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

BACKGROUND: Stroke 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. METHODS: We 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. RESULTS: The 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). CONCLUSION: From 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.

Statin Usage Increases White Matter Hyperintensities: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Progression of white matter hyperintensities (WMHs), a radiographic marker of cerebral small vessel disease, occurs with uncontrolled conventional cerebrovascular risk factors. Less certain, however, is the influence of dyslipidemia and the impact of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) on WMH progression. The goal of this study was to evaluate the influence of statins on the progression of WMH over a 4-year interval. METHODS: We performed a post hoc analysis of the SPRINT-MIND database on those with serial volumetric WMH data. WMH progression was calculated as the difference in WMH volume between the 2 scans and then segmented into tertiles due to rightward skew. We defined statin usage as no therapy (0% of visits), partial therapy (1% to 99% of visits) or full therapy (100% of visits) as logged during study visits. Analysis of variance and χ 2 tests were used for continuous and categorical variables with adjustments made for variables known to influence WMH development. RESULTS: A total of 425 individuals were included in this study: 53% without statins use, 27% partial use, and 20% full use. Demographic characteristics and baseline WMH volumes were similar among the cohort. Those with full statin use were significantly more likely to be in the top tertile of WMH progression (adjusted odds ratio: 2.30, 95% confidence interval: 1.11-4.77, P =0.025), despite improvement in dyslipidemia. CONCLUSIONS: SPRINT-MIND participants prescribed a statin were nearly 2.5 times more likely to be within the top tertile of WMH progression over 4 years, despite adjustment for synergistic risk factors and improvement in low-density lipoprotein.

Baseline Serum Biomarkers of Inflammation and Subsequent Visit-to-Visit Blood Pressure Variability: A Post Hoc Analysis of MESA.

BACKGROUND: Higher blood pressure variability (BPV) is associated with the development of major vascular diseases, independent of mean blood pressure. However, despite data indicating that serum inflammatory markers are linked to hypertension, the association between serum inflammatory markers and BPV has not been studied in humans. METHODS: This is a post hoc analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) study. The study exposure was tertiles of serum level of interleukin-6 (IL-6), C-reactive protein (CRP), d-dimer, plasmin-antiplasmin complex (PAP), fibrinogen antigen, and calibrated Factor VIII (%) at the baseline study visit. The primary outcome was visit-to-visit BPV measured as the residual standard deviation (rSD) of at least 4 study visits (2000-2018). Two logistic regression models were fit to the top tertile of rSD during follow-up: in Model 1, we adjusted for age, sex, and hypertension, and in Model 2, for patient age categories, sex, race/ethnicity, education, hypertension, diabetes, smoking, drinking, body mass index, lipid-lowering medication, and mean systolic blood pressure. RESULTS: Our analysis included 5,483 patients, with a mean (SD) age of 61.4 (10.0) years, 52.9% female, and 40.7% White. In unadjusted analyses, all markers of inflammation were associated with higher BPV, but after adjustment, only IL-6 retained significance (P < 0.001). The odds ratio for the highest tertile of BPV and IL-6 was 1.49 (95% confidence interval [CI] 1.28-1.74, P < 0.001). CONCLUSIONS: Baseline serum IL-6 was associated with increased subsequent BPV in a large multiracial cohort. Further investigation is needed to better understand the relationship between chronic inflammation and BPV.

Effect of Antihypertensives by Class on Cerebral Small Vessel Disease: A Post Hoc Analysis of SPRINT-MIND.

BACKGROUND: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. METHODS: We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. RESULTS: Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P<0.001) and systolic blood pressure (128.3±11.0 versus 126.2±9.4 mm Hg; P=0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL (P<0.001). Use of angiotensin-converting enzyme inhibitors (odds ratio, 0.36 [95% CI, 0.16-0.79]; P=0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19-0.80]; P=0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. CONCLUSIONS: Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

The association between transthoracic echocardiogram parameters and white matter hyperintensities.

OBJECTIVE: Identify abnormal cardiac chamber size and hemodynamic parameters on transthoracic echocardiogram (TTE) as predictors of advancing cerebral small vessel disease (CSVD) on brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective chart review of adults with a brain MRI and a 2-dimensional TTE was performed. WMH measured by the Fazekas score served as the primary outcome. We fit multivariate ordinal logistic regression models to the Fazekas score with the individual predictors of the TTE measurements and adjusted for potential confounders. RESULTS: 132 individuals were included. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (p = 0.818), right ventricular ejection fraction (p = 0.818) and left ventricular ejection fraction (p = 0.673). Cardiac structural markers included right atrial area (p = 0.247), right ventricular internal diameter (RVID, p = 0.020) and left atrial area (LAA, p = 0.041). RVID and LAA were identified as being predictors, although the direction of the association suggested that normal values resulted in more WMH. Analysis of isolated DWM or PVWM Fazekas scores were not associated with cardiac structure or function. CONCLUSIONS: In our study, we found that normal LAA and RVID values were associated with an increased degree of WMH on MRI. This finding may represent earlier identification of WMH prior to TTE cardiac changes. Future studies are needed for more robust quantitative comparison as well as evaluation prospectively of the association between cardiac chamber sizes and development of WMH.

Endothelial Shear Stress and Platelet FcγRIIa Expression in Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) has been characterized by the degree of arterial stenosis and downstream hypoperfusion, yet microscopic derangements of endothelial shear stress at the luminal wall may be key determinants of plaque growth, vascular remodeling and thrombosis that culminate in recurrent stroke. Platelet interactions have similarly been a principal focus of treatment, however, the mechanistic basis of anti-platelet strategies is largely extrapolated rather than directly investigated in ICAD. Platelet FcγRIIa expression has been identified as a potent risk factor in cardiovascular disease, as elevated expression markedly increases the risk of recurrent events. Differential activation of the platelet FcγRIIa receptor may also explain the variable response of individual patients to anti-platelet medications. We review existing data on endothelial shear stress and potential interactions with the platelet FcγRIIa receptor that may alter the evolving impact of ICAD, based on local pathophysiology at the site of arterial stenosis. Current methods for quantification of endothelial shear stress and platelet activation are described, including tools that may be readily adapted to the clinical realm for further understanding of ICAD.

Optimal Carotid Plaque Features on Computed Tomography Angiography Associated With Ischemic Stroke.

Background Stenosis has historically been the major factor used to determine carotid stroke sources. Recent evidence suggests that specific plaque features detected on imaging may be more highly associated with ischemic stroke than stenosis. We sought to determine computed tomography angiography (CTA) imaging features of carotid plaque that optimally discriminate ipsilateral stroke sources. Methods and Results In this institutional review board-approved retrospective cross-sectional study, 494 ipsilateral carotid CTA-brain magnetic resonance imaging pairs were available for analysis after excluding patients with alternative stroke sources. Carotid CTA and clinical markers were recorded, a multivariable Poisson regression model was fitted, and backward elimination was performed with a 2-sided threshold of P<0.10. Discriminatory value was determined using receiver operating characteristic analysis, area under the curve, and bootstrap validation. The final CTA carotid-source stroke prediction model included intraluminal thrombus (prevalence ratio, 2.8 [P<0.001]; 95% CI, 1.6-4.9), maximum soft plaque thickness (prevalence ratio, 1.2 [P<0.001]; 95% CI, 1.1-1.4), and the rim sign (prevalence ratio, 2.0 [P=0.007]; 95% CI, 1.2-3.3). The final discriminatory value (area under the curve=78.3%) was higher than intraluminal thrombus (56.4%, P<0.001), maximum soft plaque thickness (76.4%, P=0.007), or rim sign alone (69.9%, P=0.001). Furthermore, NASCET (North American Symptomatic Carotid Endarterectomy Trial) stenosis categories (cutoffs of 50% and 70%) had lower stroke discrimination (area under the curve=67.4%, P<0.001). Conclusions Optimal discrimination of ipsilateral carotid sources of stroke requires information on intraluminal thrombus, maximum soft plaque thickness, and the rim sign. These results argue against the sole use of carotid stenosis to determine stroke sources on CTA, and instead suggest these alternative markers may better diagnose vulnerable carotid plaque and guide treatment decisions.

Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of the ACCORD Eye Study.

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

Magnetic Resonance Imaging and Clinical Factors Associated With Ischemic Stroke in Patients Suspected of Cervical Artery Dissection.

Background and Purpose- Cervical artery dissection is a major cause of ischemic stroke in the young and presents with various imaging findings, including stenosis and intramural hematoma (IMH). Our goal was to determine the relative contribution of lumen findings and IMH to acute ischemic stroke and whether a heavily T1-weighted sequence could more reliably detect IMH. Methods- Institutional review board approval was obtained for this retrospective study of 254 patients undergoing magnetic resonance imaging/magnetic resonance angiography for suspected dissection. Imaging included standard turbo spin-echo (TSE) T1-fat saturation and heavily T1-weighted flow-suppressed magnetization-prepared rapid acquisition gradient-recalled echo sequences. Subjects with stents (1) or atherosclerotic disease (26) were excluded, leaving 227 subjects. Kappa analysis was used to determine IMH interrater reliability on magnetization-prepared rapid acquisition gradient-recalled echo and T1-fat saturation in 4 vessels per subject. Lumen findings, cardiovascular risk factors, medications, and nondissection stroke sources were recorded. Mixed-effects multivariate Poisson regression was used to determine the prevalence ratio of each factor with acute ischemic stroke, accounting for 4 vessels per patient with backward elimination to a threshold P value of 0.10. Results- Patients were 41.9% men, mean age of 47.3±16.6 years, with 114 dissections and 107 strokes. IMH interrater reliability was significantly higher for magnetization-prepared rapid acquisition gradient-recalled echo (κ=0.83; 95% CI, 0.78-0.86) versus T1-fat saturation (0.58; 95% CI, 0.57-0.68). The final acute stroke prediction model included magnetization-prepared rapid acquisition gradient-recalled echo-detected IMH (prevalence ratio, 2.0; 95% CI, 1.1-3.9; P=0.034), stenosis, pseudoaneurysm, male sex, current smoking, and nondissection stroke sources. The final model had high discrimination for acute stroke (area under the curve, 0.902; 95% CI, 0.872-0.932), compared with models without stenosis (0.861; 95% CI, 0.821-0.902), and without stenosis and IMH (0.831; 95% CI, 0.783-0.879). All 3 models were significantly different at P<0.05. Conclusions- Along with stenosis, IMH detection significantly contributed to acute ischemic stroke pathogenesis in patients with suspected cervical artery dissection. In addition, IMH detection can be made more reliable with heavily T1-weighted sequences.

Magnetic Resonance Imaging Detection of Intraplaque Hemorrhage.

Carotid artery atherosclerosis is a major cause of ischemic stroke. For more than 30 years, future stroke risk and carotid stroke etiology have been determined using percent diameter stenosis based on clinical trials in the 1990s. In the past 10 years, magnetic resonance imaging (MRI) sequences have been developed to detect carotid intraplaque hemorrhage. By detecting carotid intraplaque hemorrhage, MRI identifies potential stroke sources that are often overlooked by lumen imaging. In addition, MRI can dramatically improve assessment of future stroke risk beyond lumen stenosis alone. In this review, we discuss the use of heavily T1-weighted MRI sequences used to detect carotid intraplaque hemorrhage. In addition, advances in ciné imaging, motion robust techniques, and specialized neck coils will be reviewed. Finally, the clinical use and future impact of MRI plaque hemorrhage imaging will be discussed.