Risk Of Incident Ischemic Stroke Research Articles

Association of Sickle Cell Trait With Ischemic Stroke Among African Americans

African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear. To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans. This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women's Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017. Participants' SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation. Incident ischemic stroke. This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar. Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a stroke patient with SCT rather than assuming that SCT is the etiologic factor for the stroke.

A prospective study of the hypertriglyceridemic waist phenotype and risk of incident ischemic stroke in a Chinese rural population

The hypertriglyceridemic waist phenotype has been reported as a practical tool to screen people with an increased risk of coronary artery disease and type 2 diabetes. The aim of this study was to investigate the relationship between the phenotype and ischemic stroke in a rural population in south China. A total of 4081 participants aged over 35years old without a stroke history were surveyed in 2009 and followed up from May 2014 to January 2016. The hypertriglyceridemic waist phenotype was defined as a waist circumference ≥90cm and a triglyceride level ≥2.0mmol/L in males, and a waist circumference ≥85cm and a triglyceride level ≥1.5mmol/L in females. A Cox regression model was used to estimate the association of the phenotype and ischemic stroke. After a mean of 5.16years of follow-up, 138 individuals developed ischemic stroke. The hypertriglyceridemic waist phenotype was significantly associated with an increased risk of ischemic stroke before and after adjustment for confounding factors; the hazard ratios and 95% confidence intervals were 1.94 (1.27-2.96) and 1.71 (1.05-2.78), respectively. Further stratified analysis confirmed the associations in females (2.37 [1.09-5.14]) and smokers (3.20 [1.30-7.92]). A significant association of the phenotype and ischemic stroke risk was observed in subjects with normal glucose levels (2.94 [1.58-5.47]) but not in subjects with impaired fasting glucose and diabetes. The hypertriglyceridemic waist phenotype is associated with an increased risk of ischemic stroke and might be a simple tool to screen individuals with a high risk for ischemic stroke.

Residential Proximity to Major Roadways and Risk of Incident Ischemic Stroke in NOMAS (The Northern Manhattan Study).

The evidence supporting the deleterious cardiovascular health effects of living near a major roadway is growing, although this association is not universal. In primary analyses, we hypothesized that residential proximity to a major roadway would be associated with incident ischemic stroke and that cardiovascular risk factors would modify that association. NOMAS (The Northern Manhattan Study) is an ongoing, population-based cohort study designed to measure cardiovascular risk factors, stroke incidence, and other outcomes in a multiethnic urban population. Recruitment occurred from 1993 to 2001 and participants are followed-up annually by telephone. Residential addresses at baseline were geocoded and Euclidean distance to nearest major roadway was estimated and categorized as in prior studies. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for the association of this distance to incidence of stroke and other outcomes, adjusting for sociodemographic and cardiovascular risk factors, year at baseline, and neighborhood socioeconomic status. We assessed whether these associations varied by age, sex, smoking status, diabetes mellitus, and hypertension. During a median follow-up period of 15 years (n=3287), 11% of participants were diagnosed with ischemic stroke. Participants living <100 m from a roadway had a 42% (95% confidence interval, 1.01-2.02) higher rate of ischemic stroke versus those living >400 m away. This association was more pronounced among noncurrent smokers (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26) and not evident among smokers (hazard ratio, 0.69; 95% confidence interval, 0.23-2.06). There was no clear pattern of association between proximity to major roadways and other cardiovascular events including myocardial infarction, all-cause death, or vascular death. In this urban multiethnic cohort, we found evidence supporting that within-city variation in residential proximity to major roadway is associated with higher risk of ischemic stroke. An individual's smoking history modified this association, with the association remaining only among participants not currently smokers.

Body fat distribution and risk of incident ischemic stroke in men and women aged 50 to 74 years from the general population. The KORA Augsburg cohort study.

BackgroundIt remains controversial whether measures of general or abdominal adiposity are better risk predictors for ischemic stroke. Furthermore, so far it is unclear whether body fat mass index (BFMI) and fat free mass index (FFMI) are risk predictors for ischemic stroke. This study examined the sex-specific relevance of body mass index (BMI), BROCA Index, waist circumference (WC), waist-height ratio (WHtR), BFMI and FFMI for the development of ischemic stroke in a Caucasian population.Material and methodsThe prospective population-based cohort study was based on 1917 men and 1832 women (aged 50 to 74 years) who participated in the third (1994/95) or fourth (1999/2001) MONICA/KORA Augsburg survey. Subjects were free of stroke at baseline. Standardized anthropometric and bioelectric impedance measurements were obtained at baseline. Hazard ratios (HR) were estimated from Cox proportional hazard models.ResultsDuring a median follow-up of 9.3 years 128 ischemic strokes occurred in men and 81 in women, respectively. Coded as quartiles WC and WHtR were significantly associated with incident stroke in multivariable analyses in women (comparing the 4th vs. the bottom quartile), but none of the adiposity measures was significantly associated with incident stroke in multivariable adjusted analyses in men. When anthropometric measures were used as continuous variables, these findings were confirmed. After multivariable adjustment the associations between obesity measures and incident ischemic stroke were statistically significant only for WC (HR 1.39, 95%CI 1.12-1.72) and WHtR in women (HR 1.39, 95%CI 1.12-1.73) per increase of 1 standard deviation. In both sexes the measures BFMI and FFMI were no independent predictors for incident ischemic stroke.ConclusionsAbdominal obesity measures are independent predictors of incident ischemic stroke in women but not in men from the general adult population. Thus, it may be of particular importance for women to prevent central obesity in order to reduce their risk of ischemic stroke.

Abstract WMP54: High Serum Troponin Levels and Sex Differences With First Time Ischemic Stroke: Findings From the Chronic Renal Insufficiency Cohort Study

Introduction and Hypothesis: High troponin levels reflect myocardial damage in patients with heart disease and predict poor prognosis in stroke and cardiomyopathies. In the study, we test the hypothesis that high troponin levels in the setting of chronic renal insufficiency (CRI) significantly predict the risk of first time stroke. Method: The Chronic Renal Insufficiency Cohort Study enrolled a total of 3,477 patients with no previous history of stroke at baseline were used in this study. High troponin level is defined as troponin levels ≥0.03 ug/L. Incident hemorrhagic and ischemic strokes were classified using ICD-9. The associations between baseline troponin levels and incidence of hemorrhagic and ischemic stroke and risk of all-cause mortality were analyzed prospectively using multivariate Cox’s regression analysis technique. Results: With an average (SD) of 7.7 (1.5) years of follow-up, 23 participants developed incident hemorrhagic stroke (HS), and 84 developed incident ischemic stroke (IS). Participants with high troponin had significantly higher IS rate than those with low troponin (9.69% vs. 2.81%, p&lt;.0001). After adjustment for age, race, smoking, body mass index, systolic blood pressure, eGFR, total cholesterol to HDL ratio, diabetes, and myocardial infarction, Cox’s models indicate that participants with high troponin had 2.68 times higher risk of incident IS than those with low troponin (HR: 2.68, 95%CI: 1.55-4.62, p=0.0004). Females with high troponin had a significantly higher risk of IS than males (excess HR=3.41, 95%CI 1.25-8.41, p=0.016). Participants with high troponin had a significantly increased risk of all-cause mortality in both sexes. Of them, females with high troponin had a significantly higher risk of all-cause mortality than males (HR=1.57, 95%CI: 1.15-2.16, p=0.005). No statistical significance was observed for the risk of incident HS. Conclusion: In CRI patients elevated serum troponin levels were significantly associated with the risk of first time IS and higher all-cause mortality risk. The risk is further amplified significantly in females compared to males indicating sex differences play an important role in first time stroke risk in CRI. These findings represent an unexplored risk of IS.

Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study

Background and aimsIn European descent populations, shorter leukocyte telomere length (LTL) has been associated with subclinical atherosclerosis, cardiovascular disease (CVD), and mortality, while longer LTL has been associated with greater left ventricular hypertrophy. We evaluated the relationship of LTL with subclinical cardiovascular disease indices and incident clinical events and mortality in African Americans (AAs). MethodsAnalyses were restricted to 2518 participants of the Jackson Heart Study (JHS) with LTL measured by Southern blot in baseline blood samples. ResultsAdjusting for established CVD risk factors, longer LTL was significantly associated with lower prevalence of coronary artery calcification (CAC) (odds ratio (OR) = 0.810) per 1 kb increase in LTL; (95% confidence interval [CI] 0.656, 0.9998), p=0.0498). Longer LTL was also associated with higher ankle brachial index (ABI) (β = 0.023; (95% CI 0.004, 0.042), p=0.017) when comparing the highest to the lowest LTL quartile. There were no significant associations between LTL and abdominal aortic calcification, carotid intima-media thickness, or left ventricular mass. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke (hazard ratio (HR) 0.69 (95% CI 0.48, 0.99), p=0.044) and total mortality (HR 0.81 (95% CI 0.67, 0.97), p=0.026) in age and sex adjusted models, but these associations were no longer significant in fully adjusted models. ConclusionsAmong a community-based cohort of AAs, longer LTL was nominally associated with lower odds of CAC and increased ABI, indicative of decreased prevalence of subclinical atherosclerosis and peripheral arterial disease. These findings do not offer strong support for LTL as an independent biomarker of CVD risk in AAs.

Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)

Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P=0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P=0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data.

P-Wave Indices and Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis.

Atrial cardiomyopathy is associated with an increased risk of ischemic stroke. P-wave terminal force in lead V1, P-wave duration, and maximum P-wave area are electrocardiographic parameters that have been used to assess left atrial abnormalities related to developing atrial fibrillation. The aim of this systematic review and meta-analysis was to examine their values for predicting ischemic stroke risk. PubMed and EMBASE databases were searched until December 2016 for studies that evaluated the association between P-wave indices and stroke risk. Both fixed- and random-effects models were used to calculate the overall effect estimates. Ten studies examining P-wave terminal force in lead V1, P-wave duration, and maximum P-wave area were included. P-wave terminal force in lead V1 was found to be an independent predictor of stroke as both a continuous variable (odds ratio [OR] per 1 SD change, 1.18; 95% confidence interval [CI], 1.12-1.25; P<0.0001) and categorical variable (OR, 1.59; 95% CI, 1.10-2.28; P=0.01). P-wave duration was a significant predictor of incident ischemic stroke when analyzed as a categorical variable (OR, 1.86; 95% CI, 1.37-2.52; P<0.0001) but not when analyzed as a continuous variable (OR, 1.05; 95% CI, 0.98-1.13; P=0.15). Maximum P-wave area also predicted the risk of incident ischemic stroke (OR per 1 SD change, 1.10; 95% CI, 1.04-1.17). P-wave terminal force in lead V1, P-wave duration, and maximum P-wave area are useful electrocardiographic markers that can be used to stratify the risk of incident ischemic stroke.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P=0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke (P<0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P=0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P=0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.

Fine particulate matter exposure and incidence of stroke: A cohort study in Hong Kong.

We aimed to assess the association of long-term residential exposure to fine particulate matter (PM) with aerodynamic diameter less than 2.5 μm (PM2.5) with the incidence of stroke and its major subtypes. We ascertained the first occurrence of emergency hospital admission for stroke in a Hong Kong Chinese cohort of 66,820 older people (65+ years) who enrolled during 1998-2001 (baseline) and were followed up to December 31, 2010. High-resolution (1 × 1 km) yearly mean concentrations of PM2.5 were predicted from local monitoring data and US National Aeronautics and Space Administration satellite data using linear regression. Baseline residential PM2.5 exposure was used as a proxy for long-term exposure. We used Cox proportional hazards to evaluate the risk of incident stroke associated with PM2.5 exposure adjusted for potential confounders, including individual and neighborhood factors. Over a mean follow-up of 9.4 years, we ascertained 6,733 cases of incident stroke, of which 3,526 (52.4%) were ischemic and 1,175 (17.5%) were hemorrhagic. The hazard ratio for every 10 μg/m3 higher PM2.5 concentration was statistically significant at 1.21 (95% confidence interval [CI] 1.04-1.41) for ischemic and non-statistically significant at 0.90 (95% CI 0.70-1.17) for hemorrhagic stroke in fully adjusted model 3. The estimates for ischemic stroke were higher in older participants (>70 years), less educated participants, and in men for current smokers. Long-term PM2.5 exposure was associated with higher risk of incident ischemic stroke, but the association with incident hemorrhagic stroke was less clear.

Abstract P107: Leucocyte Telomere Length and Cardiovascular Disease in the Jackson Heart Study

Background: In European descent populations, shorter leucocyte telomere length (LTL) has been associated with clinical and subclinical atherosclerosis, while longer LTL has been associated with greater left ventricular hypertrophy (LVH). We evaluated the relationship of LTL with subclinical indices of cardiovascular disease (CVD) (coronary artery calcification [CAC], abdominal aorta calcification [AAC], carotid intima media thickness [CIMT], left ventricular mass [LVM], and ankle-brachial index [ABI]) in African Americans (AAs). We also examined whether LTL is associated with CVD events and mortality. Methods: Analyses included participants of the Jackson Heart Study (JHS), a prospective cohort study of AAs, with LTL data (n=2,573) measured by Southern blot analysis in DNA from the baseline exam (2000-2004). Adjudicated CVD events (coronary heart disease [CHD], heart failure [HF] and stroke) and mortality were identified through December 2012. Relationships were assessed using linear, logistic regression models, or Tobit model (CAC and AAC due to left censoring) in STATA 14. Results: In an age and sex adjusted model, longer LTL was significantly associated with lower CAC ( P =0.049, β=-0.535; 95% confidence interval [CI], -1.066,-0.003); this association was no longer significant after adjusting for body mass index, current smoking and other CVD risk factors. There were no significant associations between LTL and AAC, CIMT, or LVM. LTL was associated with higher ABI ( P =0.017, β=0.023; 95% CI, 0.004, 0.042) when the highest was compared to the lowest LTL quartile in models adjusted for CVD risk factors. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke and total mortality in age and sex adjusted models, but these associations were no longer significant in models fully adjusted for CVD risk factors. Conclusions: In conclusion, among a community-based cohort of AAs, LTL was associated with increased ABI, indicative of increased risk of peripheral arterial disease, but there were no significant associations with other CVD indices and mortality after adjustment for established risk factors.

Abstract TMP107: Regular Dental Care Reduces the Risk for Ischemic Stroke: Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Prior epidemiological studies have shown that periodontal disease (PD), also referred to as gum disease, is an independent risk factor for ischemic stroke. We assessed the hypothesis that users of regular dental care may have a lower risk for incident ischemic stroke and specific stroke subtype when compared with users of episodic dental care. Methods: In this prospective, longitudinal community-based cohort study, participants without prior stroke were assessed for dental care utilization represented by patient-reported responses to questionnaires. The pattern of dental care utilization was classified as regular use (every year), episodic use (as needed), or no use (never). Episodic visits, or visits as needed, are considered signs of inadequate utilization of dental care. These participants were followed for incident ischemic strokes. Ischemic stroke diagnoses were defined as sudden onset of neurological deficit(s) lasting ≥24 hours along with neuroimaging confirmation. Strokes were further classified according to etiologic subtype as thrombotic, lacunar, or cardioembolic stroke subtype according to criteria adopted from the National Survey of Stroke. Results: Of 11,242 participants (mean age±SD=62.8±5.6, 56% female, 78% white and 22% African-American) assessed for dental care utilization at the fourth ARIC visit (1996-1998). Over a 15-year follow-up period a total of 583 participants had incident ischemic stroke events, of who 19% were lacunar, 29% were cardioembolic and 45% were of the thrombotic stroke subtype. After adjustment for confounders (race/center, age, gender, BMI, hypertension, diabetes, LDL level, smoking, and education), regular dental care utilization was associated with lower risk for ischemic stroke overall compared with episodic dental users (adjusted HR 0.77, 95% CI 0.63-0.94). Regular dental care specifically lowered the risk of thrombotic stroke subtype (adjusted HR 0.75, 95% CI 0.56-0.99). Conclusions: Results from this prospective cohort study demonstrates an independent association between regular dental care utilization with a lower ischemic stroke risk. Further, we report the highest impact of regular dental care in lowering risk of the thrombotic stroke subtype.

Abstract WP193: Gum Disease and Ischemic Stroke Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Gum, or periodontal disease (PD) is a risk factor for cardiovascular disease. We assessed the graded association of PD levels with incident ischemic stroke as well as the etiological stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: PD was assessed by full-mouth periodontal measurements from 6 sites per tooth, in subjects without prior stroke and categorized into periodontal profile class (PPC). A Latent Class Analysis was used to identify 7 distinct PPCs using the entire cohort that included tooth level periodontal measurements and tooth loss. Stroke diagnoses were based on computer derived diagnosis medical record review and imaging confirmation. Classification required evidence of sudden onset of neurological deficit(s) lasting ≥24 hours. Strokes were classified according to etiology as thrombotic, lacunar, and cardioembolic subtypes. Results: At the fourth ARIC visit (1996-1998), a cohort of 6711 subjects (mean age±SD=62.3±5.6, 55% female, 81% white and 19% African-American) were assessed for PD. A total of 299 incident ischemic strokes (47% thrombotic, 26% cardioembolic and 20% lacunar) occurred over a 15-year period. The seven levels of PPC showed a graded association with incident ischemic stroke as noted in the figure. Participants with mild PD (adjusted HR 1.9 95% CI 1.2-3.0), moderate PD group (adjusted HR 2.1 95% CI 1.2-3.5) and severe PD (adjusted HR 2.2 95% CI 1.3-3.8) had an increased risk of incident ischemic stroke, compared with participants without PD after adjustment for confounders (age, race, gender, BMI, hypertension, diabetes, LDL cholesterol, smoking and education). There were class specific associations noted between PD with cardioembolic and thrombotic stroke subtypes. Conclusions: A graded association was noted between incident ischemic stroke and increasing levels of PPC. Further, we report class specific associations between PD with cardioembolic and thrombotic stroke subtypes.

Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Background: Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed.Objectives: We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence.Methods: We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA’s Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders.Results: Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure.Conclusions: Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence.

Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort

Background Whether obesity is a major risk factor for cardiovascular disease in the absence of metabolic comorbidities remains under debate. Indeed, some obese individuals may be at low risk of metabolic-related complications, while normal-weight individuals may not be "healthy." Aims To assess the incidence of ischemic stroke according to the metabolic health and obesity states of 5171 participants from the Vascular-Metabolic CUN cohort. Methods A Cox proportional-hazard analysis was conducted to estimate the hazard ratio and their 95% confidence interval of stroke according to the metabolic health and obesity states based on TyG index and Adult Treatment Panel-III criteria, during 9.1 years of follow-up. Results After 50,056.2 person-years of follow-up, 162 subjects developed an ischemic stroke (incidence rate 3.23 per 1000 person-years). Metabolically healthy obese subjects did not show greater risk of stroke, while metabolically unhealthy participants, obese and non-obese, had an increased risk of stroke, compared with healthy non-obese. The hazard ratios for the multivariable adjusted model were 1.55 (95% CI: 1.36-1.77) and 1.86 (95% CI: 1.57-2.21), respectively. Conclusions Metabolically unhealthy individuals exhibited a greater risk of ischemic stroke than metabolically healthy obese individuals.

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction

Background: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA₂DS₂VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. Methods: In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA₂DS₂VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. Results: White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA₂DS₂VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA₂DS₂VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). Conclusions: An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA₂DS₂VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence.

Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study.

We related a panel of inflammatory biomarkers to risk of incident ischemic stroke (IIS) in a community-dwelling sample. Stroke-free Framingham offspring attending examination cycle 7 (1998-2001) had 15 circulating inflammatory biomarkers measured. Cox proportional hazard models were used to calculate the hazard ratios (HRs) of IIS per SD increment of each biomarker. Model 1 included age and sex. Model 2 additionally adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. The continuous net reclassification improvement was used to assess the improvement in IIS risk prediction of statistically significant biomarkers from our main analysis over traditional stroke risk factors. In 3,224 participants (mean age 61 ± 9 years, 54% women), 98 experienced IIS (mean follow-up of 9.8 [±2.2] years). In model 1, ln-C-reactive protein (ln-CRP) (HR 1.28, 95% confidence interval [CI] 1.04-1.56), ln-tumor necrosis factor receptor 2 (ln-TNFR2) (HR 1.33, 95% CI 1.09-1.63), ln-total homocysteine (ln-tHcy) (HR 1.32, 95% CI 1.11-1.58), and vascular endothelial growth factor (VEGF) (HR 1.25, 95% CI 1.07-1.46) were associated with risk of IIS. All associations, except for ln-CRP, remained significant in model 2 (ln-TNFR2: HR 1.24, 95% CI 1.02-1.51; ln-tHcy: HR 1.20, 95% CI 1.01-1.43; and VEGF: HR 1.21, 95% CI 1.04-1.42). The addition of these 4 biomarkers to the clinical Framingham Stroke Risk Profile score improved stroke risk prediction (net reclassification improvement: 0.34, 0.12-0.57; p < 0.05). Higher levels of 4 biomarkers-CRP, tHcy, TNFR2, and VEGF-increased risk of IIS and improved the predictive ability of the Framingham Stroke Risk Profile score. Further research is warranted to explore their role as potential therapeutic targets.

Dietary choline and betaine; associations with subclinical markers of cardiovascular disease risk and incidence of CVD, coronary heart disease and stroke: the Jackson Heart Study.

Several mechanisms have been described through which dietary intake of choline and its derivative betaine may be associated in both directions with subclinical atherosclerosis. We assessed the association of dietary intake of choline and betaine with cardiovascular risk and markers of subclinical cardiovascular disease. Data from 3924 Jackson Heart Study (JHS) African-American participants with complete food frequency questionnaire at baseline and follow-up measurements of heart disease measures were used. Multivariable linear regression models were employed to assess associations between choline and betaine intake with carotid intima-media thickness, coronary artery calcium, abdominal aortic calcium and left ventricular mass. Cox proportional hazards regression models were used to estimate associations with time to incident coronary heart disease (CHD), ischemic stroke and cardiovascular disease (CVD). During an average nine years of follow-up, 124 incident CHD events, 75 incident stroke events and 153 incident CVD events were documented. In women, greater choline intake was associated with lower left ventricular mass (p=0.0006 for trend across choline quartiles) and with abdominal aortic calcium score. Among all JHS participants, there was a statistically significant inverse association between dietary choline intake and incident stroke, β=-0.33 (p=0.04). Betaine intake was associated with greater risk of incident CHD when comparing the third quartile of intake with the lowest quartile of intake (HR 1.89, 95% CI 1.14, 3.15). Among our African-American participants, higher dietary choline intake was associated with a lower risk of incident ischemic stroke, and thus putative dietary benefits. Higher dietary betaine intake was associated with a nonlinear higher risk of incident CHD.

Genetic susceptibility to dyslipidemia and incidence of cardiovascular disease depending on a diet quality index in the Malmö Diet and Cancer cohort.

BackgroundBy taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk.MethodsWe included 24,799 participants (62 % women, age 44–74 years) from the Malmö Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants’ dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose.ResultsThe GRSLDL-C (P = 5 × 10−6) and GRSHDL-C (P = 0.02) but not GRSTG (P = 0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk (P > 0.39). A high compared to a low diet quality attenuated the association between GRSLDL-C and the risk of incident ischemic stroke (P interaction = 0.01).ConclusionWe found some evidence of an interaction between diet quality and GRSLDL-C on ischemic stroke.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0536-0) contains supplementary material, which is available to authorized users.

Procalcitonin and Midregional Proatrial Natriuretic Peptide as Markers of Ischemic Stroke: The Northern Manhattan Study.

Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke (IS). We hypothesized that selected blood biomarkers of infection (procalcitonin [PCT]), hypothalamic-pituitary-axis function (copeptin), and hemodynamic dysfunction (midregional proatrial natriuretic peptide [MRproANP]) are associated with incident IS risk in the multiethnic, urban Northern Manhattan Study (NOMAS) cohort. A nested case-control study was performed among initially stroke-free participants. Cases were defined as first IS (n=172). We randomly selected controls among those who did not develop an event (n=344). We calculated Cox proportional hazards models with inverse probability weighting to estimate the association of blood biomarkers with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. Those with PCT and MRproANP, but not copeptin, in the top quartile, compared with the lowest quartile, were associated with IS (for PCT adjusted hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.8 and for MRproANP adjusted HR, 3.5; 95% CI, 1.6-7.5). The associations of PCT and MRproANP differed by stroke etiology; PCT levels in the top quartile were particularly associated with small vessel stroke (adjusted HR, 5.1; 95% CI, 1.4-18.7) and MRproANP levels with cardioembolic stroke (adjusted HR, 16.3; 95% CI, 3.7-70.9). Higher levels of PCT, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with IS risk. PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk. Further study is needed to validate these biomarkers and determine their significance in stroke risk prediction and prevention.