Cognition predicts days-alive-out-of-hospital after LVAD implantation.

OBJECTIVE: Cognition influences hospitalization rates for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We used cognition to predict days-alive-out-of-hospital (DAOH) in patients after LVAD surgery. METHODS: We retrospectively identified 59 HF patients with cognitive assessment prior to LVAD. Cognitive tests of attention, memory, language, and visual motor speed were averaged into one score. DAOH was converted to a percentage based on total days from LVAD surgery to either heart transplant or 900 days post-LVAD. Variables significantly associated with DAOH in univariate analyses were included in a linear regression model to predict DAOH. RESULTS: A linear regression model including LVAD type (continuous or pulsatile flow) and cognition significantly predicted DAOH (F(2,54) = 6.44, p = 0.003, R2 = .19). Inspection of each variable revealed that cognition was a significant predictor in the model (ß = .11, SE = .04, p = 0.007) but LVAD type was not (p = 0.08). CONCLUSIONS: Cognitive performance assessed prior to LVAD implantation predicted how much time patients spent out of the hospital following surgery. Further studies are warranted to identify the impact of pre-LVAD cognition on post-LVAD hospitalization.

Carotid artery structure and hemodynamics and their association with adverse vascular events in left ventricular assist device patients.

Left ventricular assist devices (LVADs) are associated with major vascular complications including stroke and gastrointestinal bleeding (GIB). These adverse vascular events may be the result of widespread vascular dysfunction resulting from pre-LVAD abnormalities or continuous flow during LVAD therapy. We hypothesized that pre-existing large artery atherosclerosis and/or abnormal blood flow as measured in carotid arteries using ultrasonography are associated with a post-implantation composite adverse outcome including stroke, GIB, or death. We retrospectively studied 141 adult HeartMate II patients who had carotid ultrasound duplex exams performed before and/or after LVAD surgery. Structural parameters examined included plaque burden and stenosis. Hemodynamic parameters included peak-systolic, end-diastolic, and mean velocity as well as pulsatility index. We examined the association of these measures with the composite outcome as well as individual subcomponents such as stroke. After adjusting for established risk factors, the composite adverse outcome was associated with pre-operative moderate-to-severe carotid plaque (OR 5.08, 95% CI 1.67-15.52) as well as pre-operative internal carotid artery stenosis (OR 9.02, 95% CI 1.06-76.56). In contrast, altered hemodynamics during LVAD support were not associated with the composite outcome. Our findings suggest that pre-existing atherosclerosis possibly in combination with LVAD hemodynamics may be an important contributor to adverse vascular events during mechanical support. This encourages greater awareness of carotid morphology pre-operatively and further study of the interaction between hemodynamics, pulsatility, and structural arterial disease during LVAD support.

Predicting post-LVAD outcome: Is there a role for cognition?

BACKGROUND: Cognition has been found to influence risk of stroke and death for a variety of patient groups but this association has not been examined in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implant. We aimed to study the relationship between cognition, stroke, and death in a cohort of patients who received LVAD therapy. It was hypothesized that cognitive test results obtained prior to LVAD placement would predict stroke and death after surgery. METHODS: We retrospectively identified 59 HF patients who had cognitive assessment prior to LVAD placement. Cognitive assessment included measures of attention, memory, language, and visualmotor speed and were averaged to produce one z-score variable per patient. Survival analyses, censored for transplant, evaluated predictors for stroke and death within a follow-up period of 900 days. RESULTS: For patients with stroke or death during the follow up period, the average cognitive z-score predicted post-LVAD stroke (HR = 0.513, 95% CI = 0.31-0.86, p = 0.012) and death (HR = 0.166, 95% CI = 0.06-0.47, p = 0.001). Cognitive performances were worse in the patients who suffered stroke or died. No other variable predicted stroke and death within the follow up period when the cognitive variable was in the model. CONCLUSION: Cognitive performance was predictive of post-LVAD risk of stroke and death. Results are consistent with findings from other studies in non-LVAD samples and may reflect early signs of neurologic vulnerability. Further studies are needed to clarify the relationship between cognition and LVAD outcomes in order to optimize patient selection, management, and advanced care planning.

Smoking-cessation pharmacotherapy for patients with stroke and TIA: Systematic review.

Data regarding the efficacy and safety of smoking-cessation pharmacotherapy after stroke are lacking. We systematically reviewed data on this topic by searching Medline, Cochrane, and Clinicaltrials.gov to identify randomized clinical trials (RCT) and observational studies that assessed the efficacy and safety of nicotine replacement therapy (NRT), varenicline, and bupropion in patients with stroke and TIA. We included studies that reported rates of smoking cessation, worsening or recurrent cerebrovascular disease, seizures, or neuropsychiatric events. We identified 2 RCTs and 6 observational studies; 3 included ischemic stroke and TIA, 2 subarachnoid hemorrhage (SAH), and 3 did not specify. Four studies assessed efficacy; cessation rates ranged from 33% to 66% with pharmacological therapy combined with behavioral interventions versus 15% to 46% without, but no individual study demonstrated a statistically significant benefit. Safety data for varenicline and buopropion in ischemic stroke were scarce. Patients with SAH who received NRT had more seizures (9% vs 2%; P = 0.024) and delirium (19% vs 7%; P = 0.006) in one study, but less frequent vasospasm in 3 studies. In conclusion, combined with behavioral interventions, smoking-cessation therapies resulted in numerically higher cessation rates. Limited safety data may prompt caution regarding seizures and delirium in patients with subarachnoid hemorrhage.

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.

A Multilevel Analysis of Surgical Category and Individual Patient-Level Risk Factors for Postoperative Stroke.

BACKGROUND AND PURPOSE: Many studies supporting the association between specific surgical procedure categories and postoperative stroke (POS) do not account for differences in patient-level characteristics between and within surgical categories. The risk of POS after high-risk procedure categories remains unknown after adjusting for such differences in patient-level characteristics. METHODS: Using inpatients in the American College of Surgeons National Surgical Quality Initiative Program database, we conducted a retrospective cohort study between January 1, 2000, and December 31, 2010. Our primary outcome was POS within 30 days of surgery. We characterized the relationship between surgical- and individual patient-level factors and POS by using multivariable, multilevel logistic regression that accounted for clustering of patient-level factors with surgical categories. RESULTS: We identified 729 886 patients, 2703 (0.3%) of whom developed POS. Dependent functional status (odds ratio [OR]: 4.11, 95% confidence interval [95% CI]: 3.60-4.69), history of stroke (OR: 2.35, 95%CI: 2.06-2.69) or transient ischemic attack (OR: 2.49 95%CI: 2.19-2.83), active smoking (OR: 1.20, 95%CI: 1.08-1.32), hypertension (OR: 2.11, 95%CI: 2.19-2.82), chronic obstructive pulmonary disease (OR: 1.39 95%CI: 1.21-1.59), and acute renal failure (OR: 2.35, 95%CI: 1.85-2.99) were significantly associated with POS. After adjusting for clustering, patients who underwent cardiac (OR: 11.25, 95%CI: 8.52-14.87), vascular (OR: 4.75, 95%CI: 3.88-5.82), neurological (OR: 4.60, 95%CI: 3.48-6.08), and general surgery (OR: 1.40, 95%CI: 1.15-1.70) had significantly greater odds of POS compared to patients undergoing other types of surgical procedures. CONCLUSIONS: Vascular, cardiac, and neurological surgery remained strongly associated with POS in an analysis accounting for the association between patient-level factors and surgical categories.

Transcranial Doppler is an effective method in assessing cerebral blood flow patterns during peripheral venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be life-saving in refractory cardiogenic shock but carries a risk of neurologic complications such as stroke and hemorrhage. As little is known about the effects of different peripheral VA-ECMO cannulation sites on cerebral blood flow (CBF), transcranial Doppler (TCD) was used to determine whether the cannulation site affects CBF. METHODS: Thirty-seven patients receiving VA-ECMO for cardiogenic shock via axillary or femoral artery cannulation were prospectively enrolled. Measured bilateral middle cerebral artery (MCA), mean flow velocities (MFV), and pulsatility indices (PI) were the primary outcomes and adverse neurologic events were secondary outcomes. RESULTS: The median age was 58 years (IQR 51-66) with 26 (70%) males. Median VA-ECMO flow was 3.8 L/min (IQR 3.2-4.9) with mean arterial pressures of 80 mm Hg (IQR 75-86). Nineteen patients received right axillary artery cannulation while 18 underwent femoral cannulation. Compared with the femoral group, MFV was higher in the axillary group in the right MCA (46 cm/s [IQR 26-57] vs 27 [17-36], P = 0.03) and left (43 [IQR 35-60] vs 29 cm/s [16-48], P = 0.05). Axillary PI was significantly lower compared with the femoral group (right: 0.48 cm/s [0.25-0.65] vs 0.83 [0.66-0.93], P = 0.02; left: 0.41 cm/s [0.29-0.63] vs 1.02 [0.7-1.3], P = 0.004). One axillary patient experienced a stroke with deficits. CONCLUSIONS: TCD appears to be an effective tool for indirect monitoring of CBF in patients with ECMO with limited pulsatility. Axillary artery cannulation seems to provide higher cerebral flow rates without any difference in neurologic outcomes. Future studies may incorporate TCD into regulating ECMO flows to achieve physiologic CBF.

Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study.

BACKGROUND: Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. METHODS: The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. RESULTS: Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants' CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr≥60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex. CONCLUSIONS: In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.

The Impact of Pregnancy on Hemorrhagic Stroke in Young Women.

BACKGROUND: Pregnancy is a sex-specific risk factor for causing hemorrhagic stroke (HS) in young adults. Unique physiological characteristics during pregnancy may alter the relative risk for HS in pregnant/postpartum (PP) women compared to HS in other young women. We compared patient characteristics and HS subtypes between young non-pregnant and PP women. METHODS: We reviewed the medical records of all women 18-45 years old admitted to our center with HS from October 15, 2008 through March 31, 2015, and compared patient characteristics and stroke mechanisms using logistic regression. RESULTS: Of the 130 young women with HS during the study period, 111 were non-PP women, and 19 PP women. PP women had lower proportions of vascular risk factors such as hypertension, prior stroke, and smoking, and a higher proportion of migraine (36.8 vs. 14.4%, p = 0.01). After adjusting for hypertension, smoking, migraine, prior stroke and prior myocardial infarction, PP women had lower odds of having an underlying vascular lesion (OR 0.14, 95% CI 0.04-0.44, p = 0.0009) and a higher proportion of the reversible cerebral vasoconstriction syndrome (RCVS) as cause of their HS. CONCLUSIONS: Women with pregnancy-associated HS had fewer cerebrovascular risk factors, lower odds of having -underlying vascular lesions, and higher proportion of -migraine and RCVS compared with similar-aged non--pregnant women. Pregnancy-associated HS appears to represent a unique pathophysiological process, requiring targeted study.

Severity of cerebral vasospasm associated with development of collaterals following aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Cerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI). METHODS: We retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals. RESULTS: Inter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not. CONCLUSIONS: The severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome.

Does cognition improve following LVAD implantation?

BACKGROUND: Studies of cognition after LVAD surgery have produced mixed results. To explore whether cognition would improve, decline, or remain stable after LVAD surgery, we examined cognition before and 1- and 3-months after LVAD surgery. Patients with post-surgical stroke were excluded. METHODS: 28 subjects (mean age = 54.31 ± 12 years) comprised an observational case series from the DuraHeart LVAS device® trial. Cognitive testing was performed at baseline, 1-month, and 3-month post-surgery, and included tests of attention, memory, language, visualmotor speed (TMT) and visualconstruction. RESULTS: No difference in cognition was found between baseline and 1-month exams (means z score improvement = 0.06, p = 0.43) but cognition improved significantly between baseline and 3-month exams (mean z score improvement = 0.34, p < 0.00001). Examination of individual test scores found, after correction for multiple comparisons, only the TMT variable was significantly different at the 3-month exam. CONCLUSIONS: We found significantly improved cognition 3 months after LVAD surgery in a subset of patients without post-surgical stroke. The reasons for the lack of cognitive improvement at the 1-month post-surgical assessment may include ongoing medical and physiological disruptions in the immediate post-operative period. Further research into the sources of delayed improvement is warranted. Cognitive assessments performed immediately after surgery should be interpreted with caution because the results may not reflect longer term cognitive outcomes. LVAD patients may require additional support to successfully manage their health in the weeks immediately following surgery but assistance needs may decrease over time.

Association Between Serum Tumor Necrosis Factor Receptor 1 and Trajectories of Functional Status: The Northern Manhattan Study.

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.

Quality of life independently predicts long-term mortality but not vascular events: the Northern Manhattan Study.

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.

Physical inactivity is a strong risk factor for stroke in the oldest old: Findings from a multi-ethnic population (the Northern Manhattan Study).

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.

Risk of Pregnancy-Associated Stroke Across Age Groups in New York State.

IMPORTANCE: Older age is associated with increased risk of pregnancy-associated stroke (PAS). Data are limited on age-specific incidence ratios of PAS compared with stroke risk in nonpregnant women. OBJECTIVES: To assess the risk of stroke by age group in pregnant and postpartum women compared with their nonpregnant contemporaries and to compare risk factors across age groups in the exposed (pregnant/postpartum) and unexposed (nonpregnant) populations. DESIGN, SETTING, AND PARTICIPANTS: International Classification of Diseases, Ninth Revision, billing codes from the calendar year 2003-2012 New York State Department of Health inpatient database and population data were used to identify all women aged 12 to 55 years with cerebrovascular events, including transient ischemic attack, ischemic and hemorrhagic stroke, cerebral venous thrombosis, and nonspecified PAS. The cumulative incidence of PAS per 100 000 pregnant/postpartum women vs nonpregnancy-associated stroke (NPAS) per 100 000 women in age cohorts of 24 years or younger, 25 to 34, 35 to 44, and 45 years or older was calculated. Risk factors between groups were compared using logistic regression models. The study included data from calendar years 2003 through 2012. Data analysis was performed from July 11, 2015, to July 16, 2016. EXPOSURES: Pregnancy, including the postpartum period up to 6 weeks after delivery. MAIN OUTCOMES AND MEASURES: Incidence risk ratios (IRRs) for stroke per age cohort, defined as cumulative risk of stroke in the exposed population divided by cumulative risk of stroke in the unexposed population, were determined, and stroke risk factors and mortality were compared between populations. RESULTS: There were 19 146 women hospitalized with stroke during the study period; 797 of the women were pregnant/post partum. The overall median (interquartile range) age of the women was 31 (25-35) years in those with PAS and 48 (41-52) years in those with NPAS. The incidence of PAS in women aged 12 to 24 years was 14 events per 100 000 pregnant/postpartum women vs NPAS incidence of 6.4 per 100 000 nonpregnant women (IRR, 2.2; 95% CI, 1.9-2.6); for ages 25 to 34 years, 21.2 per 100 000 vs 13.5 per 100 000 (IRR, 1.6; 95% CI, 1.4-1.7); for ages 35 to 44 years, 33 per 100 000 vs 31 per 100 000 (IRR, 1.1; 95% CI, 0.9-1.2); and for ages 45 to 55 years, 46.9 per 100 000 vs 73.7 per 100 000 (IRR, 0.6; 95% CI, 0.3-1.4). PAS accounted for 18% of strokes in women younger than 35 years vs 1.4% of strokes in women aged 35 to 55 years. Women in the NPAS group vs the PAS group had more vascular risk factors, including chronic hypertension (age <35 years: 437 [15.7%] vs 60 [9.8%], P < .001; age 35-55 years: 7573 [48.6%] vs 36 [19.3%], P < .001), diabetes (age <35 years: 103 [3.7%] vs 9 [1.5%], P = .002; age 35-55 years: 2618 [16.8%] vs 12 [6.4%], P < .001), and active smoking (age <35 years: 315 [11.3%] vs 29 [4.8%], P < .001; age 35-55 years: 2789 [17.9%] vs 10 [5.3%], P < .001); and had higher mortality (age <35 years: 288 [11.3%] vs 37 [6.5%], P < .001; age 35-55 years: 2121 [13.4%] vs 14 [6.1%], P < .001). CONCLUSIONS AND RELEVANCE: Younger women, but not older women, have an increased stroke risk during pregnancy and post partum compared with their nonpregnant contemporaries. These results suggest that pregnancy does not increase the risk of stroke in older women.

Racial-ethnic disparities in the association between risk factors and diabetes: The Northern Manhattan Study.

PURPOSE: To identify risk factors (RF) for diabetes within a multiethnic cohort and to examine whether race-ethnicity modified their effects. METHODS: Participants in the Northern Manhattan Study without diabetes at baseline were studied from 1993 to 2014 (n=2430). Weibull regression models with interval censoring data were fit to calculate hazard ratios and 95% confidence intervals for incident diabetes. We tested for interactions between RF and race-ethnicity. RESULTS: During a mean follow-up period of 11years, there were 449 diagnoses of diabetes. Being non-Hispanic black (HR 1.69 95% CI 1.11-2.59) or Hispanic (HR 2.25 95% CI 1.48-3.40) versus non-Hispanic white, and body mass index (BMI; HR 1.34 per SD 95% CI 1.21-1.49) were associated with greater risk of diabetes; high-density lipoprotein cholesterol (HR 0.75 95% CI 0.66-0.86) was protective. There were interactions by race-ethnicity. In stratified models, the effects of BMI, current smoking, and C-reactive protein (CRP) on risk of diabetes differed by race-ethnicity (p for interaction <0.05). The effects were greater among non-Hispanic whites than non-Hispanic blacks and Hispanics. CONCLUSIONS: Although Hispanics and non-Hispanic blacks had a greater risk of diabetes than whites, there were variations by race-ethnicity in the association of BMI, smoking, and CRP with risk of diabetes. Unique approaches should be considered to reduce diabetes as traditional RF may not be as influential in minority populations.

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.

Patterns of leisure-time physical activity using multivariate finite mixture modeling and cardiovascular risk factors in the Northern Manhattan Study.

PURPOSE: Physical activity is currently commonly summarized by simple composite scores of total activity, such as total metabolic equivalent score (METS), without further information about the many specific aspects of activities. We sought to identify more comprehensive physical activity patterns, and their association with cardiovascular disease risk factors. METHODS: The Northern Manhattan Study is a multiethnic cohort of stroke-free individuals. Questionnaires were used to capture multiple dimensions of leisure-time physical activity. Participants were grouped into METS categories and also into clusters by multivariate mixture modeling of activity frequency, duration, energy expenditure, and number of activity types. Associations between clusters and risk factors were assessed using χ(2) tests. RESULTS: Using data available in 3293 participants, we identified six model-based clusters that were differentiated by frequency and diversity of activities, rather than activity duration. High activity clusters had lower prevalence of the risk factors compared with those with lower activity; associations with obesity and hypertension remained significant after adjusting for METS (P = .027, .043). METS and risk factors were not significantly associated after adjusting for the clusters. CONCLUSIONS: Data-driven clustering method is a principled, generalizable approach to depict physical activity and form subgroups associated with cardiovascular risk factors independently of METS.

Amyloid ß-Related Angiitis Causing Coma Responsive to Immunosuppression.

Introduction. Amyloid-beta-related angiitis (ABRA) is a form of CNS vasculitis in which perivascular beta-amyloid in the intracerebral vessels is thought to act as a trigger for inflammation mediated by CD68+ macrophages and CD3+ T lymphocytes. Patients with severe ABRA may develop coma responsive to immunosuppressive treatment. Case Presentation. A 57-year-old man presented to the neurological intensive care unit febrile, obtunded, and with a left hemiparesis. He had suffered from intermittent left arm weakness and numbness for several months prior. Serum and cerebrospinal fluid studies showed a lymphocytic leukocytosis in the cerebrospinal fluid (CSF), but no other evidence of infection, and the patient underwent a brain biopsy. Histopathological examination demonstrated amyloid angiopathy, with an extensive perivascular lymphocytic infiltrate, indicative of ABRA. The patient was started on cyclophosphamide and steroids. Following a week of treatment he awakened and over several weeks made a significant neurological recovery. Conclusions. ABRA can have a variety of clinical presentations, including impairments in consciousness and coma. Accurate pathological diagnosis, followed by aggressive immunosuppression, can lead to impressive neurological improvements. This diagnosis should be considered in patients with paroxysmal recurrent neurological symptoms and an accelerated progression.