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Effect of inter-reader variability on outcomes in studies using carotid intima media thickness quantified by carotid ultrasonography

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Abstract

Systematic differences between readers or equipment in imaging studies are not uncommon; failure to account for such differences when using Carotid Ultrasonography may introduce bias into associations between carotid intima media thickness (cIMT) and outcomes. We demonstrate the impact of this source of systematic measurement error (SME) using data on 5,521 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 661 participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Participants were between 37 and 78 years old. Two outcomes were considered: (1) the effect of HIV infection on cIMT (between study) and (2) the association of cIMT with cardiovascular events (within study). All estimates were adjusted for demographics (age, gender, and ethnicity) and for traditional cardiovascular disease risk factors (smoking, blood pressure, diabetes and cholesterol). When comparing the FRAM and MESA cohorts to estimate the association of HIV infection on common cIMT, accounting for machine and reader variability (between study variability) reduced the difference associated with HIV infection from +0.080 mm (95% Confidence Interval (CI):0.065–0.095) to +0.037 mm (95% CI:0.003 to 0.072) while internal cIMT declined from +0.254 mm (95% CI:0.205–0.303) to +0.192 mm (95% CI:0.076–0.308). Attenuation of the association between cIMT and cardiovascular endpoints occurred when within study reader variability was not accounted for. The effect of SME due to use of multiple readers or machines is most important when comparisons are made between two different study populations. Within-cohort measurement error dilutes the association with events.

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Acknowledgments

This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by NIH grants RO1-DK57508, RO1-HL74814, RO1-HL 53359, M01-RR00036, M01-RR00051, M01-RR00052, M01-RR00054, M01-RR00083, M01-RR0636, M01-RR00865 and UL1-RR024131. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The funding agency had no role in the collection or analysis of the data.

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Authors and Affiliations

  1. Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Bldg.29, Suite 310, 6200 NE 74th Street, Seattle, WA, 98115, USA

    Joseph A. C. Delaney, Mary Lou Biggs & Richard Kronmal

  2. College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA

    Joseph A. C. Delaney

  3. University of California, San Francisco, CA, USA

    Rebecca Scherzer & Carl Grunfeld

  4. Medical Service, Department of Veterans Affairs Medical Center, San Francisco, CA, USA

    Rebecca Scherzer & Carl Grunfeld

  5. Tufts Medical Center, Boston, MA, USA

    Joseph Polak

  6. Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Haiying Chen

  7. Division of Research, Kaiser Permanente, Oakland, CA, USA

    Stephen Sidney

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  1. Joseph A. C. Delaney
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  2. Rebecca Scherzer
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  3. Joseph Polak
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  4. Mary Lou Biggs
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  5. Richard Kronmal
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  6. Haiying Chen
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  7. Stephen Sidney
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  8. Carl Grunfeld
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Correspondence to Joseph A. C. Delaney.

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Delaney, J.A.C., Scherzer, R., Polak, J. et al. Effect of inter-reader variability on outcomes in studies using carotid intima media thickness quantified by carotid ultrasonography. Eur J Epidemiol 25, 385–392 (2010). https://doi.org/10.1007/s10654-010-9442-8

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  • DOI: https://doi.org/10.1007/s10654-010-9442-8

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