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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]

Purpose: Cardiovascular disease is a major contributor to morbidity and mortality, and prevention relies on accurate identification of those at risk. Studies of the association between quality of life (QOL) and mortality and vascular events incompletely accounted for depression, cognitive status, social support, and functional status, all of which have an impact on vascular outcomes. We hypothesized that baseline QOL is independently associated with long-term mortality in a large, multi-ethnic urban cohort.Methods: In the prospective, population-based Northern Manhattan Study, Spitzer QOL index (SQI, range 0-10, with ten signifying the highest QOL) was assessed at baseline. Participants were followed over a median 11 years for stroke, myocardial infarction (MI), and vascular and non-vascular death. Multivariable Cox proportional hazards regression estimated hazard ratio and 95% confidence interval (HR, 95% CI) for each outcome, with SQI as the main predictor, dichotomized at 10, adjusting for baseline demographics, vascular risk factors, history of cancer, social support, cognitive status, depression, and functional status.Results: Among 3298 participants, mean age was 69.7 + 10.3 years; 1795 (54.5%) had SQI of 10. In fully adjusted models, SQI of 10 (compared to SQI <10) was associated with reduced risk of all-cause mortality (HR 0.80, 95% CI 0.72-0.90), vascular death (0.81, 0.69-0.97), non-vascular death (0.78, 0.67-0.91), and stroke or MI or death (0.82, 0.74-0.91). In fully adjusted competing risk models, there was no association with stroke (0.93, 0.74-1.17), MI (0.98, 0.75-1.28), and stroke or MI (1.03, 0.86-1.24). Results were consistent when SQI was analyzed continuously.Conclusion: In this large population-based cohort, highest QOL was inversely associated with long-term mortality, vascular and non-vascular, independently of baseline primary vascular risk factors, social support, cognition, depression, and functional status. QOL was not associated with non-fatal vascular events. [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: Previous studies of exercise have focused on measuring physical activity in totality using summary statistics such as metabolic equivalent score for total intensity or total energy count.Objective: We aimed to examine the multidimensionality of leisure-time physical activity (LTPA) and to identify the specific LTPA components that were associated with cardiovascular mortality in the elderly.Design and Participants: The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3298 participants recruited between 1993 and 2001, with a median follow-up of 17 years.Main Measures: Physical activity questionnaire data were available in 3293 NOMAS participants, who were categorized into subgroups with similar exercise patterns by model-based cluster analysis. Three subgroup-defining LTPA features were identified and were considered as primary exposures in Cox proportional hazard models: frequency of activity, number of activity types (variety), and energy-to-duration ratio (EDR). We considered cardiovascular mortality and non-cardiovascular mortality as outcomes in Cox cause-specific proportional hazard models, and all-cause mortality as outcome in Cox models.Key Results: A high activity frequency was associated with reduced cardiovascular mortality (hazard ratio, HR = 0.93, P = 0.03), but demonstrated no effect on non-cardiovascular death. A high EDR was associated with increased risk of cardiovascular death (HR = 1.30, P = 0.01). A high number of activity types was beneficial in reducing all-cause mortality (HR = 0.87, P = 0.01).Conclusions: Exercise frequency was protective against cardiovascular mortality, and a high variety of activity was protective against all-cause mortality. The performance of frequent and varied non-intense exercise in an elderly population such as ours is achievable and can reduce the risk of death. [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: high-sensitivity C-reactive protein (CRP) has been associated with cardiovascular events and mortality, but the association of CRP with functional status is not well defined. We hypothesised that serum levels of high-sensitivity CRP are associated with long-term trajectories of functional status independently of vascular risk factors and stroke and myocar-dial infarction (MI) occurring during follow-up. Design: prospective, population-based. Setting: northern Manhattan Study. Participants: stroke-free participants aged ≥40 years. Measurements: annual assessments of disability with the Barthel index (BI) for a median of 13 years. BI was analysed as a continuous variable (range 0-100). Baseline demographics, risk factors and laboratory studies were collected, including CRP (n = 2,240). Separate generalised estimating equation models estimated standardised associations between CRP and (i) baseline functional status and (ii) change in function 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, 36% were male, 55% Hispanic, 75% hypertensive and 21% diabetic; 337 MIs and 369 first strokes occurred during follow-up. Mean CRP level was 5.24 mg/l (SD 8.86). logCRP was associated with baseline BI (-0.34 BI points per unit logCRP, 95% confidence interval -0.62, -0.06) but not with change over time. Conclusions: in this large population-based study, higher serum CRP levels were associated with higher baseline disability, even when adjusting for baseline covariates and stroke and MI occurring during follow-up. Systemic inflammation may contribute to disability independently of clinical vascular events. [ABSTRACT FROM AUTHOR]

Background: Subclinical cerebrovascular disease has been associated with multiple adverse events related to aging, including stroke and dementia. The modifiable risk factors for subclinical cerebrovascular disease beyond hypertension have not been well characterized. Our objective was to examine the association between baseline, and changes over time, in lipid profile components and subclinical cerebrovascular disease on magnetic resonance imaging (MRI). Methods: Fasting plasma lipids were collected on participants in the Northern Manhattan Study, a prospective cohort study examining risk factors for cardiovascular disease in a multiethnic elderly urban-dwelling population. A subsample of the cohort underwent brain MRI between 2003 and 2008 (a median of 6.2 years, range = 0-14, after enrollment), when repeat fasting lipids were obtained. We used lipid profile components at the time of initial enrollment (n = 1,256 with lipids available) as categorical variables, as well as change in clinical categories over the two measures (n = 1,029). The main outcome measures were (1) total white matter hyperintensity volume (WMHV) using linear regression and (2) silent brain infarcts (SBI) using logistic regression. Results: None of the plasma lipid profile components at the time of enrollment were associated with WMHV. The association between baseline lipids and WMHV was, however, modified by apolipoprotein E (apoE) status (χ2 with 2 degrees of freedom, p = 0.03), such that among apoE4 carriers those with total cholesterol (TC) ≥200 mg/dl had a trend towards smaller WMHV than those with TC <200 mg/dl (difference in log WMHV -0.19, p = 0.07), while there was no difference among apoE3 carriers. When examining the association between WMHV and change in lipid profile components we noted an association with change in high-density lipoprotein cholesterol (HDL-C, >50 mg/dl for women, >40 mg/dl for men) and TC. A transition from low-risk HDL-C (>50 mg/dl for women, >40 mg/dl for men) at baseline to high-risk HDL-C at the time of MRI (vs. starting and remaining low risk) was associated with greater WMHV (difference in logWMHV 0.34, p value 0.03). We noted a similar association with transitioning to a TC ≥200 mg/dl at the time of MRI (difference in logWMHV 0.25, p value 0.006). There were no associations with baseline or change in lipid profile components with SBI. Conclusions: The association of plasma lipid profile components with greater WMHV may depend on apoE genotype and worsening HDL and TC risk levels over time. © 2014 S. Karger AG, Basel [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]

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. [ABSTRACT FROM AUTHOR]