Jennifer L. Dearborn

The case for diet: a safe and efficacious strategy for secondary stroke prevention

Diet is strongly associated with risk for first stroke. In particular, observational and experimental research suggests that a Mediterranean-type diet may reduce risk for first ischemic stroke with an effect size comparable to statin therapy. These data for first ischemic stroke suggest that diet may also be associated with risk for recurrent stroke and that diet modification might represent an effective intervention for secondary prevention. However, research on dietary pattern after stroke is limited and direct experimental evidence for a therapeutic effect in secondary prevention does not exist. The uncertain state of science in this area is reflected in recent guidelines on secondary stroke prevention from the American Heart Association, in which the Mediterranean-type diet is listed with only a class IIa recommendation (level of evidence C). To change guidelines and practice, research is needed, starting with efforts to better define current nutritional practices of stroke patients. Food frequency questionnaires and mobile applications for real-time recording of intake are available for this purpose. Dietary strategies for secondary stroke prevention are low risk, high potential, and warrant further evaluation.

Perception of risk and knowledge of risk factors in women at high risk for stroke

Background and Purpose— Women face a higher mortality after stroke and have different risk factors than men. Despite educational campaigns, women continue to underestimate their own risk for stroke. We present a theoretical model to understand risk perception in high-risk women. Methods— Eight hundred five women, ages 50 to 70 years, were selected from the University of Connecticut Cardiology Center with at least one risk factor for stroke. A 5-part questionnaire addressed stroke knowledge, risk perception, risk factors, access to health care, and demographics. Two hundred fifteen women responded by mail (28% response rate) and deidentified data were entered in SPSS. Descriptive, bivariate, and multivariate techniques assessed the proposed model. Results— The cohort was predominantly white (91.5%), higher income (33.1% of the population earned >

Obesity, Insulin Resistance, and Incident Small Vessel Disease on Magnetic Resonance Imaging: Atherosclerosis Risk in Communities Study

75 000), and well-educated (28.6% attended graduate or professional school). Only 2 of the 37 (5.4%) women with atrial fibrillation and 11 of the 71 women with heart disease (15.5%) identified their health condition as a risk factor for stroke. Predictors of risk perception included: other women’s risk (B=0.336, P<0.001), worrying about stroke (B=0.734, P<0.001), having hypertension (B=0.686, P=0.037), and having diabetes (B=0.893, P=0.004). Only 63.9% of women with atrial fibrillation (n=23) reported taking warfarin. Conclusions— Women were often unable to identify their health condition as a risk factor for stroke. In addition, many women were not undertaking primary prevention behaviors. Risk perception was low, and high-risk women perceived their risk of stroke to be the same as their peers. Educational strategies must advocate for and target high-risk women.

The Metabolic Syndrome and Cognitive Decline in the Atherosclerosis Risk in Communities Study (ARIC)

Background and Purpose— The term metabolic syndrome describes the clustering of risk factors found in many individuals with obesity. Because of their pathophysiology, we hypothesized that 2 features of metabolic syndrome, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on magnetic resonance imaging, and specifically with incident lacunar disease and not white matter hyperintensity (WMH) progression. Methods— Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study, who completed 2 brain magnetic resonance imagings ≈10 years apart. WMH progression and incident lacunes between the 2 magnetic resonance imagings were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, homeostatic model assessment-IR, body mass index, and waist circumference. Metabolic syndrome (presence/absence), using standard clinical definitions, and IR score at the first magnetic resonance imaging, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 versus Q1–Q4) and incident lacunes. Results— Metabolic syndrome (adjusted odds ratio, 1.98; 95% confidence interval, 1.28–3.05) and IR score (adjusted odds ratio per 1-SD increase, 1.33; 95% confidence interval, 1.05–1.68) were associated with incident lacunes but not with WMH progression. Insulin, homeostatic model assessment-IR, and body mass index were not associated with incident lacunes or WMH progression in separate models. Conclusions— The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease.

Adiponectin and leptin levels in migraineurs in the Atherosclerosis Risk in Communities Study

Background: Midlife metabolic syndrome (MetS) may impact cognitive health as a construct independently of hypertension, hyperlipidemia and other components. Methods: 10,866 participants aged 45-64 years at baseline were assessed for MetS and completed cognitive testing at two later time points (3 and 9 years from the baseline visit). Results: MetS is associated with increased odds of low cognitive performance in the domains of executive function and word fluency, but not with 6-year cognitive decline. Individual MetS components explained this association (hypertension, diabetes, low HDL, elevated triglycerides and increased waist circumference). Conclusions: A focus on the individual risk factors as opposed to MetS during midlife is important to reduce the incidence of cognitive impairment in later life.

Obesity Increases Stroke Risk in Young Adults Opportunity for Prevention

Objective: To evaluate adiponectin and leptin levels in older men and women with migraine. Methods: Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case–cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987–1989). A standardized headache questionnaire was completed at visit 3 (1993–1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine. Results: Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) (p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine. Conclusions: Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women.

Effect of Gender on Communication of Health Information to Older Adults

See related article, p 1690. A debate has been smoldering over the meaning of obesity in reducing the world burden of stroke. Like so many debates in medicine, it begins with disagreements about the interpretation of evidence, the meaning of statistical test results, and the role of bias. In one camp, are those who see that obesity is associated with increased risk for stroke and say that it as an important target for primary and secondary prevention. In the other, are those who agree that obesity increases stroke but say that it is more effective to treat the consequence of obesity that are responsible for stroke risk (ie, hypertension and dyslipidemia) than obesity itself. What everyone can agree on is that obesity is epidemic. In the United States, the prevalence of obesity (ie, body mass index [BMI] > 30 kg/m2) increases with age from 17% for children aged 30 kg/m2 have about a 70% increased risk for ischemic stroke compared with patients with a BMI <25 kg/m2.4,5 In this issue of Stroke , Mitchell et al6 raise further concern about obesity by showing an association with increased stroke risk in a study composed exclusively of young adults. Mitchell et al6 studied men and women …

Intracranial atherosclerosis and dementia: The Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVES: To examine the effect of gender on three key elements of communication with elderly individuals: effectiveness of the communication, perceived relevance to the individual, and effect of gender‐stereotyped content.

Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction

Objective: To explore the association of intracranial atherosclerotic disease (ICAD) with mild cognitive impairment (MCI) and dementia. Methods: From 2011 to 2013, 1,744 participants completed high-resolution vessel wall MRI from the population-based Atherosclerosis Risk in Communities Study by a sampling strategy that allowed weighting back to the cohort. We defined ICAD by plaque features (presence, territory, stenosis, number). Trained clinicians used an algorithm incorporating information from interviews and neuropsychological and neurologic examinations to adjudicate for MCI and dementia. We determined the relative prevalence ratio (RPR) of MCI or dementia after adjusting for risk factors at midlife using multinomial logistic regression. Results: A total of 601 (34.5%) participants had MCI (mean age ± SD, 76.6 ± 5.2 years), 83 (4.8%) had dementia (79.1 ± 5.3 years), and 857 (49.1%) were current or former smokers. Anterior cerebral artery (ACA) plaque (adjusted RPR 3.81, 95% confidence interval [CI] 1.57–9.23), >2 territories with plaque (adjusted RPR 2.12, 95% CI 1.00–4.49), and presence of stenosis >50% (adjusted RPR 1.92, 95% CI 1.01–3.65) were associated with increased prevalence of dementia in separate models. Posterior cerebral artery plaque was associated with MCI but did not reach statistical significance for dementia (adjusted RPR MCI 1.43, 95% CI 1.04–1.98; adjusted RPR dementia 1.58, 95% CI 0.79–2.85). There were no associations with middle cerebral artery atherosclerotic lesions or cognitive impairment. Many participants had plaque in >1 territory (n = 291, 46%) and participants with ACA plaques (n = 69) had the greatest number of plaques in other territories (mean 6.0, SD 4.4). Conclusions: This study demonstrates associations between ICAD and clinical MCI and dementia.

Pioglitazone Prevents Stroke in Patients with a Recent TIA or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial

Importance There is growing recognition that patients may respond differently to therapy and that the average treatment effect from a clinical trial may not apply equally to all candidates for a therapy. Objective To determine whether, among patients with an ischemic stroke or transient ischemic attack and insulin resistance, those at higher risk for future stroke or myocardial infarction (MI) derive more benefit from the insulin-sensitizing drug pioglitazone hydrochloride compared with patients at lower risk. Design, Setting, and Participants A secondary analysis was conducted of the Insulin Resistance Intervention After Stroke trial, a double-blind, placebo-controlled trial of pioglitazone for secondary prevention. Patients were enrolled from 179 research sites in 7 countries from February 7, 2005, to January 15, 2013, and were followed up for a mean of 4.1 years through the study’s end on July 28, 2015. Eligible participants had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or type 2 diabetes. Interventions Pioglitazone or matching placebo. Main Outcomes and Measures A Cox proportional hazards regression model was created using baseline features to stratify patients above or below the median risk for stroke or MI within 5 years. Within each stratum, the efficacy of pioglitazone for preventing stroke or MI was calculated. Safety outcomes were death, heart failure, weight gain, and bone fracture. Results Among 3876 participants (1338 women and 2538 men; mean [SD] age, 63 [11] years), the 5-year risk for stroke or MI was 6.0% in the pioglitazone group among patients at lower baseline risk compared with 7.9% in the placebo group (absolute risk difference, –1.9% [95% CI, –4.4% to 0.6%]). Among patients at higher risk, the risk was 14.7% in the pioglitazone group vs 19.6% for placebo (absolute risk difference, –4.9% [95% CI, –8.6% to 1.2%]). Hazard ratios were similar for patients below or above the median risk (0.77 vs 0.75; P = .92). Pioglitazone increased weight less among patients at higher risk but increased the risk for fracture more. Conclusions and Relevance After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk. However, the risk for fracture is also higher. Trial Registration clinicaltrials.gov Identifier: NCT00091949