Modifiable Vascular Risk Factors Research Articles

Vascular risk profile and changes of arterial hypertension after surgical revascularization in adult Moyamoya patients

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly more frequently in MMD patients with increasing age, whereas the vascular risk profile in terms of obesity, nicotine and alcohol consumption was similar to that of the general population. Antihypertensive medication was changed one year after surgical revascularization in 67.5% of patients with a tendency towards dose reduction in 43.2% of all patients. After revascularization, physicians need to be aware of a high likelihood of changes in arterial hypertension and should adjust all other modifiable systemic vascular risk factors to achieve the best treatment possible.

PRERISK: A Personalized, Artificial Intelligence-Based and Statistically-Based Stroke Recurrence Predictor for Recurrent Stroke.

Predicting stroke recurrence for individual patients is difficult, but individualized prediction may improve stroke survivors' engagement in self-care. We developed PRERISK: a statistical and machine learning classifier to predict individual risk of stroke recurrence. We analyzed clinical and socioeconomic data from a prospectively collected public health care-based data set of 41 975 patients admitted with stroke diagnosis in 88 public health centers over 6 years (2014-2020) in Catalonia-Spain. A new stroke diagnosis at least 24 hours after the index event was considered as a recurrent stroke, which was considered as our outcome of interest. We trained several supervised machine learning models to provide individualized risk over time and compared them with a Cox regression model. Models were trained to predict early, late, and long-term recurrence risk, within 90, 91 to 365, and >365 days, respectively. C statistics and area under the receiver operating characteristic curve were used to assess the accuracy of the models. Overall, 16.21% (5932 of 36 114) of patients had stroke recurrence during a median follow-up of 2.69 years. The most powerful predictors of stroke recurrence were time from previous stroke, Barthel Index, atrial fibrillation, dyslipidemia, age, diabetes, and sex, which were used to create a simplified model with similar performance, together with modifiable vascular risk factors (glycemia, body mass index, high blood pressure, cholesterol, tobacco dependence, and alcohol abuse). The areas under the receiver operating characteristic curve were 0.76 (95% CI, 0.74-0.77), 0.60 (95% CI, 0.58-0.61), and 0.71 (95% CI, 0.69-0.72) for early, late, and long-term recurrence risk, respectively. The areas under the receiver operating characteristic curve of the Cox risk class probability were 0.73 (95% CI, 0.72-0.75), 0.59 (95% CI, 0.57-0.61), and 0.67 (95% CI, 0.66-0.70); machine learning approaches (random forest and AdaBoost) showed statistically significant improvement (P<0.05) over the Cox model for the 3 recurrence time periods. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors. PRERISK is a novel approach that provides a personalized and fairly accurate risk prediction of stroke recurrence over time. The model has the potential to incorporate dynamic control of risk factors.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016–2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40–70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021

BackgroundStroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. MethodsWe included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. ResultsThe weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). ConclusionFrom 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

White matter brain age as a biomarker of cerebrovascular burden in the ageing brain.

As the brain ages, it almost invariably accumulates vascular pathology, which differentially affects the cerebral white matter. A rich body of research has investigated the link between vascular risk factors and the brain. One of the less studied questions is that among various modifiable vascular risk factors, which is the most debilitating one for white matter health? A white matter specific brain age was developed to evaluate the overall white matter health from diffusion weighted imaging, using a three-dimensional convolutional neural network deep learning model in both cross-sectional UK biobank participants (n = 37,327) and a longitudinal subset (n = 1409). White matter brain age gap (WMBAG) was the difference between the white matter age and the chronological age. Participants with one, two, and three or more vascular risk factors, compared to those without any, showed an elevated WMBAG of 0.54, 1.23, and 1.94years, respectively. Diabetes was most strongly associated with an increased WMBAG (1.39years, p < 0.001) among all risk factors followed by hypertension (0.87years, p < 0.001) and smoking (0.69years, p < 0.001). Baseline WMBAG was associated significantly with processing speed, executive and global cognition. Significant associations of diabetes and hypertension with poor processing speed and executive function were found to be mediated through the WMBAG. White matter specific brain age can be successfully targeted for the examination of the most relevant risk factors and cognition, and for tracking an individual's cerebrovascular ageing process. It also provides clinical basis for the better management of specific risk factors.

Arterial Hypertension, Structural Damage of the Brain and Cognitive Test

The arterial hypertension cause brain vascular damage (white matter lesion) and the burden and progression determine their cognitive consequences. Therefore, arterial hypertension is considered the main modifiable vascular risk factor for cognitive impairment and dementia. Therefore, the aim of the current study was to evaluate the results of cognitive tests in a sample of hypertensive patients and to establish possible associations with structural brain lesions (atrophy, white matter lesions) identified by magnetic resonance imaging Were included 70 hypertensive patients from Heart-Brain study in Argentina with magnetic resonance imaging and cognitive test. Fazekas scale and the Global Cortical Atrophy were used to quantify the white matter lesions and the brain atrophy, respectively. The Mini-Mental Status Examination, Clock Drawing test and Mini-Boston Naming test were used to evaluate the cognitive status. average age 69.7 ± 10.6 years, 55.7% female). Based on the linear regression analysis, Fazekas scale and cognitive tests were inversely associated. For each grade of increase in Fazekas scale, the clock drawing test (Coef -0.56, CI 95% -1.01 -0.10, p=0.01) and the Mini-mental Status Examination (Coef -0.7, CI 95% -1.27 -0.13, p=0.01) scores decreased. The subcortical atrophy was significantly associated with the clock drawing test (OR 3.29, CI 95% 1.25-8.63; p=0.016). Conclusion: The cognitive tests, particularly the clock drawing test could be used (in the clinical routine practice) as “subrrogate” of the brain structural hypertension-mediated damage.

The effect of insomnia on mild cognitive impairment in patients with vascular risks: results of a three-year longitudinal study

To assess the dynamics of sleep parameters based on the analysis of three items of HDRS-17, designed to measure the severity of insomnia, during 36 months of follow-up and their relationship with indicators of the cognitive phenotype in patients with vascular risk factors. The longitudinal study included 51 patients (mean age 57.7±6.2 years, 19 (37.3%) men)) who met the inclusion criteria. All participants underwent a general clinical examination with assessment of vascular risks and neuropsychological testing using the Montreal Cognitive Assessment (MoCA) and HDRS-17 at baseline and after 36 months. During the study, patients received stable basic therapy to prevent modifiable vascular risk factors. Sleeping pills were taken sporadically when there were complaints of problems falling asleep. During the 36-month study, as vascular cognitive impairment progressed from 23.7±2.6 to 22.1±2.4 points on the MoCA scale (p=0.01), mainly due to decreased attention (p=0.01), executive functions (EF) (p=0.01), memory (p=0.02), speech (p=0.02), an increase in sleep disturbances was observed (item 4: 0.8±0.02 to 1.9±0.1 points, p=0.01; point 5: 0.6±0.02 to 1.7±0.1 points, p=0.01) and depression (7.5±0.5 to 13.7±3.0 points, p=0.01) in patients with vascular risks. A strong inverse correlation was revealed between the values of items 4, 5, 6 on the HDRS-17 and the average MoCA-total scores (r=-0.85; r=-0.87; r=-0.8 (p<0.05)), memory index (r=-0.8; r=-0.75; r=-0.81 (p<0.05)), attention index (r=-0.88; r=-0.86; r=-0.83 (p<0.05)), index of executive functions (r=-0.87; r=-0.85; r=-0.8 (p<0.05)), respectively. The progression of cognitive impairment is associated with worsening insomnia disorders and depression in patients with vascular risks.

The AGED Triad: Opportunities for delaying dementia

AbstractBackgroundApathy, gait impairment, and executive dysfunction (AGED) commonly occur jointly in the elderly, sometimes masked by the generic description of “late life depression.” The recognition of the triad is clinically useful because it often results from hypertension, which is treatable and preventable. Vascular risk factors, especially hypertension, can insidiously cause brain damage which may increase the risk of dementia in older adults. Hence the AGED triad can be a behavioral marker of cerebrovascular damaging which may lead to cognitive disability. It is unclear, however, whether individuals diagnosed with the AGED triad phenotype are at higher risk of earlier conversion to dementia compared with non‐AGED triad phenotype. We also tested the hypothesis that AGED triad would have better predictive capability than each of the three components separately.MethodAfter baseline assessments 275 community‐dwelling older individuals (72.15±6.68 years of age; 58% women) from the Gait and Brain Study underwent face‐to‐face interviews every 6 months for up to 7 years (22.93±20.33 months; 6∼105). Gait performance was assessed electronically; apathy was assessed through the Geriatric Depression Scale‐3A; dysexecutive function was assessed trough the Trail Making test‐part B; dementia was diagnosed through the clinical dementia rating scale. Adjusted Cox‐regression models were used to determine early dementia risk in each exposure group.ResultA greater percentage of AGED triad individuals at baseline had more than 2 vascular risk factors (p&lt;.01) including hypertension, diabetes, hypercholesterolemia, obesity and smoking history. Incidence of dementia in the AGED triad was 16.8% vs. 6% in the non‐AGED triad. AGED triad significantly increased the risk of earlier conversion to dementia compared with non‐AGED triad by 323% independently of the number of vascular risk factors at baseline. AGED triad predicted earlier conversion to dementia more than the three components separately (HR = 6.60 95%CI 1.48 to 29.46; p = .01; see figure 1).ConclusionAGED triad phenotype predicts earlier conversion to dementia compared with non‐AGED triad; and earlier than slow gait, apathy and dysexecutive function separately. AGED triad may be a behavioral marker of severe insidious brain damage over of an individual’s life course likely caused by unmanaged modifiable vascular risk factors.

Racial and Ethnic Differences in the Risk of Dementia under Hypothetical Blood‐Pressure‐Lowering Interventions: The Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundBlack and Latino people have a higher risk of Alzheimer’s disease and related dementias (ADRD) as well as ADRD comorbidities, including hypertension. Since hypertension is perhaps the most important modifiable vascular risk factor for the development of ADRD, we aimed to study whether sustained hypothetical interventions to reduce systolic blood pressure (SBP) would differentially change ADRD risk across racial/ethnic groups.MethodWe used 19 years of follow‐up data from the Multi‐Ethnic Study of Atherosclerosis. The study population included 6806 individuals between 44 and 84 years old, free of clinically recognized CVD and dementia diagnosis at baseline. We defined two sustained interventions on SBP based on continually maintaining SBP below (1) 120 mmHg and (2) 140 mmHg. We considered incident dementia diagnoses as outcome. We applied the parametric g‐formula to adjust for baseline and time‐varying confounding. Baseline covariates included sex, age, education level, income, health insurance, and clinical variables (e.g. diabetes). Time‐varying covariates included SBP, total cholesterol, low‐density lipoprotein, body mass index, health behaviors (e.g. alcohol use), myocardial infarction, stroke, and coronary heart disease diagnosis.ResultMean age was 62.1 (SD = 10.2), 52.9% were female, 38.5% (2617) self‐identified as White, 27.8% (1890) as Black, 21.9% (1495) as Latino and 11.8% (804) as Chinese American. The observed 19‐year risk for dementia was 8.6%. Compared to no specified intervention, maintaining SBP below 120 mmHg was associated with an overall dementia risk reduction of about 5% in the full study population (risk ratio (RR): 0.95, 95%CI: 0.88, 1.02). The estimated RRs for this same comparison were: 0.95(95%CI: 0.87, 1.03) for White participants, 0.93 for Black participants (95%CI: 0.81,1.06), 0.92 for Latino participants (95%CI:0.81, 1.09), and 1.15 for Chinese American participants (95%CI: 0.74,1.63) (Table 1). Of note, the proportion of participants who would have had to have been intervened differed by race/ethnicity, where 92% Black participants, 82% of White and Chinese American, and 86% of Latino participants would have had to have been intervened to maintain SBP below 120 mmHg.ConclusionOur results highlight a heterogenous effect that should be considered for implementation of blood pressure control strategies.

6 Pulse Pressure and APOE ε4 Dose Interact to Affect Cerebral Blood Flow in Older Adults Without Dementia

Objective:Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.Participants and Methods:144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of &gt; 0.0251 pg/ml.Results:A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps &lt; .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps &lt; .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps &gt; .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps &gt; .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.Conclusions:These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.

Abstract 041: Readmission Rates and Etiologies among Patients with Intracerebral Hemorrhage: A United States Nationwide Analysis

Introduction Nontraumatic Intracerebral Hemorrhage (ICH) is the second most prevalent type of stroke worldwide and is strongly linked with severe disability and mortality. Survivors of ICH have a high risk of all‐cause readmission. Understanding characteristics of readmitted patients and etiologies of readmission may provide a framework for risk stratification and readmission prevention. Methods We identified patients with a primary diagnosis of ICH (ICD‐10 code: I61.x) from 2016‐2019 using the Nationwide Readmission Database (NRD). The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results A total of 260,854 patients were admitted with a primary diagnosis of ICH between 2016‐2019. The mean age of the cohort was 68.49 years, with 52.6% being male. The 30‐day readmission rate was 7.68% while the 90‐day readmission rate was 12.73%. There was a small but significant increase in 90‐day readmission rates from 2016 to 2019 (12.61% vs 12.93%, p=0.05), but no significant increase in 30‐day readmission rates (7.10% vs 7.72%, p=0.870). Around 60% of 90‐day readmissions occurred within the first 30 days. Patients readmitted within 30 days and within 90 days, compared to those not requiring readmission, were more likely to be younger (68 and 68.1 vs 68.53 years) and male (54.87% and 53.92% vs 52.41) (p&lt;0.001). They also had a higher prevalence of diabetes (32.43% and 32.82% vs 28.42%), dyslipidemia (44.57% and 44.81% vs 41.41%), obesity (13.19% and 13.64% vs 12.03%), prior TIA/ischemic stroke (6.46% and 6.52&amp; vs 5.60%), PVD (6.17% and 6.27% vs 4.88%), coronary artery disease (20.52% and 20.52% vs 17.83%), chronic renal failure (20.52% and 22.21% vs 17.83%), and heart failure (15.98% and 15.87% vs 12.47%) (p&lt;0.001 for all). The most common etiologies of 30‐day readmissions were cardiovascular (38.55%), infectious (12.57%), and neurological (6.96%). In contrast, the most common etiologies of 90‐day readmissions were cardiovascular (36.21%), infectious (12.42%), and respiratory (6.92%). Conclusion There was a small but significant increase in the rate of 90‐day readmissions among patients with ICH between 2016 and 2019. Patients requiring readmission within 30 and 90 days had a significantly higher prevalence of vascular risk factors and related comorbidities. While cardiovascular and infectious conditions were the most common etiologies of readmission among both groups, neurologic conditions contributed more to 30‐day readmissions, while respiratory conditions made up a higher proportion in etiologies of 90‐day readmission. This suggests that further neurologic injury, potentially related to the primary ICH, occurred relatively early on in the course of recovery. Our analysis suggests a possible role of vascular risk factor modification in preventing readmissions after ICH. However, further research is required to validate this hypothesis and to identify other potentially modifiable risk factors.

Abstract 283: Readmission Rates and Etiologies among Patients with Primary Angiitis of the Central Nervous System

Introduction Primary Angiitis of the Central Nervous System (PACNS) is a rare, relapsing inflammatory disorder of blood vessels in the brain and spinal cord presenting clinically with a spectrum of manifestations including strokes, seizures, and neurologic deficits. Limited data are available on the modifiable and nonmodifiable predictors of readmissions for patients diagnosed with PACNS, which hinders the ability of healthcare systems to risk‐stratify patients based on their specific demographics, comorbidities, and hospital status. Methods We identified patients with PACNS (ICD‐10 code: I67.7) admitted from 2016‐2019 using the Nationwide Readmission Database (NRD). The difference in days between the index admission and the readmission was used to identify patients who were readmitted within 30 and 90 days. The primary diagnosis of the readmission was used to identify the etiology of readmission. Data was weighted to allow for representative nationwide estimates. Results We identified 1,398 patients admitted with a primary diagnosis of PACNS between 2016 and 2019. The mean age was 52.81 years, with 59.20% (n=828) being female. The 30‐day readmission rate was 10.52% (n=147) and the 90‐day readmission rate was 19.60% (n=274). Nearly half of 90‐day readmissions occurred within the first 30 days. Annual variations in readmission rates were insignificant. Age and sex distribution were not statistically different between patients not requiring readmission, those readmitted within 30 days, and those readmitted within 90 days. Compared to those not requiring readmission, patients readmitted within 30 days had a higher prevalence of diabetes (38.07% vs 29.06%; p=0.023) and hypertension (65.66% vs 56.88%; p=0.035), while those readmitted within 90 days had a higher prevalence of diabetes (41.56% vs 27.19%, p&lt;0.001), dyslipidemia (48.49% vs 39.77%, p=0.009), obstructive sleep apnea (10.79% vs 6.73%, p=0.028), and ischemic stroke (32.56% vs 25.18%, p=0.013). The most common etiologies of 30‐ and 90‐day readmissions were cardiovascular (47.05% and 47.81%), neurological (26.80% and 20.61%), and infectious (9.07% and 7.58%). Conclusion The rates of 30‐ and 90‐day readmissions among patients with PACNS have remained stable between 2016 and 2019. Patients with PACNS requiring readmission had a higher incidence of vascular risk factors. Cardiovascular, neurological, and infectious conditions were the most common etiologies for 30‐ and 90‐day readmissions. While our analysis suggests a role for vascular risk factor modification to prevent readmissions in patients diagnosed with PACNS, further research is required to validate this hypothesis and identify other modifiable risk factors.

Modifiable vascular risk factors for outcomes in patients with CADASIL: A literature review and meta-analysis of cross-sectional analyzes

ObjectiveTo investigate the association between outcomes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and common modifiable vascular risk factors. MethodsStudies published between 1993 and February 2023 from PubMed, Embase, Cochrane, CNKI, and WanFang, along with their references, were systematically examined. Cross-sectional analyzes in patients with CADASIL with information on modifiable cerebrovascular risk factors and outcomes were included. Meta-analysis was conducted if at least three studies were available for each risk factor and outcome. ResultsWe included nine studies and 1687 samples in the analysis. The results of the meta-analysis showed that hypertension was positively associated with stroke in patients with CADASIL (OR = 2.69; 95 % CI: 2.02–3.57). Other vascular risk factors, including diabetes mellitus, dyslipidemia, hyperhomocysteinemia, smoking, alcohol drinking, and obesity, did not show stable correlations between the three outcomes (stroke, dementia, and disability). ConclusionsHypertension was significantly associated with stroke in patients with CADASIL. The role of other vascular risk factors in CADASIL and its outcomes: stroke, dementia, and disability, remains ambiguous.

Vascular risk factors and carotid atheromatous disease in patients over 65 years of age

Introduction: Vascular risk factors are decisive in the evolution of atherosclerotic disease and the carotid and vertebral Doppler ultrasound allows monitoring its onset and progress. The measurement of arterial wall thickening allows the early diagnosis of the disease enhancing its treatment and control of vascular risk factors. Aim: Analysing the presence of atheromatous disease in individuals aged &gt; 65 years and understanding its correlation with vascular risk factors. Materials and methods: This is a cross-sectional observational study, in individuals aged &gt; 65 years and underwent carotid echoDoppler between January 1, 2012, and December 31, 2021. The intimal-media index was calculated, as was the presence of atheromatous plaques, their hemodynamic repercussion and vascular risk factors were recorded. Results: A sample of 5885 individuals was obtained with 41.8% female and 58.2% male. The mean age was 76.59 (± 6.69), with a range between 65 and 98 years. Arterial hypertension was the most prevalent 81.3%. There was a significant positive relationship between the intima-media index and age (p = 0.001). In the presence of plaques, male gender, arterial hypertension, diabetes, dyslipidemia, and smoking it presents a positive correlation. Conclusion: In this sample, non-modifiable vascular risk factors seem to be determinants in the presence of increased arterial wall thickness. In the presence of signs of a more advanced stage of atherosclerotic disease, modifiable vascular risk factors are decisive, corroborating the already-known importance of strict control over them for their treatment.

Modifiable vascular risk factors contribute to stroke in 1080 NOTCH3 R544C carriers in Taiwan Biobank.

Previous studies have suggested cardiovascular risk factors increase the risk of not only common sporadic stroke but also of stroke in patients with monogenic stroke disorders including CADASIL. We investigated the effects of the NOTCH3 Arg544Cys (R544C) variant and associated vascular risk factors on stroke in the Taiwanese population. This study was conducted using data from the Taiwan Biobank, consisting of at least 130,000 Han Chinese participants. The genotype was derived from customized genome-wide arrays for 650,000 to 750,000 single-nucleotide polymorphisms (SNPs). Individuals with NOTCH3 R544C were subsequently matched with noncarriers based on the propensity score at a 1:10 ratio by demographic and cardiovascular risk factors. The odds ratio (OR) for stroke or other phenotypes in NOTCH3 R544C carriers and matched noncarriers was then calculated. Univariate and multivariate regression analyses were performed on cardiovascular risk factors in NOTCH3 R544C carriers with and without stroke. The polygenic risk score (PRS) model, adopted from the UK Biobank, was then applied to evaluate the role of NOTCH3 R544C in stroke. From the 114,282 participants with both genotype and questionnaire results, 1080 (0.95%) harbored the pathogenic NOTCH3 R544C variant. When compared to the matched controls (n = 10,800), the carriers presented with a history of stroke (OR: 2.52, 95% confidence interval (CI) (1.45, 4.37)), dementia (OR: 30.1, 95% CI (3.13, 289.43)), and sibling history of stroke (OR: 2.48, 95% CI (1.85, 3.34)) phenotypes. The risk of stroke increased with every 10-year increase in age (p = 0.006, Cochran-Mantel-Haenszel test). Among NOTCH3 R544C carriers, 16 (1.3%) of the 1080 carriers with a stroke history were older, male, and more likely to have hypertension, diabetes, dyslipidemia, and a family history of stroke. In the stepwise multivariate analysis, hypertension (OR: 11.28, 95% CI (3.54, 43.3)) and diabetes mellitus (OR: 4.10, 95% CI (1.31, 12.4)) were independently associated with stroke. Harboring the NOTCH3 R544C variant in the Taiwan Biobank is comparable with a 6.74 standard deviations increase in individual's polygenic risk score for stroke. While the NOTCH3 R544C variant alone increased the risk of stroke, modifiable vascular risk factors also played a role in the occurrence of stroke in Taiwanese community-dwelling individuals carrying the NOTCH3 variant.

Resolving the Smoking Paradox: No Evidence for Smoking-Induced Preconditioning in Large Vessel Occlusion Stroke

Introduction: Smoking is an established risk factor for stroke. However, several studies have reported a better outcome after stroke for patients who smoke. According to this “smoking paradox” hypothesis, smoking might promote less severe strokes, higher collateral scores, and smaller infarct cores. Methods: In this retrospective study, we screened data of 2,980 acute ischemic stroke patients with MCA-M1 occlusion treated with mechanical thrombectomy. Patients were categorized according to smoking status (current, former, or never). We assessed univariate associations between clinical characteristics and smoking status. Subsequently, we used adjusted regression analysis to evaluate associations of smoking with stroke severity on admission (National Institutes of Health Stroke Scale [NIHSS]; primary endpoint), infarct core volume, and collateral status (secondary endpoints). Results: Out of 320 patients, 19.7% (n = 63) were current smokers and 18.8% (n = 60) were former smokers. Admission NIHSS, reperfusion success, and modified Rankin Scale (mRS) after 3–6 months were similar in all groups. Current smokers were younger, more often male and less likely to have atrial fibrillation compared to former and never smokers. In regression analyses, smoking status was neither associated with admission NIHSS (estimate 0.54, 95% confidence interval [CI]: −1.27–2.35, p = 0.557) nor with collateral status (estimate 0.79, 95% CI: 0.44–1.44, p = 0.447) or infarct core volume (estimate −0.69, 95% CI: −15.15–13.77, p = 0.925 for current vs. never smokers). Conclusion: We could not confirm the smoking paradox. Our results support the fact that smoking causes stroke at a younger age, highlighting the role of smoking as a modifiable vascular risk factor.

Association between modifiable vascular risk factors and rapid progression of postradiation carotid artery stenosis.

Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients. Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed. In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression. Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer.

MINIMUM OXYGEN SATURATION LEVELS AND CAROTID ATHEROMATOSIS

Objective: Verify the relationship between the presence carotid atheromatosis getting by cervical Doppler echo and the variation of minimum levels oxygen saturation assessed by polysomnography. Design and method: Analytical, observacional and cross-sectional study was conducted with a sample of 63 individuals who had cervical Doppler echo examination and polysomnography in one year, recording multiple modifiable and no-modifiable vascular risk factors. Results: The sample consisted of 63 individuals, 29 female and 34 male. The mean age was 61.83, aged between 35 and 82 years (+/- 12.64). Regarding the presence of other risk factors under analysis, most of the sample has high prevalence of hypertension (44 individuals - 69.8%), mellitus diabetes (23 individuals - 36.5%) and dyslipidemia (36 individuals - 57.1%). In cervical Doppler echo 51 individuals (81%) have thickening of the intima-media layer and in polysomnography the minimum oxygen saturation levels has a mean value of 77.7%, between the minim of 47% and the maxim of 90% (+/- 9.71). There is a significant relationship between the presence of minimum oxygen saturation levels and the presence of the intimae-media layer thickening (p = 0.0001) and with carotid atheromatosis with hemodynamic repercussions (p = 0.0001). Conclusions: In this sample, it is possible to conclude that the minimum levels of oxygen saturation are lower in presence of carotid atheromatosis, regardless of the degree of hemodynamic compromise, with hypertension being a common risk factor.

DETECTION OF THE HYPERTENSION-MEDIATED COGNITIVE BRAIN DAMAGE. CLOCK DRAWING TEST UTILITY

Objective: Hypertension (HTN) is the main modifiable vascular risk factor for developing cognitive impairment and dementia. ‘Cognitive status’ could be a “surrogate” or ‘potential biomarker’ of HTN-mediated brain damage. Thirty percent of the hypertensive patients have cognitive impairment and/or silent brain damage (white matter hyperintensities) without cardio-renal damage. However, the involvement of the brain as a HTN-related target-organ damage (TOD) is not systematically evaluated. Then our objective were : 1) to know the prevalence of cerebral, cardiac, and renal TOD in a sample of hypertensive patients, and 2) to demonstrate the usefulness of the clock drawing test (CDT) as a cognitive screening tool to assess brain TOD HTN-mediated. Design and method: Multicentre study (4 centres in Argentina, 1 centre in Uruguay), 441 hypertensive patients were included. Age, gender, weight, height and other variables were recorded. Hypertension was defined according to ESH guidelines. TOD were defined as: renal compromise when, creatinine &gt;1.2 mg/dl and/or creatinine clearance &lt; 60 mL/min (Cockcroft-Gault equation), cardiac compromise when: left ventricular mass index &gt; 95 gr/m2 in female and &gt; 115 gr/m2 in male (transthoracic cardiac ultrasound) and cerebral impairment when: the score of the CDT &lt;/ = 5 points. Results: Average age 63.2±11.8 years, 53.4% female. The 60.5% of the sample presented some TO damage. The heart was affected in 32.8% and the kidney in 20.4% while the brain damage (abnormal CDT) was observed in 38% of the total sample, in 47.2% of the hypertensive patients with cardiac and/or renal damage, and in 30.7% of hypertensive patients without cardiac and/or renal damage. Conclusions: The CDT turned out to be a useful, fast and simple tool to be used in routine clinical practice to detect cerebral TOD (cognitive impairment) in hypertensive patients. The clinical expression of the cerebral TOD was more prevalent than pre-clinical cardiac and/or renal TOD.

Physical activity in vascular cognitive impairment: Systematic review with meta-analysis

BackgroundVascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI. MethodsA systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up. ResultsThere was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I2 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD. ConclusionsThese findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.