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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The strong link demonstrated at autopsy between coronary atherosclerosis and angina pectoris led to the important concept that a fixed obstruction of 1 or more coronary arteries was the pathophysiologic cause of angina: myocardial ischemia and angina occurred when myocardial oxygen demand out-stripped the capacity of the diseased coronary artery to deliver oxygen. Therapeutic strategies were based on attempts to lower myocardial oxygen needs induced by physical and emotional stress. However, the finding that dynamic increases in coronary vascular resistance can also either precipitate ischemia or reduce the threshold of myocardial oxygen consumption (MVO2) at which it occurs has profoundly altered our understanding of the pathophysiologic features of angina and, therefore, its treatment. Dynamic coronary obstruction can occur at the large-vessel level, causing Prinzmetal's or variant angina. It is also possible that in some patients a continuum of large-vessel coronary vasoconstrictor tone exists, causing the common clinical situation manifested by angina with variable thresholds of onset. Recent studies have demonstrated that increases in the resistance offered to flow by small coronary arteries too small to be imaged by angiography can also decrease anginal threshold. The fact that ischemia can be precipitated by dynamic increases in large- or small-vessel coronary resistance has important implications for the therapy of angina pectoris. In those persons who mostly have a dynamic component contributing to their coronary obstruction, primary intervention with vasodilator therapy, including nitrates and calcium-channel blocking agents, are probably most effective therapeutically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamic coronary obstruction as a cause of angina pectoris: implications regarding therapy. 388 18

Angina pectoris results from an imbalance between the oxygen supply and the oxygen needs of the myocardium. While the classic form of angina is usually caused by demands exceeding supply, a primary and transient decrease in coronary blood flow is more and more often recognised as an aetiological factor of myocardial ischaemia. Calcium antagonists, although new in cardiovascular therapeutics, are already recognised as the treatment of choice for some forms of angina and as useful therapeutic adjuncts in others. Few contraindications to their use exist. They are potent vasodilators and they can prevent the occurrence of coronary artery spasm responsible for the Prinzmetal's variant form of angina. They can also reduce coronary artery tone, which if high, can compromise flow through a narrowed coronary artery. Nifedipine, diltiazem and verapamil can also influence the various determinants of myocardial oxygen consumption to reduce myocardial oxygen needs. Their effects on heart rate, blood pressure and on the inotropic state of the left ventricle is, in vivo, the balance between their direct effects on the vascular wall and myocardial muscular cells and their indirect effects represented by the reflex physiological responses. Significant variations in these effects exist between the 3 calcium antagonists such that treatment can be individualised to a particular patient's needs. Precautions with their use as well as most of their side effects can be understood from a knowledge of their direct and indirect properties. Other pharmacological effects of these drugs include a regional redistribution of coronary blood flow, cardioprotection, delay in cell death and possibly in the progression of atherosclerosis. The clinical significance of these properties remains to be investigated.
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PMID:Calcium antagonists. Clinical use in the treatment of angina. 633 99

With the arteriographic demonstration of coronary arterial spasm, fundamental questions have been raised concerning the role of spasm in myocardial ischemia and infarction. It is now clear that coronary arterial spasm is the cause of Prinzmetal's variant angina pectoris in patients with and without coronary atherosclerosis. In most patients with coronary heart disease, major ischemic events frequently result from increased myocardial oxygen demand or coronary thrombosis. However, recent evidence suggests that coronary arterial spasm may initiate or contribute to the development of unstable angina pectoris, acute myocardial infarction, and sudden death in these patients. Thus, episodes of myocardial ischemia and infarction are induced by factors, acting singly or in combination, that augment myocardial oxygen demand or diminish myocardial oxygen supply, and the latter alteration can result from thrombotic coronary occlusion or a dynamic increase in coronary arterial tone (that is, coronary arterial spasm).
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PMID:The role of coronary arterial spasm in ischemic heart disease. 689 63

Prinzmetal's variant angina is a rare entity. When angina-like symptoms occur at rest, mostly at a specific hour in the early morning, together with transient ST segment elevations and angiographically normal arteries, provocative tests with ergonovine or acetylcholine should be performed. Endothelial dysfunction, a strong thrombotic tendency, an increased platelet aggregation together with changes in autonomic tone can trigger coronary vasospasms. Once treated with calcium antagonists and nitrates the prognosis is excellent and severe complications such as arrhythmias, myocardial infarction or sudden death are extremely rare. Coronary stenting can be useful for refractory coronary spasm, CABG can be used for important coronary atherosclerosis. This review is illustrated with three typical presentations of variant angina: a myocardial infarction without significant organic coronary atherosclerosis, an ergonovine-induced coronary spasm with a non-significant coronary lesion and a multivessel spasm complicated by ventricular arrhythmia. All these three patients became asymptomatic after a treatment with calcium antagonists and nitrates.
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PMID:Prinzmetal's variant angina: three case reports and a review of the literature. 1037 17

EFFICACY OF CALCIUM ANTAGONISTS: Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertensive therapy, with substantial blood pressure reduction in all age groups and races. CCBs improve endothelial function, may positively influence atherosclerosis in carotid arteries, reduce left ventricular hypertrophy, and hypertrophy of the resistance vessels, and improve arterial compliance. They do not adversely affect lipids and serum glucose. USE IN PRACTICE: CCBs are also a heterogenous class of drugs composed of the phenylalkylamine verapamil, the benzothiazepine diltiazem, and the large group of dihydropyridines (DHPs) with the prototype nifedipine, and an increasing number of newer agents (e. g. nitrendipine, nisoldipine, amlodipine, felodipine, lacidipine and lercanidipine). DHPs are primarily vasodilators, lowering blood pressure by decreasing peripheral vascular resistance at the level of the small arterioles which can be followed by an autonomic counterregulation especially in drugs with a rapid onset of action. This is markedly reduced or abolished in the treatment with the modern long acting DHPs and is also not the case in the treatment with non-DHPs. Prospective randomized controlled outcome studies demonstrated a significant reduction in stroke in elderly patients with isolated systolic hypertension compared with placebo (Syst-Eur [Syst-China]), and no significant differences in cardiovascular mortality and combined morbidity compared with diuretics, beta blockers or ACE-Inhibitors (STOP-2, INSIGHT, NORDIL, ALLHAT, INVEST). To normalize the blood pressure it is mostly necessary to combine antihypertensive drugs. Here are CCBs ideal partners for a therapy with ACE-inhibitors, AT1 antagonists or beta blockers (DHP) and diuretics (verapamil). With respect to the antihypertensive differential therapy the author recommends CCBs based on studies with the evidence grade 1-3; especially for elderly hypertensives (with isolated systolic neuhypertension and a high risk of stroke), for patients with COPD and asthma bronchiale, Raynaud's syndrome or Prinzmetal-angina, patients with diastolic function disturbances including diastolic heart failure or hypertensives with massive left ventricular hypertrophy (in combination with ACE or AT1 inhibitors).
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PMID:[Differential therapy with calcium antagonists]. 1468 11

Variant angina, defined as spontaneous angina pectoris associated with transient ST-segment elevation, has proved to be caused usually by episodic coronary spasm since Prinzmetal and his associates described a form of angina quite different from classic Heberden angina pectoris in 1959. Currently, coronary artery spasm is defined as reversible coronary stenosis, which limits coronary blood flow under resting conditions, and it plays an important role in ischemic heart disease, particularly in variant angina. Data available in respect of coronary vasospasm showed that it is closely related to atherosclerotic coronary artery disease, since intravascular ultrasound studies reveal atherosclerotic plaques in almost any spastic segment. Risk factors for coronary artery disease and coronary vasospasm, however, differ profoundly. Cigarette smoking is the only established risk factor. Although several candidates and predisposing factors, such as serotonin, histamine, thromboxane, and endothelin, have been described, the mediators and the pathogenesis of the disease remain unknown. There are abundant studies that inflammation plays an important role in the initiation, development as well as evolution of atherosclerosis, suggesting that atherosclerosis is an inflammation disease. The evidence regarding the role of inflammatory pathways in different clinical entities of coronary artery disease has significantly been accumulated. And also, primary studies have showed that inflammation may be a contributor for variant angina or vasospastic coronary disease is at least partially driven by inflammation. Although much more research is obviously needed, primary evidence provide us with some direction for that research.
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PMID:Inflammation in variant angina: is there any evidence? 1765 33

Coronary artery spasm, the pathogenic mechanism most frequently observed in the syndrome of Prinzmetal's variant angina, appears to be caused by a local, nonspecific smooth muscle hyperreactivity. The relationship between coronary atherosclerosis, endothelial dysfunction, and coronary artery spasm is still speculative. Coronary artery spasm should be distinguished from other forms of coronary vasoconstriction, which may also play a role in angina pectoris. Occlusive coronary spasm causes complete interruption of coronary blood flow and may contribute to thrombus formation. Segmental coronary hyperreactivity may also be a component of acute coronary syndromes.
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PMID:Mechanisms of coronary artery spasm. 2123 96