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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is associated with an increased prevalence of and morbidity from coronary artery disease, which is present in at least 25% of diabetic patients. Diabetes mellitus is a risk factor for recurrent cardiovascular events after myocardial infarction and after percutaneous coronary intervention procedures or coronary artery bypass surgery. Less than half of the increase in cardiovascular events with diabetes mellitus is accounted for by the presence of traditional cardiac risk factors such as hypertension, hypercholesterolemia, and hypertriglyceridemia. Vascular inflammation reflected by increased levels of high-sensitivity C-reactive protein, endothelial dysfunction associated with hyperglycemia and hyperinsulinemia, impaired fibrinolysis mediated by hyperinsulinemia, and increased platelet aggregation are now recognized as promoting the development of arteriosclerosis in diabetic patients. These factors may be present long before a diagnosis of diabetes mellitus is established. Platelets in diabetic subjects appear to be in an activated state even in the absence of vascular injury, as evidenced by greater expression of the fibrinogen-binding glycoprotein IIb/IIIa receptor, which constitutes the final common pathway of platelet activation and allows for cross-linking of individual platelets by fibrinogen molecules and formation of thrombus. Platelet inhibition with intravenous glycoprotein IIb/IIIa inhibitors has been shown to reduce morbidity and mortality in patients undergoing percutaneous coronary intervention for acute coronary syndromes, and diabetic patients appear to derive an even greater relative benefit from this treatment. The ACC/AHA 2002 guidelines for the management of acute coronary syndromes recommend the use of abciximab in diabetic patients undergoing stent implantation.
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PMID:Targeting the use of glycoprotein IIb/IIIa antagonists--the diabetic patient. 1243 33

Sitaxsentan (1) (Wu et al. J. Med. Chem. 1997, 40, 1690) is our first endothelin antagonist being evaluated in clinical trials. It has demonstrated biological effects in an acute hemodynamic study in CHF (Givertz et al. Circulation 2000, 101, 2922), an open-label 20-patient pulmonary hypertension trial (Barst et al. Chest 2002, 121, 1860-1868), and a 31-patient trial in essential hypertension (Calhoun et al. AHA Scientific Sessions 2000). In a phase 2b/3 pulmonary arterial hypertension trial, once a day treatment of 100 mg of sitaxsentan statistically significantly improved 6-min walk distance and NYHA class at 12 weeks (Barst et al. Am. J. Respir. Crit. Care Med. 2004, 169, 441). We have since reported on our efforts in generating follow-up compounds (Wu et al. J. Med. Chem. 1999, 42, 4485) and recently communicated that an ortho acyl group on the anilino ring enhanced oral absorption in this category of compounds (Wu et al. J. Med. Chem. 2001, 44, 1211). Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships. As a result, TBC3711 (7z) was identified as our second endothelin antagonist to enter the clinic due to its good oral bioavailability (approximately 100%) in rats, high potency (ET(A) IC(50) = 0.08 nM), and optimal ET(A)/ET(B) selectivity (441 000-fold). Compound 7z has completed phase-I clinical development and was well tolerated with desirable pharmacokinetics in humans (t(1/2) = 6-7 h, oral availability > 80%).
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PMID:Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist. 1505 97

Physicians are frequently concerned with the management of the surgical risk in patients with heart disease requiring non cardiac surgery. A preoperative evaluation helps to assess the cardiac risk for the planned surgery and helps to take measures to reduce that risk. We summarize the essentials in evaluating patients with coronary artery disease, valvular heart disease, arterial hypertension, arrhythmias, permanent pacemaker bearers, and those with congestive heart failure in order to prevent cardiac complications during the required surgery. Special attention has been given to the functional capacity, cardiac risk present, presence or absence of left ventricular dysfunction and the institution of protective measures. The usefulness of the ACC AHA guidelines has been summarized.
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PMID:Evaluation of cardiovascular risks for non cardiac surgery. 1659 70

Eighty percent of coronary deaths occur in people above 65 years of age. Fifty percent of deaths in persons above 85 years of age is due to coronary artery disease. The overall aging of the population and the improvement in survival of patients with coronary artery disease has been creating a growing large population of elderly adults who are elegible for secondary prevention. Multiple clinical trials and research trials have revealed evidence based information confirming the usefulness and effectiveness of secondary prevention of coronary artery disease in the elderly patient. The secondary prevention beneficial results have been obtained by addressing and controlling the predisposing items recognized a coronary risk factors. Secondary preventive measures, including lifestyle modifications and pharmacotherapy, modifying risk factors in elderly patients, have been shown to reduce morbidity and mortality from coronary artery disease. Evidence based data on prevention in elderly patients with coronary artery disease concerning smoking cessation, treatment of hypertension, control of hyperlipidemia, improved dietary patterns, physical activity, moderation in alcohol intake, management of diabetes, weight management, use of antiplatelet agents, beta blockers and renin-angiotensin-andosterone blockers is summarized. Emphasis has been given to AHA/ACC consensus statements on the prevention of coronary artery disease.
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PMID:Evidence based secondary prevention of coronary artery disease in the elderly--2006. 1720 93

Anticoagulation therapy in patients with atrial fibrillation is important. This review consists of three parts: chronic anticoagulation, anticoagulation for cardioversion, and a brief comment on anticoagulation around the time of left atrial radiofrequency ablation. The risk stratification scheme of the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines for chronic anticoagulation is briefly reviewed. Although there are several other similar schemes, they are not identical. The key point is the balance between benefit and risk. Some emerging controversies are outlined. Two specific questions explored are: is well-controlled hypertension a risk factor, and does paroxysmal atrial fibrillation confer the same risk as continuous atrial fibrillation? Differences in the risk of bleeding while taking a vitamin K antagonist noted in recent compared with older data are discussed. Risk of bleeding in the elderly and combined antithrombotic therapy with a vitamin K antagonist and an antiplatelet agent in high-risk patients are briefly discussed. Recent failures of studies attempting to find a suitable alternative to vitamin K antagonists are outlined. The treatment guidelines for anticoagulation for cardioversion are briefly reviewed. The risk of thromboembolism according to international normalized ratio and use of low-molecular-weight heparin as an alternative to warfarin are discussed. Anticoagulation before and after left atrial radiofrequency ablation is empirical, and long-term anticoagulation seems advisable for high risk patients at the present time. The two most pressing needs for further investigation are (1) clarification, simplification, and consolidated of risk stratification schemes and treatment recommendations and (2) discovery of alternatives to warfarin.
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PMID:Anticoagulation in atrial fibrillation: a contemporary viewpoint. 1733 82

The pharmacologic treatment of the cardiovascular comorbidities in patients with peripheral arterial disease (PAD) can have a profound effect on the outcomes of these patients. Guidelines for the treatment of hypertension, hyperlipidemia, diabetes, and tobacco use have been published by the American Heart Association and American College of Cardiology (AHA/ACC). Patients with PAD are often under-treated for these conditions. We sought to evaluate the adherence to these established guidelines in all new patients presenting with PAD to a vascular surgery clinic and delineate the opportunity for vascular surgeon involvement in these treatments. Consecutive new patients with symptomatic, objectively proven PAD (ankle-brachial index < 0.9) were evaluated in a vascular surgery clinic by a staff vascular surgeon. PAD risk factors, pre-visit medications, and prior cardiovascular interventions were recorded. Patients were stratified whether they were receiving appropriate preventive pharmacotherapy and whether they were meeting AHA/ACC goals. In patients without prior cardiovascular history, screening for these conditions was performed. One hundred sixty-seven new patients were evaluated over a 1-year period. Objectively diagnosed PAD included intermittent claudication in 115 (69%) and critical limb ischemia in 52 (31%) patients. Average age was 67.8 years, and 73 patients (44%) were current smokers. At initial evaluation, only 115 (69%) patients reported antiplatelet use. Patients with a recorded diagnosis of hypertension met clinical guidelines in 39 instances (71%). Eighteen patients (20%) with diabetes mellitus had poor glycemic control (Hgb-A1C > 7.0%). Seventeen (19%) of 88 patients with a history of hyperlipidemia were not adequately treated. Vascular surgeon medical interventions resulted in 31% of patients being started on antiplatelet therapy, 29% of hypertension therapies were modified, 19% of established lipid therapy was modified, and lipid therapy was initiated in 20%. A new diagnosis of hypertension was made in 10 cases (6%) and hyperlipidemia in 13 cases (7%). Despite clear guidelines for the medical community regarding cardiovascular prevention, a large percentage of patients with symptomatic PAD presenting to the vascular surgery clinic are not receiving appropriate therapy for their comorbidities or are not meeting the established goals. Vascular surgeons have an important role in promoting vascular health through the systemic prevention of ischemic events.
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PMID:Pharmacologic risk factor treatment of peripheral arterial disease is lacking and requires vascular surgeon participation. 1734 57

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.
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PMID:Current clinical applications of spectral tissue Doppler echocardiography (E/E' ratio) as a noninvasive surrogate for left ventricular diastolic pressures in the diagnosis of heart failure with preserved left ventricular systolic function. 1738 87

Gastric cancer was detected in a 71-year-old man with severe aortic stenosis. According to ACC/AHA guidelines, aortic stenosis in the patient was so severe that noncardiac surgery was considered appropriate only after aortic valve replacement. However, due to uncontrollable hemorrhage from gastric cancer, total gastrectomy was urgently required. Surgery was performed under epidural and general anesthesia. Blood pressure and heart rate were stable during anesthetic induction, tracheal intubation and skin incision. Just after peritoneal incision, however, ST decreased significantly following hypertension and sinus tachycardia, which were controllable by deepening of the anesthetic level. This ST depression was dependent on heart rate but not blood pressure. Therefore, in order to control the heart rate and prevent myocardial ischemia, low dose landiolol was infused prophylactically. This agent regulated the heart rate below 85 beats per minute without inducing hypotension and prevented myocardial ischemia during the remaining anesthetic course including extubation and recovery from anesthesia. Although beta blocker is not generally recommended in patients with aortic stenosis, present case suggests that landiolol is effective and useful to prevent cardiac ischemia even in a patient with severe aortic stenosis.
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PMID:[Landiolol prevented myocardial ischemia in a patient with severe aortic stenosis undergoing total gastrectomy]. 1751

Patients with end-stage renal disease (ESRD) are at high risk for cardiovascular disease (CVD) and therefore should be treated according to ACC/AHA Guidelines. Scant data are available concerning the actual use of cardioprotective drugs in this population. The use of angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, aspirin, and statins was assessed in 271 (72% males, 66% Caucasians) high-risk ESRD patients on hemodialysis. The study population comprised 27% smokers, 95% with hypertension, 38% with diabetes, and 44% with dyslipidemia; 44% of patients had overt CVD at baseline, including 9% with heart failure, 9% with prior myocardial infarction, and 3% with previous myocardial revascularization. One-third of all patients were not receiving any cardioprotective drugs; among those patients who were, 42% were on one drug, 21% were on two, 3.7% were on three, and 1.5% were on four. The most prescribed agent was ACE-I (35.8%), followed by aspirin (30.6%), and beta-blockers (28.0%). The use of statins was remarkably and significantly low (4.1%) (p < 0.001), even in the higher risk subgroups (patients with diabetes or macrovascular disease). ACE-I plus aspirin was the most prescribed combination (8.5%). Cardioprotective agents recommended for risk-factor modification by the ACC/AHA Guidelines for their well-established efficacy in the general population were underutilized in this cohort of high-risk hypertensive hemodialysis patients, despite an elevated prevalence of clinically evident CVD. Speculatively, this fact may be relevant to better understand the known increased cardiovascular morbidity-mortality associated with chronic renal disease.
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PMID:Underuse of American College of Cardiology/American Heart Association Guidelines in hemodialysis patients. 1765 18

This study compared the prevalence of metabolic syndrome (MS) according to World Health Organization (WHO), National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III), International Diabetes Federation (IDF) and American Heart Association/ National Heart, Lung and Blood Institute (AHA/NHLBI) definitions, to evaluate how well the different classifications agreed. The study also compared their 10-year predicted risk of coronary heart disease (CHD) with the Framingham risk score (FRS). Some 886 women and 547 men aged 18-92 years were included in the study. Demographic and personal medical history data were obtained at interview. Four operational definitions of MS were used (those of the WHO, NCEP-ATP III, AHA/NHLBI and IDF). The prevalence of metabolic syndrome was found to be 26.4% (WHO criteria), 24.0% (NCEP-ATP III criteria), 41.9% (IDF criteria) and 37.2% (AHA/NHLBI criteria). According to the definition used, central obesity ranged from 41.9% to 75.1% and high blood pressure from 52.9% to 65.8%. Agreement between classifications ranged from 75.2% (kappa=0.47) to 90.4% (kappa=0.80) and was lower in males. The 10-year predicted risk of CHD by FRS was similar between the different definitions. IDF and AHA/NHLBI definitions resulted in a higher prevalence of MS than the NCEP-ATP III or WHO definition. Overall, however, good agreement was found between definitions, and the predicted 10-year of CHD risk was similar.
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PMID:Impact of metabolic syndrome definitions on prevalence estimates: a study in a Portuguese community. 1815 2


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