Showing papers by "Danielle M. Brennan published in 2010"
TL;DR: In the CHARISMA trial, there was an increased risk of bleeding with long-term clopidogrel and moderate bleeding was strongly associated with mortality.
Abstract: Background— Uncertainty exists about the frequency, correlates, and clinical significance of bleeding with dual antiplatelet therapy (DAPT), particularly over an extended period in a stable population. We sought to determine the frequency and time course of bleeding with DAPT in patients with established vascular disease or risk factors only; identify correlates of bleeding; and determine whether bleeding is associated with mortality. Methods and Results— We analyzed 15 603 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, a double-blind, placebo-controlled, randomized trial comparing long-term clopidogrel 75 mg/d versus placebo; all patients received aspirin (75 to 162 mg) daily. Patients had either established stable vascular disease or multiple risk factors for vascular disease without established disease. Median follow-up was 28 months. Bleeding was assessed with the use of the Global Utilization of Streptokinase...
201 citations
TL;DR: Bleeding risk increased substantially with a score >10, and this score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.
Abstract: Aims To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis.
Methods and results We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32–1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0–23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score ≤6); 0.95% (7–8); 1.25% (9–10); 2.76% (≥11). The score's discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c 2 = 4.74; P = 0.69).
Conclusion Bleeding risk increased substantially with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.
120 citations
TL;DR: LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases.
Abstract: The BMI is the most frequently used marker to evaluate obesity-associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC - 65) x TG (men) and (WC - 58) x TG (women). We evaluated LAP and BMI as predictors of mortality in a high-risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty-eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P < 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity.
113 citations
TL;DR: Lp(a) levels correlate with the extent of obstructive disease and predict the need for coronary revascularization in subjects with suboptimal LDL-C control, and supports the need to intensify lipid management in patients with elevated Lp( a) levels.
75 citations
TL;DR: The addition of clopidogrel to acetylsalicylic acid did not significantly alter the rate and functional severity of stroke outcome events among high vascular risk patients enrolled in the CHARISMA trial.
Abstract: Background and Purpose— Disabling stroke is costly and considered by some patients a fate worse than death. We aimed to determine whether clopidogrel reduces the rate and functional severity of stroke among high vascular risk patients, including patients with previous transient ischemic attack or ischemic stroke, who were enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial. Methods— We randomly assigned 15 603 high vascular risk patients to receive clopidogrel (75 mg daily) or placebo in addition to background acetylsalicylic acid and followed them for a median of 28 months. The main outcome of this prespecified substudy was the functional severity of stroke outcome events as measured by the modified Rankin Scale (mRS) score at 3 months after the stroke outcome. Results— During follow-up, 436 (2.8%) patients had a definite adjudicated stroke and a follow-up assessment of the mRS at 3 months poststroke, of whom 202 had been random...
30 citations
TL;DR: In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events, and the underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation.
Abstract: Objective— The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, “troponin leak”) within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Methods and Results— Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m 2 ) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction ( P P Conclusion— In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation.
28 citations
TL;DR: Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI.
Abstract: Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twent...
19 citations
TL;DR: Patients with a high school BMI of 25 kg/m2 or greater had more CHD risk factors compared with those with an HS BMI of less than 25 kg /m2, and prevalence of CHD was also significantly higher in this group.
Abstract: OBJECTIVE : To investigate overweight/obese patients (body mass index [BMI], > or =25 kg/m) at entry to a preventive cardiology clinic who had a high school (HS) BMI of 25 kg/m or greater versus those with a BMI of less than 25 kg/m to determine coronary heart disease (CHD) prevalence, all-cause mortality. METHODS : Patients (n = 4,597) who had a BMI of 25 kg/m or greater at the time of initial visit to the prevention clinic were asked to report their weight at graduation from HS. Patients with BMI of 25 kg/m or greater in HS (n = 1,285) were compared with patients (n = 3,312) with a BMI of less than 25 kg/m in HS. Prevalent CHD was assessed at entry. Patient mortality was assessed using the Social Security Death Index for a maximum of 7 years after the initial visit. RESULTS : Mean/median values for most CHD risk factors were higher in the group with an HS BMI of 25 kg/m or greater, with the exception of low-density lipoprotein level (120 vs 132 mg/dL; P < .001), Lipoprotein (a) level (16 vs 19 mg/dL; P = .003), and systolic blood pressure (126 vs 128. 3 mm Hg; P < .001). Patients with an HS BMI of 25 kg/m or greater had a higher mean BMI at initial visit (33.9 vs 30.1; P < .001) and hemoglobin A1c (6.8% vs 6.3%; P < .001) and glucose concentrations (93 vs 91 mg/dL; P = .004), with a lower mean high-density lipoprotein level (43.2 vs 46.5 mg/dL; P < .001) as well as greater prevalence of smoking (16.2% vs 11.4%; P < .001), diabetes mellitus (32.4% vs 21.8%; P < .001), CHD (47.1% vs 43%; P = .01), and specifically myocardial infarction (25.8% vs 21.1%; P = .001). Fibrinogen and urine albumin-to-creatinine levels were elevated. After adjusting for risk factors, an HS BMI of 25 kg/m or greater was associated with a 21% higher prevalence of CHD (odds ratio, 1.20; P = .027). However, an HS BMI of 25 kg/m or greater was not a significant predictor of 7-year mortality (hazard ratio, 1.03; P = .84). CONCLUSION : Patients with an HS BMI of 25 kg/m or greater had more CHD risk factors compared with those with an HS BMI of less than 25 kg/m. Prevalence of CHD was also significantly higher in this group. However, an HS BMI of 25 kg/m or greater was not a significant predictor of mortality.
3 citations
TL;DR: Degree of mitral regurgitation and left ventricular scarring are more powerful predictors of long-term outcomes than volumes and sphericity in patients with severe ischemic cardiomyopathy.
Abstract: ss Open Acce Oral presentation Degree of mitral regurgitation and left ventricular scarring are more powerful predictors of long-term outcomes than volumes and sphericity: a multi-modality imaging study in patients with severe ischemic cardiomyopathy Deborah Kwon*, Zoran B Popovic, Venugopal Menon, Carmel M Halley, Danielle Brennan, Randall C Starling, Scott D Flamm, Paul Schoenhagen, Bruce W Lytle, Brian P Griffin and Milind Y Desai
1 citations
01 Jan 2010
TL;DR: LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases.
Abstract: The BMI is the most frequently used marker to evaluate obesity-associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC − 65) × TG (men) and (WC − 58) × TG (women). We evaluated LAP and BMI as predictors of mortality in a high-risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty-eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P < 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity.