Sleep and Stroke: New Updates on Epidemiology, Pathophysiology, Assessment, and Treatment.

PURPOSE OF REVIEW: This review aims to discuss the most recent data on sleep disorders and stroke, highlighting relevant findings for the practicing neurologist or health providers who encounter patients with sleep disorders and stroke. RECENT FINDINGS: Sleep apnea and abnormal sleep duration have the strongest association with stroke risk. Possible mechanisms include non-dipping of blood pressure during sleep, hypoxemia or reoxygenation leading to sympathetic activation, hypertension, atrial fibrillation and impaired cerebral hemodynamics. Treatment studies suggest that continuous positive airway pressure (CPAP) for sleep apnea could improve primary prevention of stroke, but data is equivocal for secondary prevention. However, CPAP could improve functional outcomes after stroke. SUMMARY: Sleep disorders present an opportunity to improve stroke risk and functional outcomes. However, new strategies are needed to determine the patients at high-risk who would most likely benefit from targeted care. Novel methods for phenotyping sleep disorders could provide personalized stroke care to improve clinical outcomes and public health strategies.

Transcranial Doppler velocities in a large, healthy population.

BACKGROUND: Transcranial Doppler (TCD) ultrasonography has been extensively used in the evaluation and management of patients with cerebrovascular disease since the clinical application was first described in 1982 by Aaslid and colleagues TCD is a painless, safe, and noninvasive diagnostic technique that measures blood flow velocity in various cerebral arteries. Numerous commercially available TCD devices are currently approved for use worldwide, and TCD is recognized to have an established clinical value for a variety of clinical indications and settings. Although many studies have reported normal values, there have been few recently, and none to include a large cohort of healthy subjects across age, race, and gender. As more objective, automated processes are being developed to assist with the performance and interpretation of TCD studies, and with the potential to easily compare results against a reference population, it is important to define stable normal values and variances across age, race, and gender, with clear understanding of variability of the measurements, as well as the yield from various anatomic segments. METHODS: To define normal TCD values in a healthy population, we enrolled 364 healthy subjects, ages 18-80 years, to have a complete, nonimaging TCD examination. Subjects with known or suspected cerebrovascular disorders, systemic disorders with cerebrovascular effects, as well as those with known hypertension, diabetes, stroke, coronary artery disease, or myocardial infarction, were excluded. Self-reported ethnicity, handedness, BP, and BMI were recorded. A complete TCD examination was performed by a single experienced sonographer, using a single gate nonimaging TCD device, and a standardized protocol to interrogate up to 23 arterial segments. Individual Doppler spectra were saved for each segment, with velocity and pulsatility index (PI) values calculated using the instrument's automated waveform tracking function. Descriptive analysis was done to determine the mean velocities and PI, and all data were analyzed for changes by decade of age, sex race, handedness, BMI, and BP. RESULTS: Among the key intracranial segments, mean blood flow velocities (MBFV) were highest in the MCA and lowest in the PCA across all ages, sexes, and ethnic groups. There was no difference in the MBFVs between left and right side segments of the Circle of Willis, with the exception of the distal M1 (P = .022) and the C1 (P < .0001), both slightly higher on the left. MBFV were higher among women than men in all segments except for the OA. MBFV decreased with advancing age in both men and women, but this was specific to Caucasian subjects. There were lower velocities in the OA for non-Caucasians. The PI was lower in the left VA (P < .0001), and for most segments was lower in women than men. The PI increased with age in all segments for women, but only in some segments for men, and this finding was also specific to Caucasian subjects. The yield of usable data ranged from 99.7% for the VA and BA, to 88.2% for C2. CONCLUSION: Our study provides normal, reference TCD values for a large cohort of healthy subjects across a wide range of age, sex, and race groups. We observed decreased MBFV and increased PI with aging, and higher MBFV in women. There were few differences in MBFV related to side or ethnicity, but the MFBV and PI changes with age were specific to Caucasians. We provide means and standard deviations of MBFVs across various demographic groups in key intracranial arteries. Such normal TCD values across age, gender, and ethnic groups in healthy subjects represent a useful reference tool for detecting individuals with TCD values outside normal limits and at increased vascular risk. TCD studies in large multiethnic populations are still required to determine differences in brain hemodynamics across various ethnic groups.

Recommendations for diabetic polyneuropathy treatment.

Diabetes is a chronic disease that requires continual medical care and patient self-management education in order to prevent acute complications and to reduce the risk of long-term complications. Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and the leading source of morbidity and mortality in diabetes patients. Diabetic polyneuropathy is primarily symmetric sensory neuropathy, initially affecting distal lower extremities. Patients have evidence of nerve damage at the time their diabetes is diagnosed in 10%-18% of cases, suggesting that even early impairment of glucose handling, classified as prediabetes, is associated with neuropathy. It is important to appreciate that there are other causes of neuropathy; these should be considered if there is any aspect of the history or clinical presentation suggesting features atypical of diabetic neuropathy. Diagnosis of diabetic neuropathy should be established according to clinical manifestations of the disease, laboratory findings (altered glucose metabolism) and results of electrophysiological examinations. Treatment of painful diabetic polyneuropathy rests on a two-pronged approach: modification of the underlying disease and control of pain symptoms. The goals of painful diabetic polyneuropathy pharmacotherapy should be reduction of pain for maximum relief commensurate with acceptable side effects and restoration/ improvement in functional measures and quality of life.

Recommendations for the management of patients with carotid stenosis.

These are evidence based guidelines for the management of patients with carotid stenosis, developed and endorsed by Croatian Society of Neurovascular Disorders, Croatian Society of Neurology, Croatian Society of Ultrasound in Medicine and Biology, Croatian Society for Radiology, Croatian Society of Vascular Surgery and Croatian Society of Neurosurgery. They consist of recommendations for noninvasive screening of patients with carotid stenosis, best medical treatment and interventions such as carotid endarterectomy and stent placement based on international randomized clinical trials.

Infectious burden and carotid plaque thickness: the northern Manhattan study.

BACKGROUND AND PURPOSE: The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multiethnic cohort. METHODS: Antibody titers to 5 common infectious microorganisms (ie, Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants and a weighted index of infectious burden was calculated based on Cox models previously derived for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness. Weighted least squares regression was used to measure the association between infectious burden and maximum carotid plaque thickness after adjusting for other risk factors. RESULTS: Serological results for all 5 infectious organisms were available in 861 participants with maximum carotid plaque thickness measurements available (mean age, 67.2+/-9.6 years). Each individual infection was associated with stroke risk after adjusting for other risk factors. The infectious burden index (n=861) had a mean of 1.00+/-0.35 SD and a median of 1.08. Plaque was present in 52% of participants (mean, 0.90+/-1.04 mm). Infectious burden was associated with maximum carotid plaque thickness (adjusted increase in maximum carotid plaque thickness 0.09 mm; 95% CI, 0.03 to 0.15 mm per SD increase of infectious burden). CONCLUSIONS: A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multiethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.

Infectious burden and risk of stroke: the northern Manhattan study.

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.

Transient ischemic attack before nonlacunar ischemic stroke in the elderly.

BACKGROUND: Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. METHODS: We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. RESULTS: We evaluated 203 patients (>or=65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 +/- 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. CONCLUSION: These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.

Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAS).

BACKGROUND: Metabolic syndrome (MetS) predisposes to cardiovascular disease. Endothelial dysfunction is thought to be an important factor in the pathogenesis of atherosclerosis. We tested the hypothesis that both MetS and endothelial dysfunction are vascular risk factors and provide additive prognostic values in predicting cardiovascular events in a multiethnic community sample. METHODS: The study population consisted of 819 subjects (467 female, mean age 66.5 +/- 8.8 years, 66% Hispanic) enrolled in the NOMAS. Metabolic syndrome was defined using the revised Adult Treatment Panel III criteria. Brachial artery flow-mediated dilation (FMD) was measured using high-resolution ultrasound. Endothelial dysfunction was defined as FMD <8.44% (lower 3 quartiles). Cox proportional hazards models were used to assess the effect of MetS and endothelial dysfunction on risk of cardiovascular events. RESULTS: During 81 +/- 21 months of follow-up, events occurred in 84 subjects. Metabolic syndrome was independently associated with cardiovascular events in a multivariate model, including cardiovascular risk factors (adjusted hazard ratio 2.08, 95% CI 1.27-3.40). Subjects with both MetS and endothelial dysfunction were at higher risk for cardiovascular events than those with either one of them alone (adjusted hazard ratio 2.60, 95% CI 1.14-5.92). CONCLUSIONS: Metabolic syndrome is associated with incident cardiovascular events. Combined use of MetS and FMD identifies those who are at higher risk of cardiovascular events. Metabolic syndrome and noninvasive FMD testing can be used concurrently for cardiovascular risk prediction.

Multiple genetic determinants of plasma lipid levels in Caribbean Hispanics.

OBJECTIVES: To identify candidate genes in relation to plasma lipid levels in Caribbean Hispanics. DESIGN AND METHODS: A total of 114 single nucleotide polymorphisms (SNPs) at 17 lipid-related genes were genotyped in 477 Caribbean Hispanics from the Northern Manhattan Study (NOMAS). Analyses for each SNP and haplotype were performed to evaluate the associations with four lipid traits: high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglyceride (TG) and total cholesterol (TC). RESULTS: We identified 19 SNPs at 10 genes that were significantly related to lipids (p<0.01), including nine involved in the reverse cholesterol transport pathway, and one involved in bile acid synthesis. Three genes, namely the apolipoprotein A5, apolipoprotein B and cytochrome p450 polypeptide 7A1 genes, accounted for the largest proportion of variation in HDL-C/TG, TC and LDL-C respectively. CONCLUSIONS: The cumulative effects of multiple genetic variants led to a substantially better prediction of inter-individual variations in lipid levels.

Recommendations for neuropathic pain treatment.

Damage to the somatosensory nervous system poses a risk for the development of neuropathic pain. Such an injury to the nervous system results in a series of neurobiological events resulting in sensitization of both the peripheral and central nervous system. The symptoms include continuous background pain (often burning or crushing in nature) and spasmodic pain (shooting, stabbing or "electrical"). The diagnosis of neuropathic pain is based primarily on the history and physical examination finding. Although monotherapy is the ideal approach, rational polypharmacy is often pragmatically used. Several classes of drugs are moderately effective, but complete or near-complete relief is unlikely. Antidepressants and anticonvulsants are most commonly used. Opioid analgesics can provide some relief but are less effective than for nociceptive pain; adverse effects may prevent adequate analgesia. Topical drugs and a lidocaine-containing patch may be effective for peripheral syndromes. Sympathetic blockade is usually ineffective except for some patients with complex regional pain syndrome.

Genetic contribution to brachial artery flow-mediated dilation: the Northern Manhattan Family Study.

BACKGROUND: Brachial artery flow-mediated dilation (FMD) is a non-invasive measure of endothelial function. Endothelial dysfunction has been associated with traditional vascular risk factors and increased risk of cardiovascular disease. The importance of genetic contribution to FMD and baseline brachial artery diameter has not been shown in Hispanic populations. The purpose of this study was to estimate the heritability of FMD. METHODS: Flow mediated dilation and brachial artery diameter were measured in a subset of Caribbean Hispanic families from the ongoing Northern Manhattan Family Study (NOMAFS), which studies the contribution of genetics to stroke and cardiovascular risk factors. The age- and sex-adjusted heritability of FMD was estimated using variance component methods. RESULTS: The current data include 620 subjects (97 probands and 523 relatives) from 97 families. The age and sex-adjusted heritability of brachial artery diameter was 0.57 (p<0.01). The age- and sex-adjusted heritability of FMD was 0.20 (p=0.01). After additional adjustment for systolic and diastolic blood pressure, body mass index, smoking, lipid, diabetes mellitus, medication, and baseline brachial artery diameter, the heritability of FMD was 0.17 (p=0.01). CONCLUSIONS: We found modest heritability of FMD. FMD might be a reasonable phenotype for further investigation of genetic contribution to atherosclerosis.

Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study.

BACKGROUND AND PURPOSE: More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. METHODS: As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. RESULTS: More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI, 1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. CONCLUSIONS: The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity.

Design of a family study among high-risk Caribbean Hispanics: the Northern Manhattan Family Study.

Stroke continues to kill disproportionately more Blacks and Hispanics than Whites in the United States. Racial/ethnic variations in the incidence of stroke and prevalence of stroke risk factors are probably explained by both genetic and environmental influences. Family studies can help identify genetic predisposition to stroke and potential stroke precursors. Few studies have evaluated the heritability of these stroke risk factors among non-White populations, and none have focused on Caribbean Hispanic populations. The aim of the Northern Manhattan Family Study (NOMAFS) is to investigate the gene-environment interaction of stroke risk factors among Caribbean Hispanics. The unique recruitment and methodologic approaches used in this study are relevant to the design and conduct of genetic aggregation studies to investigate complex genetic disorders in non-White populations. The aim of this paper is to describe the NOMAFS and report enrollment and characteristics of the participants. The NOMAFS will provide a data resource for the exploration of the genetic determinants of highly heritable stroke precursor phenotypes that are less complex than the stroke phenotype. Understanding the gene environment interaction is the critical next step toward the development of new and unique approaches to disease prevention and interventions.

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 > or =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 < or =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.

Carotid artery plaque thickness is associated with increased serum calcium levels: the Northern Manhattan study.

BACKGROUND: Elevated serum calcium concentrations are associated with vascular calcification and cardiovascular disease. It is unknown whether there is a relationship between high-normal serum calcium levels and sub-clinical vascular effects. We investigated the association between serum calcium and carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events. METHODS: Epidemiological study of 1194 subjects from the Northern Manhattan Study cohort, a prospective community-based study designed to investigate risk factors for vascular disease in different race-ethnic groups. RESULTS: Subjects with carotid plaque had higher corrected serum calcium levels within the normal range than those without carotid plaque (2.21+/-0.09 mmol/L versus 2.19+/-0.09 mmol/L, p<0.002). The relationship between carotid plaque and serum calcium persisted after adjustment for traditional cardiovascular risk factors. Subjects in the top quintile of maximal carotid plaque thickness (>or=1.7 mm) were more likely to be in the highest quintile of serum calcium level (OR=1.64, 95% CI=1.17-2.29, p<0.004). The interaction of age and corrected serum calcium was the most significant predictor of carotid plaque thickness when traditional vascular risk factors were considered (p<0.001). CONCLUSIONS: Serum calcium levels in a multi-ethnic population of older men and women were positively associated with carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events.

Ultrasound assessment of subclinical cardiovascular disease in a community-based multiethnic population and comparison to the Framingham score.

The presence of subclinical cardiovascular disease has been documented to indicate high coronary risk. This study investigated the impact of subclinical cardiovascular disease derived from echocardiography and carotid ultrasonography on traditional coronary risk stratification using the Framingham risk score (FRS) in a community-based, multiethnic population. Echocardiography and carotid ultrasonography were performed in 1,445 subjects (aged >39 years; 40% men; 53% Hispanic, 20% white, 24% black) from the Northern Manhattan Study. Subclinical cardiovascular disease was defined as the presence of left ventricular hypertrophy and/or carotid plaque greater than the gender-specific 75th percentile of the left ventricular mass index and maximal carotid plaque thickness distribution. The prevalence of subclinical cardiovascular disease was examined in each FRS category (low, intermediate, and high risk). In subjects with low or intermediate FRSs, 35% had subclinical cardiovascular disease (low FRS 29%, intermediate FRS 42%). In the intermediate FRS category, subclinical cardiovascular disease was significantly more prevalent in women than in men (53% vs 32%, p <0.0001) and in black and white subjects than in Hispanics (59% and 46% vs 33%, p <0.0001 and p = 0.040, respectively). In conclusion, the ultrasound assessment of subclinical cardiovascular disease may help reclassify 1/3 of subjects with low or intermediate FRSs into higher risk groups. In the intermediate FRS category, FRS appears to underestimate the coronary risk more in women than in men and more in whites and especially in blacks than in Hispanics.

Left ventricular systolic dysfunction and the risk of ischemic stroke in a multiethnic population.

BACKGROUND AND PURPOSE: Left ventricular dysfunction (LVD) is associated with cardiovascular mortality. Its association with ischemic stroke has been mainly documented after myocardial infarction. The stroke risk associated with LVD, especially of mild degree, in the general population is unclear. The purpose of this study was to evaluate the relationship between LVD and ischemic stroke in a multiethnic cohort. METHODS: LV systolic function was assessed by transthoracic 2-dimensional echocardiography in a subset of subjects from the Northern Manhattan Study (NOMAS), 270 patients with first ischemic stroke and 288 age-, gender- and race-matched community controls. LV ejection fraction was measured by a simplified cylinder-hemiellipsoid formula, and categorized as normal (>50%), mildly (41% to 50%), moderately (31% to 40%) or severely (< or =30%) decreased. The association between impaired ejection fraction and ischemic stroke was evaluated by logistic regression analysis after adjustment for established stroke risk factors. RESULTS: LVD of any degree was more frequent in stroke patients (24.1%) than in controls (4.9%; P<0.0001), as was moderate/severe LVD (13.3% versus 2.4%; P<0.001). A decreased ejection fraction was associated with ischemic stroke even after adjusting for other stroke risk factors. The adjusted odds ratio for any degree of LVD was 3.92 (95% CI, 1.93 to 7.97). The adjusted odds ratio for mild LVD was 3.96 (95% CI, 1.56 to 10.01) and for moderate/severe LVD 3.88 (95% CI, 1.45 to 10.39). The association between LVD of any degree and stroke was present in all age, gender and race-ethnicity subgroups. CONCLUSIONS: LVD, even of mild degree, is independently associated with an increased risk of ischemic stroke. The assessment of LV function should be considered in the assessment of the stroke risk.

Moderate alcohol consumption reduces risk of ischemic stroke: the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Moderate alcohol consumption is protective against coronary disease, but its relationship to ischemic stroke (IS) is controversial. METHODS: Stroke-free participants > or =40 years of age identified by random-digit dialing were enrolled in a prospective cohort study between 1993 and 2001. Alcohol consumption was assessed through in-person interview and categorized as none in the past year, > or =1 drink in past month to < or =2 per day (moderate drinkers), and >2 drinks daily. Lifetime drinking was also assessed. Cox proportional hazard regression modeling was used to assess hazard ratios and their 95% CIs for the association of drinking with risk of stroke and vascular events. RESULTS: Mean age among participants (n=3176) was 69.1+/-10.3 years; 62.8% were women, 20.8% were non-Hispanic white, 24.5% non-Hispanic black, and 52.4% were Hispanic. No alcohol in the previous year was present in 62.3%, and 32.5% drank moderately. After adjusting for other risk factors compared with those who did not drink in the past year, moderate drinkers had a reduced risk of IS (0.67; 95% CI, 0.46 to 0.99) and IS, myocardial infarction, or vascular death (0.74; 95% CI, 0.59 to 0.94). Results were similar when never-drinkers were used as referent group. Reduction in risk was seen for nonatherosclerotic IS subtypes, and results stratified by age, sex, and race-ethnicity were similar. CONCLUSIONS: Moderate alcohol consumption is associated with decreased risk of IS in a multiethnic population. This effect is independent of other risk factors and holds for nonatherosclerotic stroke subtypes.

Heritability of carotid artery distensibility in Hispanics: the Northern Manhattan Family Study.

BACKGROUND AND PURPOSE: Reduced arterial distensibility has been introduced as a novel risk factor for atherosclerosis. The importance of the genetic contribution to variation in distensibility is largely unknown. The purpose of this study was to estimate heritability of carotid distensibility. METHODS: The ongoing Northern Manhattan Family Study recruits high-risk Caribbean Hispanic families to study genetic effects on stroke/cardiovascular risk factors. The distensibility metrics (strain, stiffness, distensibility, and elastic modulus) were measured from the right common carotid artery, and the heritability for each was estimated. Variance component methods were used to estimate age- and sex-adjusted heritability. Correlations were calculated to evaluate the relationship between distensibility phenotypes and intimamedia thickness (IMT) at each carotid segment. RESULTS: The current data included 88 probands and 605 relatives from 88 families. Age- and sex-adjusted heritability was 25% for strain, 17% for distensibility, 20% for stiffness, and 20% for elastic modulus. Without adjustment for covariates, strong correlations were found between distensibility metrics and IMT: the absolute values of correlation coefficients were between 0.2 and 0.5, and all P values were <0.001. However, the correlation coefficients were reduced substantially after adjusting for age and sex. CONCLUSIONS: These results suggested that genetic factors explained a moderate proportion of the variability of carotid distensibility. The correlations between distensibility and IMT were mainly attributable to age and sex effects. The regulation of carotid distensibility and IMT may reflect different underlying genetic and environmental mechanisms.