Weight Loss Sale

Life Extension Magazine

LE Magazine November 2004
image
Cholesterol & Statin Drugs
Separating Hype from Reality
By William Davis, MD, FACC

Conclusion
Statin drugs do indeed help to lower cholesterol and LDL. Nevertheless, cholesterol reduction using a statin agent is far from the final word on reducing heart disease risk, as other risk factors for heart disease, such as low HDL and small LDL particles, are both independent of LDL and far more prevalent than high cholesterol. A number of interesting nutritional strategies are available to address total cholesterol, LDL, low HDL, and small LDL particles. The pattern of low HDL and small LDL particles responds powerfully to weight loss, as well as to treatment with supplements such as niacin and fish oil. These simple approaches will provide a far more effective approach to heart health than a reflex treatment of cholesterol with medication.

Dr. William Davis is an author, lecturer, and practicing cardiologist focusing on coronary disease regression. He is author of the book Track your Plaque, and can be contacted at www.trackyourplaque.com.

Editor’s note: The content of this article and the interpretation of study results are those of Dr. Davis. A consensus has yet to be reached concerning when statin drugs should be prescribed. We published this article because it articulates both sides of this issue very well.

To read our lengthy protocol on preventing atherosclerosis, refer to the Cardiovascular Disease: Comprehensive Analysis chapter in Life Extension’s Disease Prevention and Treatment book.

Lipoproteins and the VAP™ Test

“My doctor said my cholesterol was fine... So why did I have a heart attack?”

If you want to know whether a heart attack is in your future, knowing your cholesterol level may not be enough.

An excessive quantity of small LDL particles is the most common risk factor contributing to heart-attack incidence in the US—far more common, in fact, than high cholesterol. It is a hidden danger that can be uncovered only when measured specifically. You can have small LDL particles with high, low, or in-between levels of cholesterol. Small LDL particles triple the risk of heart attacks. When they occur alongside other abnormalities, such as high total cholesterol or high C-reactive protein (a measure of inflammation), the risk of heart attacks increases sixfold.62

Small LDL particles are a far more destructive force than their larger counterparts. They are like finely tuned weapons designed to wreak maximum damage. Smaller particles are better able to penetrate the cellular barrier and be deposited in the artery walls, creating atherosclerotic plaque. They also persist longer in the circulation, giving them greater opportunity to cling like little magnets to tissues within the arterial walls. Once residing in the arterial wall, small LDL particles are more prone to oxidation, stimulating the release of inflammatory and adhesive proteins.63

The growing recognition of small LDL particles as a common and potent hidden source for heart disease has led to the availability of specialized tests from several laboratories. Life Extension is now making one such technology available through its VAP™ (Vertical Auto Profile) test. VAP™ is a method of separating blood proteins into component lipoproteins, or lipid-carrying proteins. Dr. Jere Segrest, director of the Atherosclerosis Research Unit at the University of Alabama-Birmingham, developed the test, which reveals much more than simple cholesterol panels.

After you submit your blood for testing, a VAP™ report will be returned to you. LDL particle size is reported in a readily understandable format as pattern A (the less harmful large LDL) or pattern B (the dreaded small LDL). Intermediate-sized LDL particles are reported as pattern A/B. Pattern B poses maximum risk; pattern A/B poses an intermediate level of risk.

What does having pattern B, or an excess of small LDL particles, tell you? This one measurement holds a world of information. Not only is your risk for heart attacks three to six times higher, but also you are more resistant to insulin and more likely to develop the metabolic syndrome or even diabetes if you become overweight.64 It also tells you that a low-fat diet (deriving less than 20% of total calories from fat) may paradoxically heighten your risk for heart disease.65

Knowing that you are pattern B also points you toward treatment strategies that can effectively correct this hidden source of risk. Small LDL is very responsive to niacin (vitamin B3) treatment, usually disappearing with doses of 500-1000 mg per day (though long-term treatment will be necessary). Weight loss can be a very powerful treatment strategy if you are overweight. Fish oil in doses providing at least 1400 mg of EPA and 900 mg of DHA per day helps by reducing triglyceride levels, a necessary ingredient to create small LDL particles. Dietary strategies that slow or reduce sugar release (i.e., lower glycemic index) can be helpful, including eating high-fiber foods or supplements such as flaxseed, glucomannan, oat bran (beta-glucan), psyllium seed, raw nuts like almonds and walnuts, and the starch blocker white bean extract.

The VAP™ panel directly measures LDL. Many people are surprised to learn that the LDL reported to you by your doctor or hospital is calculated, not measured, and is commonly inaccurate by 30% or more.66 Lipoprotein tests like VAP™ can be crucial, and perhaps lifesaving, for people who have already been diagnosed with coronary or vascular disease. It is not uncommon for heart-attack victims to have normal cholesterol levels and be told that there is no identifiable cause for their disease. VAP™ testing uncovers one, if not several, hidden risk factors in over 90% of people with heart disease.

The information provided through VAP™ lipoprotein testing provides far greater insight into heart disease risk factors than that offered by standard cholesterol testing, which will enable you to take greater control over your risk of heart disease.

The full VAP™ test measures:

Direct Measured Lipids
• Low-density lipoprotein
(LDL)
• High-density lipoprotein (HDL)
• Total very low-density
lipoprotein (VLDL)
• Total cholesterol
• Triglycerides

Targets of Therapy
• Non-HDL cholesterol
(LDL + VLDL)
• Probable metabolic
syndrome

Risk Factors
• Lipoprotein(a)
• Remnant lipoprotein
(IDL + VLDL 3)
• LDL density pattern

Clinical Considerations
• HDL-2
• HDL-3
• Total HDL
• VLDL 1+2
• VLDL 3
• Total VLDL
• Intermediate-density
lipoprotein (IDL)
• Total cholesterol/HDL ratio

If your doctor is unfamiliar with or unwilling to order the VAP™ test and other tests discussed in this article, please call 1-800-208-3444 to order one yourself. VAP™ is normally a very expensive test, which is why it is not widely used. The retail price of the comprehensive VAP™ panel is $246.67. The test is available to Life Extension members for $185.

References

1. Pfizer, Inc. Annual Report, 2003.

2. Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998 Apr 21;97(15):1453-60.

3. Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 5,963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003 Jun 14;361(9374):2005-16.

4. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22.

5. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):23-33.

6. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57.

7. LIPID Study Group (Long-term Intervention with Pravastatin in Ischaemic Disease). Long-term effectiveness and safety of pravastatin in 9,014 patients with coronary heart disease and average cholesterol con centrations: the LIPID trial follow-up. Lancet. 2002 Apr 20;359(9315):1379-87.

8. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995 Nov 16;333(20):1301-7.

9. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998 May 27;279(20):1615-22.

10. Sacks FM, Rouleau JL, Moye LA, et al. Baseline characteristics in the Cholesterol and Recurrent Events (CARE) trial of sec- ondary prevention in patients with average serum cholesterol levels. Am J Cardiol. 1995 Mar 15;75(8):621-3.

11. Pfeffer MA, Sacks FM, Moye LA, et al. Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators. Am J Cardiol. 1995 Sep 28;76(9):98C-106C.

12. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996 Oct 3;335(14):1001-9.

13. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004 Jun 15;109(23 Suppl 1):11150-7.

14. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Circulation. 2002 Aug 20;106(8):1024-8.

15. Baker SK, Tarnopolsky MA. Statin myopathies: pathophysiologic and clinical perspectives. Clin Invest Med. 2001 Oct;24(5):258-72.

16. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for primary prevention of cardiovascular disease and stroke: 2002 update. Consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. Circulation. 2002 Jul 16;106(3):388-91.

17. Krauss RM, Dreon DM. Low-density lipoprotein subclasses and response to a low-fat diet in healthy men. Am J Clin Nutr. 1995 Aug: 62(2):478S-87S.

18. Spiller GA, Miller A, Olivera K, et al. Effects of plant-based diets high in raw or roasted almonds, or roasted almond butter on serum lipoproteins in humans. J Am Coll Nutr. 2003 Jun;22(3):195-200.

19. Sabate J, Haddad E, Tanzman JS, Jambazian P, Rajaram S. Serum lipid response to the graduated enrichment of a Step I diet with almonds: a randomized feeding trial. Am J Clin Nutr. 2003 Jun;77(6):1379-84.

20. Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003 Jul 23;290(4):502-10.

21. Tonstad S, Smerud K, Hoie L. A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipopro- teins, and plasma total homocysteine in hypercholesterolemic subjects. Am J Clin Nutr. 2002 Jul;76(1):78-84.

22. Sheehan JP, Wei IW, Ulchaker M, Tserng KY. Effect of high fiber intake in fish oil- treated patients with non-insulin-dependent diabetes mellitus. Am J Clin Nutr. 1997 Nov;66(5):1183-7.

23. Jensen CD, Haskell W, Whittam JH. Long- term effects of water-soluble dietary fiber in the management of hypercholesterolemia in healthy men and women. Am J Cardiol. 1997 Jan 1;79(1):34-7.

24. Maron DJ, Lu GP, Cai NS, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003 Jun 23;163(12):1448-53.

25. Willcox JK, Catignani GL, Lazarus S. Tomatoes and cardiovascular health. Crit Rev Food Sci Nutr. 2003;43(1):1-18.

26. Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids. 2002 Oct;37(10):931-4.

27. Ong AS, Goh SH.Palm oil: a healthful and cost-effective dietary component. Food Nutr Bull. 2002 Mar;23(1):11-22.

28. Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and lova-

statin on lipid parameters in hypercholesterolemic humans. J Nutr Biochem. 2001 Jun;12(6):318-29.

29. Kerckhoffs DA, Hornstra G, Mensink RP. Cholesterol-lowering effect of beta-glucan from oat bran in mildly hypercholes- terolemic subjects may decrease when beta- glucan is incorporated into bread and cookies. Am J Clin Nutr. 2003 Aug;78(2):221-227.

30. Maki KC, Shinnick F, Seeley MA, et al. Food products containing free tall oil-based phytosterols and oat beta-glucan lower serum total and LDL cholesterol in hypercholesterolemic adults. J Nutr. 2003 Mar;133(3):808-13.

31. Kabir M, Oppert JM, Vidal H, et al. Four- week low-glycemic index breakfast with a modest amount of soluble fibers in type 2 diabetic men. Metabolism. 2002;51(7):819-26.

32. Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the manage- ment of blood cholesterol levels. Mayo Clin Proc. 2003 Aug;78(8):965-78.

33. Hallikainen MA, Uusitupa MIJ. Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects. Am J Clin Nutr. 1999 Mar;69(3):403-10.

34. Chu N, Spiegelman D, Hitasmisligil GS, Rifai N, Stampfer M, Rimm EB. Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular dis- ease risk factors among men. Atherosclerosis. 2001 Aug;157(2):495-503.

35. Johnson MS, Figueroa-Colon R, Huang TT, Dwyer JH, Goran MI. Longitudinal changes in body fat in african american and cau- casian children: influence of fasting insulin and insulin sensitivity. J Clin Endocrinol Metab. 2001 Jul;86(7):3182-7.

36. Danadian K, Lewy V, Janosky JJ, Arslanian S. Lipolysis in african-american children: is it a metabolic risk factor predisposing to obesity? J Clin Endocrinol Metab. 2001 Jul;86(7):3022-6.

37. Zoltowska M, Ziv E, Delvin E, et al. Circulating lipoproteins and hepatic sterol metabolism in Psammomys obesus prone to obesity, hyperglycemia and hyperinsulinemia. Atherosclerosis. 2001 Jul;157(1):85-96.

38. Thakur V, Richards R, Reisin E. Obesity, hypertension, and the heart. Am J Med Sci. 2001 Apr;321(4):242-8.

39. Emdin M, Gastaldelli A, Muscelli E, et al. Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss. Circulation. 2001 Jan 30;103(4):513-9.

40. Despres JP, Pascot A, Lemieux I. Risk fac- tors associated with obesity: a metabolic perspective. Ann Endocrinol (Paris). 2000 Dec;61 Suppl 6:31-8.

41. Ceriello A. Impaired glucose tolerance and cardiovascular disease: the possible role of post-prandial hyperglycemia Am Heart J. 2004 May;147(5):803-7.

42. Lebovitz HE. Effect of the postprandial state on nontraditional risk factors. Am J Cardiol. 2001 Sep 20;88(6A):20H-5H.

43. Sasso F, Carbonara O, Nasti R. Glucose metabolism and coronary heart disease in patients with normal glucose tolerance. JAMA. 2004 Apr 21;291(15):1858-63.

44. Walsh DE, Yaghoubian V, Behforooz A. Effect of glucomannan on obese patients: a clinical study Int J Obes. 1984;8(4):289-93.

45. Vuksan V, Lyon M, Breitman P, Sievenpiper J. 3-week consumption of a highly viscous dietary fiber blend results in improvements in insulin sensitivity and reductions in body fat. Results of a double blind, placebo con- trolled trial. Presented at the 64th Annual Meeting of the American Diabetes Association. Orlando, FL; June 4-8, 2004.

46. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996 Sep 18;276(11):875-81.

47. Stampfer MJ, Krauss RM, Ma J, et al. A prospective study of triglyceride level, low- density lipoprotein particle diameter, and risk of myocardial infarction. JAMA. 1996 Sep 18;276(11):882-88.

48. Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men: Prospective results from the Quebec Cardiovascular Study. Circulation. 1997 Jan 7;95(1):69-75.

49. Kuller L, Tracy P, Arnold A, et al. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1175-80.

50. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97.

51. Gotto AM, Brinton EA. Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease.

J Am Coll Cardiol. 2004 Mar 3;43(5):717-24.

52. van Lennep JE, Westerveld HT, Van Lennep HW, Zwinderman AH, Erkelens DW, van der Wall EE. Apolipoprotein concentrations during treatment and recurrent coronary artery disease events. Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2408-13.

53. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3)356-9.

54. Taylor AJ, Merz CN, Udelson JE. 34th Bethesda Conference: “Can atherosclerosis imaging techniques improve the detection of patients at risk for ischemic heart disease?” J Amer Coll Cardiol. 2003 Jun 4;(11)41:1860-2.

55. Donatucci DA, Liener IE, Gross CJ. Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose. J Nutr. 1987 Dec;117(12):2154-60.

56. Udani J, Hardy M, Madsen DC. Blocking carbohydrate absorption and weight loss: a clinical trail using Phase 2 brand proprietary fractionated white bean extract. Altern Med Rev. 2004 Mar;9(1):63-9.

57. Kalman D, Colker CM, Wilets I, Roufs JB, Antonio J. The effects of pyruvate supplementation on body composition in over-weight individuals. Nutrition. 1999 May;15(5):337-40.

58. Black DM. Therapeutic targets in cardiovascular disease: a case for high-density lipoprotein cholesterol. Am J Cardiol. 2003 Apr 3;91(7A):40E-3E.

59. O’Keefe JH, Harris WS. From Inuit to implementation: Omega-3 fatty acids come of age. Mayo Clin Proc. 2000 Jun;75(6):607- 14.

60. Herrmann W, Biermann J, Kostner GM. Comparison of effects of n-3 to n-6 fatty acids on serum level of lipoprotein(a) in patients with coronary artery disease. Am J Cardiol. 1995 Sep 1;76(7):459-62.

61. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001 Nov 29;345(22):1583-92.

62. St-Pierre AC, Ruel IL, Cantin B, et al. Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation. 2001;104(19):2295-9.

63. Kwiterowich PO. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol. 2002 Oct;90(8A):30i-47i.

64. de Bruin TW. Lipid metabolism. Curr Opin Lipidol. 1998;9:275-8.

65. Krauss RM. Dietary and genetic effects on low-density lipoprotein heterogeneity. Ann Rev Nutr.2001;21:283-95.

66. Otvos J, Jeyarajah EJ, Cromwell WC. Measurement issues related to lipoprotein heterogeneity. Am J Cardiol. 2002 Oct;90(8A):22i-9i.