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

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 lose 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.

[1]  J J Albers,et al.  Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. , 1990, The New England journal of medicine.

[2]  J. N. Morris,et al.  WHO clofibrate/cholesterol trial: clarifications , 1992, The Lancet.

[3]  The Coronary Drug Project. Initial findings leading to modifications of its research protocol. , 1970, JAMA.

[4]  P. Leren The effect of plasma-cholesterol-lowering diet in male survivors of myocardial infarction. A controlled clinical trial. , 1968, Bulletin of the New York Academy of Medicine.

[5]  C. Isles,et al.  Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men , 1992, The Lancet.

[6]  G. Rosenhamer,et al.  Effect of combined clofibrate--nicotinic acid treatment in ischemic heart disease. , 1980, Atherosclerosis.

[7]  R. Sahni,et al.  Prevention of restenosis by lovastatin after successful coronary angioplasty. , 1991, American heart journal.

[8]  C. Mcgilchrist,et al.  Low fat, low cholesterol diet in secondary prevention of coronary heart disease. , 1978, Advances in experimental medicine and biology.

[9]  J. Stamler,et al.  Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. , 1986, Journal of the American College of Cardiology.

[10]  J. N. Morris Controlled trial of soyabean oil in myocardial infarction. , 1968 .

[11]  H. Kato,et al.  Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. , 1973, American journal of epidemiology.

[12]  M. Marmot The cholesterol papers , 1994, BMJ.

[13]  A. Keys,et al.  Seven countries. A multivariate analysis of death and coronary heart disease. , 1980 .

[14]  Begg Tb,et al.  Evaluation of clofibrate therapy in peripheral arteriopathy , 1971 .

[15]  C. Hopkins,et al.  Clinical Studies of Long-Term Estrogen Therapy in Men with Myocardial Infarction , 1962, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[16]  J. Stamler The coronary drug project. Findings leading to further modifications of its protocol with respect to dextrothyroxine. The coronary drug project research group. , 1972, JAMA.

[17]  S. Pocock,et al.  Concentrations of high density lipoprotein cholesterol, triglycerides, and total cholesterol in ischaemic heart disease. , 1989, BMJ.

[18]  W. B. Thomson,et al.  Corn Oil in Treatment of Ischaemic Heart Disease , 1965, British medical journal.

[19]  C. Shear,et al.  Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin. , 1991, The American journal of medicine.

[20]  I. Hjermann,et al.  EFFECT OF DIET AND SMOKING INTERVENTION ON THE INCIDENCE OF CORONARY HEART DISEASE , 1981 .

[21]  C. E. Becker The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. , 1984, JAMA.

[22]  G. Rosenhamer,et al.  Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. , 2009, Acta medica Scandinavica.

[23]  G. Watts,et al.  Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) , 1992, The Lancet.

[24]  J. Stamler Clofibrate and niacin in coronary heart disease. , 1975, JAMA.

[25]  R. Singh,et al.  Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up. , 1992, BMJ.

[26]  R. Goldman A Controlled Clinical Trial of Diet High In Unsaturated Fat , 1971 .

[27]  K. Detre,et al.  Long‐term Changes of Serum Cholesterol with Cholesterol‐altering Drugs in Patients with Coronary Heart Disease: Veterans Administration Drug‐Lipid Cooperative Study , 1974, Circulation.

[28]  S. Manuck,et al.  Ischaemic heart disease and cholesterol Safety of cholesterol reduction remains in doubt , 1994, BMJ.

[29]  T. Manolio,et al.  Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop. , 1992, Annals of epidemiology.

[30]  G. Davey Smith,et al.  Statistical problems. , 1994, BMJ.

[31]  M. Blombäck,et al.  Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects , 1987, British medical journal.

[32]  E. Vartiainen,et al.  Change in risk factors for coronary heart disease during 10 years of a community intervention programme (North Karelia project). , 1983, British medical journal.

[33]  W. Harris,et al.  The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. , 1993, The New England journal of medicine.

[34]  S. Hashimoto,et al.  A controlled clinical trial of a diet high in unsaturated fat. Preliminary observations. , 1962, The New England journal of medicine.

[35]  Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. The pooling project research group. , 1978, Journal of chronic diseases.

[36]  J P Matts,et al.  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) , 1990, The New England journal of medicine.

[37]  S. Grundy,et al.  Comparison of three cholesterol-lowering diets in normolipidemic men. , 1986, JAMA.

[38]  M. Law,et al.  An ecological study of serum cholesterol and ischaemic heart disease between 1950 and 1990. , 1994, European journal of clinical nutrition.

[39]  U. Goldbourt,et al.  Cholesterol and coronary heart disease mortality. A 23-year follow-up study of 9902 men in Israel. , 1990, Arteriosclerosis.

[40]  J. Huttunen,et al.  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. , 1987, The New England journal of medicine.

[41]  H. Schoch The U.S. Veterans Administration Cardiology Drug-Lipid Study: An Interim Report , 1969 .

[42]  P. Allhoff,et al.  The Lipid Research Clinics Program Prevalence Study. , 1980, Circulation.

[43]  M. Law,et al.  Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study , 1994, BMJ.

[44]  L. Michaels,et al.  LOW-FAT DIET IN MYOCARDIAL INFARCTION , 1965 .

[45]  J. Stamler,et al.  Effectiveness of estrogens for therapy of myocardial infarction in middle-age men. , 1963, JAMA.

[46]  L. Gatewood,et al.  Test of Effect of Lipid Lowering by Diet on Cardiovascular Risk: The Minnesota Coronary Survey , 1989, Arteriosclerosis.

[47]  D H Blankenhorn,et al.  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. , 1987, JAMA.

[48]  H. Wisniewski,et al.  IMMUNOSUPPRESSION BY LINOLEIC ACID , 1975, The Lancet.

[49]  Ischaemic Heart Disease: A Secondary Prevention Trial Using Clofibrate , 1971 .

[50]  D. Grafnetter,et al.  A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. , 1978, British heart journal.

[51]  James D. Neaton,et al.  Serum Cholesterol, Blood Pressure, Cigarette Smoking, and Death From Coronary Heart Disease Overall Findings and Differences by Age for 316099 White Men , 1992 .

[52]  P. Allhoff,et al.  Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle Aged Men with Dyslipidemia , 1991 .

[53]  J. Huttunen,et al.  Efficacy of gemfibrozil in dyslipidaemic subjects with suspected heart disease. An ancillary study in the Helsinki Heart Study frame population. , 1993, Annals of medicine.

[54]  B. Lewis,et al.  TOWARDS AN IMPROVED LIPID-LOWERING DIET: ADDITIVE EFFECTS OF CHANGES IN NUTRIENT INTAKE , 1981, The Lancet.

[55]  M Marmot,et al.  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. , 1977, The American journal of cardiology.

[56]  J. Crouse GENDER, LIPOPROTEINS, DIET, AND CARDIOVASCULAR RISK Sauce for the goose may not be sauce for the gander , 1989, The Lancet.

[57]  W. Martin,et al.  Colestipol hydrochloride in hypercholesterolemic patients--effect on serum cholesterol and mortality. , 1978, Journal of chronic diseases.

[58]  P. Leren The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. , 1966, Acta medica Scandinavica. Supplementum.

[59]  J. Huttunen,et al.  Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality. , 1985, JAMA.

[60]  D. Mccaughan The long-term effects of probucol on serum lipid levels. , 1981, Archives of internal medicine.

[61]  R Peto,et al.  Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. , 1991, BMJ.

[62]  S. Pocock,et al.  Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study. , 1991, BMJ.

[63]  S. Rössner,et al.  Coronary Drug Project Research Group. , 1978, Atherosclerosis.

[64]  M. Karvonen,et al.  A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. , 1979, British heart journal.

[65]  I. Holme,et al.  EFFECT OF DIET AND SMOKING INTERVENTION ON THE INCIDENCE OF CORONARY HEART DISEASE Report from the Oslo Study Group of a Randomised Trial in Healthy Men , 1981, The Lancet.

[66]  L. Wilkins Plasma Lipid Distributions in Selected North American Populations: The Lipid Research Clinics Program Prevalence Study THE LIPID RESEARCH CLINICS PROGRAM EPIDEMIOLOGY COMMITTEE , 1979, Circulation.

[67]  B. Lewis,et al.  Effective lipid lowering diets including lean meat , 1988, British medical journal.

[68]  K. Yano,et al.  Serum cholesterol and mortality among Japanese-American men. The Honolulu (Hawaii) Heart Program. , 1991, Archives of internal medicine.

[69]  Roger A. Renfrew,et al.  Lipid Research Clinics Program. , 1984, JAMA.

[70]  J. Cruickshank,et al.  Fat consumption and factor VII coagulant activity in middle-aged men. An association between a dietary and thrombogenic coronary risk factor. , 1989, Atherosclerosis.

[71]  H. Blackburn,et al.  Epidemiological studies related to coronary heart disease: characteristics of men aged 40-59 in seven countries. , 2009, Acta medica Scandinavica. Supplementum.

[72]  C. Shear,et al.  Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. , 1991, Archives of internal medicine.

[73]  M. Fisher,et al.  Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. , 1984, Circulation.

[74]  Gunnar Sigurdsson,et al.  Decline in ischaemic heart disease in Iceland and change in risk factor levels. , 1991, BMJ.

[75]  P. Elwood,et al.  EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) , 1989, The Lancet.

[76]  L. Gross,et al.  Long‐Term Cholesterol‐Lowering Effect of Colestipol Resin in Humans * , 1973, Journal of the American Geriatrics Society.

[77]  O. Larsson Studies of small vessels in patients with diabetes. A clinical, histological and immunohistochemical study of diabetic and non-diabetic subjects with special reference to the occurrence of various plasma proteins in the dermal vessel walls. , 1967, Acta medica Scandinavica. Supplementum.

[78]  J. Carstensen,et al.  Cancer incidence and cancer mortality in relation to serum cholesterol. , 1989, Journal of the National Cancer Institute.

[79]  J. Reynolds Martindale : the extra pharmacopoeia , 1972 .

[80]  L. Wilhelmsen,et al.  Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study. , 1989, BMJ.