomes. However, the time-varying behavior of BPV after EVT and its effects on functional outcome have not been well characterized. Methods: We analyzed data from an international cohort of patients with acute large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Parameters of BPV were calculated in 12-hour epochs using five established methodologies: standard deviation (SD), coefficient of variation (CV), average real variability (ARV), successive variation (SV), and residual SD (rSD). Patients’ overall mean BPV was then used to assign patients into tertiles for regression analysis: low BPV, intermediate BPV, and high BPV. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days. Results: Of the 1,791 patients (age 69 ± 14, NIHSS 15 ± 6) included in our analysis, 1,085 (60.6%) had a poor 90-day outcome (mRS >3). Patients with poor outcome had significantly higher systolic BPV (p<0.05) measured as standard deviation (SBP SD) at each epoch (Figure 1B). Compared to patients with low BPV, those in the highest tertile group had significantly greater odds of a poor functional outcome after adjusting for age, sex, hypertension, NIHSS, ASPECT, tPA, time to reperfusion, and TICI score (OR 1.5; 95% CI 1.2-2; p=0.001). Patients in the highest tertile of BPV demonstrated time-dependent variability with the highest SBP SD during the first 24 hours after thrombectomy (Figure 1A). Conclusions: Higher BPV measured by SBP SD appears to be associated with poor 90-day outcome in EVT-treated stroke patients. Early treatment strategies targeting early high BPV warrant further prospective investigation.

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

Journal of Clinical Medicine ◽

10.3390/jcm8060820 ◽

2019 ◽

Vol 8 (6) ◽

pp. 820 ◽

Cited By ~ 4

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).

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Diabetic Retinopathy and Risk of Stroke

Stroke ◽

10.1161/strokeaha.120.030350 ◽

2020 ◽

Vol 51 (12) ◽

pp. 3733-3736

Author(s):

Ka-Ho Wong ◽

Katherine Hu ◽

Cecilia Peterson ◽

Nazanin Sheibani ◽

Georgios Tsivgoulis ◽

...

Keyword(s):

Blood Pressure ◽

Diabetic Retinopathy ◽

Primary Outcome ◽

Vision Loss ◽

Proportional Hazards ◽

Cox Regression ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Increased Risk

Background and Purpose: Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which causes damage to the retina and may lead to rapid vision loss. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with DR. We sought to explore the association between DR and subsequent stroke events. Methods: This is a secondary analysis of patients enrolled in the ACCORD Eye study (Action to Control Cardiovascular Risk in Diabetes). The primary outcome was stroke during follow-up. The exposure was presence of DR at study baseline. We fit adjusted Cox proportional hazards models to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms. Results: We included 2828 patients, in whom the primary outcome of stroke was met by 117 (4.1%) patients during a mean (SD) of 5.4 (1.8) years of follow-up. DR was present in 874 of 2828 (30.9%) patients at baseline and was more common in patients with than without incident stroke (41.0% versus 30.5%; P =0.016). In an adjusted Cox regression model, DR was independently associated with incident stroke (hazard ratio, 1.52 [95% CI, 1.05–2.20]; P =0.026). This association was not affected by randomization arm in the ACCORD glucose ( P =0.300), lipid ( P =0.660), or blood pressure interventions ( P =0.469). Conclusions: DR is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to DR has larger cerebrovascular implications. This association appears not to be mediated by serum glucose, lipid, and blood pressure interventions.

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Lower TSH and higher free thyroxine predict incidence of prostate but not breast, colorectal or lung cancer

Acta Endocrinologica ◽

10.1530/eje-17-0197 ◽

2017 ◽

Vol 177 (4) ◽

pp. 297-308 ◽

Cited By ~ 14

Author(s):

Yi X Chan ◽

Matthew W Knuiman ◽

Mark L Divitini ◽

Suzanne J Brown ◽

John Walsh ◽

...

Keyword(s):

Prostate Cancer ◽

Lung Cancer ◽

Skin Cancer ◽

Thyroid Hormones ◽

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Free Thyroxine ◽

Increased Risk

Context Thyroid hormones modulate proliferative, metabolic and angiogenic pathways. However few studies have examined associations of thyroid hormones with cancer risk. Objectives To explore associations of thyrotropin (TSH), free thyroxine (FT4) and anti-thyroperoxidase antibodies (TPOAb) with the incidence of all (non-skin) cancers and specific common cancers. Design and setting A prospective cohort study of a community-dwelling population aged 25–84 years in Western Australia. Main outcome measures Archived sera from 3649 participants in the 1994/1995 Busselton Health Survey were assayed for TSH, FT4 and TPOAb. Cancer outcomes until 30 June 2014 were ascertained using data linkage. Longitudinal analyses were performed using Cox proportional hazards regression. Results During 20-year follow-up, 600 participants were diagnosed with non-skin cancer, including 126, 100, 103 and 41 prostate, breast, colorectal and lung cancers respectively. Higher TSH was associated with a lower risk of prostate cancer after adjusting for potential confounders, with a 30% lower risk for every 1 mIU/L increase in TSH (adjusted hazard ratio (HR): 0.70, 95% confidence interval (CI): 0.55–0.90, P = 0.005). Similarly, higher FT4 was associated with an increased risk of prostate cancer (adjusted HR: 1.11 per 1 pmol/L increase, 95% CI: 1.03–1.19, P = 0.009). There were no associations of TSH, FT4 or TPOAb with all non-skin cancer events combined, or with breast, colorectal or lung cancer. Conclusion In a community-dwelling population, lower TSH and higher FT4 were associated with an increased risk of prostate cancer. Further studies are required to assess if thyroid function is a biomarker or risk factor for prostate cancer.

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