Yeseon Park Moon

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 ≥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 (≥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 ≥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 ≥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 (&bgr; 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.

Duration of Diabetes and Risk of Ischemic Stroke The Northern Manhattan Study

Background and Purpose— Diabetes increases stroke risk, but whether diabetes status immediately before stroke improves prediction and whether duration is important are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. Methods— Among 3298 stroke-free participants in the Northern Manhattan Study, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median, 9 years). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors. Results— Mean age was 69±10 years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and 10% had development of diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR, 2.5; 95% CI, 1.9–3.3) and diabetes considered as a time-dependent covariate (HR, 2.4; 95% CI, 1.8–3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR, 1.03 per year with diabetes; 95% CI, 1.02–1.04). Compared to nondiabetic participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1–2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1–3.0), and ≥10 years (adjusted HR, 3.2; 95% CI, 2.4–4.5) were at increased risk. Conclusions— Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥10 years.

Infectious burden and risk of stroke: the northern Manhattan study.

OBJECTIVE To determine the association between a composite measure of serological test results for common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) and stroke risk in a prospective cohort study. DESIGN Prospective cohort followed up longitudinally for median 8 years. SETTING Northern Manhattan Study. Patients Randomly selected stroke-free participants from a multiethnic urban community. Main Outcome Measure Incident stroke and other vascular events. RESULTS All 5 infectious serological results were available from baseline samples in 1625 participants (mean [SD] age, 68.4 [10.1] years; 64.9% women). Cox proportional hazards models were used to estimate associations of each positive serological test result with stroke. Individual parameter estimates were then combined into a weighted index of infectious burden and used to calculate hazard ratios and confidence intervals for association with risk of stroke and other outcomes, adjusted for risk factors. Each individual infection was positively, though not significantly, associated with stroke risk after adjusting for other risk factors. The infectious burden index was associated with an increased risk of all strokes (adjusted hazard ratio per standard deviation, 1.39; 95% confidence interval, 1.02-1.90) after adjusting for demographics and risk factors. Results were similar after excluding those with coronary disease (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13) and adjusting for inflammatory biomarkers. CONCLUSIONS A quantitative weighted index of infectious burden was associated with risk of first stroke in this cohort. Future studies are needed to confirm these findings and to further define optimal measures of infectious burden as a stroke risk factor.

Physical activity and risk of ischemic stroke in the Northern Manhattan Study.

Background: It is controversial whether physical activity is protective against first stroke among older persons. We sought to examine whether physical activity, as measured by intensity of exercise and energy expended, is protective against ischemic stroke. Methods: The Northern Manhattan Study is a prospective cohort study in older, urban-dwelling, multiethnic, stroke-free individuals. Baseline measures of leisure-time physical activity were collected via in-person questionnaires. Cox proportional hazards models were constructed to examine whether energy expended and intensity of physical activity were associated with the risk of incident ischemic stroke. Results: Physical inactivity was present in 40.5% of the cohort. Over a median follow-up of 9.1 years, there were 238 incident ischemic strokes. Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65, 95% confidence interval [0.44–0.98]). Engaging in any physical activity vs none (adjusted HR 1.16, 95% CI 0.88–1.51) and energy expended in kcal/wk (adjusted HR per 500-unit increase 1.01, 95% CI 0.99–1.03) were not associated with ischemic stroke risk. There was an interaction of sex with intensity of physical activity (p = 0.04), such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR 0.37, 95% CI 0.18–0.78), but not in women (adjusted HR 0.92, 95% CI 0.57–1.50). Conclusions: Moderate- to heavy-intensity physical activity, but not energy expended, is protective against risk of ischemic stroke independent of other stroke risk factors in men in our cohort. Engaging in moderate to heavy physical activities may be an important component of primary prevention strategies aimed at reducing stroke risk.

CKD Associates with Cognitive Decline

Cognitive impairment and chronic kidney disease (CKD) will become increasingly prevalent in the aging US population. Although evidence exists that CKD is a risk factor for cognitive decline, longitudinal studies are limited and largely have excluded ethnically diverse populations. The Northern Manhattan Study includes a population-based, prospective, stroke-free cohort. We assessed global cognitive function annually using the modified Telephone Interview for Cognitive Status (TICS-m) and estimated kidney function using Cockcroft-Gault creatinine clearance (CCl), Modification of Diet in Renal Disease estimated GFR (eGFR), and serum creatinine (sCr). We examined the association between CKD and change in TICS-m scores over time, adjusting for sociodemographic and vascular risk factors. Of 2172 subjects (mean age 71.5 yr, mean follow-up 2.9 yr), 59% were Hispanic, 20% were black, and 63% were women. Participants with a CCl <60 ml/min and those with a CCl between 60 and 90 ml/min performed significantly worse on the TICS-m over time than those with a CCl >90 ml/min, adjusting for potential confounders. Our results were similar when we used eGFR or sCr to estimate kidney function. In conclusion, decreased kidney function associates with greater cognitive decline, even in those with mild CKD. Kidney disease may represent a novel mechanism leading to cognitive impairment and a target for early intervention.

Inflammatory Biomarkers of Vascular Risk as Correlates of Leukoariosis

Background and Purpose— Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear. Methods— The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers. We measured the association between Lp-PLA2, MPO, and hsCRP levels, and log-transformed WMHV after adjusting for sociodemographic and vascular risk factors. Results— The hsCRP (median, 2.42 mg/L; IQR, 1.04, 5.19), Lp-PLA2 (median, 220.97 ng/mL; IQR, 185.77, 268.05), and MPO (median, 15.14 ng/mL; IQR, 12.32, 19.69) levels were available in 527 The Northern Manhattan Study participants with WMHV data but no subclinical infarcts. Those with hsCRP in the upper quartile (Q4 >4.92 mg/L or >3 mg/L), Lp-PLA2 in Q4 (≥264.9 ng/mL), or MPO levels in Q3 (15.04–19.39 ng/mL) or Q4 (>19.39 ng/mL) each had greater WMHV, adjusting for sociodemographic and vascular risk factors. Adjusting for all biomarkers simultaneously, WMHV was 1.3-fold greater for Lp-PLA2 levels in Q4 compared to Q1 (&bgr;=0.28; P =0.008) and 1.25-fold greater for MPO levels above the median compared to below (&bgr;=0.22; P =0.02), but hsCRP was not associated with WMHV. Conclusions— Relative elevations of the inflammatory markers Lp-PLA2 and MPO were associated with a greater burden of WMH independent of hsCRP.

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.

Lower prevalence of silent brain infarcts in the physically active The Northern Manhattan Study

Objective: To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV). Methods: The Northern Manhattan Study (NOMAS) is a population-based prospective cohort examining risk factors for incident vascular disease, and a subsample underwent brain MRI. Our primary outcomes were SBI and WMHV. Baseline measures of leisure-time physical activity were collected in person. Physical activity was categorized by quartiles of the metabolic equivalent (MET) score. We used logistic regression models to examine the associations between physical activity and SBI, and linear regression to examine the association with WMHV. Results: There were 1,238 clinically stroke-free participants (mean age 70 ± 9 years) of whom 60% were women, 65% were Hispanic, and 43% reported no physical activity. A total of 197 (16%) participants had SBI. In fully adjusted models, compared to those who did not engage in physical activity, those in the upper quartile of MET scores were almost half as likely to have SBI (adjusted odds ratio 0.6, 95% confidence interval 0.4–0.9). Physical activity was not associated with WMHV. Conclusions: Increased levels of physical activity were associated with a lower risk of SBI but not WMHV. Engaging in moderate to heavy physical activities may be an important component of prevention strategies aimed at reducing subclinical brain infarcts.

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). Conclusion— 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.

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 ≥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. Conclusion— 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.