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Background and Purpose: To determine whether progression of MRI-defined vascular disease predicts subsequent vascular events in the elderly., Methods: The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows us to address this question because its participants had 2 MRI scans≈5 years apart and have been followed for ≈9 years since the follow-up scan for incident vascular events., Results: Both MRI-defined incident infarcts and worsened white matter grade were significantly associated with heart failure, stroke, and death, but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened white matter grade were present for heart failure (hazard ratio, 1.79; 95% confidence interval, 1.18-2.73), stroke (hazard ratio, 2.58; 95% confidence interval, 1.53-4.36), death (hazard ratio, 1.69; 95% confidence interval, 1.28-2.24), and cardiovascular death (hazard ratio, 1.97; 95% confidence interval, 1.24-3.14)., Conclusions: Progression of MRI-defined vascular disease identifies elderly people at increased risk for subsequent heart failure, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown.

Background and Purpose: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype., Methods: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly., Results: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors., Conclusions: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

Background and Purpose: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging., Methods: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade., Results: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk., Conclusions: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

Background and Purpose: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors., Methods: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.

Background and Purpose: MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts., Methods: The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged > or =65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI., Results: On follow-up MRI, 254 participants (17.7%) had 1 or more infarcts. Most were single (75.6%), subcortical (79.9%), and small (3 to 20 mm in 87.0%). Only 11.4% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index., Conclusions: Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.

Background and Purpose: Animal studies have shown that MR diffusion imaging can outline acute ischemic regions before irreversible damage (infarction) occurs. To study evolution of ischemic lesions in humans, it is therefore important to quantify absolute diffusion constants (D values), but quantitation has not been reproducible among different clinics. These problems are explained, and a method for reproducible quantitation is suggested., Methods: Diffusion-weighted and absolute diffusion images were acquired, and the absolute apparent diffusion constants in three orthogonal spatial directions (Dxx, Dyy, and Dzz) were measured. These were combined to calculate images of the orientation-independent apparent diffusion parameter Dav = 1/3 Trace[D] = 1/3(Dxx + Dyy + Dzz). Values of the individual diffusion constants and Dav were evaluated in 6 patients and 6 normal volunteers., Results: Patient data show that comparison of diffusion constants between contralateral and ipsilateral hemispheres after ischemia may give results varying by more than 100% depending on orientation. Findings in normal-appearing regions containing a mixture of gray and white matter in patients (n = 5) and in normal volunteers (n = 6) show that Dav = (0.92+/-0.11) x 10(-3) mm2/s, with a small intersubject variation, whereas Dxx, Dyy, and Dzz vary strongly. Hemispheric ratios (ipsilateral/contralateral [I/C]) in these subjects were (I/C)Dav = 1.00+/-0.05, (I/C)Dxx = 1.02+/-0.15, (I/C)Dyy = 1.07+/-0.24, and (I/C)Dzz = 0.96+/-0.28. The individual subjects in this group all had an (I/C)Dav within 10% of unity, while the other three ratios showed intersubject variations as large as 100%., Conclusions: (I/C)Dav ratios are a reliable means to quantitate changes in absolute diffusion constants for the study of stroke evolution independent of tissue orientation, gradient orientation, and diffusion time. The use of these ratios will enable reproducible intersubject and interclinic quantitation.