How Would You Prevent Subsequent Strokes in This Patient? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Stroke is a major cause of morbidity, mortality, and disability. The American Heart Association/American Stroke Association recently published updated guidelines on secondary stroke prevention. In these rounds, 2 vascular neurologists use the case of Mr. S, a 75-year-old man with a history of 2 strokes, to discuss and debate questions in the guideline concerning intensity of atrial fibrillation monitoring in embolic stroke of undetermined source, diagnosis and management of moderate symptomatic carotid stenosis, and therapeutic strategies for recurrent embolic stroke of undetermined source in the setting of guideline-concordant therapy.

Partial Meal Replacement for Weight Loss after Stroke: Results of a Pilot Clinical Trial.

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 to August 2020 due to COVID-19 pandemic restrictions on research). Eligible patients had a recent ischemic stroke and BMI 27-49.9 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 1,100-1,300 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% vs. 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.

Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.

Stages and Processes of Change for Weight Loss in Acute Stroke or TIA Patients Living with Obesity.

BACKGROUND: Obesity is associated with an increased prevalence of vascular risk factors and incidence of stroke. As such weight loss is recommended for patients living with obesity in the secondary prevention of stroke. Few studies, however, have examined the stages and processes of change for weight loss in stroke patients living with obesity. OBJECTIVE: The aim of the study was to evaluate the stages and processes of change for weight loss in patients living with obesity who have had a recent stroke or TIA. METHODS: Using a validated questionnaire, we assessed each patient's stage of behavioral change according to the transtheoretical model (precontemplation, contemplation, preparation, action, and maintenance). We also examined 4 processes of behavioral change, which quantify activities and experiences that patients undergo on the way to behavioral change: emotional reevaluation (EMR), weight management action (WMA), weight consequence evaluation, and supporting relationships. Processes scores were compared between patients in the action and maintenance stages and those in the precontemplation, contemplation, and preparation stages. RESULTS: Out of 49 patients who provided informed consent, 44 met the inclusion/exclusion criteria. Of these 44 patients, 6 (14%) were in the precontemplation stage of change, 7 (16%) were in contemplation, 2 (5%) were in preparation, 13 (30%) were in action, and 16 (36%) were in maintenance. Those in the action and maintenance stages accounted for the majority of participants (n = 29, 66%). Patients in the action and maintenance stages (N = 29) had higher EMR scores (mean 79, SD 13 vs. mean 68, SD 19, t = 2.0, p = 0.03) and WMA scores (mean 69, SD 13 vs. mean 59, SD 19, t = 2.0, p = 0.03) as compared to those in the precontemplation, contemplation, and preparation stages (N = 15). CONCLUSIONS: Our results suggest that without counseling or specific intervention, approximately two-thirds of stroke/TIA patients living with obesity are in the action or maintenance stage of behavior change with respect to weight loss and therefore more likely to succeed in intensive lifestyle-based interventions targeted towards weight loss. Patients who score higher in EMR and WMA are more likely to be in the action or maintenance stage of change.

Deintensification or No Statin Treatment Is Associated With Higher Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack.

Background and Purpose: Practice guidelines recommend that most patients receive moderate- or high-potency statins after ischemic stroke or transient ischemic attack (TIA) of atherosclerotic origin. We tested the association of different patterns of potency for prescribed statin therapy­assessed before admission and at hospital discharge for ischemic stroke or TIA­on mortality in a large, nationwide sample of US Veterans. Methods: The study population included patients with an ischemic stroke or TIA occurring during 2011 at any of the 134 Veterans Health Administration facilities. We used electronic outpatient pharmacy files to identify statin dose at hospital admission and within 7 days after hospital discharge. We categorized statin dosing as low, moderate, or high potency; moderate or high potency was considered at goal. We created 6 mutually exclusive groups to reflect patterns of statin potency from hospital admission to discharge: goal to goal, low to goal, goal to low or goal to none (deintensification), none to none, none to low, and low to low. We used logistic regression to compare 30-day and 1-year mortality across statin potency groups. Results: The population included 9380 predominately White (71.1%) men (96.3%) who were hospitalized for stroke or TIA. In this sample, 34.1% of patients (n=3194) were discharged off a statin medication. Deintensification occurred in 14.0% of patients (n=1312) and none to none in 20.5% (n=1924). Deintensification and none to none were associated with a higher odds of mortality as compared with goal to goal (adjusted odds ratio 1-year mortality: deintensification versus goal to goal, 1.26 [95% CI, 1.02­1.57]; none to none versus goal to goal, 1.59 [95% CI, 1.30­1.93]). Adjustments for differences in baseline characteristics using propensity weighted scores demonstrated similar results. Conclusions: Underutilization of statins, including no treatment or underdosing after stroke (deintensification), was observed in approximately one-third of veterans with ischemic stroke or TIA and was associated with higher mortality when compared with patients who were at goal for statin prescription dosing.

Association of Dietary Patterns in Midlife and Cognitive Function in Later Life in US Adults Without Dementia.

Importance: The association of dietary patterns, or the combinations of different foods that people eat, with cognitive change and dementia is unclear. Objective: To examine the association of dietary patterns in midlife with cognitive function in later life in a US population without dementia. Design, Setting, and Participants: Observational cohort study with analysis of data collected from 1987 to 2017. Analysis was completed in January to February 2019. Community-dwelling black and white men and women from Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburban Minneapolis, Minnesota, participating in the Atherosclerosis Risk in Communities (ARIC) study were included. Exposures: Two dietary pattern scores were derived from a 66-item food frequency questionnaire using principal component analysis. A Western, or unhealthy, dietary pattern was characterized by higher consumption of meats and fried foods. A so-called prudent, or healthier, dietary pattern was characterized by higher amounts of fruits and vegetables. Main Outcomes and Measures: Results of 3 cognitive tests (Digit Symbol Substitution Test, Word Fluency Test, and Delayed Word Recall) performed at 3 points (1990-1992, 1996-1998, and 2011-2013) were standardized and combined to represent global cognitive function. The 20-year change in cognitive function was determined by tertile of diet pattern score using mixed-effect models. The risk of incident dementia was also determined by tertile of the diet pattern score. Results: A total of 13 588 participants (7588 [55.8%] women) with a mean (SD) age of 54.6 (5.7) years at baseline were included; participants in the top third of Western and prudent diet pattern scores were considered adherent to the respective diet. Cognitive scores at baseline were lower in participants with a Western diet (z score for tertile 3 [T3], -0.17 [95% CI, -0.20 to -0.14] vs T1, 0.17 [95% CI, 0.14-0.20]) and higher in participants with a prudent diet (z score for T3, -0.09 [95% CI, -0.12 to -0.06] vs T1, -0.09 [95% -0.12 to -0.06]). Estimated 20-year change in global cognitive function did not differ by dietary pattern (difference of change in z score for Western diet, T3 vs T1: -0.01 [95% CI, -0.05 to 0.04]; and difference of change in z score for prudent diet, T3 vs T1: 0.02 [95% CI, -0.02 to 0.06]). The risk of incident dementia did not differ by dietary pattern (Western hazard ratio for T3 vs T1, 1.06 [95% CI, 0.92-1.22]; prudent hazard ratio for T3 vs T1, 0.99 [95% CI, 0.88-1.12]). Conclusions and Relevance: This study found that the dietary pattern of US adults at midlife was not associated with processing speed, word fluency, memory, or incident dementia in later life.

Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial.

Importance: In the Insulin Resistance Intervention After Stroke (IRIS) randomized clinical trial, pioglitazone, an insulin-sensitizing agent, reduced the risk for recurrent stroke or myocardial infarction (MI) among patients with insulin resistance. However, insulin resistance is not commonly measured in clinical practice. Objective: To analyze the effects of pioglitazone in patients with good adherence as well as intention-to-treat effects of pioglitazone in patients with prediabetes in the IRIS trial. Design, Setting, and Participants: The IRIS trial was a randomized multicenter clinical trial in patients with prior stroke or transient ischemic attack as well as insulin resistance but not diabetes. Patients were enrolled from February 2005 to January 2013, and the median follow-up was 4.8 years. The post hoc analyses reported here were performed from June to September 2018. Per American Diabetes Association criteria, prediabetes was defined as having a hemoglobin A1c level of 5.7% to 6.4% or fasting plasma glucose level of 100 mg/dL to 125 mg/dL (to convert to mmol/L, multiply by 0.0555). Good adherence was defined as taking 80% or more of the protocol dose. Fasting glucose and hemoglobin A1c, used to define prediabetes, and adherence of 80% or higher, stipulated in the protocol as defining good adherence, were prespecified subgroups in the analysis plan. Interventions: Participants were randomized to 15 mg of pioglitazone, with dose titrated to target of 45 mg daily, or matching placebo. Main Outcomes and Measures: The primary outcome was recurrent stroke or MI. Secondary outcomes included stroke, acute coronary syndrome, stroke/MI/hospitalization for heart failure, and progression to diabetes. Results: Among 3876 participants analyzed in the IRIS trial, 2885 were included in this analysis (1456 in the pioglitazone cohort and 1429 in the placebo cohort). The mean (SD) age of patients was 64 (11) years, and 974 (66.9%) and 908 (63.5%) of patients were men in the pioglitazone and placebo cohort, respectively. In the prediabetic population with good adherence (644 of 1456 individuals [44.2%] in the pioglitazone group and 810 of 1429 [56.7%] in the placebo group), the hazard ratios (95% CI) were 0.57 (0.39-0.84) for stroke/MI, 0.64 (0.42-0.99) for stroke, 0.47 (0.26-0.85) for acute coronary syndrome, 0.61 (0.42-0.88) for stroke/MI/hospitalization for heart failure, and 0.18 (0.10-0.33) for progression to diabetes. There was a nonsignificant reduction in overall mortality, cancer, and hospitalization, a slight increase in serious bone fractures, and an increase in weight gain and edema. Intention-to-treat results also showed significant reduction of events but to a lesser degree. Hazard ratios (95% CI) were 0.70 (0.56-0.88) for stroke/MI, 0.72 (0.56-0.92) for stroke, 0.72 (0.52-1.00) for acute coronary syndrome, 0.78 (0.63-0.96), for stroke/MI/hospitalization for heart failure, and 0.46 (0.35 to 0.61) for progression to diabetes. Conclusions and Relevance: Pioglitazone may be effective for secondary prevention in patients with stroke/transient ischemic attack and with prediabetes, particularly in those with good adherence. Trial Registration: ClinicalTrials.gov identifier: NCT00091949.