Journal of Vascular Surgery
Volume 52, Issue 1 , Pages 85-90, July 2010

Biomarkers in peripheral arterial disease patients and near- and longer-term mortality

  • Michael H. Criqui, MD, MPH

      Affiliations

    • University of California San Diego School of Medicine, La Jolla, Calif
    • Corresponding Author InformationReprint requests: Michael H. Criqui, MD, MPH, University of California, San Diego, Department of Family and Preventive Medicine, 9500 Gilman Dr. MC:0607, La Jolla, CA 92093-0607
  • ,
  • Lindsey A. Ho, MPH

      Affiliations

    • University of California San Diego School of Medicine, La Jolla, Calif
    • School of Public Health, University of North Carolina, Chapel Hill, NC
  • ,
  • Julie O. Denenberg, MA

      Affiliations

    • University of California San Diego School of Medicine, La Jolla, Calif
  • ,
  • Paul M. Ridker, MD, MPH

      Affiliations

    • School of Public Health, Harvard University, Boston, Mass
  • ,
  • Christina L. Wassel, PhD

      Affiliations

    • University of California San Diego School of Medicine, La Jolla, Calif
  • ,
  • Mary M. McDermott, MD

      Affiliations

    • Feinberg School of Medicine, Northwestern University, Chicago, Ill

Received 6 November 2009; accepted 4 February 2010. published online 17 May 2010.

Background

Whether novel biomarkers improve risk prediction of mortality beyond standard cardiovascular disease (CVD) risk markers in peripheral arterial disease (PAD) patients, and whether any such prediction differs with length of follow-up, remains controversial. Our objective was to determine in patients with PAD whether novel biomarkers improve prediction of CVD mortality and total mortality.

Methods

A cohort of 397 patients who were referred to a vascular lab had PAD diagnosed by noninvasive testing. Fifty-eight percent also had coronary or cerebrovascular disease at baseline. Predictors of total, CVD, and non-CVD mortality were assessed with Cox proportional hazards models, and the incremental value of predictors was evaluated with both the C-statistic and the integrated discrimination improvement (IDI) index.

Results

Total mortality was 11% at 2-year follow-up and 65% at an average of 6.6-year of follow-up (maximum, 11.4 years). At 2 years, hs-CRP was a strong and significant predictor of mortality, with a hazard ratio (HR) of 1.56 per standard deviation (P = .006). However, at full follow up, standard CVD risk markers were significant (age, gender, ankle-brachial index, other CVD, and hypertension), but hs-CRP no longer showed a significant relationship (HR 1.12; P = .11). None of the other biomarkers studied showed a significant independent association with mortality. Hs-CRP improved the C-statistic and the IDI beyond standard risk markers at 2 years, but not at full follow-up.

Conclusions

hs-CRP was a strong predictor of short-term mortality in this cohort of PAD patients, while standard risk markers were better at predicting longer-term mortality.

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 Supported by National Institutes of Health grant HL42973., NIH-NCRR General Clinical Research Center Program Grant M01 RR00827, American Heart Association Grant-in-Aid No. 0050002N, and a small grant from Glaxo Smith Kline.

 Dr Ridker is listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.

 The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest.

PII: S0741-5214(10)00256-9

doi:10.1016/j.jvs.2010.02.004

Journal of Vascular Surgery
Volume 52, Issue 1 , Pages 85-90, July 2010