BMJ  1990;301:309-314 (11 August), doi:10.1136/bmj.301.6747.309

Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.

Department of Medicine, University of Pittsburgh, PA 15260.

OBJECTIVE--To determine the effects of lowering cholesterol concentrations on total and cause specific mortality in randomised primary prevention trials. DESIGN--Qualitative (meta-analytic) evaluation of total mortality from coronary heart disease, cancer, and causes not related to illness in six primary prevention trials of cholesterol reduction (mean duration of treatment 4.8 years). PATIENTS--24,847 Male participants; mean age 47.5 years. MAIN OUTCOME MEASURES--Total and cause specific mortalities. RESULTS--Follow up periods totalled 119,000 person years, during which 1147 deaths occurred. Mortality from coronary heart disease tended to be lower in men receiving interventions to reduce cholesterol concentrations compared with mortality in control subjects (p = 0.06), although total mortality was not affected by treatment. No consistent relation was found between reduction of cholesterol concentrations and mortality from cancer, but there was a significant increase in deaths not related to illness (deaths from accidents, suicide, or violence) in groups receiving treatment to lower cholesterol concentrations relative to controls (p = 0.004). When drug trials were analysed separately the treatment was found to reduce mortality from coronary heart disease significantly (p = 0.04). CONCLUSIONS--The association between reduction of cholesterol concentrations and deaths not related to illness warrants further investigation. Additionally, the failure of cholesterol lowering to affect overall survival justifies a more cautious appraisal of the probable benefits of reducing cholesterol concentrations in the general population.

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• Bucher, H. C., Guyatt, G. H., Cook, D. J., Holbrook, A., McAlister, F. A., for the Evidence-Based Medicine Working Group, (1999). Users' Guides to the Medical Literature: XIX. Applying Clinical Trial Results; A. How to Use an Article Measuring the Effect of an Intervention on Surrogate End Points. JAMA 282: 771-778 [Full text]  
• Gotto, A. M. Jr (1999). Lipid-lowering therapy for the primary prevention of coronary heart disease. J Am Coll Cardiol 33: 2078-2082 [Full text]  
• Markovitz, J. H., Smith, D., Raczynski, J. M., Oberman, A., Williams, O. D., Knox, S., Jacobs, D. R. Jr (1997). Lack of Relations of Hostility, Negative Affect, and High-Risk Behavior With Low Plasma Lipid Levels in the Coronary Artery Risk Development in Young Adults Study. Arch Intern Med 157: 1953-1959 [Abstract]  
• Erickson, M. T. (1997). Lowered serum cholesterol, famine and aggression: a Darwinian hypothesis. Social Science Information 36: 211-222 [Abstract]  
• Pedersen, T. R., Berg, K., Cook, T. J., Faergeman, O., Haghfelt, T., Kjekshus, J., Miettinen, T., Musliner, T. A., Olsson, A. G., Pyorala, K., Thorgeirsson, G., Tobert, J. A., Wedel, H., Wilhelmsen, L. (1996). Safety and Tolerability of Cholesterol Lowering With Simvastatin During 5 Years in the Scandinavian Simvastatin Survival Study. Arch Intern Med 156: 2085-2092 [Abstract]  
• Marchioli, R., Marfisi, R. M., Carinci, F., Tognoni, G. (1996). Meta-analysis, Clinical Trials, and Transferability of Research Results Into Practice: The Case of Cholesterol-Lowering Interventions in the Secondary Prevention of Coronary Heart Disease. Arch Intern Med 156: 1158-1172 [Abstract]  
• Prisco, D., Caciolli, S., Del Pace, S., Gensini, G. F. (1996). State-of-the-Art Review : Sex and Cardiovascular Risk Factors. CLIN APPL THROMB HEMOST 2: 94-102  
• Newman, T. B., Hulley, S. B. (1996). Carcinogenicity of Lipid-Lowering Drugs. JAMA 275: 55-60 [Abstract]  
• Walsh, J. M. E., Grady, D. (1995). Treatment of Hyperlipidemia in Women. JAMA 274: 1152-1158 [Abstract]  
• Ellis, G. S., Kratz, A. M. (1995). Homeovitic Clearing and Detox. Complementary Health Practice Review 1: 195-203  
• The Writing Group for the DISC Collaborative Resea, , Kwiterovich, P. O., Hartmuller, G., Van Horn, L., Christoffel, K. K., Gernhoffer, N., Gidding, S., Lavigne, J. V., Lauer, R. M., Snetselaar, L., Steinmuller, P., Stickney, L., Lasser, N. L., Greenberg, R. F., Kennedy, P., Lasser, V. I., Robson, A. M., Franklin, F. A., Von Almen, K., Stevens, V. J., Craddick, S., Greenlick, M. R., Reiss, J. A., Barton, B. A., Brown, K., Canner, P. L., Kimm, S. Y. S., McMahon, R., Obarzanek, E., Cutler, J. A., Evans, M. A., Zukel, M. F., Hunsberger, S. A., Lakatos, E., Santanello, N. C., Simons-Morton, D. G., Bachorik, P. S., Gunter, E. W., Buzzard, I. M. (1995). Efficacy and Safety of Lowering Dietary Intake of Fat and Cholesterol in Children With Elevated Low-Density Lipoprotein Cholesterol: The Dietary Intervention Study in Children (DISC). JAMA 273: 1429-1435 [Abstract]  
• Luepker, R. V. (1995). Reducing Blood Cholesterol Levels in Children: What Have We Learned From the DISC Study?. JAMA 273: 1461-1462 [Abstract]  
• Iribarren, C., Reed, D. M., Wergowske, G., Burchfiel, C. M., Dwyer, J. H. (1995). Serum Cholesterol Level and Mortality Due to Suicide and Trauma in the Honolulu Heart Program. Arch Intern Med 155: 695-700 [Abstract]  
• Hamilton, V. H., Racicot, F.-E., Zowall, H., Coupal, L., Grover, S. A. (1995). The Cost-effectiveness of HMG-CoA Reductase Inhibitors to Prevent Coronary Heart Disease: Estimating the Benefits of Increasing HDL-C. JAMA 273: 1032-1038 [Abstract]  
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• Oxman, A. D., Cook, D. J., Guyatt, G. H., the Evidence-Based Medicine Working Group, , Bass, E., Brill-Edwards, P., Browman, G., Detsky, A., Farkouh, M., Gerstein, H., Haines, T., Haynes, B., Hayward, R., Holbrook, A., Jaeschke, R., Juniper, E., Laupacis, A., Lee, H., Levine, M., Moyer, V., Naylor, D., Nishikawa, J., Patel, A., Philbrick, J., Richardson, S., Sauve, S., Sacked, D., Sinclair, J., Strom, B., Trout, K. S., Tunis, S., Walter, S., Williams, J. Jr, Wilson, M. (1994). Users' Guides to the Medical Literature: VI. How to Use an Overview. JAMA 272: 1367-1371 [Abstract]  
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• Gidding, S. S. (1993). The Rationale for Lowering Serum Cholesterol Levels in American Children. Arch Pediatr Adolesc Med 147: 386-392 [Abstract]  
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• Weidner, G., Connor, S. L., Hollis, J. F., Connor, W. E. (1992). Improvements in Hostility and Depression in Relation to Dietary Change and Cholesterol Lowering: The Family Heart Study. ANN INTERN MED 117: 820-823 [Abstract]  
• Jones, K., Moon, G. (1992). Medical geography: global perspectives. Prog Hum Geogr 16: 563-572  
• The Lipid Research Clinics Investigators, (1992). The Lipid Research Clinics Coronary Primary Prevention Trial: Results of 6 Years of Post-Trial Follow-up. Arch Intern Med 152: 1399-1410 [Abstract]  
• Neaton, J. D., Blackburn, H., Jacobs, D., Kuller, L., Lee, D.-J., Sherwin, R., Shih, J., Stamler, J., Wentworth, D. (1992). Serum Cholesterol Level and Mortality Findings for Men Screened in the Multiple Risk Factor Intervention Trial. Arch Intern Med 152: 1490-1500 [Abstract]  
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• Bassler, T. J., Bassler, T. J. Jr (1992). Long-term Mortality After Primary Prevention for Cardiovascular Disease. JAMA 267: 2183-2183 [Abstract]  
• Newman, T. B., Browner, W. S., Hulley, S. B. (1992). Long-term Mortality After Primary Prevention for Cardiovascular Disease. JAMA 267: 2183-2184 [Abstract]  
• Grover, S. A., Abrahamowicz, M., Joseph, L., Brewer, C., Coupal, L., Suissa, S. (1992). The Benefits of Treating Hyperlipidemia to Prevent Coronary Heart Disease: Estimating Changes in Life Expectancy and Morbidity. JAMA 267: 816-822 [Abstract]  
• Vasan, R. S. (1992). Lowering Cholesterol and Death due to Accidents, Suicides: Unresolved Issues. Arch Intern Med 152: 414-414 [Abstract]  
• Wysowski, D. K., Gross, T. P. (1992). Lowering Cholesterol and Death due to Accidents, Suicides: Unresolved Issues-Reply. Arch Intern Med 152: 414-417 [Abstract]  
• Smith, G. D., Shipley, M. J., Marmot, M. G., Rose, G. (1992). Plasma Cholesterol Concentration and Mortality: The Whitehall Study. JAMA 267: 70-76 [Abstract]  
• Newman, T. B., Browner, W. S., Hulley, S. B. (1992). Childhood Cholesterol Screening: Contraindicated. JAMA 267: 100-101 [Abstract]  
• Criqui, M. H. (1991). Cholesterol, Primary and Secondary Prevention, and All-Cause Mortality. ANN INTERN MED 115: 973-976 [Abstract]  
• Strandberg, T. E., Salomaa, V. V., Naukkarinen, V. A., Vanhanen, H. T., Sarna, S. J., Miettinen, T. A. (1991). Long-term Mortality After 5-Year Multifactorial Primary Prevention of Cardiovascular Diseases in Middle-aged Men. JAMA 266: 1225-1229 [Abstract]  
• Paul, O., Hennekens, C. H. (1991). The Latest Report From Finland: A Lesson in Expectations. JAMA 266: 1267-1268 [Abstract]  
• Kaplan, R. M. (1991). Counseling Psychology in Health Settings: Promise and Challenge. The Counseling Psychologist 19: 376-381  
• Muldoon, M. F., Manuck, S. B., Matthews, K. A. (1991). Does Cholesterol Lowering Increase Non--Illness-Related Mortality?. Arch Intern Med 151: 1453-1453 [Abstract]  
• Wysowski, D. K., Gross, T. P. (1991). Does Cholesterol Lowering Increase Non--Illness-Related Mortality?-Reply. Arch Intern Med 151: 1453-1454 [Abstract]  
• Domenighetti, G., Lic Rer Pol, , Casabianca, A., Barazzoni, F., Lopipero, P. (1991). Cholesterol Screening of Children. JAMA 265: 3249-3249 [Abstract]  
• Resnicow, K., Berenson, G., Shea, S., Srinivasan, S., Strong, W., Wynder, E. L. (1991). The Case Against 'the Case Against Childhood Cholesterol Screening'. JAMA 265: 3003-3005 [Abstract]  
• Garber, A. M., Littenberg, B., Sox, H. C. Jr, Wagner, J. L., Gluck, M. (1991). Costs and Health Consequences of Cholesterol Screening for Asymptomatic Older Americans. Arch Intern Med 151: 1089-1095 [Abstract]  
• Stemmermann, G. N., Chyou, P.-H., Kagan, A., Nomura, A. M. Y., Yano, K. (1991). Serum Cholesterol and Mortality Among Japanese-American Men: The Honolulu (Hawaii) Heart Program. Arch Intern Med 151: 969-972 [Abstract]  
• Dalen, J. E. (1991). Detection and Treatment of Elevated Blood Cholesterol: What Have We Learned?. Arch Intern Med 151: 25-28 [Abstract]  
• Newman, T. B., Browner, W. S., Hulley, S. B. (1990). The Case Against Childhood Cholesterol Screening. JAMA 264: 3039-3043 [Abstract]  

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