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Biomedical subjects

C J Pepine

Publications and source records attributed to C J Pepine.

At least 19 recordsLinked to original sources
PubMed2005

Association between beta-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study.

OBJECTIVES: The beta-adrenergic receptor (betaAR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the beta(1)AR (ADRB1), beta(2)AR (ADRB2), beta(3)AR (ADRB3), Gs protein alpha (GNAS1), to which all three beta-receptors couple and the G protein beta3 subunit (GNB3), to which beta(3)ARs couple. DESIGN: A case-control genetic association study. SUBJECTS: A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation (WISE) study. MEASUREMENTS: Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made. RESULTS: Polymorphisms in the three betaAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity. CONCLUSIONS: Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the betaARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women.

Adipose Tissue↗
PubMed2001

Why vascular biology matters.

Cardiovascular disease has been the leading cause of death for men and women in this country since 1921 and is currently the leading cause of death in the world. Adding to the sense of urgency about disease prevention is the recent finding that the initial lesions of atherosclerotic vascular disease may begin within the first year of life-or even earlier, during fetal growth. However, the pathobiology of atherosclerosis (and in particular, the key role of low-density lipoprotein cholesterol) is now well understood. Activation of 3 major oxidative systems as well as the renin-angiotensin system-all located in the vascular wall-is an early step. In fact, the effects of statins and angiotensin-converting enzyme inhibitors on the vascular wall (improved endothelial function, inhibition of platelet aggregation, and plaque stabilization) are an important mechanism of benefit, independent of their systemic effects. Several very positive trials with these agents have been completed. However, if this information is not incorporated into clinical practice in a timely manner, cardiovascular disease will continue to present a major cause of morbidity and mortality worldwide.

Coronary Artery Disease↗
PubMed2001

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Adult↗
PubMed2001

History of anxiety disorders is associated with a decreased likelihood of angiographic coronary artery disease in women with chest pain: the WISE study.

OBJECTIVES: We sought to evaluate the ability of psychiatric anxiety-disorder history to discriminate between women with and without angiographic coronary artery disease (CAD) in a population with chest pain. BACKGROUND: A total of 435 women with chest pain underwent a diagnostic battery including coronary angiography in order to improve testing guidelines for women with suspected CAD. METHODS: Women referred for coronary angiography completed questionnaires assessing prior treatment history for anxiety disorder and current anxiety-related symptoms. Analyses controlled for standard CAD risk factors. RESULTS: Forty-four women (10%) reported receiving prior treatment for an anxiety disorder. This group acknowledged significantly higher levels of autonomic symptoms (e.g., headaches, muscle tension [F = 25.0, p < 0.0011 and higher behavioral avoidance scores (e.g., avoidance of open places or traveling alone by bus [F = 4.2, p < 0.05]) at baseline testing compared with women without prior anxiety problems. Women with an anxiety-disorder history did not differ from those without such a history with respect to the presence of inducible ischemia or use of nitroglycerin, although they were younger and more likely to describe both "tight" and "sharp" chest pain symptoms and to experience back pain and episodes of nocturnal chest pain. Logistic regression results indicated that the positive-anxiety-history group was more likely to be free of underlying significant angiographic CAD (odds ratio = 2.74, 95% confidence interval 1.15 to 6.5, p = 0.03). CONCLUSIONS: Among women with chest pain symptoms, a history of anxiety disorders is associated with a lower probability of significant angiographic CAD. Knowledge of anxiety disorder history may assist in the clinical evaluation of women with chest pain.

Adult↗
PubMed2001

The vascular biology of hypertension and atherosclerosis and intervention with calcium antagonists and angiotensin-converting enzyme inhibitors.

Recent advances in the understanding of vascular disease genesis suggest that atherosclerosis and hypertension, primary targets of therapy in the INternational VErapamil SR/trandolapril STudy (INVEST), are closely related. A unified model for the development of cardiovascular disease (CVD) is emerging from recent advances related to atherosclerosis and hypertension. The process of vascular disease appears to begin early in life, when signs of endothelial dysfunction first appear. A primary cause of CVD progression is increased oxidative stress in the endothelium caused by multiple risk factor conditions, including heredity, dyslipidemia, smoking, diabetes, and elevated systolic blood pressure (SBP > 110 mmHg). The renin-angiotensin and kallikrein-kinin systems are important regulators of blood pressure and atherosclerosis. In the renin-angiotensin system, angiotensin-converting enzyme (ACE) mediates generation of angiotensin II (ang II) at local vascular sites and in the plasma and also degrades bradykinin. Information derived from INVEST will help to identify treatment strategies, such as those containing a calcium antagonist and an ACE inhibitor, that are targeted directly at the vascular disorder responsible for hypertension and atherosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Enhancing clinical trials on the internet: lessons from INVEST.

The INternational VErapamil SR/trandolapril STudy (INVEST) is the first long-term, large-scale clinical trial being conducted primarily using Web-based technology. The Web is a powerful tool for enhancing clinical trial management because of its ability to centralize all study information and coordinate multiple trial processes in real time at lower cost. The result is improved efficiency, accuracy, and safety in clinical trials conduct. In Web-based clinical trials, sites are able to focus primarily on medicine and science, rather than on trial administration. Site training, study documentation, subject recruitment, randomization, medication dispensing, and management procedures are simplified by using Web-based software to enhance processes. This paper summarizes the advantages achieved for INVEST investigators, sponsor representatives, monitors, and subjects resulting from the centralization and coordination of multiple tasks through Web-based technology.

Clinical Trials as Topic↗
PubMed2001

Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study.

BACKGROUND: Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women; it is frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain. METHODS: We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women's Ischemia Syndrome Evaluation (WISE) study. RESULTS: Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 +/- 0.38); 85 (53%) had normal reserve (mean, 3.13 +/- 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past menopause correlated with flow velocity reserve (r = -0.18, P =.02, and r = -0.30, P <.001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction. CONCLUSIONS: Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD.

Blood Flow Velocity↗
PubMed2001

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗
PubMed2000

An ischemia-guided approach for risk stratification in patients with acute coronary syndromes.

The optimal management approach for patients with non-ST-segment elevation acute coronary syndromes continues to be an issue of debate. An ischemia-guided strategy appears to be effective as an alternative to either a very conservative "wait-and-see" approach or a very aggressive routine revascularization approach. The need for another approach is supported by the lack of conclusive evidence-based results favoring an early routine invasive treatment strategy. In the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial, there were no differences in the incidence of death or myocardial infarction (MI) between patients treated with an early invasive approach and those treated with a conservative approach to treatment. Significantly worse outcomes were shown in patients assigned to an early invasive strategy in the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial at 1-year follow-up (111 clinical events in the invasive group vs 85 in the conservative group; p = 0.05). Registry information, including that from the Organization to Assess Strategies for Ischemic Syndromes (OASIS), which included approximately 8,000 patients with unstable angina or suspected MI, has even suggested an excess hazard with a routine invasive approach. Patients with non-ST-segment elevation MI observed in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)-IIB and Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials also fared better with an ischemia-guided strategy. Even the recent FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) trial investigators had to be very selective relative to eliminating high-risk patients in the first week and treating with intense anti-ischemic therapy and 5-7 days of low-molecular-weight heparin therapy to show an advantage for assigned revascularization. A careful clinical evaluation with attention to early risk stratification is essential in the ischemia-guided approach. The Braunwald classification for unstable angina helps identify independent clinical predictors of a poor outcome; high risk is clearly associated with Braunwald class III and type C. Electrocardiographic and biochemical markers for myocardial necrosis (cardiac troponin T or I) are important tools for assessing the presence and degree of ischemia and associated risk for adverse outcome. Noninvasive evaluation of left ventricular ejection fraction is essential for identifying those at high risk due to impaired contractile function. When these conventional markers do not provide conclusive information, noninvasive stress testing is most helpful to further identify those at highest risk for revascularization.

Angina, Unstable↗
PubMed2000

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Acute Disease↗
PubMed2000

Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study.

BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone. METHODS AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

Aspirin↗
PubMed2000

Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms.

BACKGROUND: After hospitalization for chest pain, women are more likely than men to have normal coronary-artery angiograms. In such women, myocardial ischemia in the absence of clinically significant coronary-artery obstruction has long been suspected. Most methods for the detection of the metabolic effects of myocardial ischemia are highly invasive. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy is a noninvasive technique that can directly measure high-energy phosphates in the myocardium and identify metabolic evidence of ischemia. METHODS: We enrolled 35 women who were hospitalized for chest pain but who had no angiographically significant coronary-artery obstructions and 12 age- and weight-matched control women with no evidence of heart disease. Myocardial high-energy phosphates were measured with 31P-NMR spectroscopy at 1.5 tesla before, during, and after isometric handgrip exercise at a level that was 30 percent of the maximal voluntary grip strength. We measured the change in the ratio of phosphocreatine to ATP during exercise. RESULTS: Seven (20 percent) of the 35 women with chest pain and no angiographically significant stenosis had decreases in the phosphocreatine:ATP ratio during exercise that were more than 2 SD below the mean value in the control subjects without chest pain. There were no significant differences between the two groups with respect to hemodynamic variables at rest and during exercise, risk factors for ischemic heart disease, findings on magnetic resonance imaging and radionuclide perfusion studies of the heart, or changes in brachial flow during the infusion of acetylcholine. CONCLUSIONS: Our results provide direct evidence of an abnormal metabolic response to handgrip exercise in at least some women with chest pain consistent with the occurrence of myocardial ischemia but no angiographically significant coronary stenoses. The most likely cause is microvascular coronary artery disease.

Adenosine Triphosphate↗