American Journal of Epidemiology Vol. 150, No. 4: 341-353
Copyright © 1999 by The Johns Hopkins University School of Hygiene and Public Health
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Underestimation of Risk Associations Due to Regression Dilution in Long-term Follow-up of Prospective Studies
1Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Clinical Medicine Radcliffe Infirmary, Oxford, England
2Department of Epidemiology and Public Health, University College London Medical School London, England
In prospective studies, disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey. However, because of "regression dilution," this generally tends to underestimate the real associations of disease rates with the "usual" levels of such risk factors during some particular exposure period. The "regression dilution ratio" describes the ratio of the steepness of the uncorrected association to that of the real association. To assess the relevance of the usual value of a risk factor during particular exposure periods (e.g., first, second, and third decades) to disease risks, regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period (e.g., at 5, 15, and 25 years, respectively). This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol. The analyses were based on biennial remeasurements over 30 years for participants in the Framingham Study (Framingham, Massachusetts) and a 26-year resurvey for a sample of men in the Whitehall Study (London, England). They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third, the second decade by about one-half, and the third decade by about two-thirds. Hence, to correct appropriately for regression dilution, replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants. Am J Epidemiol 1999; 150: 341–53.
prospective studies; risk analysis; risk assessment
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R.W. Morris, P.H. Whincup, J.R. Emberson, F.C. Lampe, M. Walker, and A.G. Shaper North-South Gradients in Britain for Stroke and CHD: Are They Explained by the Same Factors? Stroke, November 1, 2003; 34(11): 2604 - 2609. [Abstract] [Full Text] [PDF]
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P.M. Rothwell, S.C. Howard, and J.D. Spence Relationship Between Blood Pressure and Stroke Risk in Patients With Symptomatic Carotid Occlusive Disease Stroke, November 1, 2003; 34(11): 2583 - 2590. [Abstract] [Full Text] [PDF]
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S Lewington The importance of cholesterol, blood pressure and smoking for coronary heart disease Eur. Heart J., October 1, 2003; 24(19): 1703 - 1704. [Full Text] [PDF]
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J. R Emberson, P. H Whincup, R. W Morris, and M. Walker Re-assessing the contribution of serum total cholesterol, blood pressure and cigarette smoking to the aetiology of coronary heart disease: impact of regression dilution bias Eur. Heart J., October 1, 2003; 24(19): 1719 - 1726. [Abstract] [Full Text] [PDF]
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P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
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Diuretic Versus {alpha}-Blocker as First-Step Antihypertensive Therapy: Final Results From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Hypertension, September 1, 2003; 42(3): 239 - 246. [Abstract] [Full Text] [PDF]
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D. G. Hackam and S. S. Anand Emerging Risk Factors for Atherosclerotic Vascular Disease: A Critical Review of the Evidence JAMA, August 20, 2003; 290(7): 932 - 940. [Abstract] [Full Text] [PDF]
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W. Koenig, M. Sund, M. Frohlich, H. Lowel, W. L. Hutchinson, and M. B. Pepys Refinement of the Association of Serum C-reactive Protein Concentration and Coronary Heart Disease Risk by Correction for Within-Subject Variation over Time: The MONICA Augsburg Studies, 1984 and 1987 Am. J. Epidemiol., August 15, 2003; 158(4): 357 - 364. [Abstract] [Full Text] [PDF]
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 D. A Bennett Review of analytical methods for prospective cohort studies using time to event data: single studies and implications for meta-analysis Statistical Methods in Medical Research, August 1, 2003; 12(4): 297 - 319. [Abstract] [PDF]
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Asia Pacific Cohort Studies Collaboration Cholesterol, coronary heart disease, and stroke in the Asia Pacific region Int. J. Epidemiol., August 1, 2003; 32(4): 563 - 572. [Abstract] [Full Text] [PDF]
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L. E. Eberly, J. Stamler, and J. D. Neaton Relation of Triglyceride Levels, Fasting and Nonfasting, to Fatal and Nonfatal Coronary Heart Disease Arch Intern Med, May 12, 2003; 163(9): 1077 - 1083. [Abstract] [Full Text] [PDF]
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P.H. Whincup, J. Danesh, M. Walker, L. Lennon, A. Thomson, P. Appleby, A. Rumley, and G.D.O. Lowe von Willebrand factor and coronary heart disease. Prospective study and meta-analysis Eur. Heart J., November 2, 2002; 23(22): 1764 - 1770. [Abstract] [Full Text] [PDF]
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Homocysteine Studies Collaboration Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis JAMA, October 23, 2002; 288(16): 2015 - 2022. [Abstract] [Full Text] [PDF]
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H. Tolonen, M. Mahonen, K. Asplund, D. Rastenyte, K. Kuulasmaa, D. Vanuzzo, and J. Tuomilehto Do Trends in Population Levels of Blood Pressure and Other Cardiovascular Risk Factors Explain Trends in Stroke Event Rates?: Comparisons of 15 Populations in 9 Countries Within the WHO MONICA Stroke Project Stroke, October 1, 2002; 33(10): 2367 - 2375. [Abstract] [Full Text] [PDF]
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G. Luc, J.-M. Bard, J. Ferrieres, A. Evans, P. Amouyel, D. Arveiler, J.-C. Fruchart, P. Ducimetiere, and on behalf of the PRIME Study Group Value of HDL Cholesterol, Apolipoprotein A-I, Lipoprotein A-I, and Lipoprotein A-I/A-II in Prediction of Coronary Heart Disease: The PRIME Study Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1155 - 1161. [Abstract] [Full Text] [PDF]
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E. Nurk, G. S. Tell, S. E. Vollset, O. Nygard, H. Refsum, and P. M. Ueland Plasma Total Homocysteine and Hospitalizations for Cardiovascular Disease: The Hordaland Homocysteine Study Arch Intern Med, June 24, 2002; 162(12): 1374 - 1381. [Abstract] [Full Text] [PDF]
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R. Clarke, S. Lewington, L. Youngman, P. Sherliker, R. Peto, and R. Collins Underestimation of the importance of blood pressure and cholesterol for coronary heart disease mortality in old age Eur. Heart J., February 2, 2002; 23(4): 286 - 293. [Abstract] [Full Text] [PDF]
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R. S. Vasan, J. M. Massaro, P. W.F. Wilson, S. Seshadri, P. A. Wolf, D. Levy, and R. B. D'Agostino Antecedent Blood Pressure and Risk of Cardiovascular Disease: The Framingham Heart Study Circulation, January 1, 2002; 105(1): 48 - 53. [Abstract] [Full Text] [PDF]
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R. S. Vasan, M. G. Larson, E. P. Leip, J. C. Evans, C. J. O'Donnell, W. B. Kannel, and D. Levy Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease N. Engl. J. Med., November 1, 2001; 345(18): 1291 - 1297. [Abstract] [Full Text] [PDF]
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C. L. Hart, D. J. Hole, and G. Davey Smith Are Two Really Better Than One?: Empirical Examination of Repeat Blood Pressure Measurements and Stroke Risk in the Renfrew/Paisley and Collaborative Studies Stroke, November 1, 2001; 32(11): 2697 - 2699. [Abstract] [Full Text] [PDF]
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S. Seshadri, P. A. Wolf, A. Beiser, R. S. Vasan, P. W. F. Wilson, C. S. Kase, M. Kelly-Hayes, W. B. Kannel, and R. B. D'Agostino Elevated Midlife Blood Pressure Increases Stroke Risk in Elderly Persons: The Framingham Study Arch Intern Med, October 22, 2001; 161(19): 2343 - 2350. [Abstract] [Full Text] [PDF]
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