Subject cardiovascular disease

Other Cardiovascular Agents Effecting Atherosclerosis. A large amount of clinical data is available concerning semm Upid profiles in patients subjected to dmg therapy for other cardiovascular diseases. Atheroma, for example, may be the underlying cause of hypertension and myocardial infarction. There are on the order of 1.5 million heart attacks pet year in the United States (155). 

The relationship between serum cholesterol levels and cardiovascular disease remains suggestive, despite intensive research into the subject. In any case, agents which can lower serum cholesterol levels are of therapeutic interest. Beloxamide (98),... 

Phytochemicals have been the subject of many studies evaluating their effects in relation to common chronic human illnesses such as cancer and cardiovascular diseases. These studies encounter difficulties in using this information to influence the dietary patterns of consumers because in the past they have used models or experiments with animals. However, in the last decade, researchers have moved away from animal studies in favour of human cell models or human intervention studies. Scientists still need to determine the likely incidence of illness from exposure to known amounts of a given natural compound in the diet and specifically in relation to the complex matrices of whole foods. Therefore, it is inevitable that some animal studies have to be continued for toxicological studies. 

In spite of the alleged benefits of isoflavones, some studies have produced inconsistent results in relation to their protective effect against cardiovascular diseases (Lin and others 2007 van der Schouw and others 2005 Engelman and others 2005). Some of the inconsistencies are due to the small sample size in most of the studies and to the very marked differences in metabolism among subjects (Erdman and others 2007 Visioli and others 2000). Therefore, no firm conclusions can be drawn. 

It has been already pointed out that nitric oxide exhibits antioxidant effect in LDL oxidation at the NO/ 02 ratio 1. Under these conditions the antioxidant effect of NO prevails on the prooxidant effect of peroxynitrite. Although some earlier studies suggested the possibility of NO-mediated LDL oxidation [152,153], these findings were not confirmed [154]. On the other hand, at lower values of N0/02 ratio the formed peroxynitrite becomes an efficient initiator of LDL modification. Beckman et al. [155] suggested that peroxynitrite rapidly reacts with tyrosine residues to form 3-nitrotyrosine. Later on, Leeuwenburgh et al. [156] found that 3-nitrotyrosine was formed in the reaction of peroxynitrite with LDL. The level of 3-nitrotyrosine sharply differed for healthy subjects and patients with cardiovascular diseases LDL isolated from the plasma of healthy subjects contained a very low level of 3-nitrotyrosine (9 + 7 pmol/mol 1 of tyrosine), while LDL isolated from aortic atherosclerotic intima had a 90-fold higher level (840 + 140 pmol/moD1 of tyrosine). It has been proposed that peroxynitrite formed in the human artery wall is able to promote LDL oxidation in vivo. 

Committee on Medical Aspects of Food Policy (COMA) (1984) Diet and Cardiovascular Disease. Report of the panel on Diet in Relation to Cardiovascular Disease. DHSS Report on Health and Social Subjects 28. London HMSO. 

A wealth of epidemiological, clinical, and experimental studies link estrogens with cardiovascular disease (CVD). This evidence has promoted CVD as a key area within the extragenital effects of estrogens. The question is of interest because it directly affects the wide clinical use of estrogens as contraceptive agents or as principal constituents of hormonal therapy (HT) formulations in postmenopausal women. The significance of the subject is further reinforced by the relevance of CVD as a cause of mortality and morbidity in both women and men. 

Although there are several ethical concerns with biobanks and other large-scale research repositories (Rothstein, 2002), the most important issue is informed consent. Participants in research involving human subjects must be advised of the intended research to be performed with their specimens. With biobanks, however, the future research uses of the samples are unknown at the time of collection. It would be infeasible to contact each of the donors to obtain consent every time a new research use is contemplated, yet IRBs are reluctant to approve the use of blanket consent for unspecified uses. One way to avoid this problem is for prospective sample donors to be given a menu of possible uses of their samples. Such a list might include research in mental health, HIV/AIDS, cancer, cardiovascular disease, or other areas. The donors would then have the opportunity to approve the use of their specimens for all or some of the listed uses. Other disclosures necessary to obtain informed consent include the financial interests of the biobank and researchers, whether individuals may elect to be notified of research findings, and whether it is possible for an individual to withdraw his or her sample from the bank (Rothstein, 2002). 

Of the two subjects, Mr Leene is at the greater risk for cardiovascular disease (CVD). Despite his healthier lifestyle Mr Leene has a family history of vascular disease (brother who died of a stroke), clinical signs of lipid deposits (yellow patches in skin) and a very poor lipid profile. Lipid-lowering drug intervention is required in this subject. 

There are many excellent texts on nutrition. This chapter, therefore, focuses not on nutrition per se but on how biochemistry helps us understand well established and less well established aspects of nutrition and how such knowledge fits in with other subjects discussed in this text. There is now considerable medical and lay interest in what is meant by healthy and unhealthy diets. Nutrition has become a major issue in the medical sciences and in clinical practice. It is also of concern to politicians, particularly in the link between nutrition and Western diseases such as cardiovascular disease, obesity, cancer and neurological problems. In this chapter an attempt is made to provide a biochemical basis for discussion of nutrition and development of these conditions. To this end, biochemical explanations for nutritional advice and the recommendations from national bodies are provided. Similarly, explanations for the recommendations designed for different populations, different conditions and activities (physical and mental activity, the elderly, the young, during pregnancy and space flight) are discussed. Finally, the biochemistry of malnutrition, undemutrition and ovemutrition is discussed. 

Delorme S, Chiasson J-L. Acarbose in the prevention of cardiovascular disease in subjects with impaired glucose tolerance and type 2 diabetes mellitus. Curr Opinion Pharmacol 2005 5 184-9. 

There is now emerging data that specific dietary flavonoids may improve endothelial function by increasing NO bioavailability. Longer term human intervention studies are required to establish a proven benefit on vascular function in healthy subjects as well as those who may be at increased risk of cardiovascular disease. 

Chardigny, J. M., Destaillats, F., Malpuech-Brugere, C., Moulin, J., Bauman, D. E., Lock, A. L., Barbano, D. M., Mensink, R. P., Bezelgues, J. B., Chaumont, P., Combe, N., Cristiani, I., et al. (2008). Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects Results of the trans Fatty Acids Collaboration (TRANSFACT) study. Am. ]. Clin. Nutr. 87, 558-566. 

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. 

Allman et al. (1995) noted that platelet EPA levels were more than double for individuals fed flaxseed oil compared to sunflower oil group. Platelet EPArarachidonic acid ratio (i.e., marker for thromboxane production and platelet aggregation potential) increased in the flaxseed group, thus a protective effect against cardiovascular disease, over LA-rich oils, would be expected. Their findings support the decreased platelet aggregation observed in hyperlipidemic subjects fed flaxseed (Bierenbaum et al., 1993). 

The Multiple Risk Factor Intervention Trial (Dolecek, 1992) included over 12,000 men over an 8-year period. The results showed that higher ALA intakes were associated with lower risks of death due to coronary heart disease and cardiovascular disease. Furthermore, a 28% reduction in risk of stroke was associated with a 0.06% increase in the ALA content of serum phospholipids (Simon et al., 1995). Other studies have since supported the association between ALA and reduction in stroke risk (Leng et al., 1999 Vartiainen et al., 1994). Vartiainen et al. (1994) followed a Finnish population of approximately 28,000 men and women over 20 years and found that a 60% reduction in mortality from stroke was associated with increased ALA consumption. In a study involving approximately 1,100 subjects, individuals suffering a stroke had significantly lower ALA concentrations in the red blood cell (Leng et al., 1999). 

Inflammation is an important factor in the development of cardiovascular disease. Most clinical studies involving inflammation parameters have been relatively small. The Nurses Health Study involving 727 women was the largest study designed to determine the effects of n-3 fatty acids on biomarkers of inflammation and endothelium activation (Lopez-Garcia et al., 2004). They found an inverse association between ALA intake and plasma concentrations of C-reactive protein (a marker for inflammation), Interlukin-6, and E-selectin. Bemelmans et al. (2004) also found an inverse association between C-reactive protein and ALA intake in a randomized, double-blind placebo-controlled study involving 103 hypercholesterolemic subjects. 

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