Skip to main content
PMC home page
The BMJ logoLink to The BMJ
. 1994 Feb 5;308(6925):373–379. doi: 10.1136/bmj.308.6925.373

Assessing possible hazards of reducing serum cholesterol.

M R Law 1, S G Thompson 1, N J Wald 1
PMCID: PMC2539477  PMID: 8124144

Abstract

OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration. RESULTS--The only cause of death attributable to low serum cholesterol concentration was haemorrhagic stroke. The excess risk was associated only with concentrations below about 5 mmol/l (relative risk 1.9, 95% confidence interval 1.4 to 2.5), affecting about 6% of people in Western populations. For noncirculatory causes of death there was a pronounced difference between cohort studies of employed men, likely to be healthy at recruitment, and cohort studies of subjects in community settings, necessarily including some with existing disease. The employed cohorts showed no excess mortality. The community cohorts showed associations between low cholesterol concentration and lung cancer, haemopoietic cancers, suicide, chronic bronchitis, and chronic liver and bowel disease; these were most satisfactorily explained by early disease or by factors that cause the disease lowering serum cholesterol concentration (depression causes suicide and lowers cholesterol concentration, for example). In the randomised trials nine deaths (from a total of 687 deaths not due to ischaemic heart disease in treated subjects) were attributed to known adverse effects of the specific treatments, but otherwise there was no evidence of an increased mortality from any cause arising from reduction in cholesterol concentration. CONCLUSIONS--There is no evidence that low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. This risk affects only those people with a very low concentration and even in these will be outweighed by the benefits from the low risk of ischaemic heart disease.

Full text

PDF
379

Selected References

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

  1. Alvarez C., Ramos A. Lipids, lipoproteins, and apoproteins in serum during infection. Clin Chem. 1986 Jan;32(1 Pt 1):142–145. [PubMed] [Google Scholar]
  2. Baptiste M. S., Nasca P. C., Doyle J. T., Rothenberg R. R., MacCubbin P. A., Mettlin C., Metzger B. B., Carlton K. A. Cholesterol and cancer in a population of male civil service workers. Int J Epidemiol. 1992 Feb;21(1):16–22. doi: 10.1093/ije/21.1.16. [DOI] [PubMed] [Google Scholar]
  3. Blackburn H., Jacobs D. R., Jr The ongoing natural experiment of cardiovascular diseases in Japan. Circulation. 1989 Mar;79(3):718–720. doi: 10.1161/01.cir.79.3.718. [DOI] [PubMed] [Google Scholar]
  4. Cambien F., Ducimetiere P., Richard J. Total serum cholesterol and cancer mortality in a middle-aged male population. Am J Epidemiol. 1980 Sep;112(3):388–394. doi: 10.1093/oxfordjournals.aje.a113004. [DOI] [PubMed] [Google Scholar]
  5. Chen Z., Keech A., Collins R., Slavin B., Chen J., Campbell T. C., Peto R. Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer. BMJ. 1993 Apr 3;306(6882):890–894. doi: 10.1136/bmj.306.6882.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Davey Smith G., Pekkanen J. Should there be a moratorium on the use of cholesterol lowering drugs? BMJ. 1992 Feb 15;304(6824):431–434. doi: 10.1136/bmj.304.6824.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dewar H. A., Oliver M. F. Trial of clofibrate. Br Med J. 1972 Feb 19;1(5798):506–506. doi: 10.1136/bmj.1.5798.506-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Downs J. R., Oster G., Santanello N. C. HMG CoA reductase inhibitors and quality of life. JAMA. 1993 Jun 23;269(24):3107–3108. doi: 10.1001/jama.269.24.3107. [DOI] [PubMed] [Google Scholar]
  10. Dujovne C. A., Chremos A. N., Pool J. L., Schnaper H., Bradford R. H., Shear C. L., Higgins J., Downton M., Franklin F. A., Nash D. T. Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin. Am J Med. 1991 Jul 31;91(1B):25S–30S. doi: 10.1016/0002-9343(91)90053-z. [DOI] [PubMed] [Google Scholar]
  11. Dyer A. R., Stamler J., Paul O., Shekelle R. B., Schoenberger J. A., Berkson D. M., Lepper M., Collette P., Shekelle S., Lindberg H. A. Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J Chronic Dis. 1981;34(6):249–260. doi: 10.1016/0021-9681(81)90030-8. [DOI] [PubMed] [Google Scholar]
  12. Editorial: Presentation of myocardial infarction. Br Med J. 1974 Jan 5;1(5896):1–1. doi: 10.1136/bmj.1.5896.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frank J. W., Reed D. M., Grove J. S., Benfante R. Will lowering population levels of serum cholesterol affect total mortality? Expectations from the Honolulu Heart Program. J Clin Epidemiol. 1992 Apr;45(4):333–346. doi: 10.1016/0895-4356(92)90034-k. [DOI] [PubMed] [Google Scholar]
  14. Glueck C. J., Sanghvi V. R., Laemmle P., Unger L., McCray C., Tracy T., Speirs J., Lang J., Tieger M., Kunkel R. Lack of concordance in classification of coronary heart disease risk: high-risk HDL cholesterol less than 35 mg/dl in subjects with desirable total serum cholesterol, less than 200 mg/dl. J Lab Clin Med. 1990 Sep;116(3):377–385. [PubMed] [Google Scholar]
  15. Goble A. J., Worcester M. C. Low serum cholesterol and violent death. BMJ. 1992 Sep 26;305(6856):773–773. doi: 10.1136/bmj.305.6856.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Iso H., Jacobs D. R., Jr, Wentworth D., Neaton J. D., Cohen J. D. 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):904–910. doi: 10.1056/NEJM198904063201405. [DOI] [PubMed] [Google Scholar]
  17. Jacobs D., Blackburn H., Higgins M., Reed D., Iso H., McMillan G., Neaton J., Nelson J., Potter J., Rifkind B. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation. 1992 Sep;86(3):1046–1060. doi: 10.1161/01.cir.86.3.1046. [DOI] [PubMed] [Google Scholar]
  18. Kerttula Y., Weber T. Serum lipids in pneumonia of different aetiology. Ann Clin Res. 1988;20(3):184–188. [PubMed] [Google Scholar]
  19. Klag M. J., Ford D. E., Mead L. A., He J., Whelton P. K., Liang K. Y., Levine D. M. Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med. 1993 Feb 4;328(5):313–318. doi: 10.1056/NEJM199302043280504. [DOI] [PubMed] [Google Scholar]
  20. Law M. R., Thompson S. G. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control. 1991 Jul;2(4):253–261. doi: 10.1007/BF00052142. [DOI] [PubMed] [Google Scholar]
  21. Law M. R., Wald N. J., Thompson S. G. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ. 1994 Feb 5;308(6925):367–372. doi: 10.1136/bmj.308.6925.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Leren P. The Oslo diet-heart study. Eleven-year report. Circulation. 1970 Nov;42(5):935–942. doi: 10.1161/01.cir.42.5.935. [DOI] [PubMed] [Google Scholar]
  23. Lindberg G., Råstam L., Gullberg B., Eklund G. A. Low serum cholesterol concentration and short term mortality from injuries in men and women. BMJ. 1992 Aug 1;305(6848):277–279. doi: 10.1136/bmj.305.6848.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Magni G., Garreau M., Orofiamma B., Palminteri R. Fengabine, a new GABAmimetic agent in the treatment of depressive disorders: an overview of six double-blind studies versus tricyclics. Neuropsychobiology. 1989;20(3):126–131. doi: 10.1159/000118485. [DOI] [PubMed] [Google Scholar]
  25. Menotti A., Keys A., Blackburn H., Aravanis C., Dontas A., Fidanza F., Giampaoli S., Karvonen M., Kromhout D., Nedeljkovic S. Twenty-year stroke mortality and prediction in twelve cohorts of the Seven Countries Study. Int J Epidemiol. 1990 Jun;19(2):309–315. doi: 10.1093/ije/19.2.309. [DOI] [PubMed] [Google Scholar]
  26. Morgan R. E., Palinkas L. A., Barrett-Connor E. L., Wingard D. L. Plasma cholesterol and depressive symptoms in older men. Lancet. 1993 Jan 9;341(8837):75–79. doi: 10.1016/0140-6736(93)92556-9. [DOI] [PubMed] [Google Scholar]
  27. Muldoon M. F., Manuck S. B., Matthews K. A. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ. 1990 Aug 11;301(6747):309–314. doi: 10.1136/bmj.301.6747.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Neaton J. D., Blackburn H., Jacobs D., Kuller L., Lee D. J., Sherwin R., Shih J., Stamler J., Wentworth D. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992 Jul;152(7):1490–1500. [PubMed] [Google Scholar]
  29. Oliver M. F. Reducing cholesterol does not reduce mortality. J Am Coll Cardiol. 1988 Sep;12(3):814–817. doi: 10.1016/0735-1097(88)90327-0. [DOI] [PubMed] [Google Scholar]
  30. Ooneda G., Yoshida Y., Suzuki K., Shinkai H., Hori S., Kobori K., Takayama Y., Sekiguchi M. Smooth muscle cells in the development of plasmatic arterionecrosis, arteriosclerosis, and arterial contraction. Blood Vessels. 1978;15(1-3):148–156. doi: 10.1159/000158160. [DOI] [PubMed] [Google Scholar]
  31. Pearce M. L., Dayton S. Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet. 1971 Mar 6;1(7697):464–467. doi: 10.1016/s0140-6736(71)91086-5. [DOI] [PubMed] [Google Scholar]
  32. Persson B., Johansson B. W. The Kockum study: twenty-two-year follow-up. Coronary heart disease in a population in the south of Sweden. Acta Med Scand. 1984;216(5):485–493. [PubMed] [Google Scholar]
  33. Peto R., Boreham J., Chen J., Li J., Campbell T. C., Brun T. Plasma cholesterol, coronary heart disease, and cancer. BMJ. 1989 May 6;298(6682):1249–1249. doi: 10.1136/bmj.298.6682.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Prentice R. L., Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control. 1990 Jul;1(1):81–109. doi: 10.1007/BF00053187. [DOI] [PubMed] [Google Scholar]
  35. Seppä K., Sillanaukee P., Pitkäjärvi T., Nikkilä M., Koivula T. Moderate and heavy alcohol consumption have no favorable effect on lipid values. Arch Intern Med. 1992 Feb;152(2):297–300. doi: 10.1001/archinte.1992.00400140051012. [DOI] [PubMed] [Google Scholar]
  36. Shimamoto T., Komachi Y., Inada H., Doi M., Iso H., Sato S., Kitamura A., Iida M., Konishi M., Nakanishi N. Trends for coronary heart disease and stroke and their risk factors in Japan. Circulation. 1989 Mar;79(3):503–515. doi: 10.1161/01.cir.79.3.503. [DOI] [PubMed] [Google Scholar]
  37. Smith G. D., Shipley M. J., Marmot M. G., Rose G. Plasma cholesterol concentration and mortality. The Whitehall Study. JAMA. 1992 Jan 1;267(1):70–76. [PubMed] [Google Scholar]
  38. Smith G. D., Song F., Sheldon T. A. Cholesterol lowering and mortality: the importance of considering initial level of risk. BMJ. 1993 May 22;306(6889):1367–1373. doi: 10.1136/bmj.306.6889.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Szatrowski T. P., Peterson A. V., Jr, Shimizu Y., Prentice R. L., Mason M. W., Fukunaga Y., Kato H. Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort. J Chronic Dis. 1984;37(7):569–584. doi: 10.1016/0021-9681(84)90007-9. [DOI] [PubMed] [Google Scholar]
  40. Takeya Y., Popper J. S., Shimizu Y., Kato H., Rhoads G. G., Kagan A. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: incidence of stroke in Japan and Hawaii. Stroke. 1984 Jan-Feb;15(1):15–23. doi: 10.1161/01.str.15.1.15. [DOI] [PubMed] [Google Scholar]
  41. Tanaka H., Ueda Y., Hayashi M., Date C., Baba T., Yamashita H., Shoji H., Tanaka Y., Owada K., Detels R. Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke. 1982 Jan-Feb;13(1):62–73. doi: 10.1161/01.str.13.1.62. [DOI] [PubMed] [Google Scholar]
  42. Ueshima H., Iida M., Shimamoto T., Konishi M., Tsujioka K., Tanigaki M., Nakanishi N., Ozawa H., Kojima S., Komachi Y. Multivariate analysis of risk factors for stroke. Eight-year follow-up study of farming villages in Akita, Japan. Prev Med. 1980 Nov;9(6):722–740. doi: 10.1016/0091-7435(80)90017-1. [DOI] [PubMed] [Google Scholar]
  43. Westlund K., Nicolaysen R. Ten-year mortality and morbidity related to serum cholesterol. A follow-up of 3.751 men aged 40-49. Scand J Clin Lab Invest Suppl. 1972;127:1–24. [PubMed] [Google Scholar]
  44. Wynder E. L., Hebert J. R., Kabat G. C. Association of dietary fat and lung cancer. J Natl Cancer Inst. 1987 Oct;79(4):631–637. [PubMed] [Google Scholar]
  45. Wysowski D. K., Gross T. P. Deaths due to accidents and violence in two recent trials of cholesterol-lowering drugs. Arch Intern Med. 1990 Oct;150(10):2169–2172. [PubMed] [Google Scholar]

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

RESOURCES