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Biomedical subjects

John B Kostis

Publications and source records attributed to John B Kostis.

At least 19 recordsLinked to original sources

Reduction of stroke risk factors.

In October 2006, a panel of experts participated in a teleconference to discuss the reduction of stroke risk factors in patients at risk for stroke. The panel was chaired by John B. Kostis, MD, Professor and Chairman, Department of Medicine at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ. Also participating were Philip B. Gorelick, MD, MPH, Director, Center for Stroke Research, University of Illinois College of Medicine, Chicago, IL, and Franz H. Messerli, MD, St Luke's-Roosevelt Hospital Center, New York, NY.

Antihypertensive Agents↗

Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study.

BACKGROUND: It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF. METHODS: 197HF patients (EF <35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo. RESULTS: Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p<0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8+/-5.3 at baseline, 30.7+/-10 at 2 years, p<0.05). CONCLUSIONS: (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome.

Aged↗

Conjugated equine estrogens and coronary heart disease: the Women's Health Initiative.

BACKGROUND: In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection. METHODS: A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses. RESULTS: During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97). CONCLUSIONS: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.

Age Distribution↗

Erectile dysfunction and cardiac disease: recommendations of the Second Princeton Conference.

Erectile dysfunction (ED) has been linked increasingly to cardiovascular risk factors and comorbidities. Considering the potential risk associated with sexual activity, guidelines were developed (Princeton I) for assessment and management of patients with varying degrees of cardiac risk. These guidelines were recently updated (Princeton II) based on new data concerning the link between ED and cardiovascular disease and the availability of additional phosphodiesterase type 5 inhibitors (vardenafil, tadalafil). Despite the need for careful risk assessment in all cases, sexual activity remains safe for the large majority of patients. However, all patients presenting with complaints of ED should be carefully assessed for the presence of cardiovascular risk factors (eg, obesity, hypertension, hyperlipidemia). Risk-factor modification, including lifestyle interventions (eg, exercise, weight loss) is strongly encouraged. Guidelines are presented for the management of acute coronary syndromes in patients taking phosphodiesterase type 5 inhibitors, including alternatives to the use of nitrates for these patients. Other drug interactions and the cardiovascular safety of testosterone replacement therapy are considered.

Cardiovascular Diseases↗

Celebrating 50 years of experience: an ECFMG perspective.

As indicated in its mission statement, the Educational Commission for Foreign Medical Graduates (ECFMG), established in 1956, "promotes quality health care for the public by certifying IMGs for entry into U.S. graduate medical education, and by participating in the evaluation and certification of other physicians and health care professionals. In conjunction with its Foundation for Advancement of International Medical Education and Research, and other partners, it actively seeks opportunities to promote international medical education through programmatic and research activities." From 1958 through 2005, the ECFMG certified 287,382 international medical graduates (IMGs); the number per year has varied, depending on the world political situation and other factors. Currently, IMGs constitute 25% of practicing physicians in the United States. India, followed by the United States and the Philippines, has provided the largest number of certified IMGs. The ECFMG has developed extensive resources for verifying medical school diplomas and other credentials of applicants, and it provides credentials verification services to other organizations. Under the U.S. government J-1 Exchange Visitor Program, it also has played a major role in facilitating the entry of foreign physicians to the United States for clinical training and research experience. Over the years, testing of IMGs seeking ECFMG Certification has evolved; whereas initially applicants took examinations specifically for IMGs, they now take the same United States Medical Licensing Examination (USMLE) sequence of examinations as U.S. medical graduates. Passage of the USMLE is required for ECFMG Certification and licensure in all jurisdictions.

Certification↗

The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine.

INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent disorder associated with a significant burden of illness. The prevalence and incidence of ED are strongly age-related, affecting more than half of men >60 years. The first Princeton Consensus Conference (Princeton I) in 1999 developed guidelines for safe management of cardiac patients regarding sexual activity and the treatment of ED. AIM: The second conference (Princeton II) was convened to update the recommendations based on the expanding knowledge base and new treatments available. This article reviews and expands on the Princeton II guidelines to address sexual dysfunction and cardiac risk. METHODS: A consensus panel of experts reviewed recent multinational studies in safety and drug interaction data for three phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. RESULTS: Erectile dysfunction is an early symptom or harbinger of cardiovascular disease, due to the common risk factors and pathophysiology mediated through endothelial dysfunction. Major comorbidities include diabetes, hypertension, hyperlipidemia and heart disease. Any asymptomatic man who presents with ED that does not have an obvious cause (e.g., trauma) should be screened for vascular disease and have blood glucose, lipids, and blood pressure measurements. Ideally, all patients at risk but asymptomatic for coronary disease should undergo an elective exercise electrocardiogram to facilitate risk stratification. Lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease, is literature-supported. CONCLUSIONS: The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise. Men with ED and other cardiovascular risk factors (e.g., obesity, sedentary lifestyle) should be counseled in lifestyle modification.

Adult↗

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Cardiovascular Diseases↗

Lifestyle management of erectile dysfunction: the role of cardiovascular and concomitant risk factors.

The influence and significance of lifestyle factors in erectile dysfunction (ED) have been demonstrated in cross-sectional and prospective, randomized, controlled trials. Recent epidemiologic studies in several countries have shown that modifiable lifestyle or risk factors, including physical activity in particular, are directly related to the occurrence of ED. In this article, we review several recent observational studies, 2 of which include a longitudinal follow-up component in the study design. The levels of physical activity in both of these studies predicted ED prevalence and incidence. Furthermore, the role of lifestyle changes (weight loss, physical activity) were recently demonstrated to be effective in modifying ED in a prospective, randomized Italian trial in moderately obese, sedentary men. Men without overt diabetes mellitus or cardiovascular disease participated in this landmark study. Other studies have shown that aggressive management of cardiovascular risk factors can increase the effectiveness or outcomes associated with pharmacologic management of ED. Taken together, these studies support the value of risk factor modification and lifestyle change in the clinical management in men with ED and concomitant cardiovascular illness.

Cardiovascular Diseases↗

Incidence and characteristics of angioedema associated with enalapril.

BACKGROUND: Angioedema is a rare but potentially serious adverse event of angiotensin-converting enzyme inhibitor therapy. However, no prospective, controlled studies have reported on its incidence and clinical characteristics. METHODS: We studied the occurrence of angioedema in a randomized, double-blind, controlled trial of 12 557 persons with hypertension treated with enalapril maleate, 5 to 40 mg/d, using a prospective ascertainment and adjudication of angioedema by an expert committee. RESULTS: Angioedema occurred in 86 (0.68%) of the subjects. Stepwise logistic regression identified black race (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.72-4.82), history of drug rash (OR, 3.78; 95% CI, 1.80-7.92), age greater than 65 years (OR, 1.60; 95% CI, 1.02-2.53), and seasonal allergies (OR, 1.79; 95% CI, 1.06-3.00) as independent risk factors for angioedema. The incidence of angioedema was higher after initiation of therapy (3.6/1000 patients per month) and declined to 0.4/1000 patients per month. Treatment was not given in 44 (51%) of the cases; antihistamines were administered in 35 (41%); corticosteroids, in 20 (23%); and epinephrine, in 1 (1%). Two patients were hospitalized but none had airway compromise. CONCLUSIONS: Enalapril-related angioedema is uncommon. Although it is most likely to occur early after initiation of therapy, it may occur at any time. It is more likely to occur in black patients, those older than 65 years, and those with a history of drug rash or seasonal allergies. Fatal angioedema or angioedema requiring airway protection did not occur in this study.

Adult↗

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference).

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Age Distribution↗

Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired fasting glucose concentration, and normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

BACKGROUND: Optimal first-step antihypertensive drug therapy in type 2 diabetes mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor decreases clinical complications compared with treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG). METHODS: Active-controlled trial in 31 512 adults, 55 years or older, with hypertension and at least 1 other risk factor for coronary heart disease, stratified into DM (n = 13 101), IFG (n = 1399), and NG (n = 17 012) groups on the basis of national guidelines. Participants were randomly assigned to double-blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention-to-treat analysis of fatal coronary heart disease or nonfatal myocardial infarction (primary outcome), total mortality, and other clinical complications. RESULTS: There was no significant difference in relative risk (RR) for the primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A significantly higher RR (95% confidence interval) was noted for the primary outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 [1.10-2.72]). Stroke was more common in NG participants assigned to lisinopril vs chlorthalidone (1.31 [1.10-1.57]). Heart failure was more common in DM and NG participants assigned to amlodipine (1.39 [1.22-1.59] and 1.30 [1.12-1.51], respectively) or lisinopril (1.15 [1.00-1.32] and 1.19 [1.02-1.39], respectively) vs chlorthalidone. CONCLUSION: Our results provide no evidence of superiority for treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors compared with a thiazide-type diuretic during first-step antihypertensive therapy in DM, IFG, or NG.

Aged↗

Permanent pacing is a risk factor for the development of heart failure.

No previous study has examined the importance of right ventricular pacing as a risk factor for the development of heart failure (HF) in subjects without a history of HF. A cohort study of patients who underwent initial pacemaker implantation (n = 11,426) was conducted to test the hypothesis that patients with ventricular dyssynchrony created by permanent pacing would develop HF, as shown by new HF hospitalizations or HF-related deaths, at a higher rate than matched controls.

Adult↗

Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes.

Diuretic-based antihypertensive therapy is associated with the development of diabetes but with improved clinical outcomes. It has been proposed that the duration of clinical trials has been too short to detect the adverse effects of diabetes. We assessed the long-term mortality rate of subjects in the Systolic Hypertension in the Elderly Program (n = 4,732) who were randomized to stepped-care therapy with 12.5 to 25.0 mg/day of chlorthalidone or matching placebo. If blood pressure remained above the goal, atenolol or matching placebo was added. At a mean follow-up of 14.3 years, cardiovascular (CV) mortality rate was significantly lower in the chlorthalidone group (19%) than in the placebo group (22%; adjusted hazard ratio [HR] 0.854, 95% confidence interval [CI] 0.751 to 0.972). Diabetes at baseline (n = 799) was associated with increased CV mortality rate (adjusted HR 1.659, 95% CI 1.413 to 1.949) and total mortality rate (adjusted HR 1.510, 95% CI 1.347 to 1.693). Diabetes that developed during the trial among subjects on placebo (n = 169) was also associated with increased CV adverse outcome (adjusted HR 1.562, 95% CI 1.117 to 2.184) and total mortality rate (adjusted HR 1.348, 95% CI 1.051 to 1.727). However, diabetes that developed among subjects during diuretic therapy (n = 258) did not have significant associations with CV mortality rate (adjusted HR 1.043, 95% CI 0.745 to 1.459) or total mortality rate (adjusted HR 1.151, 95% CI 0.925 to 1.433). Diuretic treatment in subjects who had diabetes was strongly associated with lower long-term CV mortality rate (adjusted HR 0.688, 95% CI 0.526 to 0.848) and total mortality rate (adjusted HR 0.805, 95% CI 0.680 to 0.952). Thus, chlorthalidone-based treatment improved long-term outcomes, especially among subjects who had diabetes. Subjects who had diabetes associated with chlorthalidone had no significant increase in CV events and had a better prognosis than did those who had preexisting diabetes.

Aged↗

The association of heart failure with insulin resistance and the development of type 2 diabetes.

Heart failure (HF) is associated with a significant risk for either concurrently having diabetes or subsequently developing diabetes. Medications that block the sympathetic nervous system (SNS) have been shown to improve clinical outcomes in patients with chronic HF but may be associated with the development of new-onset diabetes. Depending on the receptor specificity of the individual agent, beta-blockers have different effects on glucose and lipid metabolism as well as on the risk for developing new-onset diabetes. Although SNS modulation with beta-blockade reduces mortality in patients with chronic HF, certain beta-blockers may actually worsen glucose and lipid metabolism and increase the risk for new-onset diabetes. The use of vasodilating beta-blockers, on the other hand, has not produced these harmful metabolic effects.

Adipose Tissue↗

Expanding the definition and classification of hypertension.

Cardiovascular abnormalities are frequently the cause, as well as the effect, of elevated blood pressure. As such, early cardiovascular disease (CVD) may be established before identifiable blood pressure thresholds are crossed. To identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD, the Hypertension Writing Group proposes incorporating the presence or absence of cardiovascular risk factors, early disease markers, and target organ damage into the definition and classification scheme of hypertension. To describe both the complexity and progressive nature of hypertension, the following definition is proposed: "Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs and lead to premature morbidity and death." Classification of hypertension must involve assessing global cardiovascular risk to situate an individual's risk for CVD and events along a continuum. As knowledge of early CVD continues to evolve, the approach to classifying individuals along that continuum can be expected to evolve accordingly. The four categories currently used to classify hypertension are normal, prehypertension, and stages 1 and 2 hypertension. The population identified with prehypertension includes a subgroup with early CVD. We believe it would be preferable to classify all individuals as either normal or hypertensive, based on their cardiovascular evaluation, using the four categories of normal and stages 1, 2, and 3 hypertension.

Antihypertensive Agents↗