[Show abstract][Hide abstract] ABSTRACT: -Although individual protein biomarkers are associated with cardiovascular risk, rarely have multiple proteins been considered simultaneously to identify which set of proteins best predicts risk.
-In a nested case-control study of 273 death/myocardial infarction (MI) cases and 273 age- (within 10 years), sex-, and race-matched and event-free controls from among 2023 consecutive patients (median follow-up 2.5 years) with suspected coronary disease, plasma levels of 53 previously reported biomarkers of cardiovascular risk were determined in a core laboratory. Three penalized logistic regression models were fit using the elastic net to identify panels of proteins independently associated with death/MI: proteins alone (Model 1); proteins in a model constrained to retain clinical variables (Model 2); and proteins and clinical variables available for selection (Model 3). Model 1 identified 6 biomarkers strongly associated with death/MI: ICAM-1, MMP-3, NT-proBNP, IL-6, sCD40L, and IGFBP2. In Model 2, only sCD40L remained strongly associated with death/MI when all clinical risk predictors were retained. Model 3 identified a set of 6 biomarkers (ICAM-1, MMP-3, NT-proBNP, IL-6, sCD40L, and IGFBP2) and 5 clinical variables (age, red-cell distribution width, diabetes, hemoglobin, and New York Heart Association class) strongly associated with death/MI.
-Simultaneously assessing the association between multiple putative protein biomarkers of cardiovascular risk and clinical outcomes is useful in identifying relevant biomarker panels for further assessment.
Preview · Article · Nov 2014 · Circulation Cardiovascular Genetics
[Show abstract][Hide abstract] ABSTRACT: Currently, there is a lack of consensus among guidelines for the postdischarge treatment of patients presenting with acute coronary syndrome (ACS) who have a long-term indication for anticoagulation. We conducted a systematic review comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with ACS and a long-term indication for anticoagulation. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews published between January 1995 and September 2013. Each investigator screened and abstracted data, assessed applicability and quality, and graded the strength of evidence. Meta-analysis of direct comparison was performed when outcomes and follow-up periods were comparable. Fourteen observational studies were identified that contained comparative effectiveness data on DAPT versus TT. No difference in the odds of mortality (OR 1.04, 95 % CI 0.59–1.83) or stroke (OR 1.01, 95 % CI 0.38–2.67) at 1–5 years was found between TT and DAPT. Major bleeding at 1–5 years (OR 1.46, 95 % CI 1.07–2.00) and nonfatal MI at 1–5 years (OR 1.85, 95 % CI 1.13–3.02) occurred more frequently in patients receiving TT. The results of this systematic review demonstrate that treatment with TT was associated with increased rates of nonfatal MI and major bleeding when compared with treatment with DAPT in the postdischarge management of ACS patients with an indication for oral anticoagulation. Until results of ongoing randomized trials assessing antithrombotic therapies define optimal management strategies, the current analysis suggests using caution when prescribing TT to these patients.
Full-text · Article · Jun 2014 · Journal of Thrombosis and Thrombolysis
[Show abstract][Hide abstract] ABSTRACT: The clinical significance of persistent patent foramen ovale (PFO) is not well defined. Empirically, PFO has been associated with many clinical conditions. In cryptogenic stroke, migraine, and orthodeoxia/platypnea, a plausible biologic mechanism exists to support PFO closure as a possible treatment. Although transcatheter closure of PFO has been available for over 2 decades, it has remained controversial due to a paucity of evidence to guide patient and device selection. Contemporary studies investigating PFO closure as treatment for patients with these conditions have been published recently and longitudinal data regarding the safety and efficacy of the devices is now available. In this review, we aim to describe the potential clinical significance of a patent foramen in the adult, appraise the newest additions to the body of evidence, and discuss the safety, benefit, patient selection, and future of transcatheter treatment of PFO.
No preview · Article · May 2014 · Current Cardiology Reports
[Show abstract][Hide abstract] ABSTRACT: Aortic stenosis affects many people worldwide with a significant impact on morbidity and mortality with uncorrected, symptomatic aortic valve stenosis carrying mortality of 50 % at one year. Degenerative calcific pathology, the most common cause of aortic stenosis, increases in prevalence with age; estimated prevalence of 5 % in individuals over 75 years of age. Despite the malignant prognosis without valve replacement, many patients are not offered surgery due to advanced age and co-existing medical conditions; reported to be a third of symptomatic patients. In the last several years, transcatheter aortic valve replacement has emerged as an alternative treatment in patients with high or prohibitive open surgical risk. The PARTNER cohort B data, employing the Sapien valve, demonstrated a 20 % absolute mortality benefit at one year compared with medical therapy. In this review, we provide an update of this technology and discuss patient selection, procedural planning, complications, and look toward the future of transcatheter heart valves in the treatment of aortic stenosis.
No preview · Article · Jun 2013 · Current Cardiology Reports
[Show abstract][Hide abstract] ABSTRACT: QUESTION In patients with cardiovascular (CV) disease, are omega-3 fatty acid supplements (eicosapentaenoic acid [EPA] and docosahexaenoic acids [DHA]) effective for secondary prevention? REVIEW SCOPE Included studies compared omega-3 fatty acid supplements used for ≥ 1 year with placebo in adults ≥ 18 years of age who had a history of CV disease, and reported such outcome measures as CV events, sudden cardiac death, CV death, all-cause mortality, myocardial infarction, congestive heart failure, and transient ischemic attack (TIA) or stroke. REVIEW METHODS PubMed, EMBASE/Excerpta Medica, and Cochrane Library (all to Apr 2011), and bibliographies were searched for English-language, double-blind, placebo-controlled, randomized trials. 14 trials (n = 20 485, mean age 63 y, 79% men) met the selection criteria. Mean follow-up was 2 years, and mean daily dose of EPA or DHA was 1.7 g/d. 6 trials had Jadad scores of 5 out of 5, 7 had scores of 4, and 1 had a score of 3. MAIN RESULTS Meta-analysis showed that omega-3 fatty acids reduced CV mortality compared with placebo (Table). Groups did not differ for CV events, sudden cardiac mortality, all-cause mortality, myocardial infarction, congestive heart failure, or TIA or stroke (Table). CONCLUSION In patients with cardiovascular disease, omega-3 fatty acid supplements do not reduce adverse cardiovascular outcomes.Omega-3 fatty acids vs placebo in patients with cardiovascular (CV) disease*OutcomesNumber of trials (n)Weighted event ratesAt a mean 2 yOmega-3 fatty acidsPlaceboRRR (95% CI)NNT (CI)CV events14 (20 485)14.4%14.8%1% (-9 to 11)Not significantRelative risk (CI)Sudden cardiac mortality5 (11 668)--0.93 (0.66 to 1.30)CV mortality11 (13 927)--0.91 (0.84 to 0.99)All-cause mortality13 (20 245)--0.96 (0.90 to 1.02)Myocardial infarction11 (16 160)--0.81 (0.65 to 1.01)Congestive heart failure6 (8422)--0.92 (0.73 to 1.17)TIA or stroke7 (10 284)--1.13 (0.77 to 1.66)*- = data not provided or not calculable; TIA = transient ischemic attack; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rate and relative risk in article using a random-effects model.
No preview · Article · Aug 2012 · Annals of internal medicine
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular (CV) clinical trials are instrumental in understanding treatment effects and offer insights into the natural progression of CV disease. Biomarkers are a critical component of patient selection, end point definition, and safety monitoring, and clinical trials provide a platform for the discovery and validation of new biomarkers that may augment the understanding of disease mechanisms, risk stratification, and/or clinical decision-making.
We review the roles that biomarkers have played in CV clinical trials and roles that CV clinical trials have played and will continue to play in the discovery and validation of biomarkers and their implementation in clinical practice. Large biobanks containing multiple specimen types are increasingly being created from patients enrolled in clinical trials, and such biobanks, when coupled with advances in molecular techniques and bioinformatics, promise to accelerate our understanding of CV disease mechanisms and to help fuel the discovery and development of novel therapeutic targets and biomarkers of risk and treatment response.
The past, present, and future of biomarkers and clinical trials have been and will remain intertwined. Biomarkers were once the workhorses of patient selection and end point definition in clinical trials; more recently, clinical trials have been the proving ground for individual biomarkers. Attention to biobanking and the application of modern informatics and molecular techniques to samples collected within clinical trials will usher in the era of stratified and personalized medicine.
No preview · Article · Jan 2012 · Clinical Chemistry
[Show abstract][Hide abstract] ABSTRACT: Acute coronary syndromes (ACS) continue to have a large impact on morbidity and mortality in the United States. Over the last two decades, there have been several advancements in the care of patients with ACS. The use of combined antiplatelet and anticoagulants and early invasive risk stratification in high risk patients has improved the rates of major adverse cardiovascular events. However, this treatment strategy increases the risk for bleeding. Studies have found an association between bleeding and subsequent mortality and morbidity in ACS patients; therefore, minimizing bleeding risk has become a priority. This review describes the prevalence of bleeding during ACS management, risk for bleeding, and strategies to reduce bleeding risk.
No preview · Article · Jun 2011 · Current drug targets
[Show abstract][Hide abstract] ABSTRACT: Coronary artery anomalies arising from the pulmonary artery are rare, result in reversed flow in the affected coronary artery, and are commonly associated with myocardial ischemia in infancy or childhood. Uncorrected survival to adult age is rare. We present a 77-year-old individual with anomalous right coronary artery from the pulmonary artery (ARCAPA), diagnosed by coronary angiography, whose clinical presentation was governed by coexisting obstructive atherosclerotic coronary disease.
No preview · Article · Jan 2011 · The Journal of invasive cardiology
[Show abstract][Hide abstract] ABSTRACT: Coronary disease is the leading killer of individuals worldwide and a leading cause of healthcare expenditure. On a global scale, ischemic heart disease kills over 6 million individuals each year and is projected by the World Health Organization to be the greatest single-disease cause of death worldwide by an increasing margin into 2030. Nearly 17 million Americans (7.6% of the population) have prevalent coronary heart disease, 8 million of whom have had a prior myocardial infarction. It is estimated that in 2009, 550,000 will die from coronary heart disease in the United States and that the direct and indirect costs from treating coronary heart disease will exceed $165 billion. Although patients with known coronary artery disease are among the highest risk patients for future cardiac events, not all patients with coronary disease will have an ischemic event (first or recurrent). Determining which of these patients will have an ischemic event is critical to the concept of personalized cardiovascular care. Increasingly, biomarkers that can be readily assayed from blood or other body fluids will be critical to risk stratification and effective application of secondary prevention strategies, just as they have played an increasingly prominent role in risk stratification of acute coronary syndrome patients.
[Show abstract][Hide abstract] ABSTRACT: Troponin elevation above the upper limit of normal (ULN) is diagnostic of myocardial infarction, but interpretation of "gray-zone" troponin elevations (1 to 1.5x ULN) remains uncertain. Using the CRUSADE database, we explored relationships between sex and treatment and outcomes among patients with troponin 1 to 1.5x ULN.
We compared treatment and outcomes among women and men using logistic generalized estimating equation method. Overall, 5049 of 85 671 (5.9%) non-ST-segment elevation acute coronary syndromes patients (2156 women, 2893 men) had troponin 1 to 1.5x ULN within 24 hours of presentation. Compared with troponin >1.5x ULN, "gray-zone" patients less often received all guidelines-indicated acute (mean composite score, 63% versus 72%) and discharge therapies (mean composite score, 73% versus 78%), but received them more frequently than patients with troponin <1x ULN (mean composite scores, 58% acute and 67% discharge). Among "gray-zone" patients, acute and discharge therapy use was similar between women and men, except acute aspirin (adjusted odds ratio, 0.80 [95% CI, 0.65 to 0.98]) and discharge angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.77 [95% CI, 0.67 to 0.88]). "Gray-zone" patients had lower mortality (2.3%) than the >1.5x ULN (4.5%) group but higher than the <1x ULN group (1.1%). Outcomes were similar among "gray-zone" women and men (adjusted odds ratios: death, 0.88 [95% CI, 0.58 to 1.35]; death/myocardial infarction, 0.77 [95% CI, 0.55 to 1.06]; transfusion, 1.04 [95% CI, 0.85 to 1.27]).
Patients with non-ST-segment elevation acute coronary syndromes and low-level troponin elevations had lower overall risk and received less aggressive guidelines-based treatment than those with greater troponin elevations, but treatment patterns were largely similar by sex across troponin elevation groups.
Preview · Article · May 2009 · Circulation Cardiovascular Quality and Outcomes