Stroke-free Individuals Research Articles

Association of higher diastolic blood pressure levels with cognitive impairment

We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women >or=45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of <or=4 on 6-Item Screener) after adjusting for demographic and environmental characteristics, cardiovascular risk factors, depressive symptoms, and current use of any antihypertensive medication. Higher DBP levels were associated with impaired cognitive status after adjusting for demographic and environmental characteristics, risk factors, depressive symptoms, and antihypertensive medications. An increment of 10 mm Hg in DBP was associated with a 7% (95% confidence interval [CI] 1%-14%, p = 0.0275) higher odds of cognitive impairment. No independent association was identified between impaired cognitive status and SBP (odds ratio [OR] 1.02, 95% CI 0.99-1.06) or PP (OR 0.99, 95% CI 0.95-1.04). There was no evidence of nonlinear relationships between any of the BP components and impaired cognitive status. There was no interaction between age and the relationship of impaired cognitive status with SBP (p = 0.827), DBP (p = 0.133), or PP (p = 0.827) levels. Higher diastolic blood pressure was cross-sectionally and independently associated with impaired cognitive status in this large, geographically dispersed, race- and sex-balanced sample of stroke-free individuals.

Statins for Asymptomatic Middle Cerebral Artery Stenosis: The Regression of Cerebral Artery Stenosis Study

Background: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0–5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (<10%), mild (10–49%), moderate (50–90%) and severe (>90%). The primary outcome was the change in grading of MCA stenosis over 2 years. Results: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). Conclusions: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years.

Effects of statins on the progression of cerebral white matter lesion

Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.

Metabolic Syndrome Clusters and the Risk of Incident Stroke

Little is known about the metabolic syndrome (MetS) and the risk of incident stroke. This study is designed to identify particular clusters of MetS components that carry the highest risk of incident stroke. We analyzed the public use data from the population-based Atherosclerosis Risk in Communities study. At baseline, 14 993 stroke-free middle-aged individuals were followed-up over 9 years for incident stroke. MetS components were defined according to the National Heart, Lung, and Blood Institute/American Heart Association criteria. Incident stroke was identified using a standardized incident events identification and classification protocol. Proportional hazard models were used to assess the RRs and 95% CIs of ischemic stroke associated with MetS and its different clusters. At baseline, the prevalence of MetS was 39%. The mean age was 54, with 26% blacks and 55% females. The hazard ratio of incident ischemic stroke associated with MetS among women (hazard ratio, 2.41; 95% CI, 1.69 to 3.49) and men (hazard ratio, 2.11; 95% CI, 1.56-2.85) was similar. There was a dose-response relationship between the numbers of MetS components and the risk of incidence stroke. Persons with either elevated blood pressure or elevated fasting glucose in the clusters to form a MetS had the highest risk for incident stroke (hazard ratio, 2.74-4.16 comparing to the reference group) than MetS without these 2 components (hazard ratio, </=2.00 comparing to the reference group). The data support the need to target MetS, especially MetS, with these 2 highest risk components (elevated blood pressure or elevated fasting glucose) in the clusters.

Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy

To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF.

T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of stroke

Local humoral and cellular immune responses modulate the inflammatory processes involved in the development of atherosclerotic lesions, as well as in the evolution of brain infarcts in stroke patients. The role of systemic adaptive immunity on the progression of such disease manifestations is less clear. In the current study, we evaluated the percentages of T helper 1 (Th1) [interleukin (IL)-2, interferon (IFN)-gamma] and Th2 (IL-4, IL-10) cytokine-producing peripheral blood CD4+ and CD8+ T cells in 23 patients with a history of ischaemic stroke (IS) at the chronic stable phase of the disease (median post-stroke time 34.5 months). Seven stroke-free individuals matched for age and vascular risk factors (matched controls, MC) were collected for comparison. To measure cytokine values at baseline and after stimulation, we used a flow cytometry method of intracellular cytokine staining. Intrinsic Th1 and Th2 cytokine production in unstimulated T cells was negligible in all study participants. Following mitogenic stimulation with phorbol 12-myristate13-acetate/ionomycin, both the IS and the MC groups exhibited a similarly strong Th1 response; IL-2 production predominated in the CD4+ T cells and IFN-gamma in the CD8+ T cells. However, when measuring the Th2 cytokine-production capacity post-stimulation, a significant increase in the percentage of IL-4-producing T cells was observed in the IS groups, compared with the MC group, resulting in a significantly lower ratio of IFN-gamma-/IL-4-producing T cells. No such Th2 enhancement could be confirmed for the case of IL-10. We propose that in IS patients there is a systemic shift of the immune system towards Th2 responses at the late post-acute phase of stroke.

Are serum lipids measured on stroke admission prognostic?

It has been hypothesized that serum lipids measured in the early period of stroke are predictive of stroke severity and outcome. The optimal time for lipid measurement is not established. We explored whether lipid profile assessed within the first 24 h after stroke onset: (i) differs from that in stroke-free individuals; (ii) differs between stroke subtypes; and (iii) is predictive of stroke severity and outcome. We prospectively enrolled 70 acute ischemic stroke patients who presented to the Stroke Unit within 24 h of the onset of stroke symptoms, and 68 stroke-free control subjects. Triglycerides (p<0.001) and high-density lipoprotein (HDL) cholesterol (p<0.001) were significantly lower in patients than in controls. HDL cholesterol was different across stroke subtypes classified according to the Trial of ORG 10172 in Acute Stroke Treatment scale (p=0.035). Patients with more severe stroke had higher serum triglycerides (odds ratio 2.755; p=0.030). Serum triglycerides might serve as a prognostic marker in acute stroke patients.

Increased risk of cognitive impairment 3 months after mild to moderate first-ever stroke: a Community-Based Prospective Study of Nonaphasic English-Speaking Survivors.

Results of hospital-based studies indicate a high risk of cognitive impairment 3 months after stroke. There are no comprehensive data on this issue from prospective community-based studies comparing first-ever stroke patients with stroke-free subjects. We administered a comprehensive neuropsychological battery to 99 community-based nonaphasic survivors of first-ever stroke at 3 months and 99 age- and sex-matched (1:1) stroke-free individuals. Domain-specific cognitive deficits were identified by blinded neuropsychological consensus. Stroke patients were more likely to suffer any cognitive impairment (relative risk [RR], 1.5; 95% CI, 1.1 to 2.1) attributable mainly to a greater risk of single-domain cognitive impairment (RR, 2.8; 95% CI, 1.5 to 5.3) but not multiple-domain cognitive impairment (RR, 1.2; 95% CI, 0.8 to 1.9). In this community-based study, a first-ever stroke of mild to moderate severity was associated with a significant risk of cognitive impairment at 3 months, even in the absence of clinical aphasia. This was due primarily to an increased risk of solitary deficits rather than generalized deficits.

Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by neurological history and examination.

The Questionnaire for Verifying Stroke-Free Status (QVSFS) is an 8-item structured interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review in a cohort with a low prevalence (7.1%) of stroke or transient ischemic attack (TIA). The objective of this study was to evaluate the validity of the QVSFS by comparing it with stroke status as determined by neurological history and examination in a population with a higher prevalence of stroke. A research assistant administered the QVSFS to outpatients from Veterans Administration stroke and general medicine clinics. Subjects were defined as QVSFS negative if responses to all 8 questions were negative. Questions requiring rephrasing or clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and examined all subjects to determine stroke-free status, defined as no history or examination findings of previous stroke and/or TIA. One hundred fifty-five subjects were examined; mean age was 70 years; 98.1% were male. Seventy-eight subjects were determined to be stroke free by the neurologist. The negative predictive value of the QVSFS was 0.96, with positive predictive value of 0.71. No question required rephrasing or clarification >5 times. Twenty-two subjects (14.2%) required rephrasing or clarification of at least 1 question. The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population with a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke and/or TIA is lower, but the QVSFS may still be useful as a screening tool in that regard.

Serum albumin is related to the incidence of stroke -

0025 We previously reported an inverse association between serum albumin and prevalent stroke. To examine the risk of future stroke associated with serum albumin we conducted a prospective analysis of 15,271 stroke-free individuals, participants in the population-based bi-ethnic Atherosclerosis Risk in Communities (ARIC) study baseline examination (1987-1989). Over an average follow-up of 7 years, 218 incident hospitalized ischemic stroke cases were identified by standardized methods. The baseline mean levels (SD) of serum albumin were 3.77 (0.31) and 3.87 (0.27) g/dl respectively, for the incident stroke group and for those who remained free of stroke. Multivariable adjusted proportional hazard ratios (HR) and 95% CI of stroke per 1 SD (0.27 g/dl) lower albumin are presented in the table. Interactions of albumin and each of the stroke risk factors in the table were tested, and none were statistically significant. These data suggest that serum albumin is prospectively and inversely associated with the risk of ischemic stroke. This association is partially, but not fully, accounted for by the conventional risk factors, especially the hemostatic factors. Table 1.

Validating the Questionnaire to Verify Stroke-Free Status by Patient History and Physical Examination

P127 Background and Purpose: The Questionnaire to Verify Stroke-Free Status (QVSFS) is an 8-item structured telephone interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review to identify stroke status in a cohort with a low prevalence (7%) of stroke or TIA. The aim of this study was to evaluate the validity of the QVSFS using a face-to-face history and physical examination in a group with a higher prevalence of stroke. Methods: A research assistant administered the QVSFS to outpatients from VA stroke and general internal medicine clinics. Subjects were defined as QVSFS (-) if responses to all 8 questions were negative. Questions requiring clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and recorded the NIH Stroke Scale in all subjects to determine stroke-free status, defined as no history or examination findings of previous TIA or stroke. Results: Ninety-one subjects were examined, mean age was 69 years, 98% were male. Twenty-five of the subjects were judged stroke-free by the examiners and 66 had a prior history of stroke (63) or TIA (3). The negative predictive value of the QVSFS was 0.93 with positive predictive value 0.86. No question required rephrasing in more than 3 subjects; only 12 subjects (13%) required rephrasing of at least one question. Years of education was not associated with need for question rephrasing. Conclusions: The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population including a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke is slightly lower but still high. The QVSFS is valid for interviewer administration but, because of the need for question clarification in some subjects, should be further evaluated before using self- or mail-completion.

Validating the Questionnaire to Verify Stroke-Free Status by Patient History and Physical Examination

P127 Background and Purpose: The Questionnaire to Verify Stroke-Free Status (QVSFS) is an 8-item structured telephone interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review to identify stroke status in a cohort with a low prevalence (7%) of stroke or TIA. The aim of this study was to evaluate the validity of the QVSFS using a face-to-face history and physical examination in a group with a higher prevalence of stroke. Methods: A research assistant administered the QVSFS to outpatients from VA stroke and general internal medicine clinics. Subjects were defined as QVSFS (-) if responses to all 8 questions were negative. Questions requiring clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and recorded the NIH Stroke Scale in all subjects to determine stroke-free status, defined as no history or examination findings of previous TIA or stroke. Results: Ninety-one subjects were examined, mean age was 69 years, 98% were male. Twenty-five of the subjects were judged stroke-free by the examiners and 66 had a prior history of stroke (63) or TIA (3). The negative predictive value of the QVSFS was 0.93 with positive predictive value 0.86. No question required rephrasing in more than 3 subjects; only 12 subjects (13%) required rephrasing of at least one question. Years of education was not associated with need for question rephrasing. Conclusions: The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population including a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke is slightly lower but still high. The QVSFS is valid for interviewer administration but, because of the need for question clarification in some subjects, should be further evaluated before using self- or mail-completion.

Correlates of subjective well-being in stroke patients.

Data on survival and functioning after stroke needs to be supplemented by measures emphasizing the patients' subjective perception. We studied (1) subjective well-being (SWB) as a latent variable in a common-factor model with four items, (2) the reliability of these four items, and (3) variables related to SWB in stroke patients. Data on all stroke patients (n=1417) and a random subsample of stroke-free individuals of similar age (n=1439) were collected from the Nord-Trøndelag Health Survey, a cross-sectional study of 74977 persons. Based on a two-sample factor analysis model, scores of SWB were calculated, and variables explaining SWB were studied in a regression model. Four items were a priori believed to measure SWB as a latent variable ("satisfaction," "strength," "calmness," and "cheerfulness"). This was confirmed by factor analysis. The reliability of these items (the proportion of the variance of the items that can be explained by the common factor) was between .42 and .53. Regression analyses showed a significant effect of having had a stroke, gender (lower SWB in men), age (increasing SWB with increasing age), perceived general health, nervousness, loneliness, sleep problems, social support, and use of analgesics. There was no statistical interaction between these variables and having had a stroke. Higher SWB after stroke relates to female gender, older age, good general and mental health, and a firm social network.

Prevalence of stroke in Taiwan.

We investigated the prevalence of stroke in Taiwan in an epidemiologic study of stroke, diabetes, and cardiovascular disease that used a two-phase survey design. The study population was drawn by cluster sampling and consisted of both urban and rural communities from four regions of Taiwan. There were 8,705 people 36 years of age or older interviewed during the period of October 1 to December 31, 1986, and 143 cases of completed stroke were later identified by a neurologist. The point prevalence rate for people aged 36 or older in our study was 1,642/100,000 population (95% confidence interval 1,389-1,942/100,000). Prevalence rates differed significantly among the four study regions and between urban and rural communities; prevalence was greater in northern Taiwan and in urban communities. Percentages of the major types of stroke in 143 stroke survivors were as follows: cerebral infarction 67.1% (96 cases), cerebral hemorrhage 14.0% (20 cases), subarachnoid hemorrhage 4.2% (six cases), and unclassified 14.7% (21 cases). Of the stroke survivors, 67.1% were independent in activities of daily living, and 75.5% were independent in ambulation. Hypertension, heart disease, diabetes mellitus, and a family history of stroke were significantly more common in stroke survivors than in strokefree individuals.