Search

Background/Objectives: Inflammatory biomarkers have been associated with stroke and mortality, but inflammation may also have detrimental effects beyond acute events. We hypothesized that serum concentrations of interleukin-6 (IL6) and lipoprotein-associated phospholipase A2 (LpPLA2) were inversely associated with long-term functional decline independently of vascular risk factors, stroke and myocardial infarction (MI) occurring during follow-up. Design: Prospective population based cohort study Setting: The Northern Manhattan Study Participants (including the sample size): Race/ethnically diverse stroke-free individuals in northern Manhattan aged ≥40 years (n = 3298). Intervention: None Measurements: Annual functional assessments with the Barthel index (BI), for a median of 13 years. BI was analyzed as a continuous variable (range 0–100). Baseline demographics, risk factors, and laboratory studies were collected, including IL6 (n = 1679), LpPLA2 mass (n = 1912) and activity (n = 1937). Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up. Results: Mean age was 69 (SD 10) years, 35% were male, 53% Hispanic, 74% hypertensive, and 16–24% diabetic. LogIL6 was associated with decline in BI over time (-0.13 points per year, 95% CI -0.24, -0.02) and marginally with baseline BI (-0.20, 95% CI -0.40, 0.01). LpPLA2 activity levels were associated with baseline BI (-0.36, 95% CI -0.68, -0.04) but not change over time, and LpPLA2 mass levels were not associated with either. Conclusion: In this large population-based study, higher serum inflammatory biomarker levels were associated with disability, even when adjusting for baseline covariates and stroke and MI occurring during follow-up. [ABSTRACT FROM AUTHOR]

Objectives: To test associations between subclinical brain infarcts (SBIs) and functional decline independently of intervening clinical vascular events and other vascular risk factors. Design: Longitudinal follow‐up for a mean 7.3 years. Generalized estimating equation models were used to test associations between SBIs, number of perivascular spaces (PVSs), baseline Barthel Index (BI), and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors and for stroke and myocardial infarction occurring during follow‐up. Setting: Population‐based prospective cohort study. Participants: Stroke‐free individuals from the racially and ethnically diverse Northern Manhattan Study (N=1,290). Measurements: Annual functional assessments using the BI (range 0–100). Results: Mean age was 70.6 ± 9.0, 40% of participants were male, 66% were Hispanic, 193 (16%) had SBIs, and 508 (42%) had large PVSs. SBIs were not associated with baseline BI. In a fully adjusted model, there was a change in BI of –0.85 points per year (95% confidence interval (CI)=–1.01 to –0.69); those with SBI had an additional change in BI 0f –0.88 points (95% CI=–1.43 to –0.32). There were no associations between PVS and baseline BI or change in BI. Conclusion: In a large population‐based study, we found a strong and independent association between "subclinical" markers of cerebrovascular injury and important clinical, person‐centered functional trajectories. Future research could clarify the evolution of such subclinical markers over time and test strategies to prevent their progression and minimize related disability. J Am Geriatr Soc 66:2144–2150, 2018. [ABSTRACT FROM AUTHOR]

Introduction: White matter hyperintensity volume (WMHV) and subclinical brain infarcts (SBI) are associated with impaired mobility, but less is known about the association of WMHV in specific brain regions. We hypothesized that anterior WMHV would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale. Methods: The SPPB was measured a median of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric distributions for WMHV in 14 brain regions as a proportion of total cranial volume were determined. Multi-variable linear regression was performed to examine the association of SBI and regional log-WMHV with the SPPB score. Results: Among 668 participants with SPPB measurements (mean 74 ± 9 years, 37% male and 70% Hispanic), the mean SPPB score was 8.2 ± 2.9. Total (beta = –0.3 per SD, p = 0.001), anterior periventricular (beta = –0.4 per SD, p = 0.001), parietal (beta = –0.2 per SD, p = 0.02) and frontal (beta = –0.3 per SD, p = 0.002) WMHVs were associated with SPPB; other WMHV and SBI were not associated with the SPPB. Conclusions: WMHV, especially in the anterior ­cerebral regions, is associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical decline in the elderly. [ABSTRACT FROM AUTHOR]

Introduction: Gait speed is associated with multiple adverse outcomes of aging. We hypothesized that physical inactivity would be prospectively inversely associated with gait speed independently of white matter hyperintensity volume and silent brain infarcts on MRI. Methods: Participants in the Northern Manhattan Study MRI sub-study had physical activity assessed when they were enrolled into the study. A mean of 5 years after the MRI, participants had gait speed measured via a timed 5-meter walk test. Physical inactivity was defined as reporting no leisure-time physical activity. Multi-variable logistic and quantile regression was performed to examine the associations between physical inactivity and future gait speed adjusted for confounders. Results: Among 711 participants with MRI and gait speed measures (62% women, 71% Hispanic, mean age 74.1 ± 8.4), the mean gait speed was 1.02 ± 0.26 m/s. Physical inactivity was associated with a greater odds of gait speed in the lowest quartile (<0.85 m/s, adjusted OR 1.90, 95% CI 1.17-3.08), and in quantile regression with 0.06 m/s slower gait speed at the lowest 20 percentile (p = 0.005). Conclusions: Physical inactivity is associated with slower gait speed independently of osteoarthritis, grip strength, and subclinical ischemic brain injury. Modifying sedentary behavior poses a target for interventions aimed at reducing decline in mobility. [ABSTRACT FROM AUTHOR]

We hypothesized that tumor necrosis factor receptor 1 (TNFR1) levels are associated with long-term trajectories of functional status independently of vascular risk factors and the occurrence of stroke and myocardial infarction (MI) during follow-up. In the Northern Manhattan Study, stroke-free persons aged ≥40 years in northern Manhattan (New York, New York) had annual assessments with the Barthel index (BI) for a median of 13 years (1993-2015). Assessment of baseline demographic factors, risk factors, and laboratory studies included measurement of TNFR1 (n = 1,863). Generalized estimating equations models were used to estimate standardized associations between TNFR1 and 1) baseline functional status and 2) change in function over time, adjusting for demographic factors, vascular risk factors, social variables, cognition, and depression, as well as stroke and MI occurrence during follow-up. The mean age of participants was 70 (standard deviation (SD), 10) years; 66% were women, and 55% were Hispanic. The mean TNFR1 level was 2.57 mg/L. TNFR1 was associated with baseline BI (-0.93 BI points per SD increment in TNFR1; 95% confidence interval: -1.59, -0.26) and change over time (-0.36 BI points per year per SD increment in TNFR1; 95% confidence interval: -0.69, -0.03). In this large population-based study, higher TNFR1 levels were associated with greater baseline disability and disability over time, even with adjustment for baseline covariates and stroke and MI occurrence during follow-up. [ABSTRACT FROM AUTHOR]

Background: The fastest growing segment of the population is those age ⩾80 who have the highest stroke incidence. Risk factor management is complicated by polypharmacy-related adverse events. Aims: To characterize the impact of physical inactivity for stroke by age in a multi-ethnic prospective cohort study (NOMAS, n =3298). Methods: Leisure time physical activity was assessed by a validated questionnaire and our primary exposure was physical inactivity (PI). Participants were followed annually for incident stroke. We fit Cox-proportional hazard models to calculate hazard ratios and 95% confidence intervals (HR 95% CI) for the association of PI and other risk factors with risk of stroke including two-way interaction terms between the primary exposures and age (<80 vs. ⩾80). Results: The mean age was 69±10.3 years and 562 (17%) were ⩾80 at enrolment. PI was common in the cohort (40.8%). Over a median of 14 years, we found 391 strokes. We found a significant interaction of age ⩾80 on the risk of stroke with PI (p=0.03). In stratified models, PI versus any activity (adjusted HR 1.60, 95%CI 1.05-2.42) was associated with an increased risk of stroke among those ⩾80. Conclusion: Physical inactivity is a treatable risk factor for stroke among those older than age 80. Improving activity may reduce the risk of stroke in this segment of the population. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein-associated phospholipase A2 (LpPLA2) levels are associated with stroke, though whether this extends to all populations and stroke subtypes is unknown. Methods: Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed for LpPLA2 mass and activity. Participants were followed annually for stroke. Cox-proportional-hazard models were fitted to estimate hazard-ratios and 95% confidence intervals (HR, 95% CI) for the association of LpPLA2 levels with ischemic stroke (IS), after adjusting for demographic and medical risk factors. Results: Serum samples were available in 1946 participants, of whom 151 (7.8%) experienced a first IS during median follow-up 11 years. Mean age was 69 (SD 10), 35.6% were men, 20% non-Hispanic Whites, 22% non-Hispanic Blacks, and 55% Hispanics. LpPLA2 mass and activity levels were not associated with overall IS risk. LpPLA2 mass but not activity levels were associated with strokes due to large artery atherosclerosis (LAA; adjusted HR per SD 1.55, 95% CI 1.17–2.04). There was a dose-response relationship with LAA (compared to first quartile, 2nd quartile HR = 1.43, 95% CI 0.23–8.64; 3rd quartile HR = 4.47, 95% CI 0.93–21.54; 4th quartile HR = 5.07, 95% CI 1.07–24.06). The associations between LpPLA2-mass and LAA-stroke risk differed by race-ethnicity (p = 0.01); LpPLA2-mass was associated with increased risk of LAA among non-Hispanic Whites (adjusted HR per SD 1.44, 95% CI 0.98–2.11), but not other race-ethnic groups. Conclusion: LpPLA2-mass levels were associated with risk of atherosclerotic stroke among non-Hispanic White participants, but not in other race-ethnic groups in the cohort. Further study is needed to confirm these race-ethnic differences and the reasons for them. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that poor quality and diminished quantity of sleep may be independently linked to vascular events although prospective and multiethnic studies are limited. This study aimed to explore the relationship between daytime sleepiness and the risk of ischemic stroke and vascular events in an elderly, multiethnic prospective cohort.Methods and Results: As part of the Northern Manhattan Study, the Epworth Sleepiness Scale was collected during the 2004 annual follow-up. Daytime sleepiness was trichotomized using previously reported cut points of no dozing, some dozing, and significant dozing. Subjects were followed annually for a mean of 5.1 years. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for stroke, myocardial infarction, and death outcomes. We obtained the Epworth Sleepiness Scale on 2088 community residents. The mean age was 73.5 ± 9.3 years; 64% were women; 17% were white, 20% black, 60% Hispanic, and 3% were other. Over 44% of the cohort reported no daytime dozing, 47% some dozing, and 9% significant daytime dozing. Compared with those reporting no daytime dozing, individuals reporting significant dozing had an increased risk of ischemic stroke (hazard ratio, 2.74 [95% confidence interval, 1.38-5.43]), all stroke (3.00 [1.57-5.73]), the combination of ischemic stroke, myocardial infarction, and vascular death (2.38 [1.50-3.78]), and all vascular events (2.48 [1.57-3.91]), after adjusting for medical comorbidities.Conclusions: Daytime sleepiness is an independent risk factor for stroke and other vascular events. These findings suggest the importance of screening for sleep problems at the primary care level. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives: Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function., Design, Setting, Participants, & Measurements: This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m(2)using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥ 2.5 ml/min per 1.73 m(2) per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors., Results: Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m(2). Incident eGFR<60 ml/min per 1.73 m(2) developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m(2) (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98)., Conclusions: A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m(2) and upper quartile of eGFR decline in a multiethnic cohort., (Copyright © 2014 by the American Society of Nephrology.)

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.