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 ◽  
...  

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.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Varsha Muddasani ◽  
Nazanin Sheibani ◽  
Ka-ho Wong ◽  
Adam H De Havenon

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.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alison L Herman ◽  
Adam H De Havenon ◽  
Guido J Falcone ◽  
Shadi Yaghi ◽  
Shyam Prabhakaran ◽  
...  

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.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Tanya Turan ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Shyam Prabhakaran ◽  
...  

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.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Tanya Turan ◽  
Natalia Rost ◽  
...  

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.


Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 572
Author(s):  
Suguru Mizuno ◽  
Yousuke Nakai ◽  
Kazunaga Ishigaki ◽  
Kei Saito ◽  
Hiroki Oyama ◽  
...  

The incidence of pancreatic cancer (PCa) is increasing worldwide and has become one of the leading causes of cancer-related death. Screening for high risk populations is fundamental to overcome this intractable malignancy. Diabetes mellitus (DM) is classically known as a risk factor for PCa. Recently the reverse causality is in the spotlight, that is to say, DM is considered to be a manifestation of PCa. Numbers of epidemiological studies clarified that new-onset DM (≤2-year duration) was predominant in PCa patients and the relative risk for PCa inversely correlated with duration of DM. Among patients with new-onset DM, elder onset, weight loss, and rapid exacerbation of glycemic control were reported to be promising risk factors and signs, and the model was developed by combining these factors. Several pilot studies disclosed the possible utility of biomarkers to discriminate PCa-associated DM from type 2 DM. However, there is no reliable biomarkers to be used in the practice. We previously reported the application of a multivariate index for PCa based on the profile of plasma free amino acids (PFAAs) among diabetic patients. We are further investigating on the PFAA profile of PCa-associated DM, and it can be useful for developing the novel biomarker in the near future.


Author(s):  
Sloane A McGraw ◽  
Michael Scholfield ◽  
Ragu Murthy ◽  
Anupama Shivaraju ◽  
Burhan Mohamedali ◽  
...  

Background: Blood pressure (BP) control in patients with coronary artery disease (CAD) is beneficial on morbidity and mortality, however the US Joint National Committee VII (JNC-7) also recommends systolic BP (SBP) <130 and diastolic BP (DBP) <80 for diabetic patients because diabetes itself is an additional risk for a cardiac event. This can be attained using beta-blockers (BB), angiotensin agonists (ACE-I/ARB), calcium channel blockers, diuretics and nitrates. Methods: We conducted a retrospective cohort study focusing on attaining JNC-7 guidelines, comparing outcomes between 302 diabetic to the 469 non-diabetic patients; all underwent PCI between September 2004 and September 2008 at the Jesse Brown Veterans Hospital in Chicago, IL. We collected data of BP values and antihypertensive regimens on admission and at six month follow up, and correlated these into percentages of which have attained goals. Results: Among diabetics, mean SBP decreased from 134 to 130mmHg (p = 0.002) and mean DBP decreased from 72 to 70mmHg (p= 0.004); in the non-diabetics, the mean SBP decreased from 133 to 127mmHg (p<0.0001) and the mean DBP decreased from 73 to 71mmHg (p<0.0012). With regards to guidelines, the percent of diabetics at SBP goal increased from 41% to 51% (124 to 154 of 302) (p= 0.006), however the percent at DBP goal was not significant. In non-diabetics, percent at goal for SBP increased 46% to 57% (216 to 267 of 469) (p=0.0002) and for DBP increased 69% to 76% (324 to 356 of 469) (p=0.0131). At 6 months, among diabetics the medication usage increased with BB, 80% to 92% (241 to 278 of 302) (p<0.0001) and nitrates 30% to 36% (91 to 109 of 302) (p=0.035). Similarly, among non-diabetics, use of BB, 68% to 87% (319 to 408 of 469) (p<0.0001) and nitrates 19% to 24% (89 to 113 of 469) (p=0.006) increased, as well as ACE-I/ARB 52% to 71% (244 to 333 if 469) (p<0.0001). Conclusions: There were improvements in BP among both populations at six months post-PCI; both attained JNC-7 SBP goal, but only non-diabetics achieved DBP goal. Medication use increased for both groups with BB and nitrates, but also with ACE-I/ARB for non-diabetics only. This analysis suggests that tighter control needs to be obtained among diabetics, especially because they are a higher risk population than those solely with CAD.


2020 ◽  
Vol 7 (2) ◽  
pp. e23-e23
Author(s):  
Zahra Davoudi ◽  
Ilad Alavi Darazam ◽  
Farnaz Saberian ◽  
Sina Homaee ◽  
Shervin Shokouhi ◽  
...  

Introduction: As diabetes is highly prevalent worldwide, understanding particular dimensions of COVID-19 infection in diabetic patients is of significant importance. Objectives: The present research aimed to evaluate the outcome of diabetic patients with COVID-19 infection, and the clinical and biochemical characteristics in survived and non-survived patients. Patients and Methods: The present single-center, cross-sectional study examined laboratory and clinical features of 160 patients with diabetes who had moderate to severe criteria. The obtained data were categorized as survived or non-survived patients and then we compared the clinical characteristics in two groups. Results: In this study, 160 diabetic patients (75 men and 85 women) admitted with moderate to severe Covid-19 were evaluated. The mean age of studied patients was 51-90 years old, with diabetes duration of 5 to 15 years. One hundred thirty-one patients (81.9%) survived, but twenty-nine patients (18.1%) did not survive. Regarding the comparison of symptoms, only the loss of consciousness on admission was higher in non- survived patients; however, a majority of the non-survivors have been admitted to ICU, 23(79.3%) and 26 (89.6%) needed invasive mechanical ventilation; in comparison to survived patients also had a shorter duration of hospital stay (5.5±5.1 versus 8.4±6.1days). Non–survivors more probably suffer from high blood pressure [23 (79.3%) patients versus 80 (61%) patients] and chronic kidney disease [20 (69%) patients versus 9 (6.9%) patients; P<0.001]. Glycated hemoglobin (HbA1c) of more than 9%, and high fasting blood sugar, severe inflammatory response, hepatic, renal, and coagulation impairment was higher in non–survived than those who survived. Conclusion: Multifactorial parameters result in the poor prognosis in diabetic patients; therefore, it is critical for identifying the key clinical, as well as laboratory characteristics of COVID-19 cases that lead to severe disease and increase the risk of death.


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