Observational studies cardiovascular disease

Low levels of vitamin E have been associated with increased incidence of coronary artery disease. Observational studies have therefore suggested that supplemental a-tocopherol might have value in the treatment of cardiovascular disease. Clinical studies demonstrated contradicting results regarding the benefits of vitamin E in the prevention of cardiovascular disease. Four... 

The a-tocopherol, P-carotene (ATBC) Cancer Prevention study was a randomised-controlled trial that tested the effects of daily doses of either 50 mg (50 lU) vitamin E (all-racemic a-tocopherol acetate), or 20 mg of P-carotene, or both with that of a placebo, in a population of more than 29,000 male smokers for 5-8 years. No reduction in lung cancer or major coronary events was observed with any of the treatments. What was more startling was the unexpected increases in risk of death from lung cancer and ischemic heart disease with P-carotene supplementation (ATBC Cancer Prevention Study Group, 1994). Increases in the risk of both lung cancer and cardiovascular disease mortality were also observed in the P-carotene and Retinol Efficacy Trial (CARET), which tested the effects of combined treatment with 30 mg/d P-carotene and retinyl pahnitate (25,000 lU/d) in 18,000 men and women with a history of cigarette smoking or occupational exposure to asbestos (Hennekens et al, 1996). 

Observational studies have suggested possible favourable effects of estrogen replacement therapy (ERT) on the risk of coronary heart disease in postmenopausal women. Since elevated plasma cholesterol has been identified as the primary risk factor for cardiovascular disease, investigations have focused on the inverse association between plasma cholesterol concentration and soy protein consumption. The cholesterol-lowering properties of soy have been demonstrated, and a good correlation has been found in... 

Carotenoids and cardiovascular diseases — Numerous epidemiological studies aimed to study the relationship of carotenoids and cardiovascular diseases (CVDs) including coronary accident risk and stroke. It appeared then that observational studies, namely prospective and case-control studies, pointed to a protective effect of carotenoids on myocardial infarct and stroke, but also on some atherosclerosis markers such as intima media thickness (IMT) of the common carotid artery (CCA) and atheromatous plaque formation. 

Clinical trials on postmenopausal women with osteoporosis have demonstrated that raloxifene reduces bone turnover markers by 25-35% after 1 year of treatment and reduces the relative risk of the occurrence of new vertebral fractures by 30-50% after 3 years of treatment (Ettinger et al. 1999). A post hoc analysis in women at high risk for cardiovascular diseases also showed a reduction of 40% in the rate of new cardiovascular events (Barrett-Connor et al. 2002), with no observed reduction in the overall study population after 4 years of treatment in the MORE trial. 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

A glucocorticoid-resistance model has been proposed to provide an explanation for how stress might influence diseases in which excessive inflammation is observed (e.g., allergies, autoimmune diseases, rheumatoid arthritis, and cardiovascular disease). In these cases, chronic stress diminishes the immune system s sensitivity to glucocorticoids that normally terminate the inflammatory response. For example, in a study of a group of 50 parents caring for a child undergoing treatment for pediatric cancer, whole blood of parents of cancer patients exhibited a lesser dexamethasone-dependent suppression of IL-6 production in vitro compared to parents of medically healthy children.94... 

In many parts of Britain in the 1930s, excellent records of the hirthweight of hahies were made. When the causes of death in the subsequent adults were studied and medical records investigated, a strong correlation between low hirthweight, stroke incidence of mortahty from cardiovascular disease and diabetes was observed (Barker, 1998). It may be that low hirthweight is due to undemutrition of the mother. 

A modest but not significant inverse correlation between the intake of flavonols and flavones and subsequent mortality rates was found in a prospective cohort study of US Health Professionals by Rimm et al [206]. The authors do not exclude that flavonoids have a protective effect in men with established coronary heart disease although strong evidence was missing. Also other studies failed to demonstrate a significant statistical association between the intake of polyphenols and CHD. In Great Britain for instance coronary and total mortality even rose with the intake of the major flavonol source, tea [207], The most likely explanation for the latter observation is that in this study tea consumption merely acted as a marker for a lifestyle that favours the development of cardiovascular disease. Indeed, men with the highest intake of tea and flavonols tended to be manual workers, and they smoked more and ate more fat [208],... 

The hypothesis that dairy foods contain a cholesterol-lowering milk factor evolved from the observation that Maasai tribesmen of East Africa have low serum concentrations of cholesterol and a low incidence of cardiovascular disease in spite of their consumption of 4 to 5 liters/day of fermented whole milk (Mann and Spoerry 1974). Subsequently, sufficient amounts of yogurt, as well as unfermented milk (whole, lowfat, skim), were reported to exhibit a hypocholesterolemic effect both in humans and in laboratory animals in several studies (Mann 1977 Howard and Marks 1977, 1979 Nair and Mann 1977 Kritchevsky et al 1979 Richardson 1978 Hussi etal. 1981). However, not all investigators have observed a hypocholesterolemic effect of milk. This inconsistency may be explained in part by differences in the experimental design and in the specific type of dairy food used by investigators. 

In clinical trials, the preventive effect of 3-carotene supplementation on cancer or cardiovascular disease could not be demonstrated in a well-nourished population. This apparent ineffectiveness contrasts starkly with the promising results of numerous basic studies and epidemiological observations, which suggest that supplementation with this antioxidant is likely to have a protective effect. 

The observed associations between folate, antioxidant vitamins, and cardiovascular disease may be confounded by other substances in fruits and vegetables, as the following examples of studies show Flavonoids (see Chapter 31) are naturally occurring, water-soluble antioxidants found widely distributed in vegetables, fruits, tea, and wine. There is an inverse relationship between flavonoids and decreased risk of coronary heart disease. Lycopene, the key antioxidant in tomatoes, shows an inverse association with myocardial infarctions. There is an inverse association between folate and cardiovascular disease. 

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