APOE ϵ4 modifies the relationship between infectious burden and poor cognition.

OBJECTIVE: We investigated whether APOE ϵ4 is an effect modifier of the association between infectious burden (IB) and poor cognition in a multiethnic cohort, the Northern Manhattan Study. METHODS: IB was assessed by a quantitative weighted index of exposure to common pathogens associated with vascular risk, infectious burden index (IBI), and by serology for individual infections. Cognition was assessed by completion of the Mini-Mental State Examination at baseline and a full neuropsychological test battery after a median follow-up of approximately 6 years. Adjusted linear and logistic regressions estimated the association between IBI and cognition, with a term included for the interaction between APOE ϵ4 and IBI. RESULTS: Among those with full neuropsychological test results (n = 569), there were interactions between IBI and APOE ϵ4 (p = 0.07) and herpes simplex virus 1 (HSV-1) and APOE ϵ4 (p = 0.02) for processing speed. IBI was associated with slower processing speed among non-ϵ4 carriers (ß = -0.08 per SD change in IBI, 95% confidence interval [CI] -0.16 to -0.01), but not among APOE ϵ4 carriers (ß = 0.06 per SD change in IBI, 95% CI -0.08 to 0.19). HSV-1 positivity was associated with slower processing speed among non-ϵ4 carriers (ß = -0.24, 95% CI -0.45 to -0.03), but not among APOE ϵ4 carriers (ß = 0.27, 95% CI -0.09 to 0.64). CONCLUSIONS: Potential effect modification by the APOE ϵ4 allele on the relationship of infection, and particularly viral infection, to cognitive processing speed warrants further investigation.

Creatinine versus cystatin C for renal function-based mortality prediction in an elderly cohort: The Northern Manhattan Study.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is routinely utilized as a measure of renal function. While creatinine-based eGFR (eGFRcr) is widely used in clinical practice, the use of cystatin-C to estimate GFR (eGFRcys) has demonstrated superior risk prediction in various populations. Prior studies that derived eGFR formulas have infrequently included high proportions of elderly, African-Americans, and Hispanics. OBJECTIVE: Our objective as to compare mortality risk prediction using eGFRcr and eGFRcys in an elderly, race/ethnically diverse population. DESIGN: The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3,298 participants recruited between 1993 and 2001, with a median follow-up of 18 years. PARTICIPANTS: We included all Northern Manhattan Study (NOMAS) participants with concurrent measured creatinine and cystatin-C. MAIN MEASURES: The eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equations. The performance of each eGFR formula in predicting mortality risk was tested using receiver-operating characteristics, calibration and reclassification. Net reclassification improvement (NRI) was calculated based on the Reynolds 10 year risk score from adjusted Cox models with mortality as an outcome. The primary hypothesis was that eGFRcys would better predict mortality than eGFRcr. RESULTS: Participants (n = 2988) had a mean age of 69±10.2 years and were predominantly Hispanic (53%), overweight (69%), and current or former smokers (53% combined). The mean eGFRcr (74.68±18.8 ml/min/1.73m2) was higher than eGFRcys (51.72±17.2 ml/min/1.73m2). During a mean of 13.0±5.6 years of follow-up, 53% of the cohort had died. The AUC of eGFRcys (0.73) was greater than for eGFRcr (0.67, p for difference<0.0001). The proportions of correct reclassification (NRI) based on 10 year mortality for the model with eGFRcys compared to the model with eGFRcr were 4.2% (p = 0.002). CONCLUSIONS: In an elderly, race/ethnically diverse cohort low eGFR is associated with risk of all-cause mortality. Estimated GFR based on serum cystatin-C, in comparison to serum creatinine, was a better predictor of all-cause mortality.

Mentored peer review of standardized manuscripts as a teaching tool for residents: a pilot randomized controlled multi-center study.

BACKGROUND: There is increasing need for peer reviewers as the scientific literature grows. Formal education in biostatistics and research methodology during residency training is lacking. In this pilot study, we addressed these issues by evaluating a novel method of teaching residents about biostatistics and research methodology using peer review of standardized manuscripts. We hypothesized that mentored peer review would improve resident knowledge and perception of these concepts more than non-mentored peer review, while improving review quality. METHODS: A partially blinded, randomized, controlled multi-center study was performed. Seventy-eight neurology residents from nine US neurology programs were randomized to receive mentoring from a local faculty member or not. Within a year, residents reviewed a baseline manuscript and four subsequent manuscripts, all with introduced errors designed to teach fundamental review concepts. In the mentored group, mentors discussed completed reviews with residents. Primary outcome measure was change in knowledge score between pre- and post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome measures included level of confidence in the use and interpretation of statistical concepts before and after intervention, and RQI score for baseline and final manuscripts. RESULTS: Sixty-four residents (82%) completed initial review with gradual decline in completion on subsequent reviews. Change in primary outcome, the difference between pre- and post-test knowledge scores, did not differ between mentored (-8.5%) and non-mentored (-13.9%) residents (p = 0.48). Significant differences in secondary outcomes (using 5-point Likert scale, 5 = strongly agree) included mentored residents reporting enhanced understanding of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no difference between groups in level of interest in peer review (3.00 vs 3.09; p = 0.72) or the quality of manuscript review assessed by the Review Quality Instrument (RQI) (3.25 vs 3.06; p = 0.50). CONCLUSIONS: We used mentored peer review of standardized manuscripts to teach biostatistics and research methodology and introduce the peer review process to residents. Though knowledge level did not change, mentored residents had enhanced perception in their abilities to understand research methodology and manuscripts and apply study results to clinical practice.

Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study.

OBJECTIVE: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. METHODS: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). RESULTS: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (ß = -0.231 ± 0.112, p = 0.040) and episodic memory (ß = -0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. CONCLUSIONS: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.

Leisure-time physical activity and mortality in a multiethnic prospective cohort study: the Northern Manhattan Study.

PURPOSE: To examine whether the survival benefit of exercise is modified by obesity. METHODS: In the Northern Manhattan Study, we collected baseline sociodemographics and cardiovascular disease risk factors. The primary exposure was leisure-time physical activity (LTPA) and the outcomes were total, vascular, and nonvascular deaths (non-VaD). LTPA was defined as any versus none and metabolic equivalent score category (total activity weighted by intensity). We used Cox models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 3298 participants (mean age 69 years, 52% Hispanic, 63% women) were followed over a mean of 11.8 years with 1589 total deaths (641 vascular, 819 nonvascular). Any activity (adjusted HR: 0.84, 95% CI: 0.75-0.94) was associated with reduced risk of all-cause mortality and non-VaD, but not VaD. We found an interaction (P < .05) of LTPA with body mass index (BMI) less than 30 for all-cause and vascular mortality. Any LTPA was associated with reduced all-cause mortality (adjusted HR: 0.77, 95% CI: 0.68-0.87) and VaD (adjusted HR: 0.79, 95% CI: 0.65-0.97) only among those with BMI less than 30. CONCLUSIONS: We found no evidence of an independent survival benefit of LTPA among those with BMI more than 30. The health benefits of exercise should be considered in the context of obesity.

Population attributable risks of hypertension and diabetes for cardiovascular disease and stroke in the northern Manhattan study.

BACKGROUND: Understanding the population-level risk factor contribution to disease incidence is critical for effective allocation of resources for prevention. There are little data on the contribution of cardiovascular disease (CVD) risk factors in multiethnic elderly populations. METHODS AND RESULTS: The Northern Manhattan Study (n=3298) is a population-based prospective cohort study of CVD outcomes in a multiethnic urban population. Multivariable Cox's models were used to calculate hazard ratios, population attributable risk (PAR), and 95% confidence intervals (CIs) for (1) combined vascular event (VE) endpoint of stroke/myocardial infarction/vascular death (n=835) and (2) stroke (n=347). The PAR resulting from hypertension (HTN) was 24.3% (95% CI, 13.2 to 35.4) for VE and 29.9% (95% CI, 12.5 to 47.4) for stroke; PAR resulting from diabetes was 12.7% (95% CI, 8.2 to 17.2) for VE and 19.5% (95% CI, 12.4 to 26.5) for stroke. The PAR resulting from HTN and diabetes for stroke differed by race-ethnicity and age (P for differences <0.05). PAR for stroke reslting from HTN was greater among Hispanics (50.6%; 95% CI, 29.2 to 71.9) than non-Hispanic whites (2.6%; 95% CI, -33.2 to 38.6) and in those <80 years of age (35.6%; 95% CI, 18.9 to 52.3) than in those ≥80 (-0.3%; 95% CI, -34.2 to 33.6). Similarly, the PAR for stroke resulting from diabetes was 23.6% among those <80 years of age (95% CI, 15.7 to 31.5) and 2.3% among those ≥80 (95% CI, -8.2 to 12.7; P for difference=0.001). The PAR for VE did not differ by age/sex/race-ethnicity. CONCLUSIONS: HTN and diabetes have important effects on the burden of stroke, particularly among those younger than age 80 and Hispanics. Public health campaigns targeted at specific risk factors in specific populations can lead to a greater reduction in CVD.

Diabetes predicts long-term disability in an elderly urban cohort: the Northern Manhattan Study.

PURPOSE: There are limited data on vascular predictors of long-term disability in Hispanics. We hypothesized that (1) functional status declines over time and (2) vascular risk factors predict functional decline. METHODS: The Northern Manhattan Study contains a population-based study of 3298 stroke-free individuals aged 40 years or older, followed for median 11 years. The Barthel Index (BI) was assessed annually. Generalized estimating equations and Cox models were adjusted for demographic, medical, and social risk factors. Stroke and myocardial infarction occurring during follow-up were censored in sensitivity analysis. Secondarily, motor and nonmotor domains of the BI were analyzed. RESULTS: Mean age (standard deviation) of the cohort (n = 3298) was 69.2 (10) years, 37% were male, 52% Hispanic, 22% diabetic, and 74% hypertensive. There was a mean annual decline of 1.02 BI points (P < .0001). Predictors of decline in BI included age, female sex, diabetes, depression, and normocholesterolemia. Results did not change with censoring. We found similar predictors of BI for motor and nonmotor domains. CONCLUSION: In this large, population-based, multiethnic study with long-term follow-up, we found a 1% mean decline in function per year that did not change when vascular events were censored. Diabetes predicted functional decline in the absence of clinical vascular events.

Infectious burden and cognitive function: the Northern Manhattan Study.

OBJECTIVE: We hypothesized that infectious burden (IB), a composite serologic measure of exposure to common pathogens (i.e., Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) associated with vascular risk in the prospective Northern Manhattan Study (NOMAS), would also be associated with cognition. METHODS: Cognition was assessed using the Mini-Mental State Examination (MMSE) at enrollment and the modified Telephone Interview for Cognitive Status (TICS-m) at annual follow-up visits. Adjusted linear and logistic regressions were used to measure the association between IB index and MMSE. Generalized estimating equation models were used to evaluate associations with TICS-m and its change over time. RESULTS: Serologies and cognitive assessments were available in 1,625 participants of the NOMAS cohort. In unadjusted analyses, higher IB index was associated with worse cognition (change per standard deviation [SD] of IB for MMSE was -0.77, p < 0.0001, and for first measurements of TICS-m was -1.89, p < 0.0001). These effects were attenuated after adjusting for risk factors (for MMSE adjusted change per SD of IB = -0.17, p = 0.06, for TICS-m adjusted change per SD IB = -0.68, p < 0.0001). IB was associated with MMSE ≤24 (compared to MMSE >24, adjusted odds ratio 1.26 per SD of IB, 95% confidence interval 1.06-1.51). IB was not associated with cognitive decline over time. The results were similar when IB was limited to viral serologies only. CONCLUSION: A measure of IB associated with stroke risk and atherosclerosis was independently associated with cognitive performance in this multiethnic cohort. Past infections may contribute to cognitive impairment.

Interleukin 6 plasma concentration associates with cognitive decline: the northern Manhattan study.

BACKGROUND: Interleukin 6 (IL-6) is an inflammatory cytokine that has been associated with vascular disease and cognitive impairment, but few studies have examined these relationships in population-based studies that include Hispanic and Black people who often have a greater prevalence of vascular risk factors and are at an elevated risk of dementia than Whites. We examined relative elevations of plasma IL-6 concentrations in relation to cognitive decline in a stroke-free racially/ethnically diverse community-based sample from Northern Manhattan. METHODS: We used mixed effects models to measure the effect of IL-6 on change in performance on the modified Telephone Interview for Cognitive Status (TICS-m) measured annually in our cohort, adjusting for sociodemographic and vascular risk factors. RESULTS: There were 1,224 participants with IL-6 levels (median 1.5 pg/ml, interquartile range 0.83-2.57 pg/ml) and TICS-m data available (mean = 31.6 points, SD 6.5). The mean age was 71 (SD 9.3; 64% women, 59% Hispanic, 19% Black, 19% White) with 3,406 person-years and a median 3.0 years of follow-up (interquartile range 1.1-4.0 years). Participants with IL-6 levels above the median showed greater cognitive decline on the TICS-m compared to those with levels below the median, adjusting for sociodemographic and vascular factors (ß = -0.17 points/year, p = 0.02). Decline on the TICS-m among participants with IL-6 above the median differed by age (p for interaction <0.001). There was no interaction by race/ethnicity, vascular risk factors, C-reactive protein, apolipoprotein ε4 allele status, or the metabolic syndrome among nondiabetics. CONCLUSIONS: IL-6 associated with cognitive decline among older participants in this racially/ethnically diverse sample independent of other vascular risk factors and C-reactive protein.

Coronary death and myocardial infarction among Hispanics in the Northern Manhattan Study: exploring the Hispanic paradox.

PURPOSE: Prior studies have reported that Hispanics have lower cardiovascular disease (CVD) mortality despite a higher burden of risk factors. We examined whether Hispanic ethnicity was associated with a lower risk of nonfatal myocardial infarction (MI) coronary death (CD) and vascular death. METHODS: A total of 2671 participants in the Northern Manhattan Study without clinical CVD were prospectively evaluated. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of race-ethnicity with nonfatal MI, CD, and vascular death after adjusting for demographic and CVD risk factors. RESULTS: Mean age was 68.8 (10.4) years; 52.8% were Hispanic (88% Caribbean-Hispanic). Hispanics were more likely to have hypertension (73.1% vs. 62.2%, p < .001) and diabetes (22.0% vs. 13.3%, p < .001), and less likely to perform any physical activity (50.1% vs. 69.2%, p < .001) compared to non-Hispanic whites (NHW). During a mean 10 years of follow-up there were 154 nonfatal MIs, 186 CD, and 386 vascular deaths. In fully adjusted models, Hispanics had a lower risk of CD (adjusted HR = 0.36, 95% CI: 0.21-0.60), and vascular death (adjusted HR = 0.62, 95% CI: 0.43-0.89), but not nonfatal MI (adjusted HR = 0.95, 95% CI: 0.56-1.60) when compared to NHW. CONCLUSIONS: We found a "Hispanic paradox" for coronary and vascular deaths, but not nonfatal MI.

The metabolic syndrome and cognitive performance: the Northern Manhattan Study.

BACKGROUND: The metabolic syndrome (MetS) is a risk factor for diabetes, stroke, myocardial infarction, and increased mortality, and has been associated with cognition in some populations. We hypothesized that MetS would be associated with lower Mini-Mental State Examination (MMSE) scores in a multi-ethnic population, and that MetS is a better predictor of cognition than its individual components or diabetes. METHODS: We conducted a cross-sectional analysis among 3,150 stroke-free participants. MetS was defined by the modified National Cholesterol Education Program guidelines-Adult Treatment Panel III (NCEP-ATPIII) criteria. Linear regression and polytomous logistic regression estimated the association between MMSE score and MetS, its individual components, diabetes, and inflammatory biomarkers. RESULTS: MetS was inversely associated with MMSE score (unadjusted ß = -0.67; 95% CI -0.92, -0.41). Adjusting for potential confounders, MetS was associated with lower MMSE score (adjusted ß = -0.24; 95% CI -0.47, -0.01), but its individual components and diabetes were not. Those with MetS were more likely to have an MMSE score of <18 than a score of ≥ 24 (adjusted OR = 1.94; 95% CI 1.26, 3.01). There was an interaction between MetS and race-ethnicity, such that MetS was associated with lower MMSE score among non-Hispanic whites and Hispanics but not non-Hispanic blacks. CONCLUSIONS: MetS was associated with lower cognition in a multi-ethnic population. Further studies of the effect of MetS on cognition are warranted, and should account for demographic differences.

The inclusion of stroke in risk stratification for primary prevention of vascular events: the Northern Manhattan Study.

BACKGROUND AND PURPOSE: The Framingham coronary heart disease (CHD) risk score estimates 10-year risk of myocardial infarction (MI) and CHD death. Because preventive approaches to CHD and stroke are similar, a composite outcome may be more appropriate. We compared 10-year risk of (1) MI or CHD death; and (2) stroke, MI, or CHD death among individuals free of vascular disease. METHODS: The Northern Manhattan Study contains a prospective, population-based study of stroke- and CHD-free individuals≥40 years of age followed for a median of 10 years for vascular events. Framingham coronary heart disease risk score was calculated for each individual and for each category of predicted risk, Kaplan-Meier observed 10-year cumulative probabilities were calculated for (1) MI or CHD death; and (2) stroke, MI, or CHD death. The cumulative probability of (1) was subtracted from (2), and 95% CIs for the difference were obtained with 1000 bootstrap samples. Using stratified analyses by race-ethnicity, we compared risk differences among race-ethnic groups. RESULTS: Among 2613 participants (53% Hispanic, 25% non-Hispanic black, and 20% non-Hispanic white), observed 10-year risk of MI or CHD death was 14.20%. With stroke in the outcome, observed risk was 21.98% (absolute risk difference, 7.78%; 95% CI, 5.86% to 9.75%). The absolute risk difference among blacks was significantly larger than among whites (P=0.01). CONCLUSIONS: In this multiethnic urban population, adding stroke to the risk stratification outcome cluster resulted in a 55% relative increase in estimated risk and crossing of the absolute risk threshold (>20% over 10 years) considered for preventive treatments such as statins.

Race-ethnic differences in the association between lipid profile components and risk of myocardial infarction: The Northern Manhattan Study.

OBJECTIVE: The aim of this study was to explore race-ethnic differences in the association between plasma lipid components and risk of incident myocardial infarction (MI). DESIGN/METHODS: As part of the Northern Manhattan Study, 2,738 community residents without cardiovascular disease were prospectively evaluated. Baseline fasting blood samples were collected, and lipid panel components were analyzed as continuous and categorical variables. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident MI after adjusting for demographic and cardiovascular risk factors. RESULTS: The mean age was 68.8 ± 10.4 years; 36.7% were men. Of the participants, 19.9% were non-Hispanic white; 24.9%, non-Hispanic black; and 52.8%, Hispanic (>80% from the Caribbean). Hispanics had lower mean high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG)/HDL-C. During a mean 8.9 years of follow-up, there were 163 incident MIs. In the whole cohort, all lipid profile components were associated with risk of MI in the expected directions. However, HDL-C (adjusted HR per 10 mg/dL increase 0.93, 95% CI 0.76-1.12) and TG/HDL-C >2 (adjusted HR 0.89, 95% CI 0.51-1.55) were not predictive of MI among Hispanics but were predictive among non-Hispanic blacks and whites. Triglycerides/HDL-C per unit increase was associated with an 8% higher risk of MI among Hispanics (adjusted HR 1.08, 95% CI 1.04-1.12). CONCLUSIONS: In Hispanics, low HDL-C and TG/HDL-C >2 were not associated with MI risk. Our data suggest that a different TG/HDL ratio cutoff may be needed among Hispanics to predict MI risk.

Association of serum soluble receptor for advanced glycation end-products with subclinical cerebrovascular disease: the Northern Manhattan Study (NOMAS).

OBJECTIVE: Serum levels of the soluble receptor for advanced glycation end-products (sRAGE) have been associated with risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical cerebrovascular disease in an ethnically diverse population. METHODS: Clinically stroke-free participants in the multi-ethnic Northern Manhattan Study (NOMAS) underwent brain MRI to quantify subclinical brain infarcts (SBI) and white matter hyperintensity volume (WMHV) (n = 1102). Serum levels of sRAGE were measured by ELISA. Logistic and multiple linear regression were employed to estimate associations of sRAGE with SBI and WMHV, after adjusting for demographics and vascular risk factors. RESULTS: Median sRAGE levels were significantly lower in Hispanics (891.9 pg/ml; n = 708) and non-Hispanic blacks (757.4 pg/ml; n = 197) than in non-Hispanic whites (1120.5 pg/ml; n = 170), and these differences remained after adjusting for other risk factors. Interactions were observed by race-ethnicity between sRAGE levels and MRI measurements, including for SBI in Hispanics (p = 0.04) and WMHV among blacks (p = 0.03). In Hispanics, increasing sRAGE levels were associated with a lower odds of SBI, with those in the upper sRAGE quartile displaying a 50% lower odds of SBI after adjusting for sociodemographic and vascular risk factors (p = 0.05). Among blacks, those in the upper quartile of sRAGE had a similarly reduced increased risk of SBI (p = 0.06) and greater WMHV (p = 0.04). CONCLUSION: Compared to whites, Hispanics and blacks have significantly lower sRAGE levels, and these levels were associated with more subclinical brain disease. Taken together, these findings suggest sRAGE levels may be significantly influence by ethnicity. Further studies of sRAGE and stroke risk, particularly in minorities, are warranted.

Early depressed mood after stroke predicts long-term disability: the Northern Manhattan Stroke Study (NOMASS).

BACKGROUND AND PURPOSE: Depression is highly prevalent after stroke and may influence recovery. We aimed to determine whether depressed mood acutely after stroke predicts subsequent disability and mortality. METHODS: As part of the Northern Manhattan Stroke Study, a population-based incident stroke case follow-up study performed in a multiethnic urban population, participants were asked about depressed mood within 7 to 10 days after stroke. Participants were followed every 6 months the first 2 years and yearly thereafter for 5 years for death and disability measured by the Barthel Index. We fitted polytomous logistic regression models using a canonical link to examine the association between depressed mood after stroke and disability comparing moderate (Barthel Index 60 to 95) and severe (Barthel Index <60) disability with no disability (Barthel Index >or=95). Cox proportional hazards models were created to examine the association between depressed mood and mortality. RESULTS: A question about depressed mood within 7 to 10 days after stroke was asked in 340 of 655 patients with ischemic stroke enrolled, and 139 reported that they felt depressed. In multivariate analyses controlling for sociodemographic factors, stroke severity, and medical conditions, depressed mood was associated with a greater odds of severe disability compared with no disability at 1 (OR 2.91, 95% CI 1.07 to 7.91) and 2 years (OR 3.72, 95% CI 1.29 to 10.71) after stroke. Depressed mood was not associated with all-cause mortality or vascular death. CONCLUSIONS: Depressed mood after stroke is associated with disability but not mortality after stroke. Early screening and intervention for mood disorders after stroke may improve outcomes and requires further research.

Infectious burden and carotid plaque thickness: the northern Manhattan study.

BACKGROUND AND PURPOSE: The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multiethnic cohort. METHODS: Antibody titers to 5 common infectious microorganisms (ie, Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants and a weighted index of infectious burden was calculated based on Cox models previously derived for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness. Weighted least squares regression was used to measure the association between infectious burden and maximum carotid plaque thickness after adjusting for other risk factors. RESULTS: Serological results for all 5 infectious organisms were available in 861 participants with maximum carotid plaque thickness measurements available (mean age, 67.2+/-9.6 years). Each individual infection was associated with stroke risk after adjusting for other risk factors. The infectious burden index (n=861) had a mean of 1.00+/-0.35 SD and a median of 1.08. Plaque was present in 52% of participants (mean, 0.90+/-1.04 mm). Infectious burden was associated with maximum carotid plaque thickness (adjusted increase in maximum carotid plaque thickness 0.09 mm; 95% CI, 0.03 to 0.15 mm per SD increase of infectious burden). CONCLUSIONS: A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multiethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.

Lipid profile components and risk of ischemic stroke: the Northern Manhattan Study (NOMAS).

OBJECTIVE: To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. DESIGN: Population-based prospective cohort study. SETTING: Northern Manhattan, New York. PATIENTS: Stroke-free community residents. Intervention As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. RESULTS: After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53-9.51). CONCLUSIONS: Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of stroke risk.

Long-term functional recovery after first ischemic stroke: the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Several factors predict functional status after stroke, but most studies have included hospitalized patients with limited follow-up. We hypothesized that patients with ischemic stroke experience functional decline over 5 years independent of recurrent stroke and other risk factors. METHODS: In the population-based Northern Manhattan Study, patients > or =40 years of age with incident ischemic stroke were prospectively followed using the Barthel Index at 6 months and annually to 5 years. Baseline stroke severity was categorized as mild (National Institutes of Health Stroke Scale <6), moderate (6 to 13), and severe (> or =14). Follow-up was censored at death, recurrent stroke, or myocardial infarction. Generalized Estimating Equations provided ORs and 95% CIs for predictors of favorable (Barthel Index > or =95) versus unfavorable (Barthel Index <95) functional status after adjusting for demographic and medical risk factors. RESULTS: Of 525 patients, mean age was 68.6+/-12.4 years, 45.5% were male, 54.7% Hispanic, 54.7% had Medicaid/no insurance, and 35.1% had moderate stroke. The proportion with Barthel Index > or =95 declined over time (OR, 0.91; 95% CI, 0.84 to 0.99). Changes in Barthel Index by insurance status were confirmed by a significant interaction term (beta for interaction=-0.167, P=0.034); those with Medicaid/no insurance declined (OR, 0.84; P=0.003), whereas those with Medicare/private insurance did not (OR, 0.99; P=0.92). CONCLUSIONS: The proportion of patients with functional independence after stroke declines annually for up to 5 years, and these effects are greatest for those with Medicaid or no health insurance. This decline is independent of age, stroke severity, and other predictors of functional decline and occurs even among those without recurrent stroke or myocardial infarction.