IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules).

In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 .

View this table:

 Table 1 
Classes of recommendations



View this table:

 Table 2 
Levels of evidence



The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the …

/pdf/guidelines-for-the-diagnosis-and-treatment-of-non-st-segment-4i7khpy8cj.pdf

Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes

This review of the role of platelets in atherothrombosis illuminates the surprisingly numerous activities of these tiny, anucleate cells and stresses their participation in the inflammatory component of atherothrombosis. The information is presented in the context of the prevention of atherothrombosis by antiplatelet agents now in clinical use.

/pdf/platelet-activation-and-atherothrombosis-4afsrhs7f0.pdf

Platelet Activation and Atherothrombosis

▪ Abstract Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the over...

/pdf/pleiotropic-effects-of-statins-1b9b1g8457.pdf

Pleiotropic effects of statins

The establishment of a prognosis and the approach to the treatment of many diseases is aided greatly by a logical classification. For example, classification of a wide variety of neoplasms by anatomic extent, microscopic appearance, and the presence of special markers now forms the basis for selecting appropriate therapy. In cardiology, the classification of patients with acute myocardial infarction and congestive heart failure has been of enormous value in following the progress and in selecting therapy of individual patients and in comparing the outcome of similar patients treated at different locations and at different times. The purpose of this article is to provide a classification of unstable angina. This classification is designed to facilitate communication about these patients, to aid in the decision regarding diagnostic measures and therapy of individual patients, and to provide a more precise basis for including patients in and for evaluating the outcome of clinical trials.

Unstable angina : a classification

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.

Louis Roy

Papers

Platelet activation in unstable coronary disease.