[Show abstract][Hide abstract] ABSTRACT: Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomark-ers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/throm-bin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke.
PLoS ONE 09/2015; 10(8). DOI:10.1371/journal.pone.0134193 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
There is higher combined risk of stroke or death (S+D) at older ages with carotid stenting. We assess whether this can be attributed to patient or arterial characteristics that are in the pathway between older age and higher risk.
Mediation analysis of selected patient (hypertension, diabetes mellitus, and dyslipidemia) and arterial characteristics assessed at the clinical sites and the core laboratory (plaque length, eccentric plaque, ulcerated plaque, percent stenosis, peak systolic velocity, and location) was performed in 1123 carotid artery stenting-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). We assessed the association of age with these characteristics, the association of these characteristics with stroke risk, and the amount of mediation of the association of age on the combined risk of periprocedural S+D with adjustment for these factors.
Only plaque length as measured at the sites increased with age, was associated with increased S+D risk and significantly mediated the association of age on S+D risk. However, adjustment for plaque length attenuated the increased risk per 10 years of age from 1.72 (95% confidence interval, 1.26-2.37) to 1.66 (95% confidence interval, 1.20-2.29), accounting for only 8% of the increased risk.
Plaque length seems to be in the pathway between older age and higher risk of S+D among carotid artery stenting-treated patients, but it mediated only 8% of the age effect excess risk of carotid artery stenting in CREST. Other factors and mechanisms underlying the age effect need to be identified as plaque length will not identify elderly patients for whom stenting is safe relative to endarterectomy.
Clinical trial registration:
URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.
[Show abstract][Hide abstract] ABSTRACT: Sepsis is the syndrome of body-wide inflammation triggered by infection and is a major public health problem. Diet plays a vital role in immune health but its association with sepsis in humans is unclear.
We examined 21,404 participants with available dietary data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of 30,239 black and white adults ≥45 years of age living in the US. The primary exposures of interest were five empirically derived diet patterns identified via factor analysis within REGARDS participants: "Convenience" (Chinese and Mexican foods, pasta, pizza, other mixed dishes), "Plant-based" (fruits, vegetables), "Southern" (added fats, fried foods, organ meats, sugar-sweetened beverages), "Sweets/Fats" (sugary foods) and "Alcohol/Salads" (alcohol, green-leafy vegetables, salad dressing). The main outcome of interest was investigator-adjudicated first hospitalized sepsis events.
A total of 970 first sepsis events were observed over ~6 years of follow-up. In unadjusted analyses, greater adherence to Sweets/Fats and Southern patterns was associated with higher cumulative incidence of sepsis, whereas greater adherence to the Plant-based pattern was associated with lower incidence. After adjustment for sociodemographic, lifestyle and clinical factors, greater adherence to the Southern pattern remained associated with higher risk of sepsis (hazard ratio [HR] comparing the fourth to first quartile, HR 1.39, 95 % CI 1.11,1.73). Race modified the association of the Southern diet pattern with sepsis (P interaction = 0.01), with the Southern pattern being associated with modestly higher adjusted risk of sepsis in black as compared to white participants (HR comparing fourth vs. first quartile HR 1.42, 95 % CI 0.75,2.67 vs. 1.21, 95 % CI 0.93,1.57, respectively).
A Southern pattern of eating was associated with higher risk of sepsis, particularly among black participants. Determining reasons for these findings may help to devise strategies to reduce sepsis risk.
[Show abstract][Hide abstract] ABSTRACT: The incorporation of physical activity and exercise represents a clinically important aspect in the management of metabolic syndrome, hypertension, and diabetes. While the benefit of exercise and active lifestyles is well documented for prevention and risk reduction of cardiovascular and stroke outcomes, the detailed regiment and recommendations are less clear. The components of a prescribed physical activity include consideration of activity type, frequency of an activity, activity duration, and intensity of a specific physical movement. The exercise parameters prescribed as part of the management of metabolic syndrome, diabetes, and elevated blood pressure are most often proposed as separate documents while the general recommendations are similar. The evidence is strong such that physical activity and exercise recommendations in disease management guidelines are considered high quality. The general recommendations for both blood pressure and glycemic management include a regiment of physical activity with moderate- to high-intensity exercise of 30-min bouts on multiple days with a desired goal of a total of 150 min of exercise per week. While additional research is needed to identify the specific exercise/activity mode, frequencies for exercise training, intensity levels, and duration of exercise that achieve maximal blood pressure and glycemic lowering, this general recommendation showed a consistent and significant benefit in risk reduction. Similarly, the current available evidence also indicates that aerobic exercise, dynamic resistance exercise, and isometric exercises can lower blood pressure and improve glycemic control.
Current Hypertension Reports 11/2014; 16(11):492. DOI:10.1007/s11906-014-0492-2 · 3.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Response to stroke symptoms and the use of 911 can vary by race/ethnicity. The quickness with which a patient responds to such symptoms has implications for the outcome and treatment. We sought to examine a sample of patients receiving a Remote Evaluation of Acute isCHemic stroke (REACH) telestroke consult in South Carolina regarding their awareness and perception of stroke symptoms related to the use of 911 and to assess possible racial/ethnic disparities.
As of September 2013, 2325 REACH telestroke consults were conducted in 13 centers throughout South Carolina. Telephone surveys assessing use of 911 were administered from March 2012-January 2013 among 197 patients receiving REACH consults. Univariate and multivariate logistic regression was performed to assess factors associated with use of 911.
Most participants (73%) were Caucasian (27% were African–American) and male (54%). The mean age was 66 ± 14.3 years. Factors associated with use of 911 included National Institutes of Health Stroke Scale scores >4 (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.63-11.25), unknown insurance which includes self-pay or not charged (OR, 2.90; 95% CI, 1.15-7.28), and perception of stroke-like symptoms as an emergency (OR, 4.58; 95% CI, 1.65-12.67). African–Americans were significantly more likely than Caucasians to call 911 (62% vs. 43%, P = .02).
African–Americans used 911 at a significantly higher rate. Use of 911 may be related to access to transportation, lack of insurance, or proximity to the hospital although this information was not available. Interventions are needed to improve patient arrival times to telemedicine equipped emergency departments after stroke.
Journal of Stroke and Cerebrovascular Diseases 10/2014; 23(9). DOI:10.1016/j.jstrokecerebrovasdis.2014.05.011 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose Evidence indicates that center volume of cases affects outcomes for both carotid endarterectomy and stenting. We evaluated the effect of enrollment volume by site on complication rates in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). Methods The primary composite end point was any stroke, myocardial infarction, or death within 30 days or ipsilateral stroke in follow-up. The 477 approved surgeons performed >12 procedures per year with complication rates <3% for asymptomatic patients and <5% for symptomatic patients; 224 interventionists were certified after a rigorous 2 step credentialing process. CREST centers were divided into tertiles based on the number of patients enrolled into the study, with Group 1 sites enrolling <25 patients, Group 2 sites enrolling 25 to 51 patients, and Group 3 sites enrolling >51 patients. Differences in periprocedural event rates for the primary composite end point and its components were compared using logistic regression adjusting for age, sex, and symptomatic status within site-volume level. Results The safety of carotid angioplasty and stenting and carotid endarterectomy did not vary by site-volume during the periprocedural period as indicated by occurrence of the primary end point (P=0.54) or by stroke and death (P=0.87). A trend toward an inverse relationship between center enrollment volume and complications was mitigated by adjustment for known risk factors. Conclusions Complication rates were low in CREST and were not associated with center enrollment volume. The data are consistent with the value of rigorous training and credentialing in trials evaluating endovascular devices and surgical procedures. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.
[Show abstract][Hide abstract] ABSTRACT: Background:
The use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) diagnostic codes can identify racial disparities in ischemic stroke hospitalizations; however, inclusion of revascularization procedure codes as acute stroke events may affect the magnitude of the risk difference. This study assesses the impact of excluding revascularization procedure codes in the ICD-9 definition of ischemic stroke, compared with the traditional inclusive definition, on racial disparity estimates for stroke incidence and recurrence.
Patients discharged with a diagnosis of ischemic stroke (ICD-9 codes 433.00-434.91 and 436) were identified from a statewide inpatient discharge database from 2010 to 2012. Race-age specific disparity estimates of stroke incidence and recurrence and 1-year cumulative recurrent stroke rates were compared between the routinely used traditional classification and a modified classification of stroke that excluded primary ICD-9 cerebral revascularization procedures codes (38.12, 00.61, and 00.63).
The traditional classification identified 7878 stroke hospitalizations, whereas the modified classification resulted in 18% fewer hospitalizations (n = 6444). The age-specific black to white rate ratios were significantly higher in the modified than in the traditional classification for stroke incidence (rate ratio, 1.50; 95% confidence interval [CI], 1.43-1.58 vs. rate ratio, 1.24; 95% CI, 1.18-1.30, respectively). In whites, the 1-year cumulative recurrence rate was significantly reduced by 46% (45-64 years) and 49% (≥ 65 years) in the modified classification, largely explained by a higher rate of cerebral revascularization procedures among whites. There were nonsignificant reductions of 14% (45-64 years) and 19% (≥ 65 years) among blacks.
Including cerebral revascularization procedure codes overestimates hospitalization rates for ischemic stroke and significantly underestimates the racial disparity estimates in stroke incidence and recurrence.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 09/2014; 23(10). DOI:10.1016/j.jstrokecerebrovasdis.2014.06.008 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose The Carotid Revascularization Endarterectomy Versus Stenting Trial was completed with a low stroke and death rate. A lead-in series of patients receiving carotid artery stenting was used to select the physician-operators for the study, where performance was evaluated by complication rates and by peer review of cases. Herein, we assess the potential contribution of statistical evaluation of complication rates. Methods The ability to discriminate between stent operators who can successfully meet the published guideline of <3% combined rate of stroke and death is calculated under the binomial distribution, based on a small consecutive case series (n=24 patients). Results A criterion of 2 stroke or death events among the 24 patients (<8% event rate) was required of operators. Setting such a high criterion, however, ensures an inability to exclude operators who cannot meet the criteria. In fact, if a good operator is defined as having a 2% event rate and a poor operator as a 6% event rate, even a series of 240 patients would (on average) still exclude 5.4% of the good operators and include 4.6% of the poor operators. Conclusions The low periprocedural event rates in the trial suggest success in separating skillful operators from less skillful. However, it seems unlikely that statistical assessment of event rates in the lead-in contributed to successful selection, but rather successful selection was more likely because of peer review of subjective and other factors including patient volume and technical approaches. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.
[Show abstract][Hide abstract] ABSTRACT: Objective:
We evaluate associations of metabolic syndrome (MetS), C-reactive protein (CRP), and a CRP-incorporated definition of MetS (CRPMetS) with risk of all-cause mortality in a biracial population.
Research design and methods:
We studied 23,998 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of black and white adults ≥45 years old across the U.S. Elevated CRP was defined as ≥3 mg/L and MetS by the revised Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III; ATP III) criteria (three of five components). CRPMetS was defined as presence of three out of six components, with elevated CRP added to ATP III criteria as a sixth component. Cox models were used to calculate hazard ratios (HRs) for all-cause mortality, and population attributable risk (PAR) was calculated. Stratified analyses based on race and diabetes status were performed.
There were 9,741 participants (41%) with MetS and 12,179 (51%) with CRPMetS at baseline. Over 4.8 years of follow-up, 2,050 participants died. After adjustment for multiple confounders, MetS, elevated CRP, and CRPMetS were each significantly associated with increased mortality risk (HRs 1.26 [95% CI 1.15-1.38], 1.55 [1.41-1.70], and 1.34 [1.22-1.48], respectively). The PAR was 9.5% for MetS, 18.1% for CRP, and 14.7% for CRPMetS. Associations of elevated CRP and of CRPMetS with mortality were significantly greater in whites than blacks, while no differences in associations were observed based on diabetes status.
By definition, CRPMetS identifies more people at risk than MetS but still maintains a similar mortality risk. Incorporating CRP into the definition for MetS may be useful in identifying additional high-risk populations to target for prevention.
Diabetes Care 05/2014; 37(8). DOI:10.2337/dc13-2059 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a non-clinical trial setting, to determine the proportion of individuals with coronary artery disease (CAD) with optimal risk factor levels based on the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial.
In COURAGE, the addition of percutaneous coronary intervention (PCI) to optimal medical therapy did not reduce the risk of death or myocardial infarction in stable CAD patients but resulted in more revascularization procedures.
REGARDS is a national prospective cohort study of 30,239 African American and White community-dwelling individuals aged >45 years enrolled in 2003-7. We calculated the proportion of 3,167 participants with self-reported CAD meeting 7 risk factor goals based on COURAGE: 1) aspirin use, 2) systolic blood pressure <130 mmHg and diastolic blood pressure <85 mmHg (<80 mmHg if diabetic), 3) low density lipoprotein cholesterol <85 mg/dL, high density lipoprotein cholesterol >40 mg/dL, and triglycerides <150 mg/dL, 4) fasting glucose <126 mg/dL, 5) nonsmoking status, 6) body mass index <25 kg/m,(2) and 7) exercise ≥4 days per week.
The mean age of participants was 69±9 years, 33% were African American, and 35% were female. Overall, the median number of goals met was 4. Less than a quarter met ≥5 of the 7 goals, and 16% met all 3 goals for aspirin, blood pressure, and LDL-C. Older age, white race, higher income, more education, and higher physical functioning were independently associated with meeting more goals.
There is substantial room for improvement in risk factor reduction among US individuals with CAD.
Journal of the American College of Cardiology 02/2014; 63(16). DOI:10.1016/j.jacc.2013.12.042 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high-risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM-1, sICAM-1, MPO, Cathepsin-D, PDGF-AA, PDGF-AB/BB, RANTES (CCL5), tPAI-1 and NCAM-1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM-1 (2.2X10(6) ±0.8X10(6) pg/ml vs. 3.1X10(6) ±0.9X10(6) pg/ml, p<0.0001), Cathepsin-D (0.5X10(6) ±0.1X10(6) pg/ml vs. 0.7X10(6) ±0.2X10(6) pg/ml, p<0.0001), PDGF-AA (10556±4033pg/ml vs. 14173±4631pg/ml, p=0.0008), RANTES (0.1X10(6) ±0.07X10(6) pg/ml vs. 0.2X10(6) ±0.06X10(6) pg/ml, p<0.006), and NCAM-1 (0.7X10(6) ±0.2X10(6) pg/ml vs. 0.8X10(6) ±0.1X10(6) pg/ml, p<0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM-1 (p<0.001), PDGF-AA (p=0.025) and RANTES (p=0.048). Low baseline level of BDNF (p=0.025), sVCAM-1 (p=0.025), PDGF-AA (p=0.01), t-PAI-1 (p=0.025) and sICAM-1 (p=0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling.
American Journal of Hematology 01/2014; 89(1). DOI:10.1002/ajh.23586 · 3.80 Impact Factor