Coronary artery disease. See

Although requirements for vitamins and trace elements are known in health (Table 30-1), the effects of illness on these requirements are poorly understood and quantified. However, it is now apparent that as an individual develops progressively more severe depletion in vitamin or trace element status, the person passes through a series of stages with biochemical or physiological consequences. The metabolic or physiological penalty of such suboptimal nutritional status is usually not clear, but the assumption remains that the suboptimal metabolism is likely to have detrimental effects (e.g., subclinical deficiency of folic acid is associated with an increase in serum homocysteine concentration, which is an independent risk factor for coronary artery disease—see Chapter 26). Similarly, subclinical deficiency of chromium may be associated with impaired glucose tolerance in certain types of diabetes. 

Zhang R, Brennan ML, Fu X, Avdes RJ, Pearce GL, Penn MS, et al. Association between myeloperoxidase levels and risk of coronary artery disease, [see comment]. JAMA 2001 286 2136-42. 

Isosorbide, an antianginal nitrate (20 mg p.o. b.i.d.), is indicated in prevention of angina pectoris due to coronary artery disease (see also Figures 60 and 61). 

The basic biology of chemokines and their receptors is well covered in Chapters 2 and 3 of this book, and we will focus hereafter upon the roles of individual chemokines and receptors in atherosclerosis. The largest amount of data on the roles of chemokines in cardiovascular disease (C VD) has been obtained from in vitro studies and murine models, which will be discussed in detail. In man, genetic polymorphisms in chemokine and chemokine-receptor genes have pointed to an important role for specific chemokines in various atherosclerotic diseases including coronary artery disease and carotid artery occlusive disease. For properties see Table 1. 

The statins have been demonstrated to markedly lower plasma LDL levels (and triglyceride levels to a lesser extent). In fact, statins were approved by the US FDA on the basis of a surrogate endpoint reduction in plasma cholesterol levels. Since we know that increased plasma cholesterol levels are correlated with increased risk of coronary artery disease, it seems logical that reducing plasma cholesterol levels would lead to reduced risk. That turns out to be true in this case. However, see the case of hormone replacement therapy (HRT) for women for a more complex example, discussed below. 

In a totally different field, studies were being carried out on children who had a deficiency of methionine synthase and an impaired ability to convert homocysteine to methionine, so that they had increased blood levels of homocysteine. It was noted that these children had an increased incidence of thrombosis in cerebral and coronary arteries. This led to a study which eventually showed that an increased level of homocysteine was a risk factor for coronary artery disease in adults. Since methionine synthase requires the vitamins, folic acid and B12, for its catalytic activity, it has been suggested that an increased intake of these vitamins could encourage the conversion of homocysteine to methionine and hence decrease the plasma level of homocysteine. This is particularly the case for the elderly who are undernourished (see Chapter 15 for a discussion of nutrition in the elderly). 

Auricchio A, Sommariva L, Salo RW, Scafuri A, Chiariello L. Improvement of cardiac function in patients with severe congestive heart failure and coronary artery disease by dual chamber pacing with shortened AV delay, [see comment]. Pacing Clin. Electrophysiol. 1993 16 2034 3. 

Given to patients with a history of typical angina accompanied by either a past medical history of coronary artery disease or ECG/cardiac enzyme changes, low molecular weight heparins (LMWH) were more efficacious in reducing MI and revascularization, but not mortality, with fewer serious side-effects than unfractionated heparin (UFH) (see Magee et al., 2003). 

Although elevated levels of cholesterol and LDL in human plasma are linked to an increased incidence of cardiovascular disease, recent data have shown that an increase in concentration of HDL in plasma is correlated with a lowered risk of coronary artery disease. Why does an elevated HDL level in plasma appear to protect against cardiovascular disease, whereas an elevated LDL level seems to cause this disease The answer to this question is not known. An explanation currently favored is that HDL functions in the removal of cholesterol from nonhepatic tissues and the return of cholesterol to the liver, where it is metabolized and secreted. The net effect would be a decrease in the amount of plasma cholesterol available for deposit in arteries (see... 

The role of folic acid in the metabolism of homocysteine has received increased interest recently. Elevations of plasma homocysteine concentrations have been shown to be independent risk factors for coronary artery disease and probably cerebrovascular disease (see Chapter 26). The involvement of folate in its coenzyme forms with homocysteine and methionine metabolism is summarized in Figure 30-22. Folate is the principal micronutrient determinant of homocysteine status, and supplementation with folate has been used as a treatment modality to reduce circulating homocysteine concentrations. Primary (fasting) homo-cystinemia can be treated with 0.5 to 5.0mg/day of folic... 

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