Mandip S. Dhamoon

Recurrent stroke and cardiac risks after first ischemic stroke The Northern Manhattan Study

Background: Few population-based studies with long-term follow-up have compared risk of recurrent stroke and cardiac events after first ischemic stroke. The relative risk of these two outcomes may inform treatment decisions. Methods: In the population-based Northern Manhattan Study, first ischemic stroke patients age 40 or older were prospectively followed for recurrent stroke, myocardial infarction (MI), and cause-specific mortality. Fatal cardiac events were defined as death secondary to MI, congestive heart failure, sudden death/arrhythmia, and cardiopulmonary arrest. Risk of events (with 95% CIs) was calculated using Kaplan–Meier survival analysis and adjusted for sex and age using Cox proportional hazard models. Results: Mean age (n = 655; median follow-up 4.0 years) was 69.7 ± 12.7 years. The risk of recurrent stroke was more than twice that of cardiac events (including nonfatal MI) at 30 days and approximately twice cardiac risk at 5 years. The age- and sex-adjusted 5-year risk of fatal or nonfatal recurrent stroke was 18.3% (14.8 to 21.7%), and the 5-year risk of MI or fatal cardiac event was 8.6% (6.0 to 11.2%). The adjusted 5-year risk of nonfatal stroke (14.8%, 11.6 to 17.9%) was approximately twice as high as fatal cardiac events (6.4%, 4.1 to 8.6%) and four times higher than risk of fatal stroke (3.7%, 2.1 to 5.4%). Conclusions: Cardiac mortality is nearly twice as high as mortality owing to recurrent stroke, but long-term risk of all stroke, fatal or nonfatal, is approximately twice the risk of all cardiac events. The high risk of nonfatal recurrent stroke reinforces the importance of therapies aimed at preventing stroke recurrence in addition to preventing cardiac events.

Long-Term Functional Recovery After First Ischemic Stroke: The Northern Manhattan Study

Background and Purpose— Several factors predict functional status after stroke, but most studies have included hospitalized patients with limited follow-up. We hypothesized that patients with ischemic stroke experience functional decline over 5 years independent of recurrent stroke and other risk factors. Methods— In the population-based Northern Manhattan Study, patients ≥40 years of age with incident ischemic stroke were prospectively followed using the Barthel Index at 6 months and annually to 5 years. Baseline stroke severity was categorized as mild (National Institutes of Health Stroke Scale <6), moderate (6 to 13), and severe (≥14). Follow-up was censored at death, recurrent stroke, or myocardial infarction. Generalized Estimating Equations provided ORs and 95% CIs for predictors of favorable (Barthel Index ≥95) versus unfavorable (Barthel Index <95) functional status after adjusting for demographic and medical risk factors. Results— Of 525 patients, mean age was 68.6±12.4 years, 45.5% were male, 54.7% Hispanic, 54.7% had Medicaid/no insurance, and 35.1% had moderate stroke. The proportion with Barthel Index ≥95 declined over time (OR, 0.91; 95% CI, 0.84 to 0.99). Changes in Barthel Index by insurance status were confirmed by a significant interaction term (&bgr; for interaction=−0.167, P=0.034); those with Medicaid/no insurance declined (OR, 0.84; P=0.003), whereas those with Medicare/private insurance did not (OR, 0.99; P=0.92). Conclusions— The proportion of patients with functional independence after stroke declines annually for up to 5 years, and these effects are greatest for those with Medicaid or no health insurance. This decline is independent of age, stroke severity, and other predictors of functional decline and occurs even among those without recurrent stroke or myocardial infarction.

Inclusion of Stroke in Cardiovascular Risk Prediction Instruments A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

BACKGROUND AND PURPOSE Current US guideline statements regarding primary and secondary cardiovascular risk prediction and prevention use absolute risk estimates to identify patients who are at high risk for vascular disease events and who may benefit from specific preventive interventions. These guidelines do not explicitly include patients with stroke, however. This statement provides an overview of evidence and arguments supporting (1) the inclusion of patients with stroke, and atherosclerotic stroke in particular, among those considered to be at high absolute risk of cardiovascular disease and (2) the inclusion of stroke as part of the outcome cluster in risk prediction instruments for vascular disease. METHODS AND RESULTS Writing group members were nominated by the committee co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Councils Scientific Statements Oversight Committee and the AHA Manuscript Oversight Committee. The writers used systematic literature reviews (covering the period from January 1980 to March 2010), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard AHA criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. The guideline underwent extensive AHA internal peer review, Stroke Council leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. There are several reasons to consider stroke patients, and particularly patients with atherosclerotic stroke, among the groups of patients at high absolute risk of coronary and cardiovascular disease. First, evidence suggests that patients with ischemic stroke are at high absolute risk of fatal or nonfatal myocardial infarction or sudden death, approximating the ≥20% absolute risk over 10 years that has been used in some guidelines to define coronary risk equivalents. Second, inclusion of atherosclerotic stroke would be consistent with the reasons for inclusion of diabetes mellitus, peripheral vascular disease, chronic kidney disease, and other atherosclerotic disorders despite an absence of uniformity of evidence of elevated risks across all populations or patients. Third, the large-vessel atherosclerotic subtype of ischemic stroke shares pathophysiological mechanisms with these other disorders. Inclusion of stroke as a high-risk condition could result in an expansion of ≈10% in the number of patients considered to be at high risk. However, because of the heterogeneity of stroke, it is uncertain whether other stroke subtypes, including hemorrhagic and nonatherosclerotic ischemic stroke subtypes, should be considered to be at the same high levels of risk, and further research is needed. Inclusion of stroke with myocardial infarction and sudden death among the outcome cluster of cardiovascular events in risk prediction instruments, moreover, is appropriate because of the impact of stroke on morbidity and mortality, the similarity of many approaches to prevention of stroke and these other forms of vascular disease, and the importance of stroke relative to coronary disease in some subpopulations. Non-US guidelines often include stroke patients among others at high cardiovascular risk and include stroke as a relevant outcome along with cardiac end points. CONCLUSIONS Patients with atherosclerotic stroke should be included among those deemed to be at high risk (≥20% over 10 years) of further atherosclerotic coronary events. Inclusion of nonatherosclerotic stroke subtypes remains less certain. For the purposes of primary prevention, ischemic stroke should be included among cardiovascular disease outcomes in absolute risk assessment algorithms. The inclusion of atherosclerotic ischemic stroke as a high-risk condition and the inclusion of ischemic stroke more broadly as an outcome will likely have important implications for prevention of cardiovascular disease, because the number of patients considered to be at high risk would grow substantially.

Risk of Myocardial Infarction or Vascular Death After First Ischemic Stroke The Northern Manhattan Study

Background and Purpose— In national guidelines, absolute long-term risk of myocardial infarction (MI) or coronary death determines target low-density lipoprotein levels, but stroke patients are not explicitly addressed. We determined the absolute 5-year risk of cardiovascular outcomes and their predictors after first ischemic stroke in a multiethnic cohort. Methods— A population-based cohort of first ischemic stroke patients ≥40 years old was prospectively followed annually for recurrent stroke, MI and cause-specific mortality. Kaplan-Meier 5-year risks for MI or vascular death (primary outcome), and other cardiovascular events, were calculated. Univariate and multivariate Cox proportional hazards models were used to calculate hazard ratios and 95% CI for predictors of cardiovascular outcomes. Results— Mean age (n=655) was 69.7±12.7 years; 55.4% of participants were women, and 51.3% Hispanic. The 5-year risk of MI or vascular death was 17.4% (95% CI, 14.2% to 20.6%). Independent historical predictors of MI or vascular death were age >70 years (hazard ratio 1.62, 1.07 to 2.44), history of coronary artery disease (hazard ratio 1.76, 1.13 to 2.74), and atrial fibrillation (hazard ratio 1.76, 1.05 to 2.94). In the lowest risk group, those ≤70 years old without coronary artery disease, 5-year risk of MI or vascular death was 9.7%. Conclusions— The absolute risk of MI or vascular death after ischemic stroke, even in those without high-risk features, approximates levels used by national organizations to designate groups of patients at high risk of vascular events. The comparability of levels of absolute risk among stroke and cardiac patients may have treatment implications.

Stroke Location and Association With Fatal Cardiac Outcomes Northern Manhattan Study (NOMAS)

Background and Purpose— Cardiac mortality after stroke is common, and small studies have suggested an association of short-term cardiac mortality with insular location of cerebral infarction. Few population-based studies with long-term follow-up have evaluated the effect of stroke location on the long-term risk of cardiac death or myocardial infarction (MI) after first ischemic stroke. We sought to determine the association between stroke location and cardiac death or MI in a multiethnic community-based cohort. Methods— The Northern Manhattan Study is a population-based study designed to determine stroke incidence, risk factors, and prognosis in a multiethnic urban population. First ischemic stroke patients age 40 or older were prospectively followed up for cardiac death defined as fatal MI, fatal congestive heart failure, or sudden death/arrhythmia and for nonfatal MI. Primary brain anatomic site was determined by consensus of research neurologists. Hazard ratios (HRs) and 95% CIs were calculated by Cox proportional-hazards models and adjusted for vascular risk factors (age, sex, history of coronary disease, hypertension, diabetes, cholesterol, and smoking), stroke severity, infarct size, and stroke etiology. Results— The study population consisted of 655 patients whose mean age was 69.7±12.7 years; 44.6% were men and 51.3% were Hispanic. During a median follow-up of 4.0 years, 44 patients (6.7%) had fatal cardiac events. Of these, fatal MI occurred in 38.6%, fatal congestive heart failure in 18.2%, and sudden death in 43.2%. In multivariate models, clinical diagnosis of left parietal lobe infarction was associated with cardiac death (adjusted HR=4.45; 95% CI, 1.83 to 10.83) and cardiac death or MI (adjusted HR=3.30; 95% CI, 1.45 to 7.51). When analysis of anatomic location was restricted to neuroimaging (computed tomography, magnetic resonance imaging, or both [n=447]), left parietal lobe infarction was associated with cardiac death (adjusted HR=3.37; 95% CI, 1.26 to 8.97), and both left (adjusted HR=3.49; 95% CI, 1.38 to 8.80) and right (adjusted HR=3.13; 95% CI, 1.04 to 9.45) parietal lobe infarctions were associated with cardiac death or MI. We did not find an association between frontal, temporal, or insular stroke and fatal cardiac events, although the number of purely insular strokes was small. Conclusions— Parietal lobe infarction is an independent predictor of long-term cardiac death or MI in this population. Further studies are needed to confirm whether parietal lobe infarction is an independent predictor of cardiac events and death. Surveillance for cardiac disease and implementation of cardioprotective therapies may reduce cardiac mortality in patients with parietal stroke.

Quality of life declines after first ischemic stroke The Northern Manhattan Study

Objectives: Quality of life (QOL) after stroke is poorly characterized. We sought to determine long-term natural history and predictors of QOL among first ischemic stroke survivors without stroke recurrence or myocardial infarction (MI). Methods: In the population-based, multiethnic Northern Manhattan Study, QOL was prospectively assessed at 6 months and annually for 5 years using the Spitzer QOL index (QLI), a 10-point scale. Functional status was assessed using the Barthel Index (BI) at regular intervals, and cognition using the Mini-Mental State Examination at 1 year. Generalized estimating equations estimated the association between patient characteristics and repeated QOL measures over 5 years. Follow-up was censored at death, recurrent stroke, or MI. Results: There were 525 incident ischemic stroke patients ≥40 years (mean age 68.6 ± 12.4 years). QLI declined after stroke (annual change −0.10, 95% confidence interval −0.17 to −0.04), after adjusting for age, sex, race-ethnicity, education, insurance, depressed mood, stroke severity, bladder continence, and stroke laterality. This decline remained when BI ≥95 was added to the model as a time-dependent covariate, and functional status also predicted QLI. Changes in QLI over time differed by insurance status (p for interaction = 0.0017), with a decline for those with Medicaid/no insurance (p < 0.0001) but not Medicare/private insurance (p = 0.98). Conclusions: In this population-based study, QOL declined annually up to 5 years after stroke among survivors free of recurrence or MI and independently of other risk factors. QLI declined more among Medicaid patients and was associated with age, mood, stroke severity, urinary incontinence, functional status, cognition, and stroke laterality.

Trajectory of Functional Decline Before and After Ischemic Stroke The Northern Manhattan Study

Background and Purpose— Previous research in our cohort showed a delayed decline in functional status after first ischemic stroke. We compared the long-term trajectory of functional status before and after ischemic stroke. Methods— The Northern Manhattan Study contains a prospective, population-based study of stroke-free individuals age ≥40 years, followed for a median of 11 years. The Barthel index (BI), a commonly used measure of activities of daily living, was assessed annually. Generalized estimating equations were used to assess functional decline over time before stroke and beginning 6 months after stroke. Follow-up was censored at the time of recurrent stroke. Results— Among 3298 participants, 210 participants had an ischemic stroke during follow-up and had poststroke BI assessed. Mean age (±SD) was 77±9 years, 38% were men, 52% were Hispanic, 37% had diabetes, and 31% had coronary artery disease. There was no difference in rate of functional decline over time before and after stroke (P=0.51), with a decline of 0.96 BI points per year before stroke (P<0.0001) and 1.24 BI points after stroke (P=0.001). However, when stratified by insurance status, among those with Medicaid or no insurance, in a fully adjusted model, there was a difference in slope before and after stroke (P=0.04), with a decline of 0.58 BI points per year before stroke (P=0.02) and 1.94 BI points after stroke (P=0.001). Conclusions— In this large, prospective, population-based study with long-term follow-up, there was a significantly steeper decline in functional status after ischemic stroke compared with before stroke among those with Medicaid or no insurance, after adjusting for confounders.

Inclusion of Stroke as an Outcome and Risk Equivalent in Risk Scores for Primary and Secondary Prevention of Vascular Disease

Current guideline statements for primary and secondary prevention of cardiovascular disease (CVD) rely on estimates of absolute risk of coronary events. For example, the American Heart Association guidelines on primary prevention state that persons with ≥10% risk over 10 years of myocardial infarction (MI) or coronary death should be considered for antiplatelet therapy with aspirin.1 Similarly, the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines2 state that target low-density lipoprotein level should be based on projected absolute risk of future coronary events rather than on presence or absence of specific risk factors. These guidelines state that patients at high risk of MI and coronary death, defined as an absolute 10-year risk of ≥20%, should have a target low-density lipoprotein level <100 mg/dL and should receive statin therapy if needed to achieve this goal. Stroke, however, is not included as one of the outcomes contributing to these absolute risk levels. Included in the group of patients with elevated risk, moreover, are those who already have ischemic heart disease, as well as patients deemed to be “coronary heart disease (CHD) risk equivalents,” indicating those at the same elevated risk as patients with ischemic heart disease. CHD risk equivalents include patients with diabetes mellitus, those with multiple risk factors that put them at elevated risk based on calculation of their Framingham Score, and patients with “other forms of symptomatic atherosclerotic disease.” The latter group is further defined to include those with peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA), and carotid artery disease. The category of “risk equivalents” in the ATP III guidelines, however, does not include the vast majority (≈80%3) of ischemic stroke patients without carotid artery disease as cause of their stroke. Ischemic stroke is therefore notably excluded from the list of outcomes contributing to …

Ideal Cardiovascular Health Predicts Functional Status Independently of Vascular Events: The Northern Manhattan Study

Background We hypothesized that the American Heart Associations metric of ideal cardiovascular health (CVH) predicts improved long‐term functional status after adjusting for incident stroke and myocardial infarction. Methods and Results In the prospective, multiethnic Northern Manhattan Study, stroke‐free individuals in northern Manhattan aged ≥40 years had annual assessments of the primary outcome of functional status with the Barthel index (BI), for a median of 13 years. Ideal CVH was calculated as a composite of 7 measures, each scored on a scale of 0 to 2. Primary predictors were (1) number of ideal CVH metrics, and (2) total score of all CVH metrics. Of 3219 participants, mean age was 69 years (SD 10), 63% were female, 21% were white, 25% were non‐Hispanic black, and 54% were Hispanic. Twenty percent had 0 to 1 ideal CVH metrics, 32% had 2, 30% had 3, 14% had 4, and 4% had 5 to 7. Both number of ideal CVH categories and higher CVH metric scores were associated with higher mean BI scores at 5 and 10 years. 0047 Gradients persisted when results were adjusted for incident stroke and myocardial infarction, when mobility and nonmobility domains of the BI were analyzed separately, and when BI was analyzed dichotomously. At 10 years, in a fully adjusted model, differences in mean BI score were lower for poor versus ideal physical activity (3.48 points, P<0.0001) and fasting glucose (4.58 points, P<0.0001). Conclusions Ideal CVH predicts functional status, even after accounting for incident vascular events. Vascular functional impairment is an important outcome that can be reduced by optimizing vascular health.

Long-term disability after lacunar stroke Secondary prevention of small subcortical strokes

Objectives: To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke. Methods: SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0–14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile. Results: Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85–0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75–2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001). Conclusions: In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.