scholarly journals White matter damage due to pulsatile versus steady blood pressure differs by vascular territory: A cross-sectional analysis of the UK biobank cohort study

2021 ◽  
pp. 0271678X2110588
Author(s):  
Karolina A Wartolowska ◽  
Alastair JS Webb
Keyword(s):  
Blood Pressure ◽  
Cohort Study ◽  
White Matter ◽  
Linear Models ◽  
Posterior Circulation ◽  
White Matter Injury ◽  
Uk Biobank ◽  
Vascular Territory ◽  
Anterior Circulation ◽  
The Uk

Small vessel disease is associated with age, mean blood pressure (MAP) and blood pressure pulsatility (PP). We used data from the UK Biobank cohort study to determine the relative importance of MAP versus PP driving white matter injury within individual white matter tracts, particularly in the anterior and posterior vascular territory. The associations between blood pressure and diffusion indices in 27 major tracts were analysed using unadjusted and fully-adjusted general linear models and mixed-effect linear models. Blood pressure and neuroimaging data were available for 37,041 participants (mean age 64+/−7.5 years, 53% female). In unadjusted analyses, MAP and PP were similarly associated with diffusion indices in the anterior circulation. In the posterior circulation, the associations were weaker, particularly for MAP. In fully-adjusted analyses, MAP remained associated with all diffusion indices in the anterior circulation, independently of age. In the posterior circulation, the effect of MAP became protective. PP remained associated with greater mean diffusivity and extracellular free water diffusion in the anterior circulation and all diffusion indices in the posterior circulation. There was a significant interaction between PP and age. This implies discordant mechanisms for chronic white matter injury in different brain regions and potentially in the associated stroke risks.

scholarly journals Midlife blood pressure is associated with the severity of white matter hyperintensities: analysis of the UK Biobank cohort study

2020 ◽  
Author(s):  
Karolina Agnieszka Wartolowska ◽  
Alastair John Stewart Webb
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Linear Models ◽  
Population Attributable Fraction ◽  
Relative Role ◽  
Uk Biobank ◽  
Assessment Centre ◽  
The Uk

Abstract Aims White matter hyperintensities (WMH) progress with age and hypertension, but the key period of exposure to elevated blood pressure (BP), and the relative role of systolic BP (SBP) vs. diastolic BP (DBP), remains unclear. This study aims to determine the relationship between WMH and concurrent vs. past BP.  Methods and results  UK Biobank is a prospective community-based cohort of 40–69-year olds from 22 centres, with magnetic resonance imaging in a subgroup of over 40 000 people at 4–12 years after baseline assessment. Standardized associations between WMH load (WMH volume normalized by total white matter volume and logit-transformed) and concurrent vs. past BP were determined using linear models, adjusted for age, sex, cardiovascular risk factors, BP source, assessment centre, and time since baseline. Associations adjusted for regression dilution bias were determined between median WMH and usual SBP or DBP, stratified by age and baseline BP. In 37 041 eligible participants with WMH data and BP measures, WMH were more strongly associated with concurrent SBP [DBP: β = 0.064, 95% confidence interval (CI) 0.050–0.078; SBP: β = 0.076, 95% CI 0.062–0.090], but the strongest association was for past DBP (DBP: β = 0.087, 95% CI 0.064–0.109; SBP: β = 0.045, 95% CI 0.022–0.069), particularly under the age of 50 (DBP: β = 0.103, 95% CI 0.055–0.152; SBP: β = 0.012, 95% CI −0.044 to 0.069). Due to the higher prevalence of elevated SBP, median WMH increased 1.126 (95% CI 1.107–1.146) per 10 mmHg usual SBP and 1.106 (95% CI 1.090–1.122) per 5 mmHg usual DBP, whilst the population attributable fraction of WMH in the top decile was greater for elevated SBP (19.1% for concurrent SBP; 24.4% for past SBP). Any increase in BP, even below 140 for SBP and below 90 mmHg for DBP, and especially if requiring antihypertensive medication, was associated with increased WMH. Conclusions WMH were strongly associated with concurrent and past elevated BP with the population burden of severe WMH greatest for SBP. However, before the age of 50, DBP was more strongly associated with WMH. Long-term prevention of WMH may require control of even mildly elevated midlife DBP.

scholarly journals Blood Pressure Determinants of Cerebral White Matter Hyperintensities and Microstructural Injury: UK Biobank Cohort Study

Hypertension ◽  
2021 ◽  
Author(s):  
Karolina A. Wartolowska ◽  
Alastair J.S. Webb
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cohort Study ◽  
Mean Arterial Pressure ◽  
White Matter ◽  
Arterial Pressure ◽  
White Matter Injury ◽  
Uk Biobank ◽  
White Matter Damage ◽  
And Diffusion

Small vessel disease and related stroke and dementia risks are linked to aging and hypertension, but it is unclear whether the pulsatile or steady blood pressure (BP) component is more important for the development of macrostructural hyperintensities and microstructural white matter damage. This was a cross-sectional analysis of the UK Biobank cohort study of community-based adults from 22 UK centers. Linear associations were determined between neuroimaging markers (white matter hyperintensity [WMH] volume and diffusion imaging indices) and mean arterial pressure and pulse pressure (PP), both unadjusted and adjusted for age, sex, cardiovascular risk factors, antihypertensive medication, BP source, and assessment center. In 37 041 participants aged 45 to 82 years (53% female), univariable analyses demonstrated that increases in both BP components were associated with greater WMH volume and white matter injury on diffusion indices, with a larger effect for PP (standardized effect size for WMH: mean arterial BP: 0.182 [95% CIs, 0.170–0.193]; PP: 0.285 [95% CIs, 0.274–0.296]). In multivariable analyses, associations with mean arterial pressure remained similar, but associations with PP diminished, reflecting covariance with age and risk factors (standardized effect size for WMH: mean arterial BP: 0.106 [95% CIs, 0.095–0.117]; PP: 0.011 [95% CIs, −0.001 to 0.023]). The synergistic interaction between PP and age increased the effect of age on WMH and diffusion indices. Both macrostructural and microstructural white matter injury had similar associations with the pulsatile and steady components of hypertension, although PP accentuated the relationship between age and white matter damage.

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

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.

scholarly journals Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Wainberg ◽  
Stefan Kloiber ◽  
Breno Diniz ◽  
Roger S. McIntyre ◽  
Daniel Felsky ◽  
...  
Keyword(s):  
Public Health ◽  
Major Depressive Disorder ◽  
Cohort Study ◽  
Confidence Interval ◽  
Depressive Disorder ◽  
Blood Cell ◽  
Biological Processes ◽  
Uk Biobank ◽  
Major Depressive ◽  
The Uk

AbstractPrevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

scholarly journals Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Sex Differences ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Sex Difference ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

scholarly journals Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank

2018 ◽  
Vol 143 (4) ◽  
pp. 831-841
Author(s):  
Úna C. Mc Menamin ◽  
Andrew T. Kunzmann ◽  
Michael B. Cook ◽  
Brian T. Johnston ◽  
Liam J. Murray ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Reproductive Factors ◽  
Uk Biobank ◽  
Gastrointestinal Cancers ◽  
The Uk ◽  
Upper Gastrointestinal

Blood Pressure, Hypertension and The Risk of Aortic Dissection Incidence and Mortality: results from the Japan-Specific Health Checkups Study, the UK Biobank Study and a Meta-analysis of Cohort Studies

Circulation ◽  
2021 ◽  
Author(s):  
Makoto Hibino ◽  
Yoichiro Otaki ◽  
Elsa Kobeissi ◽  
Han Pan ◽  
Hiromi Hibino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aortic Dissection ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Uk Biobank ◽  
Dose Response Relationship ◽  
Fractional Polynomial ◽  
The Uk ◽  
Specific Health

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies. Methods: We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >75 mmHg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose-dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2019 ◽  
Author(s):  
Joshua Gray ◽  
Matthew Thompson ◽  
Chelsie Benca-Bachman ◽  
Max Michael Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Gray Matter ◽  
Brain Structure ◽  
Mean Diffusivity ◽  
Medial Lemniscus ◽  
Uk Biobank ◽  
Matter Volume ◽  
Increased Risk ◽  
The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2020 ◽  
Vol 45 (7) ◽  
pp. 1215-1222
Author(s):  
Joshua C. Gray ◽  
Matthew Thompson ◽  
Chelsie Bachman ◽  
Max M. Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Uk Biobank ◽  
The Uk
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