Abstract TMP99: White Matter Hyperintensity Progression and Subsequent Incident Stroke: A Secondary Analysis of the ACCORD Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Tanya Turan ◽  
Natalia Rost ◽  
...  
Keyword(s):  
Risk Factor ◽  
White Matter ◽  
Primary Outcome ◽  
Cox Model ◽  
Secondary Analysis ◽  
Exposure Period ◽  
White Matter Hyperintensity ◽  
Diabetic Patients ◽  
Cox Models ◽  
Recurrent Strokes

Introduction: Studies have shown that the volume of white matter hyperintensity (WMH) is a risk factor for stroke, but there are scarce data exploring the relationship between WMH progression on serial MRIs and subsequent risk of stroke. Hypothesis: We hypothesize that WMH progression in the ACCORD trial increases the risk of subsequent incident stroke. Methods: The exposure period was from baseline to month 40, during which an MRI was performed at both baseline and month 40. The primary outcome was incident ischemic stroke after the month 40 MRI until study completion. We fit Cox models to the primary outcome and included both the baseline and month 40 WMH volume as covariates, with the hazard ratio for the month 40 WMH volume of primary interest because it represents WMH progression in this model. Results: We included 497 patients, of whom 53.3% were male and the mean (SD) age was 62.7 (5.7) years at enrollment. Mean (SD) follow-up after the month 40 MRI was 5.2 (1.8) years. Incident stroke occurred in 17 (3.4%) patients, in whom 2 were recurrent strokes and 15 were first-ever strokes. WMH progression was associated with subsequent stroke in the Cox model (HR 1.27, 95% CI 1.03-1.57, p=0.024) and remained significant after adjusting for patient age, history of prior stroke, and cigarette smoking (HR 1.33, 95% CI 1.07-1.65, p=0.010). Conclusions: Although this preliminary analysis is underpowered, WMH progression, independent of absolute WMH burden, may be a risk factor for future stroke in diabetic patients. This novel finding could have translational implications - specifically that interventions which reduce the progression of WMH could, in turn, reduce future risk of stroke.

Abstract 133: White Matter Hyperintensity and Cardiovascular Disease Outcomes: A Secondary Analysis of the SPRINT MIND Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Tanya Turan ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Shyam Prabhakaran ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Outcome ◽  
Stroke Risk ◽  
Secondary Analysis ◽  
White Matter Hyperintensity ◽  
Secondary Outcome ◽  
Cox Models ◽  
Disease Outcomes ◽  
Hazard Ratios ◽  
The Mean

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal SBP <120 mm Hg vs. <140 mm Hg . A subset of patients enrolled in SPRINT MIND, which performed a baseline MRI and measured white matter hyperintensity volume (WMHv). We evaluated the association between WMHv and cardiovascular events. Methods: The primary outcome was a composite of stroke, MI, ACS, decompensated CHF, or CVD death. The secondary outcome was stroke. The WMHv was divided into quartiles. We fit Cox models to the outcomes and report adjusted hazard ratios for the quartiles of WMHv, and stratified by SPRINT treatment arm. Results: Among 719 included patients, the mean WMHv in the quartiles was 0.34, 1.09, 2.61, and 10.8 mL. The primary outcome occurred in 51/719 (7.1%) and the secondary outcome in 10/719 (1.4%). The WMHv was associated with both outcomes (Table 1, Figure 1). After stratifying by treatment arm, we found the association persisted in the standard, but not intensive, treatment arm (Table 2). However, the interaction term between WMHv and treatment arm was not significant. Conclusions: We observed that degree of WMH was associated with CVD and stroke risk in SPRINT MIND. The risk may be attenuated in patients randomized to intensive BP lowering. Trials are needed to determine if intensive BP lowering can prospectively reduce the high cardiovascular risk in patients with WMH.

Abstract 154: Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of Accord

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ka-ho Wong ◽  
Cecilia Peterson ◽  
Rock Theodore ◽  
Kinga aitken ◽  
Michael Dela Cruz ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Primary Outcome ◽  
Cox Model ◽  
Secondary Analysis ◽  
Cox Models ◽  
Interaction Terms ◽  
Increased Risk ◽  
Microvascular Pathology ◽  
Fundus Photographs

Background: Diabetic retinopathy is a common microvascular complication of diabetes. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with shared and, possibly, synergistic pathology. Methods: This is a secondary analysis of the subgroup of patients who enrolled in the ACCORD Eye study of ACCORD. The primary outcome is stroke during follow-up. The primary predictor was presence of diabetic retinopathy on the Early Treatment Diabetic Retinopathy Study Severity Scale as assessed from seven-field stereoscopic fundus photographs at study baseline. We fit adjusted Cox models to the primary outcome to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms. Results: We included 2,828 patients with a mean (SD) age of 62.1 years and 61.8% were male. The primary outcome of stroke was met by 117 patients during a mean (SD) of 5.4 (1.8) years of follow-up. Diabetic retinopathy was present in 874/2,828 (30.9%) of patients at baseline, and was more common in patients with stroke versus without stroke (41.0 vs 30.5%, p=0.016). In the Cox model, adjusted for baseline patient age, gender, race, total cholesterol, Hgb A1c, smoking, and randomization arm, we found that diabetic retinopathy remained associated with incident stroke (HR 1.60, 95% CI 1.10-2.32, p=0.015) (Figure 1). This association was not affected by randomization to the ACCORD glucose intervention (p=0.305), lipid intervention (p=0.546), or blood pressure intervention (p=0.422). Conclusion: Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications.

Abstract 42: Association of White Matter Hyperintensity Progression and Cognitive Decline: A Secondary Analysis of the ACCORDION MIND Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Tanya Turan ◽  
Natalia Rost ◽  
...  
Keyword(s):  
White Matter ◽  
Verbal Learning ◽  
Secondary Analysis ◽  
Pressure Control ◽  
Epidemiological Studies ◽  
Adverse Outcomes ◽  
White Matter Hyperintensity ◽  
Diabetic Patients ◽  
Patients With Diabetes ◽  
The Mean

Introduction: Retrospective and epidemiological studies have shown that white matter hyperintensity (WMH) is associated with vascular dementia, but WMH progression on serial MRIs has not been examined in a prospective study of diabetic patients, who have a higher risk of the adverse outcomes associated with WMH including dementia. Methods: This is a secondary analysis of the Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes Follow-on Study (ACCORDION). The primary outcome was 4 cognitive tests measured at a baseline visit and month 80 follow-up visit, including Rey’s Auditory Verbal Learning Test (RAVLT), Mini Mental Status Examination (MMSE), Stroop test, and Digit Symbol Coding (DSC). The primary predictor was WMH progression, represented as the WMH volume on the month 80 MRI with the baseline WMH volume included in the model. We predicted change in the cognitive scores by modelling their association with WMH progression. Results: We included 262 patients, with a mean (SD) baseline age of 62.7 (5.3) years and 56.1% male. The mean (SD) WMH volume on the baseline and month 80 MRIs was 1.9 (3.0) and 4.3 (6.0) mL, respectively. The change in WMH was significantly associated with the change in RAVLT score in the linear regression model (β Coef -0.132, p=0.029). (Table). The mean (SD) RAVLT at baseline and month 80 was 8.0 (2.4) and 8.5 (2.8). Conclusions: WMH progression in diabetic patients is associated with worse performance on memory testing over an 80 month period. Though preliminary and not able to account for location of WMH, our results are consistent with the hypothesis that WMH progression is harmful to cognition in diabetics. The SPRINT MIND trial recently reported that intensive blood pressure control attenuates WMH progression and development of mild cognitive impairment, but excluded patients with diabetes. Against this backdrop, our data suggest that diabetics should be included in future trials to reduce WMH progression.

Abstract MP14: White Matter Hyperintensity Progression, Macroalbuminuria, and Intensive Glycemic Control in Diabetics

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Varsha Muddasani ◽  
Nazanin Sheibani ◽  
Ka-ho Wong ◽  
Adam H De Havenon
Keyword(s):  
White Matter ◽  
Glycemic Control ◽  
Linear Regression ◽  
Secondary Analysis ◽  
White Matter Hyperintensity ◽  
Diabetic Patients ◽  
Intensive Glycemic Control ◽  
The Mean ◽  
Interaction Term

Introduction: White matter hyperintensity (WMH) is associated with a higher risk of stroke, dementia, and depression. Prior research has suggested that renal impairment and diabetes may predispose to the development of WMH. Here, we evaluated the association between WMH volume (WMHv), macroalbuminuria, and glycemic control in a cohort of diabetic patients. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) dataset. The primary outcome is WMH progression in mL, evaluated by fitting linear regression to WMHv on the month 40 MRI and including the WMHv on the baseline MRI in the model. The primary predictors were incident macroalbuminuria, defined as new onset urinary albumin >300mg/day, and the ACCORD glucose randomization arm. Results: We included 502 patients. The mean (SD) WMHv at baseline was 2.1 (3.9) mL and at month 40 was 3.6 (5.7) mL. Twenty-three patients (4.6%) developed macroalbuminuria during the study period, who had a higher mean WMH progression (2.9 vs. 1.4 mL, p=0.012). In a linear regression model adjusted for mean systolic blood pressure during follow-up, macroalbuminuria was a significant predictor of WMH progression (Beta 1.20, 95% CI 0.17-2.22, p=0.022). In the same model, the interaction term between glucose randomization arm and macroalbuminuria was highly significant (Beta 3.38, 95% CI 1.20-5.57, p=0.003). The predicted follow-up WMHv for the interaction term are in Figure 1, showing that macroalbuminuria with intensive glycated hemoglobin reduction (goal A1c<6%) was associated with the most WMH progression. Conclusion: In diabetic patients, the development of macroalbuminuria was associated with WMH progression over 40 months, although only in patients assigned to intensive glycemic control. This finding is consistent with the adverse events seen in ACCORD with intensive glycemic control.

Abstract 47: Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of MESA

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Ka-Ho Wong ◽  
J Scott McNally ◽  
Jennifer Majersik
Keyword(s):  
Ischemic Stroke ◽  
Total Cholesterol ◽  
Primary Outcome ◽  
Epidemiologic Study ◽  
Secondary Analysis ◽  
Serum Marker ◽  
Patient Age ◽  
Cox Models ◽  
Patient Âgé

Background: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large prospective epidemiologic study of the clinical factors that can predict transition from asymptomatic to symptomatic cardiovascular disease. Although prior studies have looked at ischemic stroke, they have not systematically examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary stroke risk. Methods: The primary outcome is incident ischemic stroke during follow-up. The predictors are 9 ultrasound-derived measurements and 5 serum measurements related to inflammation. We fit Cox models to ischemic stroke and adjusted for patient age, hypertension, diabetes, total cholesterol, and smoking. Using DeLong’s method, we compared the AUC of the baseline adjusted model to the AUC of the model with predictor variables that were significant in the Cox models, to determine if they improved stroke prediction. Results: We included 6,095 patients with an average age of 61.9 years. The primary outcome of ischemic stroke was seen in 107 patients (1.8%) and the mean follow-up time was 7.7 years. In the Cox models, we found that small artery elasticity (SAE), carotid distensibility (CD), carotid stenosis (CS), and interleukin-6 (IL6) were associated with incident stroke. The AUC of the baseline model to predict stroke, which included patient age, hypertension, diabetes, total cholesterol, and smoking, was 0.745. When we added tertiles of SAE, CD, IL6 and categories of CS, the AUC improved to 0.765 (p=0.021 for difference). Conclusions: In a multiethnic cohort of patients without CVD at baseline, we found several ultrasound measurements and a serum marker of inflammation which predicted the occurrence of a primary ischemic stroke. Adding these basic ultrasound and serum measurements significantly improved the prediction of stroke, which could have implications for primary prevention efforts.

Abstract P622: Racial Variation in White Matter Hyperintensity Progression in the ACCORDION MIND Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alison L Herman ◽  
Adam H De Havenon ◽  
Guido J Falcone ◽  
Shadi Yaghi ◽  
Shyam Prabhakaran ◽  
...  
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
Systolic Blood Pressure ◽  
White Matter Hyperintensity ◽  
Diabetic Patients ◽  
Patient Race ◽  
Black Patients ◽  
The Mean ◽  
White Patients

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

Abstract TP172: Pulmonary Function and White Matter Hyperintensity in Neurologically Healthy Adults

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Han-Yeong Jeong ◽  
Jin Ho Park ◽  
Hyung-Min Kwon
Keyword(s):  
Risk Factor ◽  
White Matter ◽  
Pulmonary Function ◽  
Independent Risk Factor ◽  
Small Vessel Disease ◽  
Pulmonary Function Tests ◽  
Cerebral Small Vessel Disease ◽  
Healthy Adults ◽  
White Matter Hyperintensity ◽  
Vessel Disease

Introduction: Cerebral small vessel disease (SVD) is considered as precursor lesion of many clinical outcomes including stroke and dementia. It is well established that obstructive sleep apnea or chronic obstructive pulmonary disease is an independent risk factor of stroke. However, there are few studies about the association between pulmonary function and the presence of cerebral small vessel disease. Purpose: This study aims to investigate the association between pulmonary function and cerebral SVD in healthy adults. Methods: We conducted a cross-sectional study of 1,528 neurologically healthy people (mean age 56.0±9.0; 847 men), who underwent brain MRI and pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1 )). Risk factors, anthropometric parameters and clinical information were obtained. For evaluating cerebral SVD, the presence of small silent infarction (SSI) and the volume of white matter hyperintensity (WMH) were assessed through axial T2 fluid-attenuated inversion recovery (FLAIR) sequences MRI. Cerebral microbleeds (CMBs) were evaluated through T2-weighted gradient-recalled echo MRI. Results: The prevalence of SSI and CMBs were 9.6% (147 subjects) and 4.1% (63 subjects), respectively. The mean volume of WMH was 2.8±6.2mm 3 . In multiple regression analysis that controlled for age, sex, and smoking status, FVC had a significant negative correlation with WMH volume (R 2 =0.005, β=-0.109, p=0.002), and FEV 1 /FVC ratio had a significant correlation with WMH volume (R 2 =0.006, β=0.083, p=<0.001). In multivariable logistic analysis, after adjusting age, gender, hypertension, and glucose, FVC was negatively associated with the presence of SSI (adjusted OR 0.63, 95% CI 0.44-0.91), and FEV 1 /FVC ratio was positively associated with the presence of SSI (adjusted OR 1.05, 95% CI 1.02-1.08). The presence of CMBs was not associated with any factor of pulmonary function tests. Conclusions: The results from our study suggest that lower pulmonary function, especially FVC, was found to be an independent risk factor of cerebral SVD in neurologically healthy adults.

Abstract WMP113: Serial Cognitive Testing Performance by Baseline Fazekas Category in Stroke Survivors: A Secondary Analysis of the SPS-3 Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Natalia Rost ◽  
Shyam Prabhakaran
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Cognitive Abilities ◽  
Secondary Analysis ◽  
College Education ◽  
Cognitive Testing ◽  
White Matter Hyperintensity ◽  
Absolute Difference ◽  
Stroke Survivors ◽  
One Year

Introduction: Prior research has shown that an increased burden of white matter hyperintensity (WMH) is an independent risk factor for the development of dementia. However, research has not focused specifically on stroke survivors, who are also predisposed to dementia. Methods: This is a secondary analysis of patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, who had a lacunar ischemic stroke within 6 months of enrollment and an MRI at study baseline. The primary outcome is change in the Cognitive Abilities Screening Instrument (CASI) from baseline to a 12 month follow-up. The primary predictor is the Fazekas score on the baseline MRI, with the scores of 0 and 1 collapsed to balance the cohort. We fit regression models to the 12 month CASI and adjusted for baseline CASI, patient age, gender, white race, Barthel Index score at 3 months from enrollment, college education, employment status, diabetes, COPD, and SPS3 randomization arm. Results: We included 2,413 patients with a mean (SD) age of 62.8 (10.6) years and 63.7% were male. There were 946 patients in Fazekas 0-1, 1,009 in Fazekas 2, and 458 in Fazekas 3. The mean (SD) CASI score at baseline and 12 months were 85.3 (12.4) and 86.0 (12.4). In the adjusted linear regression model, compared to a baseline Fazekas of 0-1, a baseline Fazekas of 2 was associated with a worse cognitive score (β coef = -0.55, 95% CI -1.01, -0.08, p=0.020), as was Fazekas of 3 (β coef = -0.76, 95% CI -1.36, -0.16, p=0.013). Conclusion: In patients with recent lacunar stroke, an increased baseline WMH burden is a risk factor for worse performance over a one year period on a validated test of global cognition. Although the absolute difference in score that we found was small (~0.5-0.8 points), this difference is over one year and, over years to decades, could become clinically significant. The implication of this finding is that lacunar ischemic stroke has additive cognitive consequences for patients with an established WMH burden, suggesting that primary stroke prevention in patients with WMH could be an important public health goal to reduce the burden of dementia.

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