Definition of Metabolic Syndrome: Report of the National Heart, Lunch, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition

https://www.ahajournals.org/doi/pdf/10.1161/01.atv.0000111245.75752.c

Prevention Conference V: Beyond secondary prevention: Identifying the high-risk patient for primary prevention: Executive summary

"This conference, “Beyond Secondary Prevention: Identifying the High-Risk Patient for Primary Prevention,” which was the fifth in a series of prevention conferences sponsored by the American Heart Association (AHA), was held October 26–28, 1998, in San Francisco, Calif. The need for this conference was precipitated by the remarkable advances in medical therapies for the prevention of coronary heart disease (CHD). The AHA has already set forth guidelines for aggressive medical therapy in patients with established CHD (secondary prevention). The major issue under consideration at this conference was the development of strategies to identify high-risk patients without established CHD who are candidates for aggressive medical therapies for primary prevention. Therefore, a central theme for the conference was the emphasis on establishing a prognosis for high-risk patients without clinical evidence of CHD. Three writing groups were established to report on the following areas: (1) medical office assessment, (2) tests for silent and inducible ischemia, and (3) noninvasive tests of atherosclerotic burden. Each working group reviewed research on existing risk-assessment strategies relevant to the prediction of risk in patients without clinical evidence of CHD. The key findings of each working group are presented in this Executive Summary of the conference. The full conference report with references is available online at http://circ.ahajournals.org/ in the January 4, 2000, issue of Circulation. The recommended strategies will assist in expanding preventive therapies, including lipid lowering, blood pressure control, smoking cessation, diet, and exercise, to patients at high risk for developing CHD. The following briefly summarizes the major conclusions of the conference.

Improving coronary heart disease risk assessment in asymptomatic people: Role of traditional risk factors and noninvasive cardiovascular tests

At least 25% of coronary patients have sudden death or nonfatal myocardial infarction without prior symptoms.1 Therefore, the search for coronary patients with subclinical disease who could potentially benefit from intensive primary prevention efforts is critically important. The American Heart Association’s (AHA) Prevention V Conference, “Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention,” addressed ways to identify more patients who are asymptomatic and clinically free of coronary heart disease (CHD) but at sufficiently high risk for a future coronary event to justify more intensive risk reduction efforts.2 In this report, we amplify on key findings and recommendations of the AHA Prevention V conference, highlight new research since the conference, and propose an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk. The recommendations are concordant with the recently released approach to risk assessment and management from the third report of the Adult Treatment Panel of the National Cholesterol Education Program (ATP-III).

Nonantithrombotic Medical Options in Acute Coronary Syndromes: Old Agents and New Lines on the Horizon

Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply-demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into “disease-modifying” agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as beta-blockers and inhibitors of the reninangiotensin-aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic pre- and post-conditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, anti-thrombotic agents, and the use of high-intensity statins

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

Objectives Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. Methods In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. Results Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. Conclusions Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injur

Integrating quality into the cycle of therapeutic development

The quality of healthcare, particularly as reflected in current practice versus the available evidence, has become a major focus of national health policy discussions. Key components needed to provide quality care include: 1) development of quality indicators and performance measures from specific practice guidelines, 2) better ways to disseminate such guidelines and measures, and 3) development of support tools to promote standardized practice. Although rational decision-making and development of practice guidelines have relied upon results of randomized trials and outcomes studies, not all questions can be answered by randomized trials, and many treatment decisions necessarily reflect physiology, intuition, and experience when treating individuals. Debate about the role of "evidence-based medicine" also has raised questions about the value of applying trial results in practice, and some skepticism has arisen about whether advocated measures of clinical effectiveness, the basic definition of quality, truly reflect a worthwhile approach to improving medical practice. We provide a perspective on this issue by describing a model that integrates quantitative measurements of quality and performance into the development cycle of existing and future therapeutics. Such a model would serve as a basic approach to cardiovascular medicine that is necessary, but not sufficient, to those wishing to provide the best care for their patients