Atherosclerosis is a process with inflammatory features and selective
cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects
by virtue of inhibiting inflammation. However, ...by decreasing vasodilatory
and antiaggregatory prostacyclin production, COX-2 antagonists may lead to
increased prothrombotic activity. To define the cardiovascular effects of
COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients
without coronary artery disease, we performed a MEDLINE search to identify
all English-language articles on use of COX-2 inhibitors published between
1998 and February 2001. We also reviewed relevant submissions to the US Food
and Drug Administration by pharmaceutical companies.Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal
Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term
Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials
with approximately 1000 patients each. The results from VIGOR showed that
the relative risk of developing a confirmed adjudicated thrombotic cardiovascular
event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated
cardiac arrest, sudden or unexplained death, ischemic stroke, and transient
ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38
(95% confidence interval, 1.39-4.00; P = .002). There
was no significant difference in cardiovascular event (myocardial infarction,
stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory
agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors
in both VIGOR and CLASS were significantly higher than that in the placebo
group of a recent meta-analysis of 23 407 patients in primary prevention
trials (0.52%): 0.74% with rofecoxib (P = .04 compared
with the placebo group of the meta-analysis) and 0.80% with celecoxib (P = .02 compared with the placebo group of the meta-analysis).The available data raise a cautionary flag about the risk of cardiovascular
events with COX-2 inhibitors. Further prospective trial evaluation may characterize
and determine the magnitude of the risk.
The early genetic pathway(s) triggering the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we describe an autosomal dominant form of CAD/MI ...(adCAD1) that is caused by the deletion of seven amino acids in transcription factor MEF2A. The deletion disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription activation, and abolishes synergistic activation by MEF2A and by the transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A protein demonstrates strong expression in the endothelium of coronary arteries. These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI.
The emerging field of mobile health Steinhubl, Steven R; Muse, Evan D; Topol, Eric J
Science translational medicine,
04/2015, Letnik:
7, Številka:
283
Journal Article
Recenzirano
Odprti dostop
The surge in computing power and mobile connectivity have fashioned a foundation for mobile health (mHealth) technologies that can transform the mode and quality of clinical research and health care ...on a global scale. Unimpeded by geographical boundaries, smartphone-linked wearable sensors, point-of-need diagnostic devices, and medical-grade imaging, all built around real-time data streams and supported by automated clinical decision-support tools, will enable care and enhance our understanding of physiological variability. However, the path to mHealth incorporation into clinical care is fraught with challenges. We currently lack high-quality evidence that supports the adoption of many new technologies and have financial, regulatory, and security hurdles to overcome. Fortunately, sweeping efforts are under way to establish the true capabilities and value of the evolving mHealth field.
Antiplatelet therapy is a cornerstone of cardiovascular medicine. Aspirin and clopidogrel have emerged as critical therapies in the treatment of cardiovascular disease. Despite their efficacy, ...patients on these medications continue to suffer complications. Millions of patients are currently on low-dose antiplatelet therapy but it is unknown how many of these patients are under-treated or on the wrong medication. Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains incompletely defined, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. These factors range from physicians who fail to prescribe these medications despite appropriate indications to polymorphisms of platelet membrane glycoproteins. Rapid and accurate diagnosis of antiplatelet resistance also remains an issue as new bedside tests are developed. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people.
Aims The aim of this study was to determine whether clopidogrel plus aspirin provides greater protection against major cardiovascular events than aspirin alone in patients with peripheral arterial ...disease (PAD). Methods and results This is a post hoc analysis of the 3096 patients with symptomatic (2838) or asymptomatic (258) PAD from the CHARISMA trial. The rate of cardiovascular death, myocardial infarction (MI), or stroke (primary endpoint) was higher in patients with PAD than in those without PAD: 8.2% vs. 6.8% hazard ratio (HR), 1.25; 95% CI 1.08, 1.44; P = 0.002. Among the patients with PAD, the primary endpoint occurred in 7.6% in the clopidogrel plus aspirin group and 8.9% in the placebo plus aspirin group (HR, 0.85; 95% CI, 0.66–1.08; P = 0.18). In these patients, the rate of MI was lower in the dual antiplatelet arm than the aspirin alone arm: 2.3% vs. 3.7% (HR, 0.63; 95% CI, 0.42–0.96; P = 0.029), as was the rate of hospitalization for ischaemic events: 16.5% vs. 20.1% (HR, 0.81; 95% CI, 0.68–0.95; P = 0.011). The rates of severe, fatal, or moderate bleeding did not differ between the groups, whereas minor bleeding was increased with clopidogrel: 34.4% vs. 20.8% (odds ratio, 1.99; 95% CI, 1.69–2.34; P < 0.001). Conclusion Dual therapy provided some benefit over aspirin alone in PAD patients for the rate of MI and the rate of hospitalization for ischaemic events, at the cost of an increase in minor bleeding.
Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic ...peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients.
NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile.
The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.
On May 21, 1999, Merck was granted approval by the Food and Drug Administration (FDA) to market rofecoxib (Vioxx). On September 30, 2004, after more than 80 million patients had taken this medicine ...and annual sales had topped $2.5 billion, the company withdrew the drug because of an excess risk of myocardial infarctions and strokes. This represents the largest prescription-drug withdrawal in history, but had the many warning signs along the way been heeded, such a debacle could have been prevented.
Neither of the two major forces in this five-and-a-half-year affair — neither Merck nor the FDA — fulfilled its . . .
Over the past 18 months, there have been notable developments in the direct-to-consumer (DTC) genomic testing arena, in particular with regard to issues surrounding governmental regulation in the ...USA. While commentaries continue to proliferate on this topic, actual empirical research remains relatively scant. In terms of DTC genomic testing for disease susceptibility, most of the research has centered on uptake, perceptions and attitudes toward testing among health care professionals and consumers. Only a few available studies have examined actual behavioral response among consumers, and we are not aware of any studies that have examined response to DTC genetic testing for ancestry or for drug response. We propose that further research in this area is desperately needed, despite challenges in designing appropriate studies given the rapid pace at which the field is evolving. Ultimately, DTC genomic testing for common markers and conditions is only a precursor to the eventual cost-effectiveness and wide availability of whole genome sequencing of individuals, although it remains unclear whether DTC genomic information will still be attainable. Either way, however, current knowledge needs to be extended and enhanced with respect to the delivery, impact and use of increasingly accurate and comprehensive individualized genomic data.
Aortocoronary saphenous vein graft disease, with its increasing clinical sequelae, presents an important and unresolved dilemma in cardiological practice. During the 1st month after bypass surgery, ...vein graft attrition results from thrombotic occlusion, while later the dominant process is atherosclerotic obstruction occurring on a foundation of neointimal hyperplasia. Although the risk factors predisposing to vein graft atherosclerosis are broadly similar to those recognized for native coronary disease, the pathogenic effects of these risk factors are amplified by inherent deficiencies of the vein as a conduit when transposed into the coronary arterial circulation. A multifaceted strategy aimed at prevention of vein graft disease is emerging, elements of which include: continued improvements in surgical technique; more effective antiplatelet drugs; increasingly intensive risk factor modification, in particular early and aggressive lipid-lowering drug therapy; and a number of evolving therapies, such as gene transfer and nitric oxide donor administration, which target vein graft disease at an early and fundamental level. At present, a key measure is to circumvent the problem of vein graft disease by preferential selection of arterial conduits, in particular the internal mammary arteries, for coronary bypass surgery whenever possible.
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