Silvia Koton

Stroke incidence and mortality trends in US communities, 1987 to 2011.

IMPORTANCE Prior studies have shown decreases in stroke mortality over time, but data on validated stroke incidence and long-term trends by race are limited. OBJECTIVE To study trends in stroke incidence and subsequent mortality among black and white adults in the Atherosclerosis Risk in Communities (ARIC) cohort from 1987 to 2011. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 14,357 participants (282,097 person-years) free of stroke at baseline was facilitated in 4 different US communities. Participants were recruited for the purpose of studying all stroke hospitalizations and deaths and for collection of baseline information on cardiovascular risk factors (via interviews and physical examinations) in 1987-1989. Participants were followed up (via examinations, annual phone interviews, active surveillance of discharges from local hospitals, and linkage with the National Death Index) through December 31, 2011. The study physician reviewers adjudicated all possible strokes and classified them as definite or probable ischemic or hemorrhagic events. MAIN OUTCOMES AND MEASURES Trends in rates of first-ever stroke per 10 years of calendar time were estimated using Poisson regression incidence rate ratios (IRRs), with subsequent mortality analyzed using Cox proportional hazards regression models and hazard ratios (HRs) overall and by race, sex, and age divided at 65 years. RESULTS Among 1051 (7%) participants with incident stroke, there were 929 with incident ischemic stroke and 140 with incident hemorrhagic stroke (18 participants had both during the study period). Crude incidence rates were 3.73 (95% CI, 3.51-3.96) per 1000 person-years for total stroke, 3.29 (95% CI, 3.08-3.50) per 1000 person-years for ischemic stroke, and 0.49 (95% CI, 0.41-0.57) per 1000 person-years for hemorrhagic stroke. Stroke incidence decreased over time in white and black participants (age-adjusted IRRs per 10-year period, 0.76 [95% CI, 0.66-0.87]; absolute decrease of 0.93 per 1000 person-years overall). The decrease in age-adjusted incidence was evident in participants age 65 years and older (age-adjusted IRR per 10-year period, 0.69 [95% CI, 0.59-0.81]; absolute decrease of 1.35 per 1000 person-years) but not evident in participants younger than 65 years (age-adjusted IRR per 10-year period, 0.97 [95% CI, 0.76-1.25]; absolute decrease of 0.09 per 1000 person-years) (P = .02 for interaction). The decrease in incidence was similar by sex. Of participants with incident stroke, 614 (58%) died through 2011. The mortality rate was higher for hemorrhagic stroke (68%) than for ischemic stroke (57%). Overall, mortality after stroke decreased over time (hazard ratio [HR], 0.80 [95% CI, 0.66-0.98]; absolute decrease of 8.09 per 100 strokes after 10 years [per 10-year period]). The decrease in mortality was mostly accounted for by the decrease at younger than age 65 years (HR, 0.65 [95% CI, 0.46-0.93]; absolute decrease of 14.19 per 100 strokes after 10 years [per 10-year period]), but was similar across race and sex. CONCLUSIONS AND RELEVANCE In a multicenter cohort of black and white adults in US communities, stroke incidence and mortality rates decreased from 1987 to 2011. The decreases varied across age groups, but were similar across sex and race, showing that improvements in stroke incidence and outcome continued to 2011.

Triggering risk factors for ischemic stroke A case-crossover study

Background: While vascular risk factors for stroke are well established, little is known about factors that may precipitate the acute event. In this study the authors investigated the association between exposure to seven potential triggers during waking hours and acute onset of ischemic stroke. Methods: In a case-crossover study, 200 consecutive stroke patients were interviewed 1 to 4 days after the event using a validated questionnaire. Reported exposure to potential triggers including negative and positive emotions, anger, sudden posture changes as response to a startling event, heavy physical exertion, heavy eating, and sudden temperature changes during a 2-hour hazard period prior to stroke onset were compared to the same period during the preceding day and to average exposures in the last year. Results: Seventy-six patients (38%) reported exposure to at least one of the study triggers during the 2-hour hazard period. For all factors combined, the OR was 8.4 (95% CI 4.5 to 18.1). The OR for negative emotions was 14.0 (95% CI 4.4 to 89.7), for anger 14.0 (95% CI 2.8 to 253.6), and for sudden changes in body posture in response to a startling event 24.0 (95% CI 5.1 to 428.9). It is important to interpret the reported ORs as estimates of a short-term 2-hour period relative risk and not as cumulative risks. Conclusions: Negative emotions, anger, and sudden changes in body posture in response to a startling event appear to be independent triggers for ischemic stroke.

Mortality and Predictors of Death 1 Month and 3 Years after First-Ever Ischemic Stroke: Data from the First National Acute Stroke Israeli Survey (NASIS 2004)

Background: Despite declining age-adjusted stroke mortality rates, the disease remains the third most common cause of death in Israel. Based on a national survey, we examined mortality rates during the first 3 years after a first-ever acute ischemic stroke (IS) and the major predictors of short-term (1 month) and long-term (3 years) mortality. Methods: In the National Acute Stroke Israeli Survey (NASIS 2004), data were collected on all hospitalized stroke patients in Israel during a 2-month period. Mortality rates for first-ever IS were assessed at 1 month and 3 years and predictors of death were evaluated using the Cox proportional hazard model. Results: A total of 1,079 first-ever IS patients were included. Survival data were complete for over 99% of patients. Cumulative mortality rates were 9.9% at 1 month and 31.1% at 3 years. Of the survivors at 1 month, 23.5% did not survive for 3 years. At 1 month, the hazard ratio (HR) for death significantly increased with stroke severity. One-month mortality was also associated with a decreased level of consciousness (HR 2.9, 95% CI 1.7–5.1), total anterior circulation infarction (TACI); HR 4.9, 95% CI 1.6–15.2), temperature on admission (HR 1.5, 95% CI 1.1–2.1 per 1°C), age (HR 1.04, 95% CI 1.02–1.07 per year) and glucose levels on admission (HR 1.003, 95% CI 1.001–1.006 per 1 mg/dl). Age-adjusted proportions of diabetes and chronic heart failure were considerably higher in the deceased compared with survivors at 3 years (48 vs. 38 and 21 vs. 9%, respectively). In the multivariate survival analyses, predictors of death at 1 month also predicted death at 3 years; however, history of dementia (HR 1.5, 95% CI 1.0–2.4), diabetes (HR 1.6, 95% CI 1.0–2.4), peripheral artery disease (HR 1.7, 95% CI 1.1–2.8), chronic heart failure (HR 1.6, 95% CI 1.1–2.4) and malignancy (HR 1.7, 95% CI 1.1–2.7) were additional predictors of long-term mortality for patients surviving the first month after stroke. Conclusions: Approximately one third of patients did not survive 3 years after the first-ever IS. While age and markers of severe stroke were the major predictors of death at 1 month, comorbidities and variables associated with atherosclerotic vascular disease predicted long-term mortality. Improved control of these factors can potentially reduce long-term mortality in stroke victims.

Cerebral leukoaraiosis in patients with stroke or TIA: clinical correlates and 1-year outcome.

Background and purpose:  Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke‐outcome in a cohort of consecutively hospitalized patients.

Trends in Management and Outcome of Hospitalized Patients With Acute Stroke and Transient Ischemic Attack: The National Acute Stroke Israeli (NASIS) Registry

Background and Purpose— Improving stroke management, guideline adherence, and outcome is a global priority. Our aim was to examine trends in nationwide use of reperfusion therapy, stroke in-hospital management, and outcome. Methods— Data were based on the triennial 2-month period of the National Acute Stroke Israeli registry (February to March 2004, March to April 2007, April to May 2010). The registry includes unselected patients admitted to all hospitals nationwide. There were in total 6279 patients: ischemic stroke, 4452 (70.9%); intracerebral hemorrhage, 485 (7.7%); undetermined stroke, 97 (1.6%); and transient ischemic attacks, 1245 (19.8%). Results— Overall use of reperfusion therapy for acute ischemic stroke increased from 0.4% in 2004% to 5.9% in 2010 (P<0.001; adjusted OR, 17.0; 95% CI, 7.5–38.7). Use of CT or MR angiography for ischemic events increased from 2.1% in 2004% to 16.6% in 2010 (P<0.001; adjusted OR, 9.7; 95% CI, 6.8–13.9). Overall use of antithrombotics and anticoagulation for atrial fibrillation did not differ between periods, whereas clopidogrel use increased nearly 3-fold to 41% and statin use nearly 2-fold to 68%. The relative odds of providing reperfusion therapy, using CT or MR angiography, and prescribing anticoagulants for atrial fibrillation were higher among hospitals with large as compared with small stroke patient volumes. In-hospital mortality after acute ischemic stroke decreased from 7.2% in 2004 to 3.9% in 2010 (P<0.001; adjusted OR, 0.7; 95% CI, 0.4–1.0), whereas there was no significant change in odds of poor functional outcome. Conclusions— Based on a nationwide stroke registry, use of reperfusion therapy, vascular imaging, and statins is steadily increasing, whereas in-hospital mortality is decreasing.

Derivation and validation of the Prolonged Length of Stay score in acute stroke patients

Background: Length of stay (LOS) is the main cost-determining factor of hospitalization of stroke patients. Our aim was to derive and validate a simple score for the assessment of the risk of prolonged LOS for acute stroke patients in a national setting. Methods: Ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in the National Acute Stroke Israeli Surveys (NASIS 2004 and 2007) were included. Predictors of prolonged LOS (LOS ≥7 days) in the NASIS 2004 (n = 1,700) were identified with logistic regression analysis and used for the derivation of the Prolonged Length of Stay (PLOS) score. The score was validated in the NASIS 2007 (n = 1,648). Results: Median (interquartile range) LOS was 6 (3–10) days in the derivation cohort (42.3% prolonged LOS) and 5 (3–8) in the validation cohort (35.7% prolonged LOS). The derivation cohort included 54.8% men, 90.8% IS and 9.2% ICH, with a mean (SD) age of 71.2 (12.5) years. Stroke severity was the strongest multivariable predictor of prolonged LOS: odds ratio (95% confidence interval [CI]) increased from 2.6 (2.0–3.3) for NIH Stroke Scale score (NIHSS) 6–10 to 4.9 (3.0–8.0) for NIHSS 16–20, compared with NIHSS ≤5. Stroke severity and type, decreased level of consciousness on admission, history of congestive heart failure, and prior atrial fibrillation were used for the derivation of the PLOS score (c statistics 0.692, 95% CI 0.666–0.718). The score performed similarly well in the validation cohort (c statistics 0.680, 95% CI 0.653–0.707). Conclusion: A simple prolonged length of stay score, based on available baseline information, may be useful for tailoring policy aimed at better use of resources and optimal discharge planning of acute stroke patients.

Cumulative exposure to particulate matter air pollution and long-term post-myocardial infarction outcomes

INTRODUCTION Chronic environmental exposure to particulate matter <2.5μm in diameter (PM2.5) has been associated with cardiovascular disease; however, the effect of air pollution on myocardial infarction (MI) survivors is not clear. We studied the association of chronic exposure to PM2.5 with death and recurrent cardiovascular events in MI survivors. METHODS Consecutive patients aged ≤65years admitted to all medical centers in central Israel after first-MI in 1992-1993 were followed through 2005 for cardiovascular events and 2011 for survival. Data on sociodemographic and prognostic factors were collected at baseline and during follow-up. Residential exposure to PM2.5 was estimated for each patient based on data recorded at air quality monitoring stations. Cox and Andersen-Gill proportional hazards models were used to study the pollution-outcome association. RESULTS Among the 1120 patients, 469 (41.9%) died and 541 (48.3%) experienced one or more recurrent cardiovascular event. The adjusted hazard ratios associated with a 10μg/m(3) increase in PM2.5 exposure were 1.3 (95% CI 0.8-2.1) for death and 1.5 (95% CI 1.1-1.9) for multiple recurrences of cardiovascular events (MI, heart failure and stroke). CONCLUSION When adjustment for socio-demographic factors is performed, cumulative chronic exposure to PM2.5 is positively associated with recurrence of cardiovascular events in patients after a first MI.

Low Cholesterol, Statins and Outcomes in Patients with First-Ever Acute Ischemic Stroke

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry. Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models. Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke. Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. ‘Reverse epidemiology’ in the association between cholesterol and outcome is possible in patients with ischemic stroke.

The association of spousal smoking status with the ability to quit smoking: the Atherosclerosis Risk in Communities Study.

Smoking is the leading cause of preventable death in the United States. Studies have shown that smoking status tends to be concordant within spouse pairs. This study aimed to estimate the association of spousal smoking status with quitting smoking in US adults. We analyzed data from 4,500 spouse pairs aged 45-64 years from the Atherosclerosis Risk in Communities Study cohort, sampled from 1986 to 1989 from 4 US communities and followed up every 3 years for a total of 9 years. Logistic regression with generalized estimating equations was used to calculate the odds ratio of quitting smoking given that ones spouse is a former smoker or a current smoker compared to a never smoker. Among men and women, being married to a current smoker decreased the odds of quitting smoking (for men, odds ratio (OR) = 0.37, 95% confidence interval (CI): 0.29, 0.46; for women, OR = 0.54, 95% CI: 0.43, 0.68). Among women only, being married to a former smoker increased the odds of quitting smoking (OR = 1.26, 95% CI: 1.04, 1.53). In conclusion, spouses of current smokers are less likely to quit, whereas women married to former smokers are more likely to quit. Smoking cessation programs and clinical advice should consider targeting couples rather than individuals.

Poor neighborhood socioeconomic status and risk of ischemic stroke after myocardial infarction

Background: Data linking neighborhood socioeconomic status (SES) to stroke risk are scarce. We examined long-term stroke incidence according to neighborhood SES in a population-based cohort of patients hospitalized with first myocardial infarction (MI). Methods: Consecutive patients aged 65 years or less, discharged from 8 hospitals in central Israel after incident MI in 1992–1993, were followed for stroke through 2005. Individual demographic, socioeconomic, and clinical data were obtained at study entry. We estimated neighborhood SES through a composite census-derived index developed by the Israel Central Bureau of Statistics. Results: During a median follow-up of 13 years, 196 incident ischemic strokes occurred in 1410 patients. Accounting for death as a competing risk, patients residing in disadvantaged neighborhoods had higher rates of ischemic stroke (cumulative survival estimates: 81%, 88%, and 89% in increasing tertiles of neighborhood SES). Upon multivariable adjustment for individual SES measures (including income, education, and employment), cardiovascular risk factors, MI characteristics and severity indices, and acute management, the overall hazard ratio for stroke in the lower versus upper tertile of neighborhood SES was 1.5 (95% confidence interval [CI] = 1.0–2.3); after 13 years, the adjusted absolute risk difference was 7.9 incident stroke cases per 100 participants with MI (95% CI = 1.7–14.1). Conclusions: Poor neighborhood SES is associated with increased risk of ischemic stroke post-MI. The association is only partly attributable to individual SES and other baseline characteristics. The potential mechanisms for this association require further study.