Catherine M. Viscoli’s research while affiliated with Yale-New Haven Hospital and other places

Background Unrecognized or silent myocardial infarction (MI) detected on an ECG is associated with first‐ever stroke, but the impact on stroke recurrence is unknown. We aimed to determine the association of silent MI with stroke recurrence in patients with a recent ischemic stroke. Methods and Results Subjects from the IRIS (Insulin Resistance Intervention After Stroke) trial with an available ECG were included. Clinical MI was defined as a history of hospitalization for MI. Silent MI was defined as ECG evidence of MI in the absence of clinical MI. The primary outcome was recurrent stroke. Ischemic stroke and subtype were assessed as secondary outcomes. Multivariable Cox regression analysis adjusted for demographics, pioglitazone, and vascular risk factors was used to examine the association between MI and stroke recurrence. A total of 2282 participants met the inclusion criteria. Clinical and silent MI were identified in 161 (7.1%) and 94 (4.1%) subjects, respectively. Over the study period, 209 recurrent strokes occurred, with 191 classified as ischemic. In the fully adjusted model, silent MI was significantly associated with any stroke (hazard ratio [HR], 2.29 [95% CI, 1.34–3.90]) and ischemic stroke (HR, 2.09 [95% CI, 1.18–3.70]) recurrence. Clinical MI was associated with stroke recurrence in the unadjusted analysis but not in the fully adjusted model (HR, 1.31 [95% CI, 0.81–2.11]). Silent MI was not associated with potential cardioembolic subtypes (HR, 1.50 [95% CI, 0.70–3.22]). Conclusions Among patients with a recent ischemic stroke, silent MI was associated with stroke recurrence. Tailored prevention strategies in this population warrant future investigation. Registration URL: https://clinicaltrials.gov . Unique Identifier: NCT00091949.

Introduction: For stroke survivors, blood pressure (BP) reduction significantly lowers the risk of recurrence; a 10mmHg decrease in systolic BP is associated with a 20% risk reduction. Despite the magnitude of this benefit, existing data quantifying post-stroke BP control is limited to small cohorts, national surveys relying on self-report of stroke, and cross-sectional surveys from closed health systems. We aim to determine rates of post-stroke BP control from a broader population within the first year of stroke from multiple cohorts of patients, including from a large US fee-for-service health system, TriNetX (global data source), and two randomized control trials. Methods: We analyzed rates of uncontrolled BP ( > 140/90 mmHg) after stroke in 4 cohorts of individuals 18 years or older: 1) patients in the Yale New Haven Health System (YNHHS) between 2015-2020 at 6 months after stroke (both ischemic and hemorrhagic) hospitalization, 2) patients in TriNetX from 01/01/20 to 07/20/2024 with hypertension (ICD-10 code I10) and a hospital diagnosis of ischemic stroke (ICD-10 code I63), 3) participants with ischemic stroke in the Insulin Resistance Intervention after Stroke (IRIS) trial, and 4) the control arm of the blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomized trial. For TriNetX, IRIS, and SPS3, BP was evaluated at one year after hospitalization. Results: Among YNHHS patients with stroke [n=3,339; mean age 67, 21% Black race, 10% Hispanic ethnicity, 49% male], the rate of uncontrolled BP was 31%. Ischemic strokes accounted for 83.2% of population, while hemorrhagic strokes accounted for 16.8%. In TriNetX [n= 495,474; mean age 69, 17.7% Black race, 5.9% Hispanic ethnicity, 48.6% male], the rate of uncontrolled BP was 33.4%. In the IRIS trial [n=3,135; mean age was 63, 11% Black race, 4% Hispanic ethnicity, and 67% male], 29% of participants were classified with uncontrolled BP. In the SPS3 trial [n=1,519; mean age was 63, 17% Black race, 31% Hispanic ethnicity, 65% male], 40.1% of participants were classified as uncontrolled BP. Conclusion: Among individuals with stroke in clinical trial and real-world cohorts, the rate of uncontrolled BP post-stroke ranged from 29 to 41%. These results support the tremendous need for improved BP management strategies for stroke survivors.

Importance Stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this bias remains unclear. Objective To investigate the association between poststroke disability and the rate of recurrent stroke during long-term follow up. Design, Setting, and Participants This cohort study is a post hoc analysis of the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) and Insulin Resistance Intervention After Stroke (IRIS) secondary prevention clinical trial datasets. PRoFESS enrolled patients from 2003 to 2008, and IRIS enrolled patients from 2005 to 2015. Data were analyzed from September 23, 2023, to May 16, 2024. Exposure The exposure was poststroke functional status at study baseline, defined as modified Rankin Scale (mRS; range, 0-5; higher score indicates more disability) score of 0 vs 1 to 2 vs 3 or greater. Main Outcomes and Measures The primary outcome was recurrent stroke. The secondary outcome was major cardiovascular events (MACE), defined as recurrent stroke, myocardial infarction, new or worsening heart failure, or vascular death. Results A total of 20 183 PRoFESS participants (mean [SD] age, 66.1 [8.5] years; 12 931 [64.1%] male) and 3265 IRIS participants (mean [SD] age, 62.7 [10.6] years; 2151 [65.9%] male) were included. The median (IQR) follow-up was 2.4 (1.9-3.0) years in PRoFESS and 4.7 (3.2-5.0) years in IRIS. In PRoFESS, the recurrent stroke rate was 7.2%, among patients with an mRS of 0, 8.7% among patients with an mRS of 1 or 2, and 10.6% among patients with an mRS of 3 or greater (χ ² 2 = 27.1; P < .001); in IRIS the recurrent stroke rate was 6.4% among patients with an mRS of 0, 9.0% among patients with an mRS of 1 or 2, and 11.7% among patients with an mRS of 3 or greater (χ ² 2 = 11.1; P < .001). The MACE rate was 10.1% among patients with an mRS of 0, 12.2% among patients with an mRS of 1 or 2, and 17.2% among patients with an mRS of 3 or greater (χ ² 2 = 103.4; P < .001) in PRoFESS and 10.9% among patients with an mRS of 0, 13.3% among patients with an mRS of 1 or 2, and 15.3% among patients with an mRS of 3 or greater (χ ² 2 = 5.8; P = .06) in IRIS. Compared with patients with an mRS of 0, patients with an mRS of 3 or greater had increased hazard for recurrent stroke in PRoFESS (hazard ratio [HR], 1.63; 95% CI, 1.38-1.92; P < .001) and in IRIS (HR, 1.91; 95% CI, 1.28-2.86; P = .002). There was also increased hazard for MACE in PRoFESS (HR, 1.90; 95% CI, 1.66-2.18; P < .001) and in IRIS (HR, 1.45; 95% CI, 1.03-2.03; P = .03). Conclusions and Relevance This cohort study found that higher baseline poststroke disability was associated with increased rates of recurrent stroke and MACE. Including more patients with greater baseline disability in stroke prevention trials may improve the statistical power and generalizability of these studies.

Background: Ischemic stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this skew on trial event rates is unclear. Methods: We included participants with ischemic stroke in two secondary stroke prevention trials, PRoFESS and IRIS. The exposure was functional status at entry, defined as modified Rankin Scale (mRS) 0 vs. 1-2 vs. >2. The primary outcome was recurrent stroke (ischemic or hemorrhagic). The secondary outcome was a composite of major adverse cardiovascular events (MACE=stroke, myocardial infarction, heart failure, and vascular death). Results: The cohorts had 20,384 participants from PRoFESS and 3,374 from IRIS. The mean duration of follow-up was 2.4 years in PRoFESS and 3.8 years in IRIS. The rate of recurrent stroke in the mRS categories (0 vs. 1-2 vs. >2) was 7.2%, 8.7%, and 10.6% in PRoFESS and 6.2%, 9.1%, and 11.9% in IRIS (both p≤0.001). The rate of MACE in the mRS categories was 10.1%, 12.2%, and 17.3% in PRoFESS (p<0.001) and 10.6%, 13.3%, and 15.3% in IRIS (p=0.030). In both trials we saw consistent increases in the hazard ratio for recurrent stroke (Table 1) and MACE (Table 2) across mRS categories, after adjusting for potential confounders. There was no evidence that treatment effects differed across mRS categories (mRS by treatment interaction p>0.4). Conclusion: Secondary stroke prevention trial participants with higher levels of baseline disability have increased rates of recurrent stroke and MACE. By enrolling participants across the full range of disability, stroke trials would observe more recurrent stroke events, enhance statistical power, and improve generalizability of results.

Background: Prior data suggest that unrecognized or silent myocardial infarction (MI) detected on routine ECG is associated with first-ever stroke, but the impact on stroke recurrence is unknown. We aimed to determine the association of silent MI with stroke recurrence in patients with recent ischemic stroke. Methods: We included all subjects with an index stroke and available baseline ECG enrolled in the Insulin Resistance in Ischemic Stroke (IRIS) trial. Clinical MI was defined as a prior hospitalization for MI. Silent MI was defined as ECG evidence of MI (Q wave or equivalent patterns) without prior hospitalization for MI. The primary outcome was recurrent stroke. Ischemic stroke and ischemic stroke subtype were assessed as secondary outcomes. Multivariate cox regression adjusted for age, sex, race, pioglitazone, and vascular risk factors was performed for analysis. Results: Of 2285 participants analyzed, prior clinical and silent MI were identified in 164 (7.2%) and 94 (4.1%) patients respectively. Over an average of 4.5 years, 209 recurrent strokes occurred with 191 classified as ischemic. In the fully adjusted model, silent MI was associated with stroke (HR 2.27, CI 1.33-3.88) and ischemic stroke (HR 2.08, CI 1.17-3.68) recurrence. Clinical MI was associated with stroke and ischemic stroke recurrence in the unadjusted analysis; however, the association was no longer significant after adjustment (all stroke: HR 1.31, CI 0.81-2.11; ischemic stroke: HR 1.42, CI 0.87-2.32). No association between silent MI and stroke subtype was significant. Discussion: Among patients with a recent ischemic stroke, silent MI is associated with stroke recurrence. Tailored secondary stroke prevention strategies in this population require future investigation.

Introduction: Over half of patients with acute ischemic stroke are overweight or obese as defined by a body mass index (BMI) ≥25 kg/m2. Professional and government agencies recommend weight management for these persons to improve risk factors for cardiovascular disease, including hypertension, dyslipidemia, vascular inflammation, and diabetes. However, approaches to weight loss have not been adequately tested specifically in patients with stroke. In anticipation of a larger trial with vascular or functional outcomes, we tested the feasibility and safety of a 12-week partial meal replacement (PMR) intervention for weight loss in overweight or obese patients with a recent ischemic stroke. Methods: This randomized open-label trial enrolled participants from December 2019 to February 2021 (with hiatus from March-August 2020 due to COVID-19 pandemic restrictions on research). Eligible patients had a recent ischemic stroke and BMI 27 to 49·9 kg/m². Patients were randomized to a PMR diet (OPTAVIA® Optimal Weight 4 & 2 & 1 Plan®) plus standard care (SC) or SC alone. The PMR diet consisted of four meal replacements supplied to participants, two meals with lean protein and vegetables (self-prepared or supplied) and a healthy snack (also self-prepared or supplied). The PMR diet provided 1,100 to 1,300 calories per day. SC consisted of one instructional session on a healthy diet. Co-primary outcomes were ≥5% weight loss at 12 weeks and to identify barriers to successful weight loss among participants assigned to PMR. Safety outcomes included hospitalization, falls, pneumonia or hypoglycemia requiring treatment by self or others. Due to the COVID-19 pandemic, study visits after August 2020 were by remote communication. Results: We enrolled 38 patients from two institutions. Two patients in each arm were lost and could not be included in outcome analyses. At 12 weeks, 9/17 patients in the PMR group and 2/17 patients in the SC group achieved ≥5% weight loss (52·9% v. 11·9%; Fisher's exact p=0·03). Mean percent weight change in the PMR group was -3·0% (SD 13·7) and -2·6% (SD 3·4) in the SC group (Wilcoxon rank sum p=0·17). No adverse events were attributed to study participation. Some participants had difficulty completing home monitoring of weight. In the PMR group, participants reported that food cravings and dislike for some food products were barriers to weight loss. Conclusion: A PMR diet after ischemic stroke is feasible, safe and effective for weight loss. In future trials, in-person or improved remote outcome monitoring may reduce anthropometric data variation.

Background: At some US Academic Health Centers (AHCs), patients with predominantly Medicaid insurance are seen in one clinic and patients with other insurance are seen in another. The extent of this practice and implications are unknown. Objective: To estimate the proportion of AHCs that have at least two primary care internal medicine clinics that differ substantially in proportion of patients with Medicaid and to compare patient demographic, staffing, and operational features. Participants: General internal medicine chiefs and clinic directors at 40 randomly selected US AHCs plus the top 10 AHCs in terms of NIH funding. Main measure: An AHC was classified as maintaining clinics that differed substantially in the proportion of patients with Medicaid if any two differed by ≥ 40% (absolute). Other criteria were used for pre-specified secondary analyses (e.g., ≥ 30%). Key results: Thirty-nine of 50 AHCs (78%) participated. Four of 39 (10%; 95% CI, 3 to 24%) had two clinics differing by ≥ 40% in the proportion of patients with Medicaid, eight (21%; 95% CI, 9 to 36%) had clinics differing by ≥ 30%, and 15 (38%; 95% CI, 23 to 55%) had clinics differing by ≥ 20%. Clinics with more patients with Medicaid by any of the three criteria were more likely to employ resident physicians as providers of longitudinal care (with faculty supervision) and more likely to have patients who were Black or Hispanic. Conclusions: Some US AHCs maintain separate clinics defined by the proportion of patients with Medicaid. Clinics with a higher proportion of patients insured by Medicaid are more likely to employ residents (with faculty oversight), feature residents as providers of longitudinal care, and serve patients who are Black and Hispanic. Further research is needed to understand why some AHCs have primary care clinics distinguishable by insurance mix with the goal of ensuring that racism and discrimination are not root causes.

Background In individuals with hypertension, lowering blood pressure after stroke can lower the risk of stroke recurrence, but many patients do not reach goal. Home blood pressure monitoring (HBPM) can help patients get to goal, but rates of use and quality of technique have not been evaluated. Methods We conducted a cross-sectional study of patients with stroke. Patients were eligible if they had a stroke within two years, had hypertension, and lived at home. We classified patients as correctly performing HBPM if they used an arm cuff, sat >1 min before measurement, took >2 measurements, and use within 6 months. The primary outcome was the proportion of patients who had a HBPM and used it correctly, which we calculated according to race and ethnicity. We also asked patients what they would do if they found results outside goal. Results Among 150 participants, 120 (81%) possessed a HBPM and 29 (21%) used it correctly. We observed no significant disparity in rates of possession or correct use between non-Hispanic White participants and participants from underrepresented groups. Seventy percent of non-Hispanic White patients said they would contact their provider if their BP was above goal vs. 52% of underrepresented patients (p=0.21). Conclusions Most patients after stroke have a HBPM, but only about 1 in 5 use it correctly. Approximately half of patients from underrepresented racial or ethnic groups do not have a plan for responding to values above goal. Our results indicate opportunities to improve the dissemination and correct use of HBPM.