Abstract
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.
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.
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.
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.
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).
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.
BACKGROUND AND PURPOSE—Although studies have attempted to differentiate intracranial vascular disease using vessel wall magnetic resonance imaging (VWI), none have incorporated multicontrast imaging. ...This study uses T1- and T2-weighted VWI to differentiate intracranial vasculopathies.
METHODS—We retrospectively reviewed patients with clinically defined intracranial vasculopathies causing luminal stenosis/irregularity who underwent VWI studies. Two blinded experts evaluated T1 precontrast and postcontrast and T2-weighted VWI characteristics, including the pattern of wall thickening; presence, pattern, and intensity of postcontrast enhancement; and T2 signal characteristics.
RESULTS—Twenty-one cases of atherosclerosis (intracranial atherosclerotic disease ICAD), 4 of reversible cerebral vasoconstriction syndrome, and 4 of vasculitis were identified, with a total of 118 stenotic lesions (81 ICAD, 22 reversible cerebral vasoconstriction syndrome, and 15 vasculitic lesions). There was substantial to excellent inter-reader agreement for the assessment of lesional T2 hyperintensity (κ=0.80), pattern of wall thickening (κ=0.87), presence (κ=0.90), pattern (κ=0.73), and intensity (κ=0.77) of enhancement. ICAD lesions were significantly more likely to have eccentric wall involvement (90.1%) than reversible cerebral vasoconstriction syndrome (8.2%; P<0.001) and vasculitic lesions (6.7%; P<0.001) and were also more likely to have T2 hyperintensity present than the other 2 vasculopathies (79% versus 0%; P<0.001). There were also significant differences in the presence, intensity, and pattern of enhancement between all lesion types. Combining T1 and T2 VWI increased the sensitivity of VWI in differentiating ICAD from other vasculopathies from 90.1% to 96.3%.
CONCLUSIONS—Multicontrast VWI can be a complementary tool for intracranial vasculopathy differentiation, which often leads to more invasive workups when reversible cerebral vasoconstriction syndrome and vasculitis are in the differential diagnosis.
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.
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.
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.
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.
ABSTRACT
BACKGROUND AND PURPOSE
In patients with symptomatic vertebrobasilar intracranial atherosclerotic disease (ICAD), impaired distal flow predicts recurrent stroke, but limited data exist on the ...association between perfusion status and recurrent stroke in anterior circulation ICAD.
METHODS
This is a retrospective study of patients hospitalized for symptomatic ICAD with 50‐99% stenosis of the intracranial carotid or middle cerebral artery. The primary outcome is recurrent symptomatic ischemic stroke in the territory of the artery with ≥50% stenosis within 90 days. The primary predictor is distal hypoperfusion on magnetic resonance (MR) or computed tomography (CT) perfusion, defined as a ≥15 mL volume of territory of the symptomatic artery with Tmax >6 seconds.
RESULTS
Fifty patients met inclusion criteria, including 15 (30%) with recurrent stroke and 15 (30%) with distal hypoperfusion. Distal hypoperfusion was present in 10 of 15 (66.7%) with recurrent stroke versus 5 of 35 (14.3%) without recurrent stroke (P < .001). The hazard ratio for recurrent stroke in patients with distal hypoperfusion was 6.80 (95% confidence interval CI 2.31‐20.0).
CONCLUSION
Distal hypoperfusion in acutely symptomatic ICAD with 50‐99% stenosis is associated with stroke recurrence. Distal hypoperfusion could be used to enrich future trials of secondary stroke prevention in ICAD patients.
BACKGROUND AND PURPOSE—Our goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal ...imaging alone.
METHODS—We retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathiesatherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases.
RESULTS—Thirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion88.8% versus 36.1%; P<0.001 and per-patient96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (κ=0.72) and only slight agreement for luminal imaging (κ=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (κ=0.69 versus 0.18; P<0.001).
CONCLUSIONS—IVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.
Growing evidence suggests breast cancer susceptibility gene (BRCA) mutations may augment cerebrovascular risk factors. With this influence in mind, we aimed to identify if BRCA mutations increased ...the prevalence of cerebral small vessel disease (CSVD).
We performed a retrospective cross-sectional analysis of adults undergoing malignancy evaluation with confirmed BRCA mutations compared to BRCA wildtype individuals. A standard-of-care brain MRI was reviewed. Chi-squared or Fisher's, Wilcoxon rank-sum and the Student's t-test analyses were used when appropriate. Adjusted logistic regression models were fit to calculate odds ratio. Multicollinearity was tested by variance inflation factor calculation and for goodness-of-fit via the Hosmer-Lemeshow test.
Of 116 individuals, 44.8% (52/116) carried a BRCA mutation. Demographic and cerebrovascular risk factors did not differ. Cerebral microbleeds were more common in those with BRCA mutation: 32.7% (17/52) vs. 17.2% (11/64), p = 0.05 with an adjusted odds ratio of 2.8 (95%CI 1.08-6.89, p = 0.03). Other markers of CSVD were similar amongst the cohort.
We identified a nearly 3-fold increase in identified cerebral microbleed in those with BRCA mutations compared with BRCA wildtype individuals suggestive of an interaction between the BRCA gene and cerebral microbleed formation. Further studies are needed to confirm our findings and to understand clinical implications.
Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high‐resolution diffusion‐weighted (DW) imaging can provide quantitative ...diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW‐stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW‐SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two‐group comparison Wilcoxon–Mann–Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH‐positive versus IPH‐negative; and IPH‐positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW‐SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10−3 mm2/s, p < 0.001). ADC was also significantly lower in IPH‐positive versus IPH‐negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10−3 mm2/s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH‐positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10−3 mm2/s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW‐SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.
This work provides strong evidence that ADC measurements from 3D DW‐SOS correlate with symptomatic status of extracranial internal carotid artery plaque. Further, ADC further improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.
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