Cardiovascular disease (CVD) is one of the main causes of early death in the United Kingdom [1]. In England more than 110,000 people die every year of coronary heart disease (CHD). More than 1.4 million people suffer from angina and 275,000 people have a heart attack annually. CVD has a complex aetiology, and usually results in a narrowing of the arteries (atherosclerosis) and an occlusion through the formation of a blood clot in a narrowed artery (thrombosis) [3]. These events have been found to be associated with changes in vascular reactivity, increasing platelet aggregation, increases in plasma triglycerides and an increase in systemic markers of inflammation [4-7]. Of these, inflammation is of central importance, and may underpin the development of other forms of chronic disease such as cancer and cognitive decline [8].
Dietary advice to consume at least five portions of fruit and vegetable per day in order to reduce the risk of developing these chronic diseases is largely based upon observational data from epidemiological studies that have associated diets rich in fruits and vegetables with a reduction in age related chronic illness [8].
There is now a substantial body of epidemiological evidence that states that diets rich in cruciferous vegetables can reduce the risk of incidence and progression of cancer at various sites [12-18].
Broccoli or calabrese (Brassica oleracea var italica) is a representative member of the cruciferous vegetables. This family of vegetables is unique in the synthesis and accumulation of glucosinolates in their edible parts [34]. These sulphur containing glycosides are stored within the cell vacuole. Following tissue damage they are hydrolysed via a plant thioglucosidase (myrosinase) to several products, of which isothiocyanates from methionine-derived glucosinolates and indoles from tryptophan-derived glucosinolates are the most abundant [35]. If myrosinase has been denatured by blanching prior to freezing or by cooking, ingested glucosinolates are hydrolysed to isothiocyanates and indoles by the action of microbial thioglucosidases in the colon. These degradation products are highly bioactive, and many of the health benefits of cruciferous vegetables have been associated with the activity of these compounds, although experimental data in humans is almost entirely absent. Brassica vegetables are also particularly good sources of other compounds that have been associated with health benefits, notably vitamin C, folates, carotenoids, calcium and magnesium [36, 37]. Distinguishing the biological activity of any one group of compounds in food products such as broccoli is very complex. However, to facilitate studies on glucosinolates, cultivars of broccoli that specifically have elevated levels of methionine-derived glucosinolates compared to standard broccoli, but without any change in other potentially bioactive compounds have been developed [38, 39]. Thus, these novel genotypes can be used to test hypotheses in humans concerned with the contribution of a single class of bioactive compound within a complex food.
Several epidemiological studies suggest certain polymorphisms within one or more members of the glutathione-S-transferases (GST) gene family can be risk factors for cancer. Variation in this gene family has also been implicated in CVD where several studies have examined the relationship between null genotypes and CVD. There are at present eight classes of GST [42], with the most work carried out on. GST-mu (GSTM1), GST-theta (GSTT1) and GST-pi (GSTT1) and their polymorphisms. Approximately 40% of the population have a homologous deletion of the GSTM1 gene resulting in a null genotype, and 20% has a deletion of the GSTT1 gene. The GST gene family convert reactive electrophiles, by conjugation with glutathione, to compounds that can be excreted from the body more easily. Polymorphisms may therefore impair the defence mechanisms which could result in the development of a large number of diseases including CVD [43]. Polymorphisms with GST have also been shown to interact with cruciferous vegetable consumption to influence cancer risk [43].
As we age, our arteries stiffen which causes an increase in myocardial demand resulting in higher systolic blood pressures and a widening of the pulse pressure. The stiffening process results from structural changes, the degeneration of elastin responsible for the elasticity of the artery and an increase in collagen causing a thickening of the arterial wall [44]. This increase in arterial stiffness and central systolic pressure along with a decrease in coronary artery perfusion pressure dramatically increases the risk of heart attack, stroke and heart failure. Arterial stiffness has also been associated with many of the common risk factors associated with CVD such as age, high blood pressure, smoking, cholesterol levels and obesity, but importantly have also been shown to be independent predictors of cardiovascular morbidity and mortality in several population groups [45]. The measurement of arterial stiffness is increasingly being used as a tool in the clinical assessment of patients with CVD. Augmentation index (Aix) has been shown to be a strong independent risk marker for coronary artery disease and pulse-wave velocity (PWV) has been shown to be an independent predictor of morbidity and mortality in hypertensive patients [46, 47]. Epidemiological and clinical studies have shown that an increase in arterial stiffness is an independent marker of CVD in patients with end-stage renal failure and those with hypertension [46, 48, 49]. Carotid-femoral PWV is considered the gold standard in the direct measurement of arterial stiffness [50, 51].
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USPTO Backgrounds