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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews some of the early work that has been performed to investigate the potential roles of circulating nucleic acids as prediction markers in acute illness and injury. Circulating DNA and RNA concentrations are elevated early in patients with trauma, stroke and ACS, and are generally highest in patients with a high risk of death. Circulating nucleic acids may be useful markers for the evaluation and risk-stratification of such patients.
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PMID:Circulating nucleic acids and critical illness. 1710 20

The Clinical Trials described in this article were presented at the Hotline and Clinical Trial Update Sessions of the European Society of Cardiology Congress held in September 2007 in Vienna, Austria. The sessions chosen for this article represent the scope of interest of Cardiovascular Drugs and Therapy. The presentations should be considered preliminary, as further analyses could alter the final publication of the results of these studies. PROSPECT evaluated echocardiographic criteria for optimal selection of patients with moderate to severe heart failure who may benefit from cardiac resynchronisation therapy, however concluded that no single echocardiographic measure can be recommended. EVEREST found that tolvaptan, a vasopressin V(2) antagonist, resulted in early weight reduction and improvement of dyspnoea in patients with acute heart failure, but lacked long term improvement. In ARISE, the anti-oxidant succinobucal did not affect the primary outcome in high risk cardiovascular patients, but improved the combination of cardiovascular death, myocardial infarction and stroke, and diabetic control in diabetics. ALOFT showed that the addition of the renin inhibitor aliskiren to an ACE inhibitor or ARB and a beta-blocker leads to favourable effects on neurohormonal actions in heart failure. FINESSE markedly improved coronary patency before PCI with half-dose reteplase/abciximab in STEMI patients, however without significantly improving short-term outcome. The Prague-8 Study evaluated whether routine clopidogrel administered >6 h pre-angiography would be a safe way to achieve therapeutic drug levels in case a follow-up intervention would be considered immediately, but appeared not justified because of bleeding complications. CARESS in MI showed that high risk patients with evolving STEMI who undergo thrombolytic therapy should undergo PCI early after the thrombolysis. Finally, the ACUITY trial found that in moderate or high risk Non ST elevation ACS patients triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical management, bivalirudin, with or without associated GPIIb/IIIa inhibitor therapy, resulted in a marked reduction of bleeding at 30 days whilst preserving the ischemic and mortality benefit at 1 year follow up.
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PMID:Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY. 1799 67

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.
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PMID:Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome. 1808 36

In randomized clinical trials enoxaparin in non ST-elevation acute coronary syndromes (NSTE-ACS) has been shown to be more effective than unfractionated heparin in preventing the combined endpoint of death and myocardial infarction. Clopidogrel in combination with aspirin reduced the combined endpoint of death, myocardial infarction and stroke in NSTE-ACS patients compared to aspirin alone. Aim of the present study was to determine the clinical impact of optimized antithrombotic therapy with enoxaparin, clopidogrel and aspirin compared to standard therapy with unfractionated heparin (UFH) and aspirin in NSTE-ACS in clinical practice. We analyzed data of 2,956 consecutive patients with NSTE-ACS and either antithrombotic therapy with enoxaparin, clopidogrel and aspirin or with aspirin and UFH, which were prospectively enrolled in the acute coronary syndromes registry (ACOS) from July 2000 until the end of November 2002. After adjustment for baseline characteristics and PCI the combined endpoint of hospital death and non-fatal reinfarctions was lower in the group with optimized antithrombotic therapy including clopidogrel, enoxaparin and aspirin compared to the control-group with aspirin and UFH (odds ratio 0.30, 95% confidence interval 0.16-0.53). There was no significant difference in major bleedings between the two treatment groups (1.5% vs. 0.9%, P = 0.35), while overall there were more bleeding complications in the group with optimized antithrombotic therapy (4.9% vs. 2.0%, P = 0.005). In clinical practice optimized antithrombotic therapy with aspirin, clopidogrel and enoxaparin in NSTE-ACS is associated with a reduction in the combined endpoint of death and non-fatal reinfarctions compared to standard therapy with aspirin and UFH without increase in major bleeding complications.
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PMID:Efficacy and safety of optimized antithrombotic therapy with aspirin, clopidogrel and enoxaparin in patients with non-ST segment elevation acute coronary syndromes in clinical practice. 1910 83

Plasma levels of von Willebrand factor (VWF) are increased in patients with cardiovascular risk factors. Various studies aimed to elucidate the relation of VWF with thromboembolic cardiovascular events, ischaemic stroke as well as with peripheral arterial occlusive disease. In the general population, there is only a weak association between VWF levels and future cardiovascular events or stroke. In contrast, VWF levels are predictive in patients with documented vascular disease. Those patients with increased VWF suffer a higher incidence of major adverse cardiac events including death. The extent of the VWF release and its levels independently predict clinical outcome in patients with acute coronary syndromes. Elevated VWF levels have also been observed in patients with atrial fibrillation compared to controls and predict outcome. This may at least in part be attributable to the association of VWF with underlying cardiovascular risk factors. Hence, VWF correlates with Framingham and CHADS stroke risk stratification score and can be used as a marker in patients with AF. However, VWF is not only a predictor; it also plays a crucial role in thrombogenesis. This fact has made VWF a promising target for research into new antiplatelet therapies that specifically inhibit VWF. This review focuses on the role of VWF in ACS, ischaemic stroke and peripheral arterial disease and the relevance of therapeutic interventions targeting VWF for ACS patients.
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PMID:Role of von Willebrand factor in vascular disease. 1915 43

Myocardial infarction and stroke are caused by blood clots forming over a ruptured or denuded atherosclerotic plaque (atherothrombosis). Production of prostaglandin E(2) (PGE(2)) by an inflamed plaque exacerbates atherothrombosis and may limit the effectiveness of current therapeutics. Platelets express multiple G-protein coupled receptors, including receptors for ADP and PGE(2). ADP can mobilize Ca(2+) and through the P(2)Y(12) receptor can inhibit cAMP production, causing platelet activation and aggregation. Clopidogrel (Plavix), a selective P(2)Y(12) antagonist, prevents platelets from clotting but thereby increases the risk of severe or fatal bleeding. The platelet EP(3) receptor for PGE(2), like the P(2)Y(12) receptor, also inhibits cAMP synthesis. However, unlike ADP, facilitation of platelet aggregation via the PGE(2)/EP(3) pathway is dependent on co-agonists that can mobilize Ca(2+). We used a ligand-based design strategy to develop peri-substituted bicylic acylsulfonamides as potent and selective EP(3) antagonists. We show that DG-041, a selective EP(3) antagonist, inhibits PGE(2) facilitation of platelet aggregation in vitro and ex vivo. PGE(2) can resensitize platelets to agonist even when the P(2)Y(12) receptor has been blocked by clopidogrel, and this can be inhibited by DG-041. Unlike clopidogrel, DG-041 does not affect bleeding time in rats, nor is bleeding time further increased when DG-041 is co-administered with clopidogrel. This indicates that EP(3) antagonists potentially have a superior safety profile compared to P(2)Y(12) antagonists and represent a novel class of antiplatelet agents.
ACS Chem Biol 2009 Feb 20
PMID:Antagonists of the EP3 receptor for prostaglandin E2 are novel antiplatelet agents that do not prolong bleeding. 1919 56

To determine the prevalence of concomitant microvascular and macrovascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 diabetic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 +/- 11.4 years, mean duration of diabetes was 15.4 +/- 7.5 years, mean age at the onset of nephropathy was 61.5 +/- 12.4 years, and mean duration of nephropathy was 3.9 +/- 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression into ESRD.
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PMID:Concomitant macro and microvascular complications in diabetic nephropathy. 1941 42

The main results of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in the primary end point of all-cause mortality or nonfatal myocardial infarction [MI] or major secondary end points (composites of death/MI/stroke; hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year follow-up in 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). We sought to assess the impact of PCI when added to OMT on major prespecified tertiary cardiovascular outcomes (time to first event), namely cardiac death and composites of cardiac death/MI, cardiac death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac death/MI/ACS/stroke, during study follow-up. There were no significant differences between treatment arms for the composite of cardiac death or MI (15% in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite cardiovascular events during long-term follow-up, even after excluding periprocedural MI as an outcome of interest. Overall, cause-specific cardiovascular outcomes paralleled closely the primary and secondary composite outcomes of the trial as a whole. In conclusion, compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.
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PMID:Impact of optimal medical therapy with or without percutaneous coronary intervention on long-term cardiovascular end points in patients with stable coronary artery disease (from the COURAGE Trial). 1957 11

Activation of the coagulation cascade and platelet functions occurs in ACS and may lead to subsequent thrombus formation, vessel occlusion, distal embolisation, myocardial ischaemia, necrosis and eventually death. Over the last 20 years, the outcome of ACS and PCI patients has considerably improved, thanks to better pharmacologic environment, urgent reperfusion in STEMI (ST elevation myocardial infarction), timely revascularisation in non-ST elevation ACS (NSTEACS) and improved PCI techniques, particularly widespread use of stents. In this context, bleeding was long considered as inherent to the modern therapeutic approach and without real consequences. Actually, bleeding has a strong impact on outcome, with a four- to five-fold increase in the rate of death, myocardial infarction and stroke at 30 days and six months. In addition, blood transfusion may have deleterious effects. Recent evidence shows that reduced risk of bleeding leads to a reduced risk of ischemic events (death, myocardial infarction and stroke). The exact mechanisms by which bleeding impacts on outcome are as yet poorly understood. The interruption of active treatment may play an important role. Activation of coagulation or inflammation in case of bleeding, and depletion of 2,3DPG and nitric oxide, inflammatory and immunologic reactions triggered by blood transfusion, are among the potential mechanisms. Prevention of bleeding has become as important as prevention of ischaemic events. Risk stratification for bleeding is as important as overall risk stratification for further ischaemic events. In patients at high risk of bleeding, appropriate choice and dosage of drugs, combinations of drugs, and the use of radial rather than femoral approach are essential components of bleeding prevention.
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PMID:Acute Coronary Syndromes and Percutaneous Coronary Interventions: impact of bleeding and blood transfusion. 1988 79

Prasugrel was associated with a statistically significant reduction in rates of cardiac ischemic events in patients with ACS who had undergone PCI. Rates of post-PCI death from cardiovascular causes, nonfatal MI, or nonfatal stroke were also significantly reduced with the use of prasugrel versus clopidogrel. Major bleeding was significantly increased with the use of prasugrel versus clopidogrel. Mortality did not differ significantly between the groups.
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PMID:Reducing cardiac ischemic events in patients with ACS: prasugrel versus clopidogrel. Commentary. 1798 82


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