Risk Factors for Cardiovascular Disease

Risk Factors for Cardiovascular Disease: Main Image

Cardiovascular disease affects the heart and major blood vessels and is the number one cause of death in the United States. Several health disorders have a role in the development of cardiovascular disease. Refer to these sections for further information: angina, atherosclerosis, high cholesterol, high homocysteine, high triglycerides, and hypertension.

Cardiovascular Disease Prevention and Options

Age

Aging increases the risk for cardiovascular disease. Men are considered to be at higher risk after the age of 45 years. Women are usually at low risk for cardiovascular disease until after menopause, and are considered at high risk only after age 55.1

Alcohol

Moderate drinking (one to two drinks per day) increases protective HDL cholesterol.2 This effect is not further affected by the type of alcohol-containing beverage consumed.3, 4 Alcohol also acts as a blood thinner,5 an effect that probably lowers the risk of heart disease. However, alcohol consumption can cause liver disease, cancer, high blood pressure, alcoholism, and, at high intake, an increased risk of heart disease. As a result, many healthcare practitioners never recommend alcohol, even for people with high cholesterol. Nevertheless, those who have one to two drinks per day are clearly less likely to have heart disease.6 Therefore, some people at very high risk of heart disease who are not alcoholics, have healthy livers and normal blood pressure, and are not at an especially high risk for cancer, may benefit from light drinking. In deciding whether light drinking might do more good than harm, people with high cholesterol should consult a healthcare practitioner.

Male Pattern Baldness

Men over 40 who have male pattern baldness on the vertex (the topmost part of the skull) have been found to be at increased risk for coronary heart disease-related events, such as nonfatal heart attack and angina pectoris, especially if they have hypertension or high cholesterol levels.7 Depending on the extent of the baldness, the increase in risk ranged from 23% to 36%.

Cardiovascular Disease (pre-existing)

People who have already had a heart attack,8 or have been diagnosed with arterial disease in the heart,9 arms, legs, abdomen,10 or neck,11 are at very high risk of having a heart attack. These people should reduce their blood cholesterol levels—even if those levels are in the normal range12—and also lower other risks of cardiovascular disease.

Cholesterol (high)

Although it is by no means the only major risk factor, elevated serum cholesterol is clearly associated with a high risk of heart disease in most people. More specifically, a high level of LDL, the “bad” cholesterol, raises heart disease risks significantly,13 while a high level of HDL, the “good” cholesterol, lowers the risk.14 Strategies that lower LDL15 or raise HDL16 reduce the risk of heart disease in most people.

High blood cholesterol does not raise heart disease risk as much in the elderly as it does in younger adults,17 though some increased risk is evident.18 Elderly people who already have heart disease may benefit from cholesterol-lowering treatments,19 but whether elderly people with no heart disease symptoms benefit from lowering their cholesterol levels remains unclear.20,21

Diabetes

People with diabetes are at unusually high risk for cardiovascular disease.22 Having diabetes increases a woman’s heart disease risk more than a man’s.23 Controlling blood sugar and reducing other cardiovascular disease risks are important ways for people with diabetes to reduce their risk of heart disease.

Diet: Cholesterol

Diets high in cholesterol have increased the risk of cardiovascular disease in several reports.24, 25 Most dietary cholesterol comes from egg yolks. Egg consumption can not only increase serum cholesterol,26 but it can also make LDL (“bad”) cholesterol more susceptible to free radical damage,27 a change linked to high risk of heart disease. However, eating eggs (and therefore consuming a diet high in cholesterol) does not increase blood levels of cholesterol as much as eating foods high in saturated fat;28 and eating eggs does not appear to increase serum cholesterol at all in people who eat an otherwise low-fat diet.29 Moreover, a recent study found no relationship between the number of eggs eaten per week and the risk of heart disease.30 More research is needed to resolve these conflicting pieces of evidence. As a result, a consensus does not exist among nutritionally oriented doctors regarding the relative importance of removing eggs from the diet.

Diet: Fish and Fish Oil

Eating fish has been reported to increase HDL (“good”) cholesterol31 and is associated with a reduced risk of heart disease in most,32 but not all, studies.33 Fish contain very little saturated fat, and fish oil contains EPA and DHA, omega-3 oils that may help protect against heart disease.34

Diet: Nuts

Although nuts are a source of omega-6 oils and most healthcare practitioners do not advocate increased intake of omega-6 oils, research consistently shows that people who frequently eat nuts have a dramatically reduced risk of heart disease35, 36 due in part to a lowering of cholesterol levels caused by eating nuts.37, 38 Nuts may also reduce the risk of heart disease by replacing harmful foods in the diet.39, 40 The most protective nuts may be almonds, walnuts, hazelnuts, and pistachios, while macadamia nuts may be the least beneficial.41, 42, 43

Diet: Olive Oil

People from countries that use significant amounts of olive oil are at low risk for heart disease.44 Olive oil lowers LDL (“bad”) cholesterol,45 especially when the olive oil replaces saturated fat in the diet.46 Olive oil also contains antioxidants that protect LDL cholesterol particles from free radical damage.47 Oxidized LDL has been linked with increased heart disease.48 Diets enriched with olive oil increase LDL protection in human studies.49, 50

Diet: Omega-6 Oils

Many vegetable oils, nuts, and seeds contain omega-6 polyunsaturated fatty acids that lower total and LDL (“bad”) cholesterol.51 Most research has suggested that diets high in omega-6 fatty acids can help prevent heart disease.52, 53, 54

Paradoxically, a few studies have actually associated polyunsaturated fat intake with an increased risk of atherosclerosis in humans.55, 56 Israelis, who have a high intake of omega-6 fatty acids, have a very high risk of cardiovascular disease, though this relationship might be caused by other factors.57 Animal research has suggested that omega-6 fats could also contribute to cancer risks.58 Finally, a higher fat intake from any source makes weight loss more difficult to achieve, an important health goal for overweight people trying to reduce their risk of heart disease.59 For these reasons, most nutritionally oriented doctors and many cardiologists no longer recommend increasing dietary omega-6 polyunsaturated fat for the prevention of heart disease.

Diet: Saturated Fat

Diets high in animal foods containing saturated fat are associated with high serum cholesterol,60 plaque, excessive blood clotting in the arteries of the heart,61 and heart disease.62 Significant amounts of animal-based saturated fat are found in beef, pork, veal, poultry (particularly in poultry skins and dark meat), cheese, butter, ice cream, and all other forms of dairy products not labeled “fat free.” Avoiding consumption of these foods reduces cholesterol and has even been reported to reverse existing heart disease in conjunction with other lifestyle changes.63 In addition to large amounts of saturated fat from animal-based foods, Americans eat small amounts of saturated fat from coconut and palm oils. Palm oil has been reported to elevate cholesterol.64, 65 Research results regarding coconut oil are mixed, with some studies finding no link to heart disease66 and other trials finding that coconut oil elevates serum cholesterol.67, 68

Diet: Trans Fatty Acids

Trans fatty acids (TFAs) are found in many processed foods containing hydrogenated oils and in restaurant foods fried in these oils. Margarine often contains particularly high levels of TFAs, and margarine consumption is associated with increased risk of heart disease.69 Eating TFAs increases the ratio of LDL to HDL cholesterol.70 While the relative importance of TFAs as a cause of heart disease is still debated,71 most authorities now agree that reducing trans fatty acids along with saturated fats will likely help prevent heart disease.72, 73 Butter contains high amounts of saturated fat and is therefore not a healthful replacement for margarine; many healthcare practitioners now recommend using olive oil instead.

Diet: Vegetarian

Vegetarians have lower blood levels of cholesterol74 and lower risk of heart disease75 than do meat eaters, in part because they avoid animal fat. Vegans (people who eat no meat, dairy, or eggs) have the lowest cholesterol levels,76 and switching to a vegan diet has reversed heart disease when combined with other lifestyle changes.77

Family history of premature coronary artery disease

A person who has an immediate family member who either suffered a heart attack or was diagnosed with premature heart disease is at increased risk for heart disease.78 79 80 Coronary heart disease is considered premature when it occurs in men before the age of 55 or in women before the age of 65.81 People with a family history of premature heart disease should strive to minimize all of their other cardiovascular disease risk factors.

Fiber

Soluble fiber from beans,82 oats,83 psyllium seed,84 and fruit pectin85 has lowered cholesterol levels in most trials.86 Healthcare practitioners often recommend that people with elevated cholesterol eat more of these high soluble fiber foods. However, even grain fiber (which contains insoluble fiber and does not lower cholesterol) has been linked to protection against heart disease, though the reason for that protection remains unclear.87

Gender

Though cardiovascular disease is the leading cause of death in both male and female Americans, adult men of any age have a higher risk of heart disease than do younger (premenopausal) women. Following menopause, women gradually develop heart disease risks closer to that of men.88, 89

Homocysteine (high)

Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,90, 91 though uncertainty remains about whether elevated homocysteine actually causes heart disease.92, 93 Homocysteine can be measured by a laboratory test, and elevated levels can be treated with vitamins.

Hypertension

Hypertension is the medical term for high blood pressure. Hypertension is a major risk factor for cardiovascular disease, and the risk increases as blood pressure rises.94 Even after blood pressure has normalized as a result of drug treatment, people with a history of high blood pressure are still at higher risk for cardiovascular disease compared to people who never had high blood pressure.95 Many dietary and lifestyle changes can lower blood pressure and should be adopted by people with high blood pressure.

Iron (excess)

In 1992, a Finnish study found a strong link between unnecessary exposure to iron and increased risk for heart disease.96 Since then many studies have not found that link,97, 98, 99 though several have confirmed the outcome of the original report.100, 101 One 1999 analysis of 12 studies looking at iron status and heart disease found no overall relationship,102 but another 1999 analysis of published reports came to a different conclusion.103 While the effect of unnecessary exposure to iron, including iron supplements, on the risk of heart disease remains unclear, there is no benefit in supplementing iron in the absence of a deficiency. Nutritionally oriented doctors recommend that people who are not iron deficient avoid iron supplements, at least until more is known.

Meal Frequency

Studies have found that people who eat small, frequent meals during the day (sometimes called “grazing”) have lower cholesterol levels compared with those who eat two or three large meals per day.104, 105, 106 One study also found evidence of reduced atherosclerosis (hardening of the arteries) in people eating small, frequent meals.107 Redistributing the contents of two or three large meals per day into four or five smaller meals may be beneficial for reducing cardiovascular disease risk.

Obesity

Excess body fat increases heart disease risk,108 in part because obesity can lead to diabetes, hypertension, low HDL (“good”) cholesterol, and high LDL (“bad”) cholesterol—all risk factors for heart disease. Abdominal weight gain is especially likely to increase heart disease risk.109, 110 Losing excess body weight reduces many risk factors for heart disease. Unfortunately, unsuccessful long-term weight control resulting in large fluctuations in body weight (often called “yo-yo dieting”) may also increase risk of heart disease, according to some,111 but not all, reports.112, 113

Quercetin

Quercetin, a flavonoid, protects LDL (“bad”) cholesterol from damage.114 Some,115, 116, 117 but not all,118, 119 studies have reported an association between consumption of foods high in quercetin and a low risk of heart disease. Quercetin is found in apples, onions, black tea, and as a supplement. In some studies, the dietary level of quercetin associated with protection from heart disease has been as low as 35 mg per day.

Sedentary Lifestyle

A sedentary lifestyle has been reported to double the risk of cardiovascular disease.120 Conversely, moderate exercise, including brisk walking for 30 minutes per day, has a well-known protective effect against cardiovascular disease.121, 122 The benefits of exercise are at least partially attributable to reductions in body weight, blood pressure, triglycerides, cholesterol, and glucose intolerance.

Selenium

In some studies, people who consume more selenium from their diet have a lower risk of heart disease.123, 124 In one double-blind report, individuals who already had one heart attack were given 100 mcg of selenium per day or placebo for six months.125 At the end of that trial, four deaths from heart disease occurred in the placebo group, compared with none in the selenium group (although the numbers were too small for this difference to be statistically significant). Some nutritionally oriented doctors recommend that people with atherosclerosis supplement with 100–200 mcg of selenium per day.

Smoking

Both smoking126 and exposure to second-hand smoke127 significantly increase cardiovascular disease risk. If you are a smoker, you should quit—a critical step in reducing the risk of cardiovascular disease and many other health conditions. Both smokers and nonsmokers should avoid exposure to second-hand smoke.

Triglycerides (high)

A person with high blood triglycerides most often also has either a high total cholesterol level and/or a low HDL (“good”) cholesterol level. Perhaps as a result, researchers have had a hard time hunting for the effect of high triglycerides on heart disease independent of the effect of high total cholesterol or low HDL cholesterol.128, 129, 130 Nonetheless, a recent analysis of previous studies has shown that high triglycerides are associated with an increased risk for heart disease independent of other factors.131 The outcome of some research suggests that triglyceride levels in the high range of normal parameters should also be lowered to reduce the risk of heart disease.132

Vitamin C

Experimentally increasing homocysteine levels in humans has led to temporary dysfunction of the cells lining blood vessels. Researchers are concerned that this dysfunction may be linked to atherosclerosis and heart disease. Vitamin C has been reported to reverse the dysfunction caused by increases in homocysteine.133 Vitamin C also protects LDL (“bad”) cholesterol from oxidative damage.134

Despite these protective mechanisms attributed to vitamin C, researchers have been unable to consistently associate high vitamin C intake to a reduced risk of heart disease. Trials failing to find vitamin C protective have mostly been conducted in groups of people that all consume at least 90 mg of vitamin C per day—a level beyond which further protection of LDL cholesterol may not occur. Studies comparing people whose diets contain lower amounts of vitamin C to people whose amounts are significantly higher than 90 mg per day, however, have found an association between increasing dietary vitamin C and protection from heart disease. Therefore, leading vitamin C researchers have begun to suggest that vitamin C may be important in preventing heart disease, but only up to modest levels: perhaps 100–200 mg per day.135

Vitamin E

Vitamin E is an antioxidant that protects LDL (“bad”) cholesterol from oxidative damage136 and has been linked to prevention of nonfatal heart disease in double-blind research.137 Many doctors recommend 400–800 IU of vitamin E per day to lower the risk of atherosclerosis and heart attacks. However, a large double-blind trial recently found no benefit from vitamin E supplementation in the prevention of non-fatal heart attacks among people at high risk.138 Participants, who had a history of diabetes or existing cardiovascular disease, took 400 IU of natural vitamin E for 4.5 years. It is not known why these results so strongly contradict previous findings of a protective effect from vitamin E.139, 140, 141 Further studies are needed to resolve the conflicting findings of these large trials.

References

1. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

2. Dai WS, Laporte RE, Hom DL, et al. Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics. Am J Epidemiol 1985;122:620–7.

3. Marques-Vidal P, Ducimetiere P, Evans A, et al. Alcohol consumption and myocardial infarction: a case-control study in France and northern Ireland. Am J Epidemiol 1996;143:1089–93.

4. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? BMJ 1996;312:731–6 [review].

5. Hendriks HF, Veenstra J, Wierik EJMV, et al. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors. BMJ 1994;304:1003–6.

6. Hein HO, Suadicani P, Gyntelberg F. Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study. BMJ 1996;736–41.

7. Lotufo PA, Chae CU, Ajani UA, et al. Male pattern baldness and coronary heart disease: the Physicians' Health Study. Arch Intern Med 2000;160:165–71.

8. Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol after myocardial infarction. N Engl J Med 1990;323:1112–9.

9. Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med 1990;322:1700–7.

10. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381–6.

11. Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 1991;11:1245–9.

12. Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med 1990;322:1700–7.

13. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham Study. JAMA 1987;257:2176–80.

14. Gordon DJ, Probstfeld JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989;79:8–15.

15. Law MR, Wald NJ, Thompson SM. By how much and how quickly does reduction serum cholesterol concentration lower risk of ischemic heart disease? BMJ 1994;308:367–73.

16. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease: the Lifestyle Heart Trial. Lancet 1990;336:129–33.

17. Kaiser FE. Cholesterol and the older adult. South Med J 1993;86(10):2S11–4 [review].

18. Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population. Arch Intern Med 1999;159:1670–8 [review].

19. Smith SC Jr. Review of recent clinical trials of lipid lowering in coronary artery disease. Am J Cardiol 1997;80(8B):10H–3H [review].

20. Chen YT, Krumholz HM. Impact of cholesterol on cardiovascular morbidity and mortality in older adults. Nutrition 1999;15:242–4 [review].

21. Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population. Arch Intern Med 1999;159:1670–8 [review].

22. Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987;3:463–524 [review].

23. Barrett-Connor E, Wingard DL. Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study. Am J Epidemiol 1983;118:489–96.

24. Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet 1989;1:1177–9.

25. Grundy SM, Barrett-Connor E, Rudel LL, Miettinen T, Spector AA. Workshop on the impact of dietary cholesterol on plasma lipoproteins and atherogenesis. Arteriosclerosis 1988;8:95–101.

26. Connor SL, Connor WE. The importance of dietary cholesterol in coronary heart disease. Prev Med 1983;12:115–23 [review].

27. Levy Y, Maor I, Presser D, Aviram M. Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Ann Nutr Metabol 1996;40:243–51.

28. Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990;31:1149–72 [review].

29. Edington JD, Geekie M, Carter R, et al. Serum lipid response to dietary cholesterol in subjects fed a low-fat, high-fiber diet. Am J Clin Nutr 1989;50:58–62.

30. Hu FB, Stampfer MJ, Rimm EB, et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. JAMA 1999;281:1387–94.

31. Santos MJ, Lopez-Jurado M, Llopis J, et al. Influence of dietary supplementation with fish on plasma total cholesterol and lipoprotein cholesterol fractions in patients with coronary heart disease. J Nutr Med 1992;3:107–15.

32. Kromhout D, Bosschieter EB, Coulander CdL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205–9.

33. Ascherio A, Rimm EG, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977–82.

34. Albert CM, Manson JE, O’Donnell C, et al. Fish consumption and the risk of sudden death in the Physicians’ Health Study. Circulation 1996;94 (suppl 1):I–578 [abstract #3382].

35. Hu FB, Stampfer MJ, Manson JE, et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ 1998;317:1341–5.

36. Fraser GE, Sabaté J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease. Arch Intern Med 1992;152:1416–24.

37. Abbey M, Noakes M, Belling GB, Nestel PJ. Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol. Am J Clin Nutr 1994;59:995–9.

38. Sabaté J, Frasser GE, Burke K, Knutsen S, et al. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 1993;328:603–7.

39. Mirkin G. Walnuts and serum lipids. N Engl J Med 1993;329:358 [letter].

40. Mann GV. Walnuts and serum lipids. N Engl J Med 1993;329:358 [letter].

41. Fraser GE. Nut consumption, lipids, and risk of a coronary event. Clin Cardiol 1999;22(Suppl III):III-11–5 [review].

42. Durak I, Köksal I, Kaçmaz M, et al. Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels. Clin Chim Acta 1999;284:113–5 [letter].

43. Edwards K, Kwaw I, Matud J, Kurtz I. Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia. J Am Coll Nutr 1999;18:229–32.

44. Keys A, ed. Coronary heart disease in seven countries. Circulation 1970;41(suppl q):I1–211.

45. Baggio G, Pagnan A, Muraca M, et al. Olive-oil-enriched diet: effect on serum lipoprotein levels and biliary cholesterol saturation. Am J Clin Nutr 1988;47:960–4.

46. Grundy SM. Monounsaturated fatty acids and cholesterol metabolism: implications for dietary recommendations. J Nutr 1989;119:529–33 [review].

47. Visioli F, Bellomo G, Montedoro G, Galli C. Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents. Atherosclerosis 1995;117:25–32.

48. Holvoet P, Collen D. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 1998;137:S33–8 [review].

49. Aviram M, Eias K. Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. Ann Nutr Metab 1993;37:75–84.

50. Baroni SS, Amelio M, Sangiorgi Z, et al. Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (type IIb) patients. Free Radic Res 1999;30:275–85.

51. Howell WH, McNamara DJ, Tosca MA, et al. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am J Clin Nutr 1997;65:1747–64.

52. Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and the risk of coronary heart disease in women. N Engl Med J 1997;337:1491–9.

53. Heyden S. Polyunsaturated and monounsaturated fatty acids in the diet to prevent coronary heart disease via cholesterol reduction. Ann Nutr Metab 1994;38(3):117–22 [review].

54. Sacks F. Dietary fats and coronary heart disease. J Cardiovasc Risk 1994;1:3–8 [review].

55. Felton CV, Crook D, Davies MJ, et al. Dietary polyunsaturated fatty acids and composition of human aortic plaques. Lancet 1994;344:1195–6.

56. Hodgson JM, Wahlqvist ML, Boxall JA, et al. Can linoleic acid contribute to coronary artery disease? Am J Clin Nutr 1993;58:228–34.

57. Yam D, Eliraz A, Berry EM. Diet and disease—the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Isr J Med Sci 1996;32:1134–43 [review].

58. Rose DP. Dietary fatty acids and prevention of hormone-responsive cancer. Proc Soc Exp Biol Med 1997;216:224–33.

59. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, et al. Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. JAMA 1995;274:1450–5.

60. Kromhout D, Menotti A, Bloemberg B, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med 1995;24:308–15.

61. Renaud S, de Lorgeril M. Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention. J Intern Med 1989;225:39–46 [review].

62. Tell GS, Evans GW, Folsom AR, et al. Dietary fat intake and carotid artery wall thickness: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 1994;139:979–89.

63. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129–33.

64. Denke MA, Grundy SM. Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. Am J Clin Nutr 1992;56:895–8.

65. Zock PL, de Vries JHM, Katan MB. Impact of myristic acid versus palmitic acid on serum lipid and lipoprotein levels in healthy women and men. Arterioscler Thromb 1994;14:567–75.

66. Kumar PD. The role of coconut and coconut oil in coronary heart disease in Kerala, south India. Trop Doct 1997;27:215–7.

67. Denke MA, Grundy SM. Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. Am J Clin Nutr 1992;56:895–8.

68. Mendis S, Kumarasunderam R. The effect of daily consumption of coconut fat and soya-bean fat on plasma lipids and lipoproteins of young normolipidaemic men. Br J Nutr 1990;63:547–52.

69. Willett WC, Stampfer MJ, Manson JE, et al. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993;341:581–5.

70. Khosla P, Hayes KC. Dietary trans-monounsaturated fatty acids negatively impact plasma lipids in humans: critical review of the evidence. J Am Coll Nutr 1996;15:235–9.

71. Anonymous. Position paper on trans fatty acids. ASCN/AIN Task Force on Trans Fatty Acids. American Society for Clinical Nutrition and American Institute of Nutrition. Am J Clin Nutr 1996;63:663–70.

72. Nelson GJ. Dietary fat, trans fatty acids, and risk of coronary heart disease. Nutr Rev 1998;56(8)250–2.

73. Ascherio A, Willett WC. Health effects of trans fatty acids. Am J Clin Nutr 1997;66(suppl):1006S–10S [review].

74. Thorogood M, Carter R, Benfield L, et al. Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain. Br Med J (Clin Res Ed) 1987;295:351–3.

75. Burr ML, Sweetnam PM. Vegetarianism, dietary fiber and mortality. Am J Clin Nutr 1982;36:873–7.

76. Resnicow K, Barone J, Engle A, et al. Diet and serum lipids in vegan vegetarians: a model for risk reduction. J Am Dietet Assoc 1991;91:447–53.

77. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129–33.

78. Conroy RM, Mulcahy R, Hickey N, Daly L. Is a family history of coronary heart disease an independent coronary risk factor? Br Heart J 1985;53:378–81.

79. Hopkins PN, Williams RR, Kuida H, et al. Family history as an independent risk factor for incident coronary artery disease in a high-risk cohort in Utah. Am J Cardiol 1988;62:703–7.

80. Jorde LB, Williams RR. Relation between family history of coronary artery disease and coronary risk variables. Am J Cardiol 1988;62:708–13.

81. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

82. Anderson JW, Chen WJL. Legumes and their soluble fiber: effect on cholesterol-rich lipoproteins. In Unconventional Sources of Dietary Fiber, I Furda (ed.), Washington, DC: American Chemical Society, 1983.

83. Ripsin CM, Keenan JM, Jacobs DR, et al. Oat products and lipid lowering—a meta-analysis. JAMA 1992;267:3317–25.

84. Williams CL, Bollella M, Spark A, Puder D. Soluble fiber enhances the hypocholesterolemic effect of the Step I diet in childhood. J Am Coll Nutr 1995;14:251–7.

85. Miettinen TA, Tarpila S. Effect of pectin on serum cholesterol, fecal bile acids and biliary lipids in normolipidemic and hyperlipidemic individuals. Clin Chim Acta 1977;79:471–7.

86. Glore SR, Van Treeck D, Knehans AW, Guild M. Soluble fiber and serum lipids: a literature review. J Am Dietet Assoc 1994;94:425–36.

87. Rimm EB, Ascherio A, Giovannucci E, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996;275:447–51.

88. Thom TJ. Cardiovascular disease mortality among United States women. In Coronary heart disease in women, Eaker ED, Packard B, Wenger NK, et al. (eds.). New York: Haymarket Doyma, 1987, 33–41.

89. Rosenberg L, Miller DR, Kaufman DW, et al. Myocardial infarction in women under 50 years of age. JAMA 1983;250:2801–6.

90. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in U.S. physicians. JAMA 1992;268:877–81.

91. Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077–80.

92. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204–10.

93. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196–9 [editorial/review].

94. Kannel WB. Office assessment of coronary candidates and risk factor insights from the Framingham study. J Hypertens Suppl 1991;9:S13–9.

95. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

96. Salonen JT, Nyssönen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992;86:803–11.

97. Van Asperen IA, Feskens EJM, Bowles CH, Kromhout D. Body iron stores and mortality due to cancer and ischaemic heart disease: a 17-year follow-up study of elderly men and women. Int J Epidemiol 1995;24:665–70.

98. Iribarren C, Sempos CT, Eckfeldt JH, Folsom AR. Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis 1998;139:189–95.

99. Corti M-C, Guralnik JM, Salive ME, et al. Serum iron level, coronary artery disease, and all-cause mortality in older men and women. Am J Cardiol 1997;79:120–7.

100. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary heart disease risk: a study from Greece. Am J Epidemiol 1998;147:161–6.

101. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis. Circulation 1997;96:3300–7.

102. Danesh J, Appleby P. Coronary heart disease and iron status. Meta-analyses of prospective studies. Circulation 1999;99:852–4.

103. De Valk B, Marx MMJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 1999;159:1542–8 [review].

104. Jenkins DJA, Khan A, Jenkins AL, et al. Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids. Metabolism 1995;44:549–55.

105. Edelstein SL, Barrett-Connor EL, Wingard DL, Cohn BA. Increased meal frequency associated with decreased cholesterol concentrations; Rancho Bernardo, CA, 1984–1987. Am J Clin Nutr 1992;55:664–9.

106. Redondo MR, Ortega RM, Zamora MJ, et al. Influence of the number of meals taken per day on cardiovascular risk factors and the energy and nutrient intakes of a group of elderly people. Int J Vitam Nutr Res 1997;67:176–82.

107. Powell JT, Franks PJ, Poulter NR. Does nibbling or grazing protect the peripheral arteries from atherosclerosis? J Cardiovasc Risk 1999;6:19–22.

108. Hubert HB, Feinleib M, McNamara PM, et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968–77.

109. Larsson B. Regional obesity as a health hazard in men: prospective studies. Acta Med Scand 1988;723:45–51 [review].

110. Larsson B, Bengtsson C, Bjorntorp P, et al. Is abdominal body fat distribution a major explanation for the sex difference in the incidence of myocardial infarction? The study of men born in 1913 and the study of women. Am J Epidemiol 1992;135:266–73.

111. Lissner L, Odell PM, D’Agostino RB, et al. Variability of body weight and health outcomes in the Framingham population. N Engl J Med 1991;324:1839–44.

112. Jeffery RW. Does weight cycling present a health risk? Am J Clin Nutr 1996;63:452S–5S [review].

113. Muls E, Kempen K, Vansant G, et al. Is weight cycling detrimental to health? A review of the literature in humans. Int J Obes Relat Metab Disord 1995;19 Suppl 3:S46–50 [review].

114. Ronzio RA. Antioxidants, nutraceuticals and functional foods. Townsend Letter for Doctors and Patients 1996;Oct:34–5 [review].

115. Hertog MGL, Feskens EJM, Hollman PCH, et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1007–11.

116. Hertog MGL, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med 1995;155:381–6.

117. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 1996;312:478–81.

118. Rimm EB, Katan MB, Ascherio A, et al. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 1996;125:384–9.

119. Hertog MGL, Sweetnam PM, Fehily AM, et al. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr 1997;65:1489–94.

120. Miller TD, Balady GJ, Fletcher GF. Exercise and its role in the prevention and rehabilitation of cardiovascular disease. Ann Behav Med 1997;19:220–9 [review].

121. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990;132:612–28.

122. Fletcher GF, Blair SN, Blumenthal J, et al. Benefits and recommendations for physical activity programs for all Americans: a statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation 1992;86:340–4.

123. Salonen JT et al. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982;ii:175.

124. Shamberger RJ, Willis CE. Epidemiological studies on selenium and heart disease. Fed Proc 1976;35:578 [abstract #2061].

125. Korpela H, Kumpulainen J, Jussila E, et al. Effect of selenium supplementation after acute myocardial infarction. Res Comm Chem Pathol Pharmacol 1989; 65:249–52.

126. Freund KM, Belanger AJ, D’Agostino RB, Kannel WB. The health risks of smoking. The Framingham Study: 34 years of follow-up. Ann Epidemiol 1993;3:417–24.

127. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. BMJ 1997;315:973–80.

128. Avins AL, Haber RJ, Hulley SB. The status of hypertriglyceridemia as a risk factor for coronary heart disease. Clin Lab Med 1989;9:153–68.

129. Hulley SB, Avins, AL. Asymptomatic hypertriglyceridemia: insufficient evidence to treat. BMJ 1992;304:394–6.

130. Grundy SM, Vega GL. Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Arch Intern Med 1992;152:28–34.

131. Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213–9.

132. Miller M, Seidler A, Moalemi A, et al. Normal triglyceride levels and coronary artery disease events: the Baltimore Coronary Observational Long-Term Study. J Am Coll Cardiol 1998;31:1252–7.

133. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156–60.

134. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113S–8S.

135. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

136. Belcher JD, Balla J, Balla G, et al. Vitamin E, LDL, and endothelium: Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb 1993;13:1779–89.

137. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–6.

138. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-60.

139. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.

140. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet 1996;347:781-6.

141. [No authors listed]. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza

References

1. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

2. Dai WS, Laporte RE, Hom DL, et al. Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics. Am J Epidemiol 1985;122:620–7.

3. Marques-Vidal P, Ducimetiere P, Evans A, et al. Alcohol consumption and myocardial infarction: a case-control study in France and northern Ireland. Am J Epidemiol 1996;143:1089–93.

4. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? BMJ 1996;312:731–6 [review].

5. Hendriks HF, Veenstra J, Wierik EJMV, et al. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors. BMJ 1994;304:1003–6.

6. Hein HO, Suadicani P, Gyntelberg F. Alcohol consumption, serum low density lipoprotein cholesterol concentration, and risk of ischaemic heart disease: six year follow up in the Copenhagen male study. BMJ 1996;736–41.

7. Lotufo PA, Chae CU, Ajani UA, et al. Male pattern baldness and coronary heart disease: the Physicians' Health Study. Arch Intern Med 2000;160:165–71.

8. Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol after myocardial infarction. N Engl J Med 1990;323:1112–9.

9. Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med 1990;322:1700–7.

10. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381–6.

11. Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 1991;11:1245–9.

12. Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med 1990;322:1700–7.

13. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framingham Study. JAMA 1987;257:2176–80.

14. Gordon DJ, Probstfeld JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989;79:8–15.

15. Law MR, Wald NJ, Thompson SM. By how much and how quickly does reduction serum cholesterol concentration lower risk of ischemic heart disease? BMJ 1994;308:367–73.

16. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease: the Lifestyle Heart Trial. Lancet 1990;336:129–33.

17. Kaiser FE. Cholesterol and the older adult. South Med J 1993;86(10):2S11–4 [review].

18. Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population. Arch Intern Med 1999;159:1670–8 [review].

19. Smith SC Jr. Review of recent clinical trials of lipid lowering in coronary artery disease. Am J Cardiol 1997;80(8B):10H–3H [review].

20. Chen YT, Krumholz HM. Impact of cholesterol on cardiovascular morbidity and mortality in older adults. Nutrition 1999;15:242–4 [review].

21. Grundy SM, Cleeman JI, Rifkind BM, et al. Cholesterol lowering in the elderly population. Arch Intern Med 1999;159:1670–8 [review].

22. Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987;3:463–524 [review].

23. Barrett-Connor E, Wingard DL. Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study. Am J Epidemiol 1983;118:489–96.

24. Shekelle RB, Stamler J. Dietary cholesterol and ischaemic heart disease. Lancet 1989;1:1177–9.

25. Grundy SM, Barrett-Connor E, Rudel LL, Miettinen T, Spector AA. Workshop on the impact of dietary cholesterol on plasma lipoproteins and atherogenesis. Arteriosclerosis 1988;8:95–101.

26. Connor SL, Connor WE. The importance of dietary cholesterol in coronary heart disease. Prev Med 1983;12:115–23 [review].

27. Levy Y, Maor I, Presser D, Aviram M. Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Ann Nutr Metabol 1996;40:243–51.

28. Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990;31:1149–72 [review].

29. Edington JD, Geekie M, Carter R, et al. Serum lipid response to dietary cholesterol in subjects fed a low-fat, high-fiber diet. Am J Clin Nutr 1989;50:58–62.

30. Hu FB, Stampfer MJ, Rimm EB, et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. JAMA 1999;281:1387–94.

31. Santos MJ, Lopez-Jurado M, Llopis J, et al. Influence of dietary supplementation with fish on plasma total cholesterol and lipoprotein cholesterol fractions in patients with coronary heart disease. J Nutr Med 1992;3:107–15.

32. Kromhout D, Bosschieter EB, Coulander CdL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205–9.

33. Ascherio A, Rimm EG, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977–82.

34. Albert CM, Manson JE, O’Donnell C, et al. Fish consumption and the risk of sudden death in the Physicians’ Health Study. Circulation 1996;94 (suppl 1):I–578 [abstract #3382].

35. Hu FB, Stampfer MJ, Manson JE, et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ 1998;317:1341–5.

36. Fraser GE, Sabaté J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease. Arch Intern Med 1992;152:1416–24.

37. Abbey M, Noakes M, Belling GB, Nestel PJ. Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol. Am J Clin Nutr 1994;59:995–9.

38. Sabaté J, Frasser GE, Burke K, Knutsen S, et al. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 1993;328:603–7.

39. Mirkin G. Walnuts and serum lipids. N Engl J Med 1993;329:358 [letter].

40. Mann GV. Walnuts and serum lipids. N Engl J Med 1993;329:358 [letter].

41. Fraser GE. Nut consumption, lipids, and risk of a coronary event. Clin Cardiol 1999;22(Suppl III):III-11–5 [review].

42. Durak I, Köksal I, Kaçmaz M, et al. Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels. Clin Chim Acta 1999;284:113–5 [letter].

43. Edwards K, Kwaw I, Matud J, Kurtz I. Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia. J Am Coll Nutr 1999;18:229–32.

44. Keys A, ed. Coronary heart disease in seven countries. Circulation 1970;41(suppl q):I1–211.

45. Baggio G, Pagnan A, Muraca M, et al. Olive-oil-enriched diet: effect on serum lipoprotein levels and biliary cholesterol saturation. Am J Clin Nutr 1988;47:960–4.

46. Grundy SM. Monounsaturated fatty acids and cholesterol metabolism: implications for dietary recommendations. J Nutr 1989;119:529–33 [review].

47. Visioli F, Bellomo G, Montedoro G, Galli C. Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents. Atherosclerosis 1995;117:25–32.

48. Holvoet P, Collen D. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 1998;137:S33–8 [review].

49. Aviram M, Eias K. Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. Ann Nutr Metab 1993;37:75–84.

50. Baroni SS, Amelio M, Sangiorgi Z, et al. Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (type IIb) patients. Free Radic Res 1999;30:275–85.

51. Howell WH, McNamara DJ, Tosca MA, et al. Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis. Am J Clin Nutr 1997;65:1747–64.

52. Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and the risk of coronary heart disease in women. N Engl Med J 1997;337:1491–9.

53. Heyden S. Polyunsaturated and monounsaturated fatty acids in the diet to prevent coronary heart disease via cholesterol reduction. Ann Nutr Metab 1994;38(3):117–22 [review].

54. Sacks F. Dietary fats and coronary heart disease. J Cardiovasc Risk 1994;1:3–8 [review].

55. Felton CV, Crook D, Davies MJ, et al. Dietary polyunsaturated fatty acids and composition of human aortic plaques. Lancet 1994;344:1195–6.

56. Hodgson JM, Wahlqvist ML, Boxall JA, et al. Can linoleic acid contribute to coronary artery disease? Am J Clin Nutr 1993;58:228–34.

57. Yam D, Eliraz A, Berry EM. Diet and disease—the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Isr J Med Sci 1996;32:1134–43 [review].

58. Rose DP. Dietary fatty acids and prevention of hormone-responsive cancer. Proc Soc Exp Biol Med 1997;216:224–33.

59. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, et al. Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. JAMA 1995;274:1450–5.

60. Kromhout D, Menotti A, Bloemberg B, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med 1995;24:308–15.

61. Renaud S, de Lorgeril M. Dietary lipids and their relation to ischaemic heart disease: from epidemiology to prevention. J Intern Med 1989;225:39–46 [review].

62. Tell GS, Evans GW, Folsom AR, et al. Dietary fat intake and carotid artery wall thickness: the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 1994;139:979–89.

63. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129–33.

64. Denke MA, Grundy SM. Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. Am J Clin Nutr 1992;56:895–8.

65. Zock PL, de Vries JHM, Katan MB. Impact of myristic acid versus palmitic acid on serum lipid and lipoprotein levels in healthy women and men. Arterioscler Thromb 1994;14:567–75.

66. Kumar PD. The role of coconut and coconut oil in coronary heart disease in Kerala, south India. Trop Doct 1997;27:215–7.

67. Denke MA, Grundy SM. Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. Am J Clin Nutr 1992;56:895–8.

68. Mendis S, Kumarasunderam R. The effect of daily consumption of coconut fat and soya-bean fat on plasma lipids and lipoproteins of young normolipidaemic men. Br J Nutr 1990;63:547–52.

69. Willett WC, Stampfer MJ, Manson JE, et al. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet 1993;341:581–5.

70. Khosla P, Hayes KC. Dietary trans-monounsaturated fatty acids negatively impact plasma lipids in humans: critical review of the evidence. J Am Coll Nutr 1996;15:235–9.

71. Anonymous. Position paper on trans fatty acids. ASCN/AIN Task Force on Trans Fatty Acids. American Society for Clinical Nutrition and American Institute of Nutrition. Am J Clin Nutr 1996;63:663–70.

72. Nelson GJ. Dietary fat, trans fatty acids, and risk of coronary heart disease. Nutr Rev 1998;56(8)250–2.

73. Ascherio A, Willett WC. Health effects of trans fatty acids. Am J Clin Nutr 1997;66(suppl):1006S–10S [review].

74. Thorogood M, Carter R, Benfield L, et al. Plasma lipids and lipoprotein cholesterol concentrations in people with different diets in Britain. Br Med J (Clin Res Ed) 1987;295:351–3.

75. Burr ML, Sweetnam PM. Vegetarianism, dietary fiber and mortality. Am J Clin Nutr 1982;36:873–7.

76. Resnicow K, Barone J, Engle A, et al. Diet and serum lipids in vegan vegetarians: a model for risk reduction. J Am Dietet Assoc 1991;91:447–53.

77. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129–33.

78. Conroy RM, Mulcahy R, Hickey N, Daly L. Is a family history of coronary heart disease an independent coronary risk factor? Br Heart J 1985;53:378–81.

79. Hopkins PN, Williams RR, Kuida H, et al. Family history as an independent risk factor for incident coronary artery disease in a high-risk cohort in Utah. Am J Cardiol 1988;62:703–7.

80. Jorde LB, Williams RR. Relation between family history of coronary artery disease and coronary risk variables. Am J Cardiol 1988;62:708–13.

81. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

82. Anderson JW, Chen WJL. Legumes and their soluble fiber: effect on cholesterol-rich lipoproteins. In Unconventional Sources of Dietary Fiber, I Furda (ed.), Washington, DC: American Chemical Society, 1983.

83. Ripsin CM, Keenan JM, Jacobs DR, et al. Oat products and lipid lowering—a meta-analysis. JAMA 1992;267:3317–25.

84. Williams CL, Bollella M, Spark A, Puder D. Soluble fiber enhances the hypocholesterolemic effect of the Step I diet in childhood. J Am Coll Nutr 1995;14:251–7.

85. Miettinen TA, Tarpila S. Effect of pectin on serum cholesterol, fecal bile acids and biliary lipids in normolipidemic and hyperlipidemic individuals. Clin Chim Acta 1977;79:471–7.

86. Glore SR, Van Treeck D, Knehans AW, Guild M. Soluble fiber and serum lipids: a literature review. J Am Dietet Assoc 1994;94:425–36.

87. Rimm EB, Ascherio A, Giovannucci E, et al. Vegetable, fruit, and cereal fiber intake and risk of coronary heart disease among men. JAMA 1996;275:447–51.

88. Thom TJ. Cardiovascular disease mortality among United States women. In Coronary heart disease in women, Eaker ED, Packard B, Wenger NK, et al. (eds.). New York: Haymarket Doyma, 1987, 33–41.

89. Rosenberg L, Miller DR, Kaufman DW, et al. Myocardial infarction in women under 50 years of age. JAMA 1983;250:2801–6.

90. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in U.S. physicians. JAMA 1992;268:877–81.

91. Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077–80.

92. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204–10.

93. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196–9 [editorial/review].

94. Kannel WB. Office assessment of coronary candidates and risk factor insights from the Framingham study. J Hypertens Suppl 1991;9:S13–9.

95. National Cholesterol Education Program. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994;89:1333–445.

96. Salonen JT, Nyssönen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992;86:803–11.

97. Van Asperen IA, Feskens EJM, Bowles CH, Kromhout D. Body iron stores and mortality due to cancer and ischaemic heart disease: a 17-year follow-up study of elderly men and women. Int J Epidemiol 1995;24:665–70.

98. Iribarren C, Sempos CT, Eckfeldt JH, Folsom AR. Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis 1998;139:189–95.

99. Corti M-C, Guralnik JM, Salive ME, et al. Serum iron level, coronary artery disease, and all-cause mortality in older men and women. Am J Cardiol 1997;79:120–7.

100. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary heart disease risk: a study from Greece. Am J Epidemiol 1998;147:161–6.

101. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis. Circulation 1997;96:3300–7.

102. Danesh J, Appleby P. Coronary heart disease and iron status. Meta-analyses of prospective studies. Circulation 1999;99:852–4.

103. De Valk B, Marx MMJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 1999;159:1542–8 [review].

104. Jenkins DJA, Khan A, Jenkins AL, et al. Effect of nibbling versus gorging on cardiovascular risk factors: serum uric acid and blood lipids. Metabolism 1995;44:549–55.

105. Edelstein SL, Barrett-Connor EL, Wingard DL, Cohn BA. Increased meal frequency associated with decreased cholesterol concentrations; Rancho Bernardo, CA, 1984–1987. Am J Clin Nutr 1992;55:664–9.

106. Redondo MR, Ortega RM, Zamora MJ, et al. Influence of the number of meals taken per day on cardiovascular risk factors and the energy and nutrient intakes of a group of elderly people. Int J Vitam Nutr Res 1997;67:176–82.

107. Powell JT, Franks PJ, Poulter NR. Does nibbling or grazing protect the peripheral arteries from atherosclerosis? J Cardiovasc Risk 1999;6:19–22.

108. Hubert HB, Feinleib M, McNamara PM, et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968–77.

109. Larsson B. Regional obesity as a health hazard in men: prospective studies. Acta Med Scand 1988;723:45–51 [review].

110. Larsson B, Bengtsson C, Bjorntorp P, et al. Is abdominal body fat distribution a major explanation for the sex difference in the incidence of myocardial infarction? The study of men born in 1913 and the study of women. Am J Epidemiol 1992;135:266–73.

111. Lissner L, Odell PM, D’Agostino RB, et al. Variability of body weight and health outcomes in the Framingham population. N Engl J Med 1991;324:1839–44.

112. Jeffery RW. Does weight cycling present a health risk? Am J Clin Nutr 1996;63:452S–5S [review].

113. Muls E, Kempen K, Vansant G, et al. Is weight cycling detrimental to health? A review of the literature in humans. Int J Obes Relat Metab Disord 1995;19 Suppl 3:S46–50 [review].

114. Ronzio RA. Antioxidants, nutraceuticals and functional foods. Townsend Letter for Doctors and Patients  1996;Oct:34–5 [review].

115. Hertog MGL, Feskens EJM, Hollman PCH, et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1007–11.

116. Hertog MGL, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med 1995;155:381–6.

117. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 1996;312:478–81.

118. Rimm EB, Katan MB, Ascherio A, et al. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 1996;125:384–9.

119. Hertog MGL, Sweetnam PM, Fehily AM, et al. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr 1997;65:1489–94.

120. Miller TD, Balady GJ, Fletcher GF. Exercise and its role in the prevention and rehabilitation of cardiovascular disease. Ann Behav Med 1997;19:220–9 [review].

121. Berlin JA, Colditz GA. A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990;132:612–28.

122. Fletcher GF, Blair SN, Blumenthal J, et al. Benefits and recommendations for physical activity programs for all Americans: a statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation 1992;86:340–4.

123. Salonen JT et al. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982;ii:175.

124. Shamberger RJ, Willis CE. Epidemiological studies on selenium and heart disease. Fed Proc 1976;35:578 [abstract #2061].

125. Korpela H, Kumpulainen J, Jussila E, et al. Effect of selenium supplementation after acute myocardial infarction. Res Comm Chem Pathol Pharmacol 1989; 65:249–52.

126. Freund KM, Belanger AJ, D’Agostino RB, Kannel WB. The health risks of smoking. The Framingham Study: 34 years of follow-up. Ann Epidemiol 1993;3:417–24.

127. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. BMJ 1997;315:973–80.

128. Avins AL, Haber RJ, Hulley SB. The status of hypertriglyceridemia as a risk factor for coronary heart disease. Clin Lab Med 1989;9:153–68.

129. Hulley SB, Avins, AL. Asymptomatic hypertriglyceridemia: insufficient evidence to treat. BMJ 1992;304:394–6.

130. Grundy SM, Vega GL. Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Arch Intern Med 1992;152:28–34.

131. Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213–9.

132. Miller M, Seidler A, Moalemi A, et al. Normal triglyceride levels and coronary artery disease events: the Baltimore Coronary Observational Long-Term Study. J Am Coll Cardiol 1998;31:1252–7.

133. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156–60.

134. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113S–8S.

135. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.

136. Belcher JD, Balla J, Balla G, et al. Vitamin E, LDL, and endothelium: Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb 1993;13:1779–89.

137. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–6.

138. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-60.

139. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.

140. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet 1996;347:781-6.

141. [No authors listed]. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447-55.

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