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      Recent advances in the management of chronic stable angina I: Approach to the patient, diagnosis, pathophysiology, risk stratification, and gender disparities

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          Abstract

          The potential importance of both prevention and personal responsibility in controlling heart disease, the leading cause of death in the USA and elsewhere, has attracted renewed attention. Coronary artery disease is preventable, using relatively simple and inexpensive lifestyle changes. The inexorable rise in the prevalence of obesity, diabetes, dyslipidemia, and hypertension, often in the risk cluster known as the metabolic syndrome, drives the ever-increasing incidence of heart disease. Population-wide improvements in personal health habits appear to be a fundamental, evidence based public health measure, yet numerous barriers prevent implementation. A common symptom in patients with coronary artery disease, classical angina refers to the typical chest pressure or discomfort that results when myocardial oxygen demand rises and coronary blood flow is reduced by fixed, atherosclerotic, obstructive lesions. Different forms of angina and diagnosis, with a short description of the significance of pain and silent ischemia, are discussed in this review. The well accepted concept of myocardial oxygen imbalance in the genesis of angina is presented with new data about clinical pathology of stable angina and acute coronary syndromes. The roles of stress electrocardiography and stress myocardial perfusion scintigraphic imaging are reviewed, along with the information these tests provide about risk and prognosis. Finally, the current status of gender disparities in heart disease is summarized. Enhanced risk stratification and identification of patients in whom procedures will meaningfully change management is an ongoing quest. Current guidelines emphasize efficient triage of patients with suspected coronary artery disease. Many experts believe the predictive value of current decision protocols for coronary artery disease still needs improvement in order to optimize outcomes, yet avoid unnecessary coronary angiograms and radiation exposure. Coronary angiography remains the gold standard in the diagnosis of coronary artery obstructive disease. Part II of this two part series will address anti-ischemic therapies, new agents, cardiovascular risk reduction, options to treat refractory angina, and revascularization.

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          Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score.

          Despite improved understanding of atherothrombosis, cardiovascular prediction algorithms for women have largely relied on traditional risk factors. To develop and validate cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors. Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years (through March 2004) for incident cardiovascular events (an adjudicated composite of myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death). We used data among a random two thirds (derivation cohort, n = 16 400) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women (validation cohort, n = 8158). Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models. In the validation cohort, we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score. In the derivation cohort, a best-fitting model (model A) and a clinically simplified model (model B, the Reynolds Risk Score) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III. In the validation cohort, all measures of fit, discrimination, and calibration were improved when either model A or B was used. For example, among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5% to less than 10% (n = 603) or 10% to less than 20% (n = 156), model A reclassified 379 (50%) into higher- or lower-risk categories that in each instance more accurately matched actual event rates. Similar effects were achieved for clinically simplified model B limited to age, systolic blood pressure, hemoglobin A(1c) if diabetic, smoking, total and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and parental history of myocardial infarction before age 60 years. Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score. We developed, validated, and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40% to 50% of women at intermediate risk into higher- or lower-risk categories.
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            Pathophysiology of coronary artery disease.

            During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
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              A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.

              Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women. We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes). During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older. In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vascular Health and Risk Management
                Vascular Health and Risk Management
                Dove Medical Press
                1176-6344
                1178-2048
                2010
                2010
                9 August 2010
                : 6
                : 635-656
                Affiliations
                The Cardiometabolic Research Institute, Houston, Texas 77054 USA
                Author notes
                Correspondence: Richard Kones, MD, Cardiometabolic Research Institute, 8181 Fannin Street, #314, Houston, TX 77055 USA, Tel +1 713 790 9100, Fax +1 713 790 9292, Email drrkones@ 123456comcast.net
                Article
                vhrm-6-635
                10.2147/VHRM.S7564
                2922325
                20730020
                8e0fb6d7-fe01-4403-b81e-8f46e2be7335
                © 2010 Kones, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 14 July 2010
                Categories
                Review

                Cardiovascular Medicine
                angina,coronary artery disease,ischemic heart disease,myocardial oxygen balance,cardiovascular risk assessment,acute coronary syndrome,electrocardiographic stress testing,stress myocardial perfusion imaging,gender disparities in heart disease,silent ischemia,coronary angiography

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