External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris

AbstractObjectivesThe goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD).BackgroundIn patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described.MethodsWe prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 ± 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound.ResultsExternal counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 ± 2.1%, p = 0.01), compared with controls (3.1 ± 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 ± 2.8% vs. 10.2 ± 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 ± 2.7 nitrate tablets vs. 0.4 ± 0.5 nitrate tablets, p <0.001 and 4.5 ± 2.3 nitrate tablets vs. 4.4 ± 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 ± 0.5 vs. 1.9 ± 0.3, p <0.0001 and 3.3 ± 0.6 vs. 3.5 ± 0.5, p = 0.89, respectively).ConclusionsExternal counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism

Statin Efficacy and Safety for Lipid Modification in Apparently Healthy Male Military Aircrew

Introduction: Military aircrew men represent an elite group of relatively young, fit, and healthy people. The effectiveness of statin treatment in reducing low-density lipoprotein cholesterol (LDL-C) according to the current National Cholesterol Education Program (NCEP) guidelines, its safety, and compliance in this group of people has not yet been determined. Methods: We prospectively evaluated 84 military aircrew men (mean age 43 Ϯ 7 yr) with LDL-C above the current NCEP guidelines. The patients were divided into two groups according to their coronary risk factors: Group 1, LDL-C goal Ͻ 160 mg ⅐ dL Ϫ1 ; Group 2, LDL-C goal Ͻ 130 mg ⅐ dL Ϫ1 . All patients received statins in addition to therapeutic lifestyle changes and were followed for a mean of 3 Ϯ 1 yr according to a simple flow chart. Lipoprotein levels, liver function tests, creatinine phosphokinase, and subjective adverse reactions were checked periodically. Results: LDL-C significantly declined by 32% (p Ͻ 0.0001) within the first month of treatment and 99% of subjects achieved their LDL-C goal within 114 Ϯ 35 d from statin therapy initiation. The Framingham estimated 10-yr coronary risk showed a reduction at an average of 12 mo after statin therapy initiation from a baseline value of 6.54% to 3.95% (p ϭ 0.003). No subjects were grounded or disqualified from duty, there were no cardiovascular events during follow-up, and compliance to therapy was high [82/84 (98%)]. Discussion: Statin treatment in this highly select, relatively young group of aircrew men significantly and safely lowered LDL-C cholesterol levels

Is platelet inhibition due to thienopyridines increased in elderly patients, in patients with previous stroke and patients with low body weight as a possible explanation of an increased bleeding risk?

Background The TRITON-TIMI 38 study has identified three subgroups of patients with a higher risk of bleeding during treatment with the thienopyridine prasugrel: patients with a history of stroke or transient ischaemic attack (TIA), patients ≥75 years and patients with a body weight <60 kg. However, the underlying pathobiology leading to this increased bleeding risk remains to be elucidated. The higher bleeding rate may be due to a stronger prasugrelinduced inhibition of platelet aggregation in these subgroups. The aim of the present study was to determine whether on-treatment platelet reactivity is lower in these risk subgroups as compared with other patients in a large cohort on the thienopyridine clopidogrel undergoing elective coronary stenting. Methods A total of 1069 consecutive patients were enrolled. On-clopidogrel platelet reactivity was measured in parallel by light transmittance aggregometry, the Verify- Now®P2Y12 assay and the PFA-100 collagen/ADP cartridge. Results Fourteen patients (1.5%) had a prior history of stroke or TIA, 138 patients (14.5%) were older than 75 years and 30 patients (3.2%) had a body weight <60 kg. Age ≥75 years and a history of stroke were independent predictors of a higher on-treatment platelet reactivity. In contrast, a body weight <60 kg was significantly associated with a lower on-treatment platelet reactivity. Conclusion In two high-risk subgroups for bleeding, patients ≥75 years and patients with previous stroke, onclopidogrel platelet reactivity is increased. In contrast, in patients with a low body weight, on-clopidogrel platelet reactivity is decreased, suggesting that a stronger response to a thienopyridine might only lead to more bleeds in patients with low body weight

Residual platelet ADP reactivity after clopidogrel treatment is dependent on activation of both the unblocked P2Y1 and the P2Y12 receptor and is correlated with protein expression of P2Y12

Two ADP receptors have been identified on human platelets: P2Y1 and P2Y12. The P2Y12 receptor blocker clopidogrel is widely used to reduce the risks in acute coronary syndromes, but, currently, there is no P2Y1 blocker in clinical use. Evidence for variable responses to clopidogrel has been described in several reports. The mechanistic explanation for this phenomenon is not fully understood. The aim of this study was to examine mechanisms responsible for variability of 2MeS-ADP, a stable ADP analogue, induced platelet reactivity in clopidogrel-treated patients. Platelet reactivity was assessed by flow cytometry measurements of P-selectin (CD62P) and activated GpIIb/IIIa complex (PAC-1). Residual 2MeS-ADP activation via the P2Y12 and P2Y1 receptors was determined by co-incubation with the selective antagonists AR-C69931 and MRS2179 in vitro. P2Y1 and P2Y12 receptor expression on both RNA and protein level were determined, as well as the P2Y12 H1 or H2 haplotypes. Our data suggest that the residual platelet activation of 2MeS-ADP after clopidogrel treatment is partly due to an inadequate antagonistic effect of clopidogrel on the P2Y12 receptor and partly due to activation of the P2Y1 receptor, which is unaffected by clopidogrel. Moreover, a correlation between increased P2Y12 protein expression on platelets and decreased response to clopidogrel was noticed, r2=0.43 (P<0.05). No correlation was found between P2Y12 mRNA levels and clopidogrel resistance, indicating post-transcriptional mechanisms. To achieve additional ADP inhibition in platelets, antagonists directed at the P2Y1 receptor could be more promising than the development of more potent P2Y12 receptor antagonists

Cardiovascular Events in Patients Received Combined Fibrate/Statin Treatment versus Statin Monotherapy: Acute Coronary Syndrome Israeli Surveys Data

The effect of combination of fibrate with statin on major adverse cardiovascular events (MACE) following acute coronary syndrome (ACS) hospitalization is unclear. The main aim of this study was to investigate the 30-day rate of MACE in patients who participated in the nationwide ACS Israeli Surveys (ACSIS) and were treated on discharge with a fibrate (mainly bezafibrate) and statin combination vs. statin alone.The study population comprised 8,982 patients from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 8,545 (95%) received statin alone and 437 (5%) received fibrate/statin combination. MACE was defined as a composite measure of death, recurrent MI, recurrent ischemia, stent thrombosis, ischemic stroke and urgent revascularization.Patients from the combination group were younger (58.1±11.9 vs. 62.9±12.6 years). However, they had significantly more co-morbidities (hypertension, diabetes), current smokers and unfavorable cardio-metabolic profiles (with respect to glucose, total cholesterol, triglyceride and HDL-cholesterol). Development of MACE was recorded in 513 (6.0%) patients from the statin monotherapy group vs. 13 (3.2%) from the combination group, p = 0.01. 30-day re-hospitalization rate was significantly lower in the combination group: 68 (15.6%) vs. 1691 (19.8%) of patients, respectively; p = 0.03. Multivariable analysis identified the fibrate/statin combination as an independent predictor of reduced risk of MACE with odds ratio of 0.54, 95% confidence interval 0.32–0.94.A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy. However, caution should be exercised in interpreting these findings taking into consideration baseline differences between our observational study groups

Cigarette Smoking and Erectile Dysfunction: Focus on NO Bioavailability and ROS Generation

Introduction.  Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem, which seriously affects the quality of life of patients and their partners, ED becomes increasingly prevalent with age and chronic smoking is a major risk factor in the development of ED. Aim.  To review available evidence concerning the effects of cigarette smoking on vascular changes associated with decreased nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS) generation. Methods.  We examined epidemiological and clinical data linking cigarette smoking and ED, and the effects of smoking on vascular NO bioavailability and ROS generation. Main Outcome Measures.  There are strong parallels between smoking and ED and considerable evidence supporting the concept that smoking-related ED is associated with reduced bioavailability of NO because of increased ROS. Results.  Cigarette smoking-induced ED in human and animal models is associated with impaired arterial flow to the penis or acute vasospasm of the penile arteries. Long-term smoking produces detrimental effects on the vascular endothelium and peripheral nerves and also causes ultrastructural damage to the corporal tissue, all considered to play a role in chronic smoking-induced ED. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium-dependent smooth muscle relaxation or more specifically by affecting NO production via increased ROS generation. Whether nicotine or other products of cigarette smoke mediate all effects related to vascular damage is still unknown. Conclusions.  Smoking prevention represents an important approach for reducing the risk of ED. The characterization of the components of cigarette smoke leading to ED and the mechanisms by which these components alter signaling pathways activated in erectile responses are necessary for a complete comprehension of cigarette smoking-associated ED. Tostes RS, Carneiro FS, Lee AJ, Giachini FRC, Leite R, Osawa Y, and Clinton Webb R. Cigarette smoking and erectile dysfunction: Focus on NO bioavailability and ROS generation. J Sex Med 2008;5:1284–1295.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75024/1/j.1743-6109.2008.00804.x.pd

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011