Skip to main content
PMC home page
The BMJ logoLink to The BMJ
. 1994 Feb 5;308(6925):367–372. doi: 10.1136/bmj.308.6925.367

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?

M R Law 1, N J Wald 1, S G Thompson 1
PMCID: PMC2539460  PMID: 8043072

Abstract

OBJECTIVE--To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease. DESIGN--Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). MAIN OUTCOME MEASURE--Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration. RESULTS--For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being close to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. CONCLUSIONS--The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18,000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change, lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45,000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

Full text

PDF
371

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Begg T. B., Rifkind B. M. Valutazione della terapia con clofibrate nelle arteriopatie periferiche. Minerva Med. 1971 Sep 26;62(72):3469–3475. [PubMed] [Google Scholar]
  2. Blankenhorn D. H., Nessim S. A., Johnson R. L., Sanmarco M. E., Azen S. P., Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987 Jun 19;257(23):3233–3240. [PubMed] [Google Scholar]
  3. Bradford R. H., Shear C. L., Chremos A. N., Dujovne C., Downton M., Franklin F. A., Gould A. L., Hesney M., Higgins J., Hurley D. P. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991 Jan;151(1):43–49. doi: 10.1001/archinte.151.1.43. [DOI] [PubMed] [Google Scholar]
  4. Brensike J. F., Levy R. I., Kelsey S. F., Passamani E. R., Richardson J. M., Loh I. K., Stone N. J., Aldrich R. F., Battaglini J. W., Moriarty D. J. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984 Feb;69(2):313–324. doi: 10.1161/01.cir.69.2.313. [DOI] [PubMed] [Google Scholar]
  5. Brown G., Albers J. J., Fisher L. D., Schaefer S. M., Lin J. T., Kaplan C., Zhao X. Q., Bisson B. D., Fitzpatrick V. F., Dodge H. T. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990 Nov 8;323(19):1289–1298. doi: 10.1056/NEJM199011083231901. [DOI] [PubMed] [Google Scholar]
  6. Buchwald H., Varco R. L., Matts J. P., Long J. M., Fitch L. L., Campbell G. S., Pearce M. B., Yellin A. E., Edmiston W. A., Smink R. D., Jr Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH) N Engl J Med. 1990 Oct 4;323(14):946–955. doi: 10.1056/NEJM199010043231404. [DOI] [PubMed] [Google Scholar]
  7. Burr M. L., Fehily A. M., Gilbert J. F., Rogers S., Holliday R. M., Sweetnam P. M., Elwood P. C., Deadman N. M. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989 Sep 30;2(8666):757–761. doi: 10.1016/s0140-6736(89)90828-3. [DOI] [PubMed] [Google Scholar]
  8. Canner P. L., Berge K. G., Wenger N. K., Stamler J., Friedman L., Prineas R. J., Friedewald W. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986 Dec;8(6):1245–1255. doi: 10.1016/s0735-1097(86)80293-5. [DOI] [PubMed] [Google Scholar]
  9. Carlson L. A., Rosenhamer G. Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand. 1988;223(5):405–418. doi: 10.1111/j.0954-6820.1988.tb15891.x. [DOI] [PubMed] [Google Scholar]
  10. Chen Z., Peto R., Collins R., MacMahon S., Lu J., Li W. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. BMJ. 1991 Aug 3;303(6797):276–282. doi: 10.1136/bmj.303.6797.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crouse J. R., 3rd Gender, lipoproteins, diet, and cardiovascular risk. Sauce for the goose may not be sauce for the gander. Lancet. 1989 Feb 11;1(8633):318–320. doi: 10.1016/s0140-6736(89)91320-2. [DOI] [PubMed] [Google Scholar]
  12. Detre K. M., Shaw L. Long-term changes of serum cholesterol with cholesterol-altering drugs in patients with coronary heart disease. Veterans Administration Drug-Lipid Cooperative Study. Circulation. 1974 Nov;50(5):998–1005. doi: 10.1161/01.cir.50.5.998. [DOI] [PubMed] [Google Scholar]
  13. Dorr A. E., Gundersen K., Schneider J. C., Jr, Spencer T. W., Martin W. B. Colestipol hydrochloride in hypercholesterolemic patients--effect on serum cholesterol and mortality. J Chronic Dis. 1978 Jan;31(1):5–14. doi: 10.1016/0021-9681(78)90076-0. [DOI] [PubMed] [Google Scholar]
  14. Frantz I. D., Jr, Dawson E. A., Ashman P. L., Gatewood L. C., Bartsch G. E., Kuba K., Brewer E. R. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis. 1989 Jan-Feb;9(1):129–135. doi: 10.1161/01.atv.9.1.129. [DOI] [PubMed] [Google Scholar]
  15. Frick M. H., Elo O., Haapa K., Heinonen O. P., Heinsalmi P., Helo P., Huttunen J. K., Kaitaniemi P., Koskinen P., Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987 Nov 12;317(20):1237–1245. doi: 10.1056/NEJM198711123172001. [DOI] [PubMed] [Google Scholar]
  16. Frick M. H., Heinonen O. P., Huttunen J. K., Koskinen P., Mänttäri M., Manninen V. Efficacy of gemfibrozil in dyslipidaemic subjects with suspected heart disease. An ancillary study in the Helsinki Heart Study frame population. Ann Med. 1993 Feb;25(1):41–45. doi: 10.3109/07853899309147855. [DOI] [PubMed] [Google Scholar]
  17. Goldbourt U., Yaari S. Cholesterol and coronary heart disease mortality. A 23-year follow-up study of 9902 men in Israel. Arteriosclerosis. 1990 Jul-Aug;10(4):512–519. doi: 10.1161/01.atv.10.4.512. [DOI] [PubMed] [Google Scholar]
  18. Gross L., Figueredo R. Long-term cholesterol-lowering effect of colestipol resin in humans. J Am Geriatr Soc. 1973 Dec;21(12):552–556. doi: 10.1111/j.1532-5415.1973.tb01662.x. [DOI] [PubMed] [Google Scholar]
  19. Grundy S. M., Nix D., Whelan M. F., Franklin L. Comparison of three cholesterol-lowering diets in normolipidemic men. JAMA. 1986 Nov 7;256(17):2351–2355. [PubMed] [Google Scholar]
  20. Heady J. A., Morris J. N., Oliver M. F. WHO clofibrate/cholesterol trial: clarifications. Lancet. 1992 Dec 5;340(8832):1405–1406. doi: 10.1016/0140-6736(92)92588-7. [DOI] [PubMed] [Google Scholar]
  21. Henriksson P., Edhag O. Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects. Br Med J (Clin Res Ed) 1986 Aug 16;293(6544):413–415. doi: 10.1136/bmj.293.6544.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hunninghake D. B., Stein E. A., Dujovne C. A., Harris W. S., Feldman E. B., Miller V. T., Tobert J. A., Laskarzewski P. M., Quiter E., Held J. The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. N Engl J Med. 1993 Apr 29;328(17):1213–1219. doi: 10.1056/NEJM199304293281701. [DOI] [PubMed] [Google Scholar]
  23. Isles C. G., Hole D. J., Hawthorne V. M., Lever A. F. Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men. Lancet. 1992 Mar 21;339(8795):702–706. doi: 10.1016/0140-6736(92)90599-x. [DOI] [PubMed] [Google Scholar]
  24. Law M. R., Wald N. J., Wu T., Hackshaw A., Bailey A. Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study. BMJ. 1994 Feb 5;308(6925):363–366. doi: 10.1136/bmj.308.6925.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Leren P. The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl. 1966;466:1–92. [PubMed] [Google Scholar]
  26. Lewis B., Hammett F., Katan M., Kay R. M., Merkx I., Nobels A., Miller N. E., Swan A. V. Towards an improved lipid-lowering diet: additive effects of changes in nutrient intake. Lancet. 1981 Dec 12;2(8259):1310–1313. doi: 10.1016/s0140-6736(81)91339-8. [DOI] [PubMed] [Google Scholar]
  27. Livesley B. Running out of staff for the NHS. BMJ. 1989 Jul 1;299(6690):1–2. doi: 10.1136/bmj.299.6690.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. MARMORSTON J., MOORE F. J., HOPKINS C. E., KUZMA O. T., WEINER J. Clinical studies of long-term estrogen therapy in men with mvocardial infarction. Proc Soc Exp Biol Med. 1962 Jun;110:400–408. doi: 10.3181/00379727-110-27531. [DOI] [PubMed] [Google Scholar]
  29. Manolio T. A., Pearson T. A., Wenger N. K., Barrett-Connor E., Payne G. H., Harlan W. R. Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop. Ann Epidemiol. 1992 Jan-Mar;2(1-2):161–176. doi: 10.1016/1047-2797(92)90051-q. [DOI] [PubMed] [Google Scholar]
  30. McCaughan D. The long-term effects of probucol on serum lipid levels. Arch Intern Med. 1981 Oct;141(11):1428–1432. [PubMed] [Google Scholar]
  31. Miettinen T. A., Huttunen J. K., Naukkarinen V., Strandberg T., Mattila S., Kumlin T., Sarna S. Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality. JAMA. 1985 Oct 18;254(15):2097–2102. [PubMed] [Google Scholar]
  32. Miller G. J., Cruickshank J. K., Ellis L. J., Thompson R. L., Wilkes H. C., Stirling Y., Mitropoulos K. A., Allison J. V., Fox T. E., Walker A. O. Fat consumption and factor VII coagulant activity in middle-aged men. An association between a dietary and thrombogenic coronary risk factor. Atherosclerosis. 1989 Jul;78(1):19–24. doi: 10.1016/0021-9150(89)90154-8. [DOI] [PubMed] [Google Scholar]
  33. Neaton J. D., Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992 Jan;152(1):56–64. [PubMed] [Google Scholar]
  34. Pocock S. J., Shaper A. G., Phillips A. N. Concentrations of high density lipoprotein cholesterol, triglycerides, and total cholesterol in ischaemic heart disease. BMJ. 1989 Apr 15;298(6679):998–1002. doi: 10.1136/bmj.298.6679.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Puska P., Salonen J. T., Nissinen A., Tuomilehto J., Vartiainen E., Korhonen H., Tanskanen A., Rönnqvist P., Koskela K., Huttunen J. Change in risk factors for coronary heart disease during 10 years of a community intervention programme (North Karelia project). Br Med J (Clin Res Ed) 1983 Dec 17;287(6408):1840–1844. doi: 10.1136/bmj.287.6408.1840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. ROSE G. A., THOMSON W. B., WILLIAMS R. T. CORN OIL IN TREATMENT OF ISCHAEMIC HEART DISEASE. Br Med J. 1965 Jun 12;1(5449):1531–1533. doi: 10.1136/bmj.1.5449.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Robertson T. L., Kato H., Rhoads G. G., Kagan A., Marmot M., Syme S. L., Gordon T., Worth R. M., Belsky J. L., Dock D. S. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease. Am J Cardiol. 1977 Feb;39(2):239–243. doi: 10.1016/s0002-9149(77)80197-5. [DOI] [PubMed] [Google Scholar]
  38. Rosenhamer G., Carlson L. A. Effect of combined clofibrate--nicotinic acid treatment in ischemic heart disease. Atherosclerosis. 1980 Sep;37(1):129–142. doi: 10.1016/0021-9150(80)90100-8. [DOI] [PubMed] [Google Scholar]
  39. STAMLER J., PICK R., KATZ L. N., PICK A., KAPLAN B. M., BERKSON D. M., CENTURY D. Effectiveness of estrogens for therapy of myocardial infarction in middle-age men. JAMA. 1963 Feb 23;183:632–638. doi: 10.1001/jama.1963.03700080040013. [DOI] [PubMed] [Google Scholar]
  40. Sahni R., Maniet A. R., Voci G., Banka V. S. Prevention of restenosis by lovastatin after successful coronary angioplasty. Am Heart J. 1991 Jun;121(6 Pt 1):1600–1608. doi: 10.1016/0002-8703(91)90002-y. [DOI] [PubMed] [Google Scholar]
  41. Shipley M. J., Pocock S. J., Marmot M. G. Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study. BMJ. 1991 Jul 13;303(6794):89–92. doi: 10.1136/bmj.303.6794.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sigfusson N., Sigvaldason H., Steingrimsdottir L., Gudmundsdottir I. I., Stefansdottir I., Thorsteinsson T., Sigurdsson G. Decline in ischaemic heart disease in Iceland and change in risk factor levels. BMJ. 1991 Jun 8;302(6789):1371–1375. doi: 10.1136/bmj.302.6789.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Singh R. B., Rastogi S. S., Verma R., Laxmi B., Singh R., Ghosh S., Niaz M. A. Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up. BMJ. 1992 Apr 18;304(6833):1015–1019. doi: 10.1136/bmj.304.6833.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Stemmermann G. N., Chyou P. H., Kagan A., Nomura A. M., Yano K. Serum cholesterol and mortality among Japanese-American men. The Honolulu (Hawaii) Heart Program. Arch Intern Med. 1991 May;151(5):969–972. [PubMed] [Google Scholar]
  45. Törnberg S. A., Holm L. E., Carstensen J. M., Eklund G. A. Cancer incidence and cancer mortality in relation to serum cholesterol. J Natl Cancer Inst. 1989 Dec 20;81(24):1917–1921. doi: 10.1093/jnci/81.24.1917. [DOI] [PubMed] [Google Scholar]
  46. Watts G. F., Ahmed W., Quiney J., Houlston R., Jackson P., Iles C., Lewis B. Effective lipid lowering diets including lean meat. Br Med J (Clin Res Ed) 1988 Jan 23;296(6617):235–237. doi: 10.1136/bmj.296.6617.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Watts G. F., Lewis B., Brunt J. N., Lewis E. S., Coltart D. J., Smith L. D., Mann J. I., Swan A. V. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) Lancet. 1992 Mar 7;339(8793):563–569. doi: 10.1016/0140-6736(92)90863-x. [DOI] [PubMed] [Google Scholar]
  48. Woodhill J. M., Palmer A. J., Leelarthaepin B., McGilchrist C., Blacket R. B. Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Adv Exp Med Biol. 1978;109:317–330. doi: 10.1007/978-1-4684-0967-3_18. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES