Biomedical subjects

Ralph Sacco

Publications and source records attributed to Ralph Sacco.

5 recordsLinked to original sources

PubMed2006

The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort.

BACKGROUND: Brachial artery flow-mediated dilation (FMD) may predict cardiovascular events in selected high-risk patients. Whether FMD testing predicts cardiovascular events in asymptomatic, lower risk individuals from the general population is unknown. METHODS AND RESULTS: As a part of a multi-ethnic, prospective cohort study, the Northern Manhattan Study, we examined FMD by high-resolution ultrasonography in 842 community participants who were free of stroke or myocardial infarction. Lower FMD levels predicted cardiovascular events (myocardial infarction, stroke and vascular death) at 36 months of follow-up (hazard ratio (HR)=1.12 for every 1% decrease in FMD, 95% CI 1.01-1.25, p=0.03). The risk of events in patients with FMD in the lower two tertiles (FMD<7.5%) was significantly higher than those in the highest tertile (HR=3.28, 95% CI 1.07-10.06, p=0.04 for lowest versus highest tertile, and HR=3.05, 95% CI 1.03-9.66, p=0.04 for middle versus highest tertile). In a multivariate analysis including cardiovascular risk factors, the increase in risk associated with FMD was no longer statistically significant. CONCLUSIONS: Non-invasive FMD testing predicts incident cardiovascular events in this multi-ethnic, population-based sample, but its predictive value is not independent of cardiovascular risk factors.

Aged↗

PubMed2006

Lessons from adult stroke trials.

Before designing epidemiologic, genetic, or treatment trials in pediatric stroke, we should learn from adult trials which preceded. Adult trialists state that there is a need for improved animal models to mimic human disease. Dose-response curves with blinded outcome measures would improve preclinical data. Functional and histologic outcome measures would improve the animal model. In regard to human Phase 2 medication trials, safety, delivery, end points, and surrogate markers are necessary. The detection of biologic activity can be defined in Phase 2B trials. For Phase 3 trials, the experiment needs to be simple with global outcome measures as end points. New statistical designs such as futility analysis may improve and streamline trials in both adults and children. Clinical trials are a long process, and care needs to be incorporated at every step. Why is there a propensity of failed studies for acute ischemic stroke in adults? The reasons include (a) the animal model fails us, (b) the Phase 2 trials are ineffective in defining dose, and (c) the Phase 3 trials are poorly done. Because clinical trials, more often than not, fail to give positive (effective treatment) results, it seems reasonable to attempt to learn from others' past experiences before initiating pediatric stroke trials.

Adult↗

PubMed2005

Effect of the Glycine Antagonist Gavestinel on cerebral infarcts in acute stroke patients, a randomized placebo-controlled trial: The GAIN MRI Substudy.

BACKGROUND AND PURPOSE: Gavestinel, GV150526, is a selective antagonist at the glycine site of the N-methyl-D-aspartate receptor. The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials]. A planned MRI substudy within these trials investigated the effect of gavestinel on infarct volume. METHODS: Patients enrolled in the GAIN trials at designated MRI substudy sites were eligible if they had a pretreatment acute cortical lesion on diffusion-weighted MRI of at least 1.5 cm diameter or 5 cm(3). Final lesion assessment was performed on T(2)-weighted MRI at month 3. Blinded image analysis was performed centrally. The primary hypothesis was that gavestinel would attenuate lesion growth from baseline relative to placebo. RESULTS: A total of 106 patients were eligible, 75 (34 gavestinel, 41 placebo) of whom had month 3 scans (primary analysis population). No effects of gavestinel on infarct volume were observed in the primary or other analyses. However, significant associations of lesion volume to clinical severity and outcomes were observed. Ischemic lesion volume decrease was predictive of substantial clinical improvement. CONCLUSION: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed. Concordance of results of the clinical outcome trials with those of this infarct volume substudy as well the associations of infarct volume to clinical outcomes further support the potential role of infarct volume as a marker of outcome in dose finding and proof of principle acute stroke trials.

Cerebral Infarction↗

PubMed2004

Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke.

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke. There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to rhabdomyolysis. These adverse effects may be due to a coenzyme Q(10) (CoQ(10)) deficiency because inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ(10). OBJECTIVE: To measure CoQ(10) levels in blood from hypercholesterolemic subjects before and after exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days. DESIGN: Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels of CoQ(10). SETTING: Stroke center at an academic tertiary care hospital. Patients We examined a cohort of 34 subjects eligible for statin treatment according to National Cholesterol Education Program: Adult Treatment Panel III criteria. RESULTS: The mean +/- SD blood concentration of CoQ(10) was 1.26 +/- 0.47 micro g/mL at baseline, and decreased to 0.62 +/- 0.39 micro g/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease was already detectable after 14 days of treatment (P<.001). CONCLUSIONS: Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.

Aged↗

PubMed2003

Obstacle training programme for individuals post stroke: feasibility study.

OBJECTIVE: The purposes were threefold: to develop an obstacle ambulation training programme, to recruit and retain individuals post chronic stroke and to assess the effectiveness of the obstacle ambulation training programme. DESIGN: Intervention study; case series; baseline to post-intervention measures and one month follow-up after intervention. SETTING: An outpatient department. SUBJECTS: Five individuals with chronic stroke with mild to moderate functional limitations; convenience sample. INTERVENTIONS: Therapy consisted of twice weekly sessions for four weeks during which subjects walked along a walkway and over obstacles. MAIN OUTCOME MEASURES: Motor Assessment Scale--walking section (MAS--time), Six-minute Walk Test distance, walking velocity, and Medical Outcomes Study-36 Health Status Measurement (SF-36). RESULTS: Significant improvements were seen baseline to post intervention for walking velocity, Six-minute Walk Test, MAS and SF-36 physical function score (p < or = 0.025 for all measures). Most improvements noted at the end of training were retained one month later. The effect sizes ranged from 0.33 to 1.20. CONCLUSIONS: Substantial improvement in ambulation function and disability level were seen as a result of the obstacle training programme for individuals with chronic stroke. Further investigation is warranted.

Adult↗