Stroke and Myocardial Infarct

In apoptosis a series of events takes place in an orderly sequence involving the activation of various proteases which are called caspases, for cysteine and aspartate proteases. Several distinct caspases act in a cascade vaguely reminiscent of the blood-clotting cascade of complement proteins. If one wishes to interfere with the apoptotic process, then one strategy would be to develop drugs that inhibit various caspases, a current effort underway in the pharmaceutical industry. 

While stroke and myocardial infarct involve very different organs, they display notable similarities. Most prominently, both are usually caused by clots that occlude blood vessels. Moreover, in both of these conditions efforts to modulate cell death offer therapeutic promise. 

Lipid Peroxidation DNA Strand Breaks Protein Damage 

Even in the absence of nitric oxide, hypoxic mitochondria will generate lethal free radicals. Superoxide can evolve into hydroxyl free radical without the intervention of 

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In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Blood pressure lowering drugs reduce risk of stroke (and myocardial infarction and death) in middle aged patients and even better in the elderly (NNT 86 vs 29 over 5 years) (Pearce 1998). However in the elderly the dysfunction in the autoregulation of brain blood flow, salt and fluids, and increased sensitivity to adverse effects and symptoms may change the picture. 

Cardiovascular safety. Both drug types promote salt retention, can exacerbate heart failure and tend to raise blood pressure. COX-2 selective drugs also appear to raise the risks of thrombotic events, notably stroke and myocardial infarction, and recent evidence suggests that non-selective NSAIDs also raise these risks, though it is unclear whether to the same degree. For both drug types, dose and duration of treatment appear to affect risk. 

The most significant toxicity from diazoxide has been excessive hypotension, resulting from the recommendation to use a fixed dose of 300 mg in all patients. Such hypotension has resulted in stroke and myocardial infarction. The reflex sympathetic response can provoke angina, electrocardiographic evidence of ischemia, and cardiac failure in patients with ischemic heart disease, and diazoxide should be avoided in this situation. 

Although hormonal contraceptives provide an easy and effective means of birth control, their use has been limited somewhat by potentially serious side effects. In particular, contraceptive medications have been associated with cardiovascular problems such as thrombophlebitis, stroke, and myocardial infarction.153 The incidence of these adverse effects, however, seems to depend to a large extent on whether the user has other risk factors associated with cardiovascular disease (smoking cigarettes, hyperlipidemia, hypertension, and so forth).84,120,162 Likewise, cardiovascular risks may be diminished with the newer forms of hormonal contraceptives, which contain relatively less estrogen than their predecessors. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

A 58-year-old white deaf man, with a history of pulmonary embolism, two first-degree relatives with a history of stroke and myocardial infarction, and one first-degree relative who died suddenly, developed a new episode of pulmonary embolism shortly after clozapine was begun (55). 

The principal long-term aim in most patients is the prevention of stroke and myocardial infarction reduction in the latter also requires attention to other risk factors such as smoking and plasma cholesterol. The more immediate aim of treatment is to reduce the blood pressure as near to normal as possible without causing symptomatic h)q)otension or otherwise impairing wellbeing (quality of life). 

Effective treatment reduces the risk of all complications strokes and myocardial infarction, but also hecirt failure, renal failure, and possibly dementia. It is easier in individual trials to demonstrate the benefits of treatment in preventing stroke, because the curve relating risk of stroke to blood pressiure is almost twice as steep as that for myocardial infarction. What this tells us is not that the relative risk of myocardial infarction due to hypertension is irreversible but that substantial reduction in the absolute risk of myocardial infarction needs attention to hypercholesterolaemia as well as hypertension. ... 

A large percentage of patients develop asymptomatic VTE. PE occurs in 25% of patients with thrombotic complications and contributes significantly to mortality. Arterial thrombosis occurs less commonly. Limb artery occlusion, stroke, and myocardial infarction are the most commonly reported arterial events. Heparin-induced skin lesions occur in 10% to 20% of patients with HIT. Lesions range from painful, localized erythematous plaques to widespread dermal necrosis. Amputation in such cases frequently is required. Mortality from HIT may be as high as 36% in patients with acute thrombosis. The relatively high frequency of thrombotic complications and poor outcomes... 

A number of plants and phytochemicals have attracted attention for their ability to reduce many of the risk factors associated with cardiovascular disease. Research into these diseases has shown the relationship between lesions, fatty streaking and plaque formation in blood vessels and the development of strokes and myocardial infarctions. These effects are linked to levels of plasma lipids which comprise triglycerides, cholesterol and other fat substances. It is known that the biosynthesis of lipids involves the condensation of several molecules of acetylcoenzyme A and malonylcoenzyme A in a gradual process of elongation of the fatty acid chain involving the sequential addition of two carbon units giving rise to fatty acids such as lauric acid (12 carbons) and eventually to palmitic acid (16 carbons). Palmitic acid is the precursor... 

Since the previous report in 1992, important new findings have provided fresh insight into CN mechanisms of action in both neural and cardiac tissue, the primary targets of CN intoxication. Most studies use CN to produce chemical hypoxia or to mimic conditions caused by stroke and myocardial infarction. Generally, actions of CN resemble those of ischemia and hypoxia, so information gained from CN studies is as important for the analysis of the chemical itself as for study of common pathological conditions. 

Alterations in the amounts of Bcl-2 proteins have been associated with diseases in which too much or too little cell death occurs (this is referred to as cell loss and cell accumulation, respectively). These diseases include cancer, autoimmune disorders such as lupus, immunodeficiency associated with human immunodeficiency virus (HIV) infection, and ischemia-reperfusion injury during stroke and myocardial infarction, among others [31]. 

In order to avoid potential biases, the choice of the specific outcome should be considered. The previous section emphasized the advantages of prospective collection and possibly adjudication of outcome events. However, even in the presence of randomization, there may be differences in ascertainment between the treatment arms. For example, if an unrelated side effect of a tieafmenf resulfs in additional health care utilization, there may be more opportunity to detect the outcome of interest. The use of hard outcomes may offer some profections against this phenomenon. For example, if vital status can be obtained for the whole analysis population, then a death outcome would not exhibit this phenomenon. Stroke and myocardial infarction may be more consistently and unbiasedly ascertained than other cardiovascular events such as arrhythmia and transient ischemic attacks. 

The risk of stroke and myocardial infarction increased with total Hey. 

Wilhelmsen L, Suardsudd K, Korsan-Bengsten K, Larsson B, Welvin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984 311 501-505. 

Maresca G, Diblasio A, Marchioli R et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction An update. Arteriosclerosis Thrombosis and Vascular Biology 1999 19 1368-1377. 

The risks of strokes and myocardial infarctions have been calculated in patients who received ranibizumab (0.3 or 0.5 mg... 

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