Cardiovascular disease risk reduction

Peterson J, Dwyer J, Adlercreutz H, Scalbert A, Jacques P, McCullough ML. Dietary lignans physiology and potential for cardiovascular disease risk reduction. Nutr Rev. 2010 68 571—603. 

Over the last two decades, the scientific community has become aware of the potential health-related benefits of antioxidants and the properties of polyphenols-rich dark chocolate and cocoa. More than 200 studies were reported on bioactive compounds, chemical compositions, and health benefits of cocoa and cocoa products. Many of the proposed health-protective activities associated with the crmsumption of cocoa and chocolate have been attributed to flavan-3-ols, including monomers. Reported pharmacological activities of procyanidins include antioxidative and anticancer effects, protection against cardiovascular disease, risk reduction of blood clotting, protection against urinary tract infectirms, decrease of LDL-c, decrease of blood pressure, and improvement of endothelium vasodilatation. Moreover, there is some scientific evidence about an increase in blood flow and perfusion of the brain by... 

Data on the effect of calcium antagonists on cardiovascular disease risks in patients with hypertension are available from one moderate-to-large scale randomized, placebo-controlled trial. In the Systolic Hypertension in Europe (Syst-Eur) trial, nitrendipine-based therapy produced an approximate 10/5 mmHg reduction in SBP-DBP in patients with systolic hypertension and a 42% reduction in the risk of stroke. Similar results were observed in two large, nonrandomized, placebo-controlled trials (with alternate treatment assignment), i.e. the Shanghai Trial of Nifedipine in the Elderly and the Systolic Hypertension in China (Syst-China) trial. 

Tea is another important dietary source for flavonoids, In fact, about half of the flavonoid intake in western populations is derived from black tea. Tea was the major source of flavonoids in the Dutch [6,13] and Welsh studies [17]. Only a small number of studies investigated the association between tea consumption and cardiovascular disease risk. No association between tea consumption and cardiovascular disease risk were reported in Scottish men and women [28] and in U.S. men in the Health Professionals follow-up study [29]. However, in a Norwegian population an inverse association was reported between tea intake, serum cholesterol, and mortality from coronary heart disease [30]. Several studies reported that tea consumption did not affect plasma antioxidant activity [31] and hemostatic factors [32]. However, a recent prospective study (the Rotterdam study) of 3,454 men and women 55 years and older followed for 2 to 3 years, showed a significant, inverse association of tea intake with severe (> 5 cm the length of the calcified area) aortic atherosclerosis. Odds ratios decreased approximately 70 % for drinking more than 500 mL/day (4 cups per day). The associations were stronger in women than in men. However, the risk reductions for moderate and mild atherosclerosis were only weak or absent [33]. 

Markers of inflammation, especially CRP (measured with a highly sensitive technique, referred to as hs-CRP), have become the center of attention in recent years (22). This increased interest stems from several important observations made by Ridker and co-workers. Serum CRP has been shown to be an independent cardiovascular disease risk factor (23,24). High levels predict CAD death in healthy middle-aged men (25) and in patients with unstable CAD (26). In acute coronary syndromes, serum CRP concentrations correlate with the severity of endothelial dysfunction (27). In the CARE trial, subjects with elevated markers of inflammation (CRP and serum amyloid A > 90th percentile) were at high cardiovascular risk and responded best to pravastatin treatment in terms of cardiovascular risk reduction (28). The statin also reduced serum CRP concentrations (29). CRP co-incubated with LDL is readily taken up by macrophages, in contrast to native LDL, suggesting that CRP could promote foam cell formation (30). A link with endothelial dysfunction may be related to the fact that CRP decreases endothelial nitric oxide synthase (eNOS) expression and bioactivity in human aortic endothelial cells (31). 

In a study with nearly 1500 patients at high cardiovascular disease risk who did not achieve LDL-C treatment targets, switching from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg produced reductions in LDL-C and attainment of LDL-C <100 or <70mg/dL than uptitration of rosuvastatin to 20mg. Moreover, the addition of ezetimibe to atorvastatin 20 mg also produced reductions in total cholesterol, non-high-density lipoprotein cholesterol (HDL-C) and all measured lipid and lipoprotein ratios than either atorvastatin 40 mg or rosuvastatin 20 mg [6]. 

For certain vitamins and minerals there are indications that an intake beyond the recommended daily intake required to prevent deficiencies may be beneficial for the prevention of certain diseases. For instance, it has been established that increased intake of folic acid during pregnancy can reduce the incidence of neural tube defects in the newborn. There is also evidence to suggest that the risk of developing cardiovascular disease may be decreased by increasing vitamin E and folic acid intakes, but this remains to be firmly established. Calcium-enriched products are also believed to have a role to play in bone health. These are just a few of the growing number of links being made between vitamins and minerals and disease risk reduction. 

HDL cholesterol is inversely associated with cardiovascular disease risk. The mechanism by which HDL reduces cardiovascular disease risk may involve reverse cholesterol transport and reductions in cholesterol accumulation in the arterial wall. Intakes of LA within the normal ranges of intakes in most populations do not appear to alter HDL cholesterol concentrations. However, very high intakes—above 12% of energy—can lower HDL cholesterol concentrations. 

In a study with 3427 male and female patients having DBP of 95—109 mm Hg (12—15 Pa), and no clinical evidence of cardiovascular diseases, half of the patients were placebo-treated and half were SC antihypertensive dmg-treated, ie, step 1, chlorothiazide step 2, methyldopa, propranolol [525-66-6], or pindolol [13523-86-9], and step 3, hydralazine, or clonidine [4205-90-7] (86). Overall, when the DBP was reduced below 100 mm Hg (13 Pa), there were more deaths in the dmg-treated group than in the placebo group. The data suggest reduction of blood pressure by antihypertensive dmg treatment that includes a diuretic is accompanied by increased cardiovascular risks. 

Supplements of 400 Ig/d of folate begun before conception result in a significant reduction in the incidence of neural mbe defects as found in spina bifida. Elevated blood homocysteine is an associated risk factor for atherosclerosis, thrombosis, and hypertension. The condition is due to impaired abihty to form methyl-tetrahydrofolate by methylene-tetrahydrofolate reductase, causing functional folate deficiency and resulting in failure to remethylate homocysteine to methionine. People with the causative abnormal variant of methylene-tetrahydrofolate reductase do not develop hyperhomocysteinemia if they have a relatively high intake of folate, but it is not yet known whether this affects the incidence of cardiovascular disease. 

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). 

Elevated homocysteine concentrations have been associated with an increased risk for cardiovascular disease in both epidemiologic and clinical studies.43 Several studies have evaluated the benefit of lowering homocysteine levels with folic acid supplementation. One study reported a reduction in major cardiac events with the combination of folic acid, vitamin B12, and vitamin B6 following PCI.44 However, a more recent study found an increased risk of instent restenosis and the need for target-vessel revascularization with folate supplementation following coronary stent placement.45 The role of folate in the management of IHD is currently unclear. 

In addition to effects on bone, raloxifene may have effects in breast tissue and on the cardiovascular system. A secondary end point of the MORE trial evaluated the effects of raloxifene on the primary prevention of breast cancer and found a significant reduction in all types of breast cancer.33 Raloxifene decreases total and low-density lipoprotein (LDL) cholesterol,34 and studies are evaluating its effect on reducing the risk of cardiovascular disease.35... 

Increased awareness by consumers of the link between an increased intake of omega-3 fatty acids and a reduction in the risk of cardiovascular disease, has led to an increased demand for products with a higher content of these... 

The effects of flavonoids derived from soybean, cocoa, wine, and green tea on the reduction of risk for chronic cardiovascular diseases have been studied the most. 

Because of comorbidity with diabetes, dyslipidemia, hypertension, and stroke, the presence of increased serum uric acid levels or gout should prompt evaluation for cardiovascular disease and the need for appropriate risk reduction measures. Clinicians should also look for possible correctable causes of hyperuricemia (e.g., medications, obesity, and alcohol abuse). 

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. 

Lowering cholesterol levels can arrest or reverse atherosclerosis in all vascular beds and can significantly decrease the morbidity and mortality associated with atherosclerosis. Each 10% reduction in cholesterol levels is associated with an approximately 20% to 30% reduction in the incidence of coronary heart disease. Hyperlipidemia, particularly elevated serum cholesterol and low density lipoprotein (LDL) levels, is a risk factor in the development of atherosclerotic cardiovascular disease. 

Older patients have predominantly Type 2 diabetes mellitus, which shares with Type 1 the risk for retinopathy, nephropathy and neuropathy, but carries a greater risk for macrovascular complications such as coronary artery disease, stroke and peripheral vascular disease. Many such patients have associated obesity, hypertension and hyperlipidemia, compounding the risk of cardiovascular disease. The goals of treatment of DM in the elderly are to decrease symptoms related to hyperglycaemia and to prevent long-term complications. Treatment of type 2 DM can improve prognosis. In the UKPDS trial, sulphonylureas, insulin, and metformin were all associated with a reduction in diabetes-related... 

Life-style measures that are widely agreed to lower blood pressure and that should be considered in all patients in whom they may apply are weight reduction, reduction of excessive alcohol consumption, reduction of high salt intake and increase in physical activity. Particular emphasis should be placed on cessation of smoking and on healthy eating patterns that contribute to the treatment of associated risk factors and cardiovascular diseases. 

Scheiber MD, Liu, JH, Subbiah, MTR, Rebar RW, Setchell KDR. Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause 8, 384-392, 2001. 

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