scholarly journals Plasma Biomarkers of Angiogenesis Related to Small Vessel Brain Disease in SPRINT

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 670-671
Author(s):  
Nicholas Pajewski ◽  
Fanny Elahi ◽  
Joachim Ix ◽  
Ilya Nasrallah ◽  
Jason Hinman ◽  
...  

Abstract Meta-analyses incorporating the Systolic Blood Pressure Intervention Trial (SPRINT) have shown a reduced incidence of dementia with blood pressure lowering. However, mechanistic explanations for this effect are lacking, apart from slowed progression of cerebral white matter lesions (WML). Here we examine possible biomarkers of angiogenesis related to small vessel brain disease including bFGF, FLT1, PLGF, TIE-2, VEGF, VEGF-C, and VEGF-D. The biomarkers were assayed in plasma at baseline and during follow-up (median follow-up = 3.8 years) in a subgroup of participants 60 to 89 years old from SPRINT (N=517). We modeled changes in each biomarker using robust linear mixed models accounting for treatment group, time since randomization, and kidney function. Participants were 69.8 ± 7.1 (standard deviation) years of age, 42.1% female, with a mean systolic blood pressure (SBP) of 138.2 ± 17.0 mm Hg. At baseline, none of the biomarkers were associated with WML lesion volume or total brain volumes adjusting for age (all p>0.05), while FLT1, PLGF, and TIE-2 were negatively associated with frontal gray matter cerebral blood flow (partial correlations of -0.11, -0.10, and -0.12 respectively, all p<0.05). For both intensive (target SBP<120 mm Hg) and standard (target SBP<140 m Hg) blood pressure control, mean levels for the majority of biomarkers increased during follow-up, with the exceptions of TIE-2 (decreased over follow-up) and VEGF-D (no change). We did not observe significant between-group differences for the change in these plasma biomarkers of angiogenesis comparing intensive to standard blood pressure treatment.

1999 ◽  
Vol 46 (6) ◽  
pp. 827-833 ◽  
Author(s):  
Frank-Erik De Leeuw ◽  
Jan Cees De Groot ◽  
Matthijs Oudkerk ◽  
Jacqueline C. M. Witteman ◽  
Albert Hofman ◽  
...  

2003 ◽  
Vol 15 (S1) ◽  
pp. 147-151 ◽  
Author(s):  
Charles DeCarli

Multiple epidemiological and brain imaging studies show a strong association between elevations in systolic blood pressure and lesions of cerebral white matter. The association between white-matter lesions and systolic blood pressure persists even if individuals are receiving treatment, suggesting that these individuals may be undertreated. In addition, these studies suggest that lesions of cerebral white matter may serve as markers for atherosclerotic vascular disease. Treatment strategies, therefore, should focus on early and aggressive management of elevated blood pressure, but definitions of elevated blood pressure may need to be revised downward to achieve best results.


BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e042594
Author(s):  
Xijie Wang ◽  
Bin Dong ◽  
Sizhe Huang ◽  
Zhaogeng Yang ◽  
Jun Ma ◽  
...  

ObjectiveTo identify various systolic blood pressure (SBP) trajectories in Chinese boys between 7 and 18 years of age, and to explore their high blood pressure (HBP) risk in their late adolescence years.Design and settingsA population-based cohort study in Guangdong, China.Participants4541 normal tensive boys who started primary school in 2005 in Zhongshan, Guangdong were included.OutcomesBlood pressure and relevant measurements were obtained by annual physical examinations between 2005 and 2016. HBP was defined by SBP or diastolic blood pressure ≥95th percentile for children under 13, and BP ≥130/80 mm Hg for children ≥13 years old. Logit regression for panel data and log-binomial regression model was used to estimate the risk of HBP among SBP trajectory groups.ResultsFour distinct SBP trajectory groups via group-based trajectory modelling: low stable (13.0%), low rising (42.4%), rising (37.4%) and high rising (7.3%). The overall incidence rates of HBP during the follow-up ranged from 40.24 (95% CI 36.68 to 44.19)/1000 person-years in the low stable group to 97.08 (95% CI 94.93 to 99.27)/1000 person-years in the high rising group. Compared with children with low stable SBP, those of other SBP trajectories suffered 3.05 (95% CI 2.64 to 3.46) to 4.64 (95% CI 4.18 to 5.09) times of higher risk of HBP in their late adolescence, regardless of their age, body mass index and BP level at baseline.ConclusionsSubgroups of SBP trajectories existed in Chinese boys, and are related to hypertension risk at late adolescence. Regular physical examinations could help identify those with higher risks at the beginning of pubertal growth.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
TE Graca Rodrigues ◽  
N Cunha ◽  
P Silverio-Antonio ◽  
P Couto Pereira ◽  
B Valente Silva ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction There is some evidence suggesting that exaggerated hypertensive response to exercise (HRE) may be associated with higher risk of future cardiovascular events, however the relationship between systolic blood pressure (SPB) during exercise test and stroke is not fully understood. Purpose To evaluate the ability to predict the risk of stroke in patients with HRE in exercise test. Methods Single-center retrospective study of consecutive patients submitted to exercise test from 2012 to 2015 with HRE to stress test. HRE was defined as a peak systolic blood pressure (PSBP) > 210 mmHg in men and > 190 mmHg in women, or a rise of the SBP of 60 mmHg in men or 50 mmHg in women or as a diastolic blood pressure > 90 mmHg or a rise of 10 mmHg. Patient’s demographics, baseline clinical characteristics, vital signs during the stress test and the occurrence of stroke during follow-up were analysed Results We included 458 patients with HRE (76% men, 57.5 ± 10.83 years). The most frequent comorbidities were hypertension (83%), dyslipidaemia (61%), previously known coronary disease (32%), diabetes (28%) and smoking (38%). Atrial fibrillation was present in 5.9% of patients. During a mean follow-up of 60 ± 2 months, the incidence of stroke was 2.1% (n = 8), all with ischemic origin. Considering the parameters analysed on exercise test, only PSBP demonstrated to be an independent predictor of stroke (HR 1.042, CI95% 1.002-1.084, p = 0.039,) with moderate ability to predict stroke (AUC 0.735, p = 0.0016) with a most discriminatory value of 203 mmHg (sensibility 56%, specify 67%). Regarding baseline characteristics, after age, sex and comorbidities adjustment, previously controlled hypertension was found to be an independent protective factor of stroke (OR 4.247, CI 95% 0.05-0.9, p = 0.036) and atrial fibrillation was an independent predictor of stroke occurrence (HR 8.1, CI95% 1.4-46.9, p = 0.018). Atrial fibrillation was also associated with hospitalization of cardiovascular cause and major cardiovascular events occurrence (mortality, coronary syndrome and stroke). Baseline SBP was associated with atrial fibrillation development (p = 0.008). Conclusion According to our results, PSBP during exercise test is an independent predictor of stroke occurrence and should be considered as a potencial additional tool to predict stroke occurrence, particularly in high risk patients. The identification of diagnosed hypertension as a protective factor of stroke may be explained by the cardioprotective effect of antihypertensive drugs.


Author(s):  
Kyle C. Kern ◽  
Clinton B. Wright ◽  
Kaitlin L. Bergfield ◽  
Megan C. Fitzhugh ◽  
Kewei Chen ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alison L Herman ◽  
Adam H De Havenon ◽  
Guido J Falcone ◽  
Shadi Yaghi ◽  
Shyam Prabhakaran ◽  
...  

Introduction: White matter hyperintensities (WMH) are linked to cognitive decline and stroke. We hypothesized that Black race would be associated with greater WMH progression in the ACCORDION MIND trial. Methods: The primary outcome is WMH progression in mL, evaluated by fitting linear regression to WMH volume on the month 80 MRI and including the WMH volume on the baseline MRI. The primary predictor is patient race, with the exclusion of patients defined as “other” race. We also derived predicted probabilities of our outcome for systolic blood pressure (SBP) levels. Results: We included 276 patients who completed the baseline and month 80 MRI, of which 207 were white, 48 Black, and 21 Hispanic. During follow-up, the mean number of SBP, LDL, and A1c measurements per patient was 21, 8, and 15. The mean (SD) WMH progression was 3.3 (5.4) mL for blacks, 2.5 (3.2) mL for Hispanics, and 2.4 (3.3) mL for whites. In the multivariate regression model (Table 1), Black, compared to white, patients had significantly more WMH progression (β Coefficient 1.26, 95% CI 0.45-2.06, p=0.002). Hispanic, compared to white, patients did not have significantly different WMH progression (p=0.392), nor was there a difference when comparing Hispanic to Black patients (p=0.162). The predicted WMH progression was significantly higher for Black compared to white patients across a mean SBP of 117 to 139 mm Hg (Figure 1). Conclusions: Black diabetic patients in ACCORDION MIND have a higher risk of WMH progression than white patients across a normal range of systolic blood pressure.


BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e022930 ◽  
Author(s):  
James P Sheppard ◽  
Jenni Burt ◽  
Mark Lown ◽  
Eleanor Temple ◽  
John Benson ◽  
...  

IntroductionRecent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multimorbidity. However, there is a lack of evidence to support deprescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up.Methods and analysisThis trial will use a primary care-based, open-label, randomised controlled trial design. A total of 540 participants will be recruited, aged ≥80 years, with systolic blood pressure <150 mm Hg and receiving ≥2 antihypertensive medications. Participants will have no compelling indication for medication continuation and will be considered to potentially benefit from medication reduction due to existing polypharmacy, comorbidity and frailty. Following a baseline appointment, individuals will be randomised to a strategy of medication reduction (intervention) with optional self-monitoring or usual care (control). Those in the intervention group will have one antihypertensive medication stopped. The primary outcome will be to determine if a reduction in medication can achieve a proportion of participants with clinically safe blood pressure levels at 12-week follow-up (defined as a systolic blood pressure <150 mm Hg), which is non-inferior (within 10%) to that achieved by the usual care group. Qualitative interviews will be used to understand the barriers and facilitators to medication reduction. The study will use economic modelling to predict the long-term effects of any observed changes in blood pressure and quality of life.Ethics and disseminationThe protocol, informed consent form, participant information sheet and all other participant facing material have been approved by the Research Ethics Committee (South Central—Oxford A; ref 16/SC/0628), Medicines and Healthcare products Regulatory Agency (ref 21584/0371/001–0001), host institution(s) and Health Research Authority. All research outputs will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numberEudraCT 2016-004236-38;ISRCTN97503221; Pre-results.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Khawlah Alateeq ◽  
Erin Walsh ◽  
Walter Abhayaratna ◽  
Nicolas Cherbuin

Objective: To quantify the association between blood pressure (BP) across its full range and brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), antihypertensive medication, and other risk factors. Methods: UK Biobank participants ( N =36,260) aged 40 to 70 years were included and stratified by sex and age into four groups (age ≤ 45, 46-55, 56-65 and > 65 years old). Multi-level regression analyses were used to assess the association between mean arterial (MAP), systolic (SBP), and diastolic (DBP) blood pressure, and brain volumes segmented using the FreeSufer software (gray matter [GMV], white matter [WMV], left [L] and right hippocampal volume [RHCV]) and WMLs. We also investigated the interaction effects between body mass index (BMI) and antihypertensive medication and BP in predicting brain volumes and WMLs. Results: Every 10-mmHg higher DBP was associated with lower brain volumes (GMV: -1300– -2800) [SE=34–90]; WMV: -903.44– -1171.7[SE=34.66–53.03]; LHCV: -7.7– -14.26 [SE=0.44–0.57]; RHCV: -6.25– -22.64[SE=0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker, in men. Also, every 10-mmHg higher MAP was associated with larger WMLs across all age groups but peaked > 65 years (0.1 [SE=0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and across the life course. Therefore, it is important that prevention efforts be directed at younger adults with focus on achieving optimal BP to decrease future risk of developing dementia.


2019 ◽  
Vol 28 (3) ◽  
pp. 145-152
Author(s):  
E. G. Warmerdam ◽  
G. J. Krings ◽  
T. A. Meijs ◽  
A. C. Franken ◽  
B. W. Driesen ◽  
...  

Abstract Background Despite a successful repair procedure for coarctation of the aorta (CoA), up to two-thirds of patients remain hypertensive. CoA is often seen in combination with abnormal aortic arch anatomy and morphology. This might be a substrate for persistent hypertension. Therefore, we performed endovascular aortic arch stent placement in patients with CoA and concomitant aortic arch hypoplasia or gothic arch morphology. The goal of this retrospective analysis was to investigate the safety and efficacy of aortic arch stenting. Methods A retrospective analysis was performed in patients who underwent stenting of the aortic arch at the University Medical Center Utrecht. Measurements collected included office blood pressure, use of antihypertensive medication, invasive peak-to-peak systolic pressure over the arch, and aortic diameters on three-dimensional angiography. Data on follow-up were obtained at the date of most recent outpatient visit. Results Twelve patients underwent stenting of the aortic arch. Mean follow-up duration was 14 ± 11 months. Mean peak-to-peak gradient across the arch decreased from 39 ± 13 mm Hg to 7 ± 8 mm Hg directly after stenting (p < 0.001). There were no major procedural complications. Mean systolic blood pressure decreased from 145 ± 16 mm Hg at baseline to 128 ± 9 mm Hg at latest follow-up (p = 0.014). Conclusion This retrospective study shows that stenting of the aortic arch is successful when carried out in a state-of-the-art manner. A direct optimal angiographic and haemodynamic result was shown. No major complications occurred during or after the procedure. At short- to medium-term follow-up a decrease in mean systolic blood pressure was observed.


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