|LE Magazine June 2001|
Does Cholesterol Cause Artery Disease?
Starting in the 1950’s, a raging debate began as to whether high levels of cholesterol caused heart attacks and strokes. Those involved in alternative medicine pointed to studies showing elevated rates of heart attack and stroke in people who consumed diets high in fat and cholesterol.
On the other side were conventional doctors and the FDA who adamantly proclaimed that there was no relationship between cholesterol and artery disease. The FDA actually published in the Federal Register that it was illegal to disseminate information on food labels that cholesterol was a causative factor in the development of artery disease. To document the government’s unscientific position on the cholesterol issue, we have re-printed (on the last page of this article) excerpts from what the FDA published in the Federal Register in 1959 and 1965.
Starting in the 1990’s, the dangers of high LDL-cholesterol became so apparent that the FDA backed away from interfering with companies who stated that consuming foods low in cholesterol (such as fruits,
vegetables, fiber) might help prevent heart attack and stroke.(1-3)
It is now accepted that cholesterol levels above 200 increase the risk for heart attacks and strokes.(4-11) Having a cholesterol reading above 240 may be particularly dangerous. Studies dating back to the 1970’s show that maintaining high levels of beneficial HDL cholesterol may be as important as suppressing high LDL-cholesterol readings.(12-16)
The cholesterol debate, however, has carried on to this day, as newer human studies produce conflicting results as to how dangerous high cholesterol really is. There are some nutritionally-oriented doctors who think that LDL-cholesterol is not dangerous as long as it is protected against oxidation by antioxidant supplements such as vitamin E and coenzyme Q10.(17-20) Others who question the risks of high cholesterol point to studies showing that people suffering heart attacks often have normal cholesterol levels.(21-28) While there is merit to these theories, they do not justify health-conscious people ignoring high cholesterol levels.
We now know that LDL-cholesterol is only one of several known artery-disease risk factors in the blood. High levels of homocysteine, fibrinogen, triglycerides and C-reactive protein are all independent risk factors for developing a heart attack or stroke.(29-50) The presence of high levels of these other risk factors can result in a person suffering a cardiovascular event, even though their cholesterol level is low. This does not mean, however, that chronically high levels of LDL-cholesterol should be ignored.
As far as guarding against LDL-cholesterol oxidation, this may help to protect against atherosclerosis,(51) but it is still critical to keep cholesterol levels in check for those who intend to live a long and healthy life.(52) In other words, a person who takes antioxidant supplements may protect against LDL-cholesterol oxidation, but at some point, chronically high levels LDL levels could still cause a heart attack or stroke, perhaps much later in life. Evidence for this can be seen in 80-year-old people who develop coronary artery disease.(53-55) There appears to be a point in the aging process in some people when the atherosclerosis process accelerates, meaning that even slightly elevated cholesterol levels can be lethal.(56, 57)
One reason LDL-cholesterol becomes more dangerous as people age was documented in a recent study that found LDL-cholesterol is more susceptible to oxidation when there is a deficiency of DHEA. These scientists showed that DHEA is part of an integral shield against LDL oxidation and that vitamin E does not fully protect against oxidation unless adequate levels of DHEA are present. The scientists pointed out that the amount of DHEA in LDL-cholesterol “disappears to almost undetectable levels during aging.” When these scientists replaced DHEA in the LDL-cholesterol molecule, protection against oxidation was regained.(53)
A number of published studies show that people with high cholesterol who take certain cholesterol lowering drugs have a significantly lower risk of suffering a heart attack or stroke.(58) These studies cannot be ignored, as they indicate that cholesterol plays a role in the development of heart disease and stroke at least in some people.
Based on a review of all the published literature, it would appear that the ideal cholesterol level to maintain is between 180 to 200 (milligrams per deciliter of blood). Cholesterol levels above 200, increase the risk for heart attacks and strokes. (59, 60)
It is important to point out that cholesterol levels that are too low can also be lethal. An interpretation from existing published findings indicates that cholesterol levels should not drop too far below 180 in middle-aged people,(61-63) and that cholesterol levels below 150 might increase the risk of a hemorrhagic stroke (also known as a cerebral hemorrhage).(64) When it comes to stroke, high cholesterol definitely increases the risk of the more widespread ischemic stroke,(65) but cholesterol levels that are too low appear to be a factor in the less common hemorrhagic stroke. Fortunately, enough published data exists to confidently recommend that maintaining cholesterol levels between 180 and 200 is the best way of protecting against either type of stroke.(66-68)
In the first article that appears in this issue, we describe a natural supplement that has been shown to work as well as the popular “statin” drugs in lowering serum cholesterol. The advantages of this natural approach is that it is completely non-toxic, raises beneficial HDL-cholesterol levels, inhibits abnormal platelet aggregation and costs far less than prescription drugs.
Foundation members should know that there are few dietary supplements that lower cholesterol as well as prescription drugs. Most people cannot tolerate niacin, and red rice yeast extract is just another way of putting a “statin” (lovastatin) into your body. Certain dietary fibers can help lower cholesterol, but many people experience gastro-intestinal side effects when taking the high amounts of these fibers needed to lower cholesterol.
Based on the multiple beneficial mechanisms that can be attributed to this new natural supplement, it would appear to be superior to “statin” drugs in protecting against cardiovascular disease. Our article about this octacosonal-derivative is supported by a surprising large number of published studies in peer-reviewed scientific journals. In other countries, this natural supplement is sold as a “drug” for the specific purpose of lowering dangerous LDL-cholesterol and increasing beneficial HDL-cholesterol.
In our article about this natural cholesterol-lowering agent, we present only the facts as they appear in the published scientific literature. We will leave the decision to the individual as to whether to use diet modification, “statin” drugs and/or this new natural substance to control their cholesterol levels. We do recommend, however, that everyone reduce their risk of heart attack and stroke by maintaining their cholesterol levels in the safe range (180-200 mg/dl).
For longer life,
1. Liu S, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. Am J Clin Nutr 2000 Oct;72(4):922-8.
2. Gramenzi A, et al. Association between certain foods and risk of acute myocardial infarction in women. BMJ 1990 Mar 24;300(6727):771-3.
3. Singh RB, et al. Effects on serum lipids of adding fruits and vegetables to prudent diet in the Indian Experiment of Infarct Survival (IEIS). Cardiology 1992;80(3-4):283-93.
4. Laemmle P, et al. Know your cholesterol: population screening. J Lab Clin Med 1988 Nov;112(5):567-74.
5. Stone NJ, et al. Controlling cholesterol levels through diet. Postgrad Med 1988 Jun;83(8):229-37, 241-2.
6. Hulley SB. A national program for lowering high blood cholesterol. Am J Obstet Gynecol 1988 Jun;158(6 Pt 2):1561-7.
7. “Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.” The Expert Panel. Arch Intern Med 1988 Jan;148(1):36-69.
8. Vogt HB. Hyperlipoproteinemias: Part III. When to treat. S D J Med 1991 Apr;44(4):97-100.
9. Leis HP. The relationship of diet to cancer, cardiovascular disease and longevity. Int Surg 1991 Jan-Mar;76(1):1-5.
10. Gil VF, et al. [The validity of the separate determination of total cholesterol in the primary prevention of coronary risk]. Med Clin (Barc) 1995 Apr 29;104(16):612-6.
11. Iribarren C, et al. Low serum cholesterol and mortality. Which is the cause and which is the effect? Circulation 1995 Nov 1;92(9):2396-403.
12. Enger SC, et al. High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study. Artery 1979 Feb;5(2):170-81.
13. Micheli H, et al. High density lipoprotein cholesterol in male relatives of patients with coronary heart disease. Atherosclerosis 1979 Mar;32(3):269-76.
14. Pometta D, et al. [Low HDL cholesterol in close relatives and patients with myocardial infarct]. [Article in French] Schweiz Med Wochenschr 1978 Dec 2;108(48):1888-91.
15. Goldbourt U, et al. High density lipoprotein cholesterol and incidence of coronary heart disease--the Israeli Ischemic Heart Disease Study. Am J Epidemiol 1979 Mar;109(3):296-308.
16. Noma A, et al. High and low density lipoprotein cholesterol in myocardial and cerebral infarction. Atherosclerosis 1979 Mar;32(3):327-31.
17. Thomas SR, et al. Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme Q in atherogenesis? Mol Aspects Med 1997;18 Suppl:S85-103.
18. Stocker R, et al. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A 1991 Mar 1;88(5):1646-50.
19. Thomas SR, et al. Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. Chem Res Toxicol 1998 May;11(5):484-94.
20. Thomas SR, et al. A role for reduced coenzyme Q in atherosclerosis? Biofactors 1999;9(2-4):207-24.
21. Bo M, et al. Cholesterol and long-term mortality after acute myocardial infarction in elderly patients. Age Ageing 1999 May;28(3):313-5.
22. Jadhav PP, et al. Evaluation of apolipoproteins A1 and B in survivors of myocardial infarction. J Assoc Physicians India 1994 Sep;42(9):703-5.
23. Bux-Gewehr I, et al. Recurring myocardial infarction in a 35 year old woman. Heart 1999 Mar;81(3):316-7.
24. Fournier JA, et al. Normal angiogram after myocardial infarction in young patients: a prospective clinical-angiographic and long-term follow-up study. Int J Cardiol 1997 Aug 8;60(3):281-7.
25. Schmidt HH, et al. Elevated lipoprotein(a) is lowered by a cholesterol synthesis inhibitor in a normocholesterolaemic patient with premature myocardial infarction. Blood Coagul Fibrinolysis 1993 Feb;4(1):173-5.
26. Prati PL . [The periodic flashes of E. Brunwald: lowering cholesterol levels in subjects with myocardial infarction and normal cholesterol levels]. G Ital Cardiol 1997 Jan;27(1):76-8.
27. Lawless C, et al. Lipid lowering in post-MI patients with normal cholesterol. J Fam Pract 1997 Jan;44(1):30.
28. Hartley H. [The reduction of cardiovascular events after a myocardial infarct in patients with normal cholesterol levels]. Rev Clin Esp 1996 Dec;196(4 Monografico): 43-6.
29. Genest JJ, et al. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J Am Coll Cardiol 1990 Nov;16(5):1114-9.
30. Stampfer MJ, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992 Aug 19;268(7):877-81.
31. Brattstrom L, et al. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Invest 1992 Mar;22(3):214-21.
32. Taylor LM, et al. The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg 1991 Jan;13(1):128-36.
33. Di Napoli M, et al. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke 2001 Jan;32(1):133-8.
34. Wedzicha JA, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost 2000 Aug;84(2):210-5.
35. Maresca G, et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999 Jun;19(6):1368-77.
36. Maresca G, et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999 Jun;19(6):1368-77.
37. Fukujima MM, et al. [Fibrinogen as independent risk factor for ischemic stroke]. Arq Neuropsiquiatr 1997 Dec;55(4):737-40.
38. Ferrara E, et al. [Fibrinogen, a cardiovascular risk factor]. Minerva Cardioangiol 1989 Nov;37(11):473-5.
39. Benfante RJ, et al. Risk factors in middle age that predict early and late onset of coronary heart disease. J Clin Epidemiol 1989;42(2):95-104.
40. Salonen JT, et al. Relation of serum cholesterol and triglycerides to the risk of acute myocardial infarction, cerebral stroke and death in eastern Finnish male population. Int J Epidemiol 1983 Mar;12(1):26-31.
41. Carlson LA, et al. Risk factors for myocardial infarction in the Stockholm prospective study. A 14-year follow-up focussing on the role of plasma triglycerides and cholesterol. Acta Med Scand 1979;206(5):351-60.
42. Welin L, et al. Triglycerides, a major coronary risk factor in elderly men. A study of men born in 1913. Eur Heart J 1991 Jun;12(6):700-4.
43. Ducimetiere P, et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980 Sep;19(3):205-10.
44. Malmberg K, et al. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988 Mar;9(3):259-64.
45. Hughes LO, et al. Disturbances of insulin in British Asian and white men surviving myocardial infarction. BMJ 1989 Aug 26;299(6698):537-41.
46. Liu S, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr 2000 Jun;71(6):1455-61.
47. Egger M, et al. Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error. Atherosclerosis 1999 Apr;143(2):275-84.
48. Asakawa H, et al. Comparison of risk factors of macrovascular complications. Peripheral vascular disease, cerebral vascular disease, and coronary heart disease in Japanese type 2 diabetes mellitus patients. J Diabetes Complications 2000 Nov-Dec;14(6):307-13.
49. Soderberg S, et al. Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 1999 Feb;30(2):328-37.
50. Burchfiel CM, et al. Glucose intolerance and 22-year stroke incidence. The Honolulu Heart Program. Stroke 1994 May;25(5):951-7.
51. Gokce N, et al. Basic research in antioxidant inhibition of steps in atherogenesis. J Cardiovasc Risk 1996 Aug;3(4):352-7.
52. Scheuermann W, et al. Effectiveness of a decentralized, community-related approach to reduce cardiovascular disease risk factor levels in Germany. Eur Heart J 2000 Oct;21(19):1591-7.
53. Khalil A, et al. Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J Lipid Res 2000 Oct;41(10):1552-61.
54. Iwamoto T, et al. [Clinical findings of arteriosclerosis and serum lipoprotein(a) concentration in elderly patients]. Nippon Ronen Igakkai Zasshi 2000 Oct;37(10):811-8.
55. Stavenow L, et al. Eighty-year-old men without cardiovascular disease in the community of Malmo. Part I. Social and medical factors, with special reference to the lipoprotein pattern. J Intern Med 1990 Jul;228(1):9-15.
56. Beckett N, et al. Is it advantageous to lower cholesterol in the elderly hypertensive? Cardiovasc Drugs Ther 2000 Aug;14(4):397-405.
57. Guize L, et al. [Cholesterolemia and total, cardiovascular and cancer mortality. Study of a cohort of 220,000 people]. Bull Acad Natl Med 1998;182(3):631-47; discussion 647-50.
58. Kashyap ML. Cholesterol and atherosclerosis: a contemporary perspective. Ann Acad Med Singapore 1997 Jul; 26(4):517-23.
59. Iribarren C, et al. Low serum cholesterol and mortality. Which is the cause and which is the effect? Circulation 1995 Nov 1;92(9):2396-403.
60. Iribarren C, et al. Serum total cholesterol and mortality. Confounding factors and risk modification in Japanese-American men. JAMA 1995 Jun 28;273(24):1926-32.
61. Gatchev O, et al. Subarachnoid hemorrhage, cerebral hemorrhage, and serum cholesterol concentration in men and women. Ann Epidemiol 1993 Jul;3(4):403-9.
62. Okumura K, et al. Low serum cholesterol as a risk factor for hemorrhagic stroke in men: a community-based mass screening in Okinawa, Japan. Jpn Circ J 1999 Jan;63(1):53-8.
63. Iso H, et al. Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial. N Engl J Med 1989 Apr 6;320(14):904-10.
64. Jacobs DR. The relationship between cholesterol and stroke. Health Rep 1994;6(1):87-93.
65. Gil-Nunez AC, et al. Advantages of lipid-lowering therapy in cerebral ischemia: role of hmg-coa reductase inhibitors. Cerebrovasc Dis 2001 Feb;11 Suppl 1:85-95.
66. Liu S, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. Am J Clin Nutr 2000 Oct;72(4):922-8.
67. Gramenzi A, et al. Association between certain foods and risk of acute myocardial infarction in women. BMJ 1990 Mar 24;300(6727):771-3.
68. Singh RB, et al. Effects on serum lipids of adding fruits and vegetables to prudent diet in the Indian Experiment of Infarct Survival (IEIS). Cardiology 1992;80(3-4):283-93.
Back to the Magazine Forum