Elevated Systolic Blood Pressure Research Articles

Periodontitis and hypertension are linked through systemic inflammation: A 5-year longitudinal study.

To investigate the associations between periodontitis and hypertension and potential mediation via systemic inflammation through a 5-year longitudinal study. The severity and extent of periodontitis were determined using probing depth (PD). Oral hygiene was assessed using plaque scores. The associations between periodontal variables and 5-year blood pressure changes or incident hypertension were analysed using linear or Poisson regression, adjusting for potential confounders. Mediation analysis of two systemic inflammatory biomarkers, namely white blood cell count (WBC) and C-reactive protein (CRP) levels, was performed. The study population included 901 hypertension-free participants, aged 50-73 years. Greater mean PD, higher percentage of sites with PD ≥ 6 mm and poor oral hygiene were associated with elevated systolic blood pressure and increased hypertension risk (relative risks = 1.17 [95% confidence interval [CI]: 1.02-1.34], 1.13 [95% CI: 1.02-1.26] and 1.08 [95% CI: 1.03-1.13], respectively). Periodontitis and poor oral hygiene were associated with higher WBC and CRP levels (p < .05), which, in turn, were associated with increased hypertension risk (p < .05). WBC and CRP jointly mediated 14.1%-26.9% of the associations between periodontal variables and incident hypertension. Periodontitis and poor oral hygiene were associated with increased hypertension risk, and systemic inflammation was, in part, a mediator of these associations.

Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants.

It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71-1.26), 1.08 (0.80-1.44), and 0.91 (0.69-1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (P=0.88 for interaction). Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Blood Pressure Trajectories and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke.

Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes. We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios. There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50]). Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes.

Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

Prevalence of High Blood Pressure, Risks Factors, and Knowledge Deficit in Apparently Healthy College Students

Background: College students are assumed to be generally healthy, thus, elevated blood pressure can be easily missed in this population. However, recent research on college students has demonstrated increasing rates of elevated blood pressure. Situations that increase risk of elevated BP include higher levels of stress related to college education as well as other common stress producing events in life. Additionally, college students may engage in behaviors that increase risk such as eating poor diets, drinking alcohol, and not exercising regularly. The purpose of this study was to assess the prevalence of elevated blood pressure and risk factors in undergraduate college students and develop a campus wide educational initiative. Methods: Undergraduate students at a faith-based, Midwestern university (n = 138) participated in a cross-sectional study. Demographic data, standardized BP measurements, risk factors, and perceived stress levels were collected via a Google form and in-person assessments. Results: Fifty-two percent of college students had an elevated systolic blood pressure, and 30% had elevated diastolic blood pressure. Male students had significantly higher systolic (X2 = 101.343, p = .005) and diastolic blood pressure readings (X2 = 144.44, p &lt; .001) compared to female students. There was no association between year in school and stress levels (X2 = 315.83, p = .102). Stress and systolic blood pressure were not correlated (r = .121, p = .180) nor were stress and diastolic blood pressure (r = .075, p = .408). Following the educational initiative, 96% of students (n = 91) were able to accurately define elevated blood pressure, risk factors for hypertension, and strategies to lower blood pressure. Conclusions: It is vital that blood pressure assessments become a priority for college students. These assessments must be followed by interventions aimed at reducing blood pressure levels, stress, and risk factors related to hypertension to prevent the long-term effects of cardiovascular disease. Healthcare providers on college campuses, including and perhaps most effectively students in health-related fields, should be involved in working with this population to increase awareness and screening efforts.

Thyroid Disorders and Peripheral Arterial Disease.

Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.

Association of consumption of sugar-sweetened beverages with elevated blood pressure among college students in Yunnan Province, China.

Although some studies have examined the association between eating behaviour and elevated blood pressure (EBP) in adolescents, current data on the association between sugar-sweetened beverages (SSB) and EBP in adolescents in Yunnan Province, China, are lacking. Cluster sampling was used to survey freshmen at a college in Kunming, Yunnan Province, from November to December. Data on SSB consumption were collected using an FFQ measuring height, weight and blood pressure. A logistic regression model was used to analyse the association between SSB consumption and EBP, encompassing prehypertension and hypertension with sex-specific analyses. The analysis included 4781 college students. Elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) were detected in 35·10 % (1678/4781) and 39·34 % (1881/4781) of patients, respectively. After adjusting for confounding variables, tea beverage consumption was associated with elevated SBP (OR = 1·24, 95 % CI: 1·03, 1·49, P = 0·024), and carbonated beverage (OR = 1·23, 95 % CI: 1·04, 1·45, P = 0·019) and milk beverage (OR = 0·81, 95 % CI: 0·69, 0·95, P = 0·010) consumption was associated with elevated DBP in college students. Moreover, fruit beverage (OR = 1·32, 95 % CI: 1·00, 1·75, P = 0·048) and milk beverage consumption (OR = 0·69, 95 % CI: 0·52, 0·93, P = 0·014) was associated with elevated DBP in males. Our findings indicated that fruit and milk beverage consumption was associated with elevated DBP in males, and no association was observed with EBP in females.

Spatiotemporal patterns of rheumatic heart disease burden attributable to high systolic blood pressure, high sodium diet, and lead exposure (1990 to 2019): a longitudinal observational study.

Rheumatic heart disease (RHD) continues to be a significant global health concern, exhibiting unique regional disparities. Although there is a noted decline in the burden of RHD, the specific causatives for this decrease remain unclear. This study aims to identify and quantify the spatiotemporal patterns related to the RHD-attributable risk burden. The data pertaining to deaths and disability-adjusted life years (DALYs) attributable to RHD risk were drawn from the Global Burden of Disease (GBD) study conducted from 1990 to 2019. These data, categorized by age, gender, and geographical location, highlighted risk factors including diets high in sodium, elevated systolic blood pressure (SBP), and lead exposure. To examine the long-term trends in RHD changes due to these specific risk factors, the average annual percentage change (AAPC) method was used. During the past 30 years, the highest decrease in RHD burden was attributed to high SBP. An AAPC of -2.73 [95% confidence interval (CI): -2.82 to -2.65] and - 2.45 (95% CI: -2.55 to -2.36) in deaths and DALYs was attributable to high SBP, while an AAPC of -3.99 (95% CI: -4.14 to -3.85) and - 3.74 (95% CI: -3.89 to -3.6) in deaths and DALYs was attributed to a diet high in sodium. Moreover, the trends in deaths and DALYs due to lead exposure also showed decreases with an AAPC of -2.94 (95% CI: -3 to -2.89) and - 3.46 (95% CI: -3.58 to -3.34) from 1990 to 2019. Oceania showed an upward trend of the RHD DALYs due to high SBP, with an AAPC of 0.23 (95% CI: 0.13 to 0.33). In general, countries in Oceania, East Asia, and South Asia had higher age-standard deaths and DALY rates of RHD due to diets high in sodium. Our study has revealed that high SBP remains the prime risk factor contributing to the RHD burden. There are decreasing spatiotemporal patterns in RHD-related deaths and burdens. Gaining this knowledge is fundamental to making informed public health strategies and clinical decisions, especially concerning risk assessment, screening, and prevention initiatives.

Impact of hypertensive heart disease, risk factors, and age-period-cohort models across 204 nations and regions from 1990 to 2019: a global perspective from the 2019 global burden of disease study.

Hypertensive heart disease (HHD) is a major global public health issue resulting from hypertension-induced end-organ damage. The aim of this study was to examine the global impact, risk factors, and age-period-cohort (APC) model of HHD from 1990 to 2019. Data from the 2019 Global Burden of Disease were used to assess age-adjusted HHD prevalence, disability-adjusted life years (DALYs), mortality rates, and contributions of HHD risk factors with 95% uncertainty intervals (UIs). APC models were used to analyze global age, period, and cohort mortality trends for HHD. In 2019, 18.6 million prevalent HHD cases led to 1.16 million fatalities and 21.51 million DALYs. Age-adjusted rates were 233.8 (95%UI = 170.5-312.9) per 100,000 individuals for prevalence, 15.2 (11.2-16.7) for mortality, and 268.2 (204.6-298.1) for DALYs. Regionally, the Cook Islands (703.1), Jordan (561.6), and Kuwait (514.9) had the highest age-standardized incidence of HHD in 2019. There were significant increases in HHD prevalence in Andean Latin America (16.7%), western sub-Saharan Africa (5.6%), and eastern sub-Saharan Africa (4.6%). Mortality rate varied widely among countries. Risk factors like elevated systolic blood pressure and high body mass index significant influenced DALY rates, especially in females. The APC model revealed an association between mortality rates and age, with a decreasing mortality risk over time and improved survival rates for a later birth cohort. Despite the reduction in prevalence, HHD remains a significant public health issue, particularly in nations with low sociodemographic indices. To alleviate the impact of HHD, prevention efforts should concentrate on the management of hypertension, weight loss, and lifestyle improvement.

Comorbidity of obesity and smoking and their association with cardiometabolic risk factors: Results from the 2016-2017 National Health Survey

The comorbidity between obesity and smoking and its association with cardiometabolic risk factors has been little explored. Describe the prevalence of such comorbidity and to explore its association with cardiometabolic risk factors. The study was based on the 2016-2017 Chilean National Health Survey and included 6,233 participants. The independent variables were general obesity according to Body Mass Index (BMI), central obesity measured by Waist-to-Height Ratio (WTHR) and Waist Circumference (WC), and daily tobacco consumption (DTC). The dependent variables were blood lipids, fasting glucose and blood pressure. The association analysis was performed by multivariate logistic regression and excluded subjects with a medical record of hypertension, diabetes mellitus and dyslipidemia to avoid reverse causality. The prevalence of General obesity-DTC comorbidity was 7.7%, WTHR risk-DTC was 10.8% and elevated WC-DTC was 13.2%. A total of 3,132 participants were included in logistic regressions. General obesity alone, and DTC-general obesity comorbidity had statistically significant association with elevated triglycerides, decreased HDL, elevated non-HDL and total cholesterol, elevated fasting glucose, and elevated blood pressure. The comorbidities DTC-risk WTHR and DTC-increased WC were associated with increased triglycerides and non-HDL cholesterol. DTC alone was associated with elevated systolic blood pressure. DTC-general obesity comorbidity is more frequently associated with the cardiometabolic risk factors explored than DTC-central obesity comorbidity. Smoking cessation can be a cost-effective intervention in this risk comorbidity.

Impact of changes in antihypertensive medication on treatment intensity at hospital discharge and 30 days afterwards.

Little is known about the cumulative effect of changes in antihypertensive medications on treatment intensity. This study analyzed how changes in antihypertensive medications affect the intensity of antihypertensive treatment at hospital discharge and 30days afterwards. A prospective observational study of 299 hospitalized adult medical patients with antihypertensive therapy was conducted. The effect of medication changes on treatment intensity was evaluated by the Total Antihypertensive Therapeutic Intensity Score (TIS). At discharge, antihypertensive medications were changed in 62% of patients (184/299), resulting in a very small median reduction in TIS of -0.16. Treatment intensity was reduced more with increasing number of antihypertensive medications at admission, whereas it increased with elevated inpatient systolic blood pressure. Thirty days after discharge, antihypertensive medications were changed in 37% of patients (88/239) resulting in a median change in TIS of -0.02. Among them, 90% (79/88) had already undergone a change at discharge. The change in treatment intensity after discharge was inversely correlated with a change at discharge. Changes in antihypertensive medication frequently occurred at discharge but had a minimal impact on the intensity of antihypertensive treatment. However, these adjustments exposed patients to further medication changes after discharge, evidencing the need for treatment reassessment in the first month post-discharge.

Progression risk factors in glaucoma patients with disc haemorrhage

Aims/Purpose: In this study, we investigated the clinical characteristics of disc haemorrhage relating to hemodynamic factors and their impact on glaucoma progression.Methods: This was a retrospective cohort study, including 81 eyes with open angle glaucoma accompanying DH. Eyes were classified as non‐recurrent DH and recurrent DH. Eyes with recurrent DH were sub‐classified into three groups according to the location of DH. Visual field progression was determined by event‐based analysis using the Guided Progression Analysis (GPA) software. The coefficient of variation (CV) of systolic and diastolic blood pressure (BP) was used to measure visit‐to‐visit variability. Kaplan–Meier survival analyses were used to compare the cumulative risk ratio of progression between groups.Results: Recurrent DH group showed a significantly higher systolic and diastolic BP (p = 0.014 and 0.021, respectively), with higher proportion of VF progression (p = 0.019), compared to non‐recurrent DH group. Particularly, female with recurrent DH showed highest cumulative probability of VF progression (p = 0.047, Log‐rank test). Recurrent DH at a different quadrant showed a greater cumulative probability of VF progression than non‐recurrent DH group (p = 0.038, Log‐rank test). In the Cox regression analyses, higher visit‐to visit variability of diastolic BP, female gender, recurrence DH in a different quadrant significantly contributed the progression of glaucoma.Conclusions: The presence of recurrent DH was associated with elevated systolic and diastolic BP, while increased visit‐to visit variability in diastolic BP was linked to the progression of glaucoma. Our study emphasize the role of hemodynamic factors in the pathogenesis of DH in glaucoma.

Δ BP-Net: Monitoring "Changes" in Blood Pressure Using PPG with Self-contrastive Masking.

Estimating blood pressure (BP) values from physiological signals (e.g., photoplethysmogram (PPG)) using deep learning models has recently received increased attention, yet challenges remain in terms of models' generalizability. Here, we propose taking a new approach by framing the problem as tracking the "changes" in BP over an interval, rather than directly estimating its value. Indeed, continuous monitoring of acute changes in BP holds promising implications for clinical applications (e.g., hypertensive emergencies). As a solution, we first present a self-contrastive masking (SCM) model, designed to perform pair-wise temporal comparisons within the input signal. We then leverage the proposed SCM model to introduce ΔBPNet, a model trained to detect elevations/drops greater than a given threshold in the systolic blood pressure (SBP) over an interval, from PPG. Using data from PulseDB, 1) we evaluate the performance of ΔBP-Net on previously unseen subjects, 2) we test ΔBP-Net's ability to generalize across domains by training and testing on different datasets, and 3) we compare the performance of ΔBP-Net with existing PPG-based BP-estimation models in detecting over-threshold SBP changes. Formulating the problem as a binary classification task (i.e., over-threshold SBP elevation/ drop or not), ΔBP-Net achieves 75.97%/73.19% accuracy on data from subjects unseen during training. Additionally, the proposed ΔBP-Net outperforms ΔSBP estimations derived from existing PPG-based BP-estimation methods. Overall, by shifting the focus from estimating the value of SBP to detecting overthreshold "changes" in SBP, this work introduces a new potential for using PPG in clinical BP monitoring, and takes a step forward in addressing the challenges related to the generalizability of PPG-based BP-estimation models.

Endometrioid Karsinomanın Çoklu Beyin Metastazında Eşzamanlı Tümöriçi Kanama: Nadir Bir Metastazın Nadir Bir Bulgusu

Metastasis of endometrioid carcinomas to the brain is rare, usually solitary, and has a poor prognosis. Intratumoral bleeding is also a poor prognostic factor for metastatic brain tumors but rarely occurs in gynecological cancers. A female patient who was under chemotherapy for endometrioid carcinoma was admitted to the emergency department for recent deterioration and seizures. She had confusion and left hemiparesis, along with an elevated systolic blood pressure and platelet count of 45,000 /mL. An emergent computerized tomography and subsequent magnetic resonance imaging revealed multiple hemorrhagic metastatic lesions in both hemispheres and cerebellum. Brain metastasis of endometrioid carcinoma is rare and can present with intratumoral hemorrhage, which is associated with a poor prognosis and is more likely to occur in the setting of low platelet counts. This case highlights the importance of monitoring brain metastasis in patients with endometrioid carcinoma and considering the possibility of intratumoral hemorrhage.

Association between systolic blood pressure and low-density lipoprotein cholesterol with coronary heart disease according to age.

The impact of elevated systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD) at different stages of life is unclear. We aimed to investigate whether genetically mediated SBP/LDL-C is associated with the risk of CHD throughout life. We conducted a three-sample Mendelian randomization analysis using data from the UK Biobank including 136,648 participants for LDL-C, 135,431 participants for SBP, and 24,052 cases for CHD to assess the effect of duration of exposure to the risk factors on risk of CHD. Analyses were stratified by age at enrolment. In univariable analyses, there was a consistent association between exposure to higher LDL-C and SBP with increased odds of incident CHD in individuals aged ≤55 years, ≤60 years, and ≤65 years (p-value for heterogeneity = 1.00 for LDL-C and 0.67 for SBP, respectively). In multivariable Mendelian randomization analyses, exposure to elevated LDL-C/SBP early in life (age ≤55 years) was associated with a higher risk of CHD independent of later life levels (age >55 years) (odds ratio 1.68, 95% CI 1.20-2.34 per 1 mmol/L LDL-C, and odds ratio 1.33, 95% CI 1.18-1.51 per 10 mmHg SBP). Genetically predicted SBP and LDL-C increase the risk of CHD independent of age. Elevated SBP and LDL-C in early to middle life is associated with increased CHD risk independent of later-life SBP and LDL-C levels. These findings support the importance of lifelong risk factor control in young individuals, whose risk of CHD accumulates throughout life.

Exploratory analysis of the contributing factors of stroke

Stroke is a medical condition that occurs when the blood supply to the brain is interrupted, which causes cell death. Previous studies have shown that the leading risk factors of stroke include elevated systolic blood pressure, poor diet, high body mass index, high fasting plasma glucose, ambient particulate matter pollution, smoking, high low-density lipoprotein, kidney dysfunction, alcohol use, and low physical activity. However, how these factors differentially contribute to the occurrence of stroke remains elusive. In this study, 5110 cases and 11 risk factors were investigated and machine learning models were built to predict the occurrence of stroke and the importance of each of the factors. It was found that the random forest model showed the best performance in predicting stroke and age, glucose level, and body mass index were the top three most important risk factors underlying stroke. These findings shed light on future research in the prevention and diagnosis of stroke.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP&lt;120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP&lt;140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP&lt;120 mm Hg compared to the SBP achieved by enhanced usual care (SBP = 135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP&lt;120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP&lt;140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP&lt;120 mm Hg compared to the SBP achieved by enhanced usual care (SBP≥135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

The modifying effects of cardiovascular risk factors on the relationship between lifetime discrimination and cognitive function: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundDiscrimination is a root cause of health inequities contributing to the excess burden of cognitive impairment among Black Americans. Using the Study of Healthy Aging in African Americans (STAR) we examined whether the effect of lifetime discrimination on late‐life cognitive decline was magnified by early adulthood cardiovascular risk factors.MethodSTAR enrolled long‐term Kaiser Permanente Northern California members ages 50+ who identify as Black/African American. In early adulthood, participants completed Multiphasic Health Check‐ups (MHC; 1964‐1985) where systolic blood pressure (BP), total cholesterol, and body mass index (BMI) were assessed. A latent class analysis identified groups based on responses to the Major Experiences of Discrimination Scale and gender. Standardized z‐scores for executive function (EF) and verbal episodic memory (VEM) were measured over 3 waves (2018‐2022) using the Spanish and English Neuropsychological Assessment Scales. Linear mixed models with random intercepts and slopes associated latent class with cognitive decline adjusting for age at MHC, age at baseline cognitive assessment, education, and assessment mode (in‐person/telephone). Separate models tested class*cardiovascular risk factor interactions.ResultParticipants (n = 646) averaged 27.7(SD = 7.3) years of age at MHC and 68.5(SD = 8.8) at baseline cognitive assessment (Table 1). Four latent classes were identified: men reporting widespread discrimination (Class‐1men; 12%), women reporting widespread discrimination (Class‐2women; 22%), men and women reporting unfair police treatment (Class‐3police; 17%), and men and women reporting little/no discrimination (Class‐4no_discimination; 49%). Using Class‐4no_discimination as reference, those in Class‐2women had significantly higher baseline EF (β(95% CI):0.18(0.03,0.34)) while Class‐1men (β:0.04(‐0.15,0.23)) and Class‐3police (β:‐0.08(‐0.25,0.09)) did not differ (Figure 1). Class‐2women (β:0.17(0.00,0.33)) had higher baseline VEM compared to Class‐4no_discrimination while Class‐1men (β:‐0.40(‐0.60,‐0.19)) and Class‐3police (β:‐0.27(‐0.46,‐0.09)) had significantly lower (Figure 1). There were no differences in rate of decline. There was a systolic BP*class interaction (p = 0.04) where 5 mm Hg higher systolic BP in early adulthood was associated with worse EF for Class‐3police (β:‐0.07(‐0.12,‐0.02)) compared to Class‐4no_discrimination while Class‐1men and Class‐2women did not differ (Figure 2). This pattern was similar for VEM but non‐significant (interaction p = 0.07). We found no interactions with total cholesterol or BMI.ConclusionFor Black Americans, discriminatory experiences may differentially impact late‐life cognition, and elevated systolic BP in early adulthood may exacerbate this harm.

Effect of Age Range on Power for a Clinical Trial Investigating the Effect of Intensive Systolic Blood Pressure Control on White Matter Hyperintensity Volume Accumulation

AbstractBackgroundEpidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (&lt;120 mm Hg) in midlife to lower future ADRD risk has ever been attempted. Clinical outcomes are not practical in the age range of interest (45‐65 or 45‐70) during an initial trial period of 5 years however robust evidence demonstrates white matter hyperintensity volume (WMHV) as an MRI finding associated with and predictive of incident ADRD.MethodWe used four data sets (SPRINT, Wisconsin Registry for Alzheimer’s Prevention, Framingham, and UK Biobank) with longitudinal MRI data to examine the effect of age range on power for a clinical trial proposal investigating the effect of intensive SBP control on annualized rates of WMHV accumulation in persons starting in middle age. Analyses were conducted separately in each data set. We calculated mean, standard deviations, and annualized rates of WMHV accumulation (derived from T2 FLAIR MRI), using the linear rate of change for accumulation rate, first stratifying by SBP ( = 132 mm Hg vs &lt;132mm Hg except in SPRINT where groups were stratified by goal SBP group) and then by various age ranges. Next, we examined the effect of age range on necessary sample size with 80% power and two‐tailed alpha of 0.05 for a prospective clinical trial.ResultAs expected, annualized WMHV accumulation rate is lower with younger age in all data sets. However, variability decreased (all four data sets) and the percent reduction achieved at lower SBPs is higher at younger ages (3/4 data sets), thus increasing power when excluding older individuals (e.g., &gt;65 years old, Table 1).ConclusionRestricting age to individuals to = 65 years‐old may unexpectedly increase power in a clinical trial designed to investigate the effect of goal SBP&lt;120 mm Hg on annualized WMHV accumulation rate. 45‐65 years‐old is a practical age range for the first ever clinical trial intended to investigate the effects of a lower SBP goal in middle age to reduce future ADRD risk.