Longitudinal Impacts of Precision Greenness on Alzheimer's Disease.

BACKGROUND: The potential for greenness as a novel protective factor for Alzheimer's disease (AD) requires further exploration. OBJECTIVES: This study assesses prospectively and longitudinally the association between precision greenness - greenness measured at the micro-environmental level, defined as the Census block - and AD incidence. DESIGN: Older adults living in consistently high greenness Census blocks across 2011 and 2016 were compared to those living in consistently low greenness blocks on AD incidence during 2012-2016. SETTING: Miami-Dade County, Florida, USA. PARTICIPANTS: 230,738 U.S. Medicare beneficiaries. MEASUREMENTS: U.S. Centers for Medicare and Medicaid Services Chronic Condition Algorithm for AD based on ICD-9 codes, Normalized Difference Vegetation Index, age, sex, race/ethnicity, neighborhood income, and walkability. RESULTS: Older adults living in the consistently high greenness tertile, compared to those in the consistently low greenness tertile, had 16% lower odds of AD incidence (OR=0.84, 95% CI: 0.76-0.94, p=0.0014), adjusting for age, sex, race/ethnicity, and neighborhood income. Age, neighborhood income and walkability moderated greenness' relationship to odds of AD incidence, such that younger ages (65-74), lower-income, and non-car dependent neighborhoods may benefit most from high greenness. CONCLUSIONS: High greenness, compared to low greenness, is associated with lower 5-year AD incidence. Residents who are younger and/or who reside in lower-income, walkable neighborhoods may benefit the most from high greenness. These findings suggest that consistently high greenness at the Census block-level, may be associated with reduced odds of AD incidence at a population level.

Diastolic Blood Pressure and Cognitive Functioning: Differences by Systolic Blood Pressure Among US Adults.

BACKGROUND: The role of diastolic blood pressure (DBP) with cognitive functioning is under-explored in relation to levels of systolic blood pressure (SBP). METHODS: We studied 5466 participants from the National Health and Nutrition Examination Survey. Blood pressure was measured 3 times manually with a standardized sphygmomanometer and averaged. Cognitive functioning was measured using the digit symbol substitution test (DSST). RESULTS: Participants were 60 years or older, 55% female, and 81% non-Hispanic White. Most participants had a DBP between 70 to <80 mmHg (33.7%), between 60 to <70 mmHg (29.3%), or <60 mmHg (18.8%). From multivariable linear regression analyses, each 5 mmHg increment of DBP was associated with significantly higher DSST scores among individuals with SBP <120 only (ß: 0.56, 95% CI: 0.09, 1.03). CONCLUSIONS: Among older US adults, at non-elevated levels of SBP, higher DBP is associated with better cognitive performance.

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Two separate, large cohorts reveal potential modifiers of age-associated variation in visual reaction time performance.

To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (ntotal = 75,666, nwomen = 47,700, nmen = 27,966; ages 18-85 years old, mean (M)Age = 46.54, standard deviation (SD)Age = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (ntotal = 158,249 nwomen = 89,333 nmen = 68,916; ages 40-70 years old, MAge = 55.81, SDAge = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (ntotal = 39,795, nwomen = 29,640, nmen = 10,155; ages 40-70 years old, MAge = 56.59, SDAge = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.

Smoking is associated with impaired verbal learning and memory performance in women more than men.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. MATERIALS AND METHODS: Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. RESULTS: The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. CONCLUSIONS: In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

Utility of blood pressure genetic risk score in admixed Hispanic samples.

Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age2, sex and body mass index. Results were combined using an inverse-variance meta-analysis. The risk score was significantly associated with blood pressure in our combined sample (P=5.65 × 10-4 for systolic and P=1.65 × 10-3 for diastolic) but the magnitude of the effect sizes varied by degree of European, African and Native American admixture. Further studies among other Hispanic sub-populations are needed to elucidate the role of these 29 variants and identify additional genetic and environmental factors contributing to blood pressure variability in Hispanics.

Statin therapy does not affect the radiographic and clinical profile of patients with TIA and minor stroke.

BACKGROUND AND PURPOSE: Acute statin therapy improves neurologic outcome and diminishes infarct growth in animal models of stroke. Clinical studies suggest that premorbid and early statin use is associated with improved outcome after major stroke. We studied the association between statin therapy and radiographic and clinical outcomes in patients with high-risk TIA and minor stroke. MATERIALS AND METHODS: Patients with high-risk TIA and minor stroke (NIHSS ≤3) were prospectively enrolled within 24 hours of symptom onset. Patients were followed clinically for 3 months, and a subset had a repeat MR imaging at 90 days. RESULTS: Of 418 patients, 23% were prescribed statins before their stroke. Statins were continued in 20% and initiated in 42%. Patients on prior statin therapy were older and more hypertensive, treated with aspirin, and more likely to have symptomatic carotid disease compared with those not on statin. Adjusting for these differences, prior statin treatment was not associated with DWI positivity (adjusted OR = 1.3; 95% CI, 0.77-2.1; P = .32) or smaller median baseline infarct volume, 1.1 mL (interquartile range = 4) versus 1 mL (interquartile range = 2.5; P = .56). Early or continued treatment with statins did not improve the risk of clinical deterioration (adjusted OR = 0.66; 95% CI, 0.27-1.6; P = .35) or poor functional outcome at 3 months (adjusted OR = 0.66; 95% CI, 0.35-1.24; P = .19). CONCLUSIONS: Prestroke or early-stroke statin therapy was not associated with a reduction in the number of DWI lesions, infarct volume, or improved clinical or functional outcome at 3 months. The effect of acute statin treatment in patients with ischemic stroke/TIA remains unclear and needs further investigation.

Differences in lipid profiles in two Hispanic ischemic stroke populations.

BACKGROUND AND PURPOSE: The study aims to compare lipid profiles among ischemic stroke patients in a predominantly Caribbean-Hispanic population in Miami and a Mestizo Hispanic population in Mexico City. METHODS: We analyzed ischemic stroke Hispanic patients with complete baseline fasting lipid profile enrolled contemporaneously in the prospective registries of two tertiary care teaching hospitals in Mexico City and Miami. Demographic characteristics, risk factors, medications, ischemic stroke subtype, and first fasting lipid profile were compared. Vascular risk factor definitions were standardized. Multiple linear regression analysis was performed to compare lipid fractions. RESULTS: A total of 324 patients from Mexico and 236 from Miami were analyzed. Mexicans were significantly younger (58 · 1 vs. 67 · 4 years), had a lower frequency of hypertension (53 · 4% vs. 79 · 7%), and lower body mass index (27 vs. 28 · 5). There was a trend toward greater prevalence of diabetes in Mexicans (31 · 5 vs. 24 · 6%, P = 0 · 07). Statin use at the time of ischemic stroke was more common in Miami Hispanics (18 · 6 vs. 9 · 4%). Mexicans had lower total cholesterol levels (169 · 9 ± 46 · 1 vs. 179 · 9 ± 48 · 4 mg/dl), lower low-density lipoprotein (92 · 3 ± 37 · 1 vs. 108 · 2 ± 40 · 8 mg/dl), and higher triglyceride levels (166 · 9 ± 123 · 9 vs. 149 · 2 ± 115 · 2 mg/dl). These differences remained significant after adjusting for age, gender, hypertension, diabetes, body mass index, smoking, ischemic stroke subtype, and statin use. CONCLUSION: We found significant differences in lipid fractions in Hispanic ischemic stroke patients, with lower total cholesterol and low-density lipoprotein, and higher triglyceride levels in Mexicans. These findings highlight the heterogeneity of dyslipidemia among the Hispanic race-ethnic group and may lead to different secondary prevention strategies.

Perivascular spaces are associated with atherosclerosis: an insight from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. MATERIALS AND METHODS: Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm identified on brain axial T1-weighted MR imaging were scored as perivascular spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. RESULTS: The studied sample included 706 participants (mean age, 72.6 ± 8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (ß = 0.01 per year, P = < .001), non-Hispanic black race-ethnicity (ß = 0.16, P = .02), hypertension (ß = 0.24, P = < .001), and carotid plaque (ß = 0.22, P < .001). In multivariable analysis, only age (ß = 0.01, P = .02), hypertension (ß = 0.17, P = .01), and carotid plaque (ß = 0.22, P = < .001) remained independently associated with perivascular spaces. CONCLUSIONS: Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism.

OBJECTIVE: We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN: Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. RESULTS: Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. CONCLUSIONS: In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.

Impact of statins on the coagulation status of type 2 diabetes patients evaluated by a novel thrombin-generation assay.

PURPOSE: Dyslipidemia is common in type 2 diabetes (T2D) and contributes to cardiovascular disease (CVD) by exacerbating atherosclerosis and hypercoagulability. Statins can stabilize atherosclerotic plaque and reduce prothrombotic status. In the present study we aimed to evaluate the coagulation activity and the effect of statins on procoagulant state of T2D patients using a novel activated protein C (APC)-dependent thrombin-generation assay. METHODS: Procoagulant status (by HemosIL ThromboPath (ThP) assay) and in vivo platelet activation (by plasma soluble (s)CD40L levels) were analyzed in a retrospective, cross-sectional study of 198 patients with long-standing T2D and 198 controls. RESULTS: Procoagulant status of T2D patients was enhanced when compared to control subjects (p < 0.0001). Similarly, sCD40L levels were increased in T2D (p < 0.0001). When testing ThP as the dependent variable in a multivariate regression model, sCD40L (p < 0.0001) and statin treatment (p = 0.019) were independent predictors of the procoagulant state of T2D patients. Subgroup analysis showed a significant improvement of coagulability in T2D patients on statins (p = 0.012). CONCLUSIONS: The use of a standardized, easy-to-run, and commercially available APC-dependent thrombin-generation assay detected the presence of a procoagulant status in a large series of patients with long-standing T2D and demonstrated a significant impact of statins in the coagulation status of patients with T2D.

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.

Cardiac structure and diastolic function in mild primary hyperparathyroidism.

CONTEXT: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: To evaluate the heart in PHPT, we assessed cardiac structure and diastolic function in patients with mild PHPT compared with age- and sex-matched controls. DESIGN: This was a case-control study. SETTINGS: The study was conducted in a university hospital Metabolic Bone Diseases Unit. PARTICIPANTS: Fifty-four men and women with PHPT and 76 controls without PHPT participated in the study. OUTCOME MEASURES: We measured left ventricular mass index (LVMI), the presence of mitral annular calcification, the ratio of early to late diastolic mitral inflow velocities (E/A), and early diastolic velocity of the lateral mitral annulus using Doppler tissue imaging (tissue Doppler e'). RESULTS: Patients had mild disease with mean (+/-sd) serum calcium 10.5 +/- 0.5 mg/dl and PTH 96 +/- 45 pg/ml. LVMI and diastolic function were normal in PHPT. There was no difference in LVMI (98 +/- 23 vs. 96 +/- 24 g/m(2), P = 0.69) or the frequency of mitral annular calcification between PHPT cases and controls. Diastolic function variables (E/A and tissue Doppler e') were higher (better) in cases compared with controls, although both were within the reference range. PHPT patients with low E/A had higher serum PTH (121 +/- 36 vs. 89 +/- 46 pg/ml, P = 0.03) and calcium (10.8 +/- 0.4 vs. 10.5 +/- 0.5 mg/dl, P = 0.05) than those with normal values. Finally, we found LVMI to be inversely associated with serum 25-hydroxyvitamin D in PHPT (r = -0.29, P < 0.05). All findings persisted after adjustment for group differences in cardiovascular risk factors. CONCLUSIONS: Patients with biochemically mild PHPT do not have evidence of increased left ventricular mass, diastolic dysfunction, or increased valvular calcifications. However, the data support an association between low vitamin D levels and the development of left ventricular hypertrophy in this disorder. Finally, the increased serum calcium and PTH levels in those with diastolic dysfunction suggest that disease severity may determine the presence of cardiac manifestations in PHPT.

Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study.

BACKGROUND AND PURPOSE: Endovascular brain cooling as a method for rapid and selective induction of hypothermic neuroprotection has not been systematically studied in humans. In this clinical pilot study we investigated the feasibility, safety, and physiologic responses of short-term brain cooling with IC-CSI. MATERIALS AND METHODS: We studied 18 patients (50 +/- 10 years old, 9 women) undergoing follow-up cerebral angiography after previous treatment of vascular malformations. Isotonic saline (4-17 degrees C) was infused into 1 internal carotid artery at 33 mL/min for 10 minutes. Brain (JVB) and bladder/esophageal temperature measurements (n = 9) were performed. Both MCAs were monitored with transcranial Doppler sonography (n = 13). Arterial and JV blood were sampled to estimate hemodilution and brain oxygen extraction. RESULTS: JVB temperature dropped approximately 0.84 +/- 0.13 degrees C and systemic temperature by 0.15 +/- 0.08 degrees C from baseline (JVB versus systemic temperature: P = .0006). Systolic MCA-flow velocities decreased from 101 +/- 27 to 73 +/- 18 cm/s on the infused side and from 83 +/- 24 to 78 +/- 21 cm/s on the contralateral side (relative changes, -26 +/- 8% versus -4 +/- 27%; P = .009). Changes in hematocrit (-1.2 +/- 1.1%) and cerebral arteriovenous oxygen difference (0.2 +/- 1.0 mL O(2)/100 mL) were not significant. Doppler data showed no signs of vascular spasm or microemboli. No focal neurologic deficits occurred. Pain was not reported. CONCLUSIONS: The results of this pilot study suggest that brain cooling can be achieved safely, rapidly, and selectively by means of IC-CSI, opening a new potential avenue for acute neuroprotection. Clinical investigations with control of infusion parameters and measurements of CBF, oxygen consumption, and brain temperature are warranted.

Carotid vascular abnormalities in primary hyperparathyroidism.

CONTEXT: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. OBJECTIVE: This study evaluated carotid structure and function in PHPT patients compared with population-based controls. DESIGN: This is a case-control study. SETTING: The study was conducted in a university hospital metabolic bone disease unit. PARTICIPANTS: Forty-nine men and women with PHPT and 991 controls without PHPT were studied. OUTCOME MEASURES: We measured carotid intima-media thickness (IMT), carotid plaque presence and thickness, and carotid stiffness, strain, and distensibility. RESULTS: IMT, carotid plaque thickness, carotid stiffness, and distensibility were abnormal in PHPT patients, and IMT was higher in patients than controls (0.959 vs. 0.907 mm, P < 0.0001). In PHPT, PTH levels, but not calcium concentration, predicted carotid stiffness (P = 0.04), strain (P = 0.06), and distensibility (P = 0.07). Patients with increased carotid stiffness had significantly higher PTH levels than did those with normal stiffness (141 +/- 48 vs. 94.9 +/- 44 pg/ml, P = 0.002), and odds of abnormal stiffness increased 1.91 (confidence interval = 1.09-3.35; P = 0.024) for every 10 pg/ml increase in PTH, adjusted for age, creatinine, and albumin-corrected calcium. CONCLUSIONS: Mild PHPT is associated with subclinical carotid vascular manifestations. IMT, a predictor of cardiovascular outcomes, is increased. Measures of carotid stiffness are associated with extent of PTH elevation, suggesting that those with more severe PHPT may have impaired vascular compliance and that PTH, rather than calcium, is the mediator.