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Thromb Haemost 2007; 98(05): 1114-1117
DOI: 10.1160/TH07-04-0300
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Low protein Z levels in patients with peripheral arterial disease

Francesco Sofi
1   Thrombosis Centre, University of Florence, Italy
,
Francesca Cesari
1   Thrombosis Centre, University of Florence, Italy
,
Giovanni Pratesi
2   Unit of Vascular Surgery, Department of Medical and Surgical Critical Care, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Center for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to DEvelop NOvel Therapies, University of Florence, Italy
,
Anna Paola Cellai
1   Thrombosis Centre, University of Florence, Italy
,
Raffaele Pulli
2   Unit of Vascular Surgery, Department of Medical and Surgical Critical Care, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Center for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to DEvelop NOvel Therapies, University of Florence, Italy
,
Carlo Pratesi
2   Unit of Vascular Surgery, Department of Medical and Surgical Critical Care, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Center for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to DEvelop NOvel Therapies, University of Florence, Italy
,
Gian Franco Gensini
1   Thrombosis Centre, University of Florence, Italy
3   Don Carlo Gnocchi Foundation, IRCCS, Florence, Italy
,
Rosanna Abbate
1   Thrombosis Centre, University of Florence, Italy
,
Sandra Fedi
1   Thrombosis Centre, University of Florence, Italy
› Author Affiliations
Further Information

Publication History

Received 24 April 2007

Accepted after resubmission 13 July 2007

Publication Date:
30 November 2017 (online)

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Summary

Conflicting findings regarding the association between protein Z and atherosclerotic disease have been reported. The aim of this case-control study was to evaluate the role of protein Z in a peripheral localization of atherosclerosis. We studied protein Z levels in 120 patients (102 male, 18 female; median age: 75 years) admitted to the Unit of Vascular Surgery of the University of Florence with a clinical manifestation of peripheral arterial disease (PAD), and in 360 healthy subjects selected to be comparable to the patients group in terms of age and gender. Protein Z levels were found to be significantly (p < 0.05) lower in PAD patients [1,594 (89–3,635) ng/ml] compared to the healthy control group [1,728 (300–3,736) ng/ml].A logistic regression analysis showed, at univariate analysis, a significantly increased risk of PAD in patients with low levels of protein Z (<5th percentile of our control group: < 601 ng/ml) (OR: 5.72, 95%CI 3.07–10.66; p < 0.0001). After adjustment for age, gender and traditional cardiovascular risk factors the association was confirmed (OR: 5.83, 95%CI 2.83–12.01; p < 0.0001). Moreover, a significant association between low protein Z levels and clinical severity of the disease, evaluated through Fontaine’s stages, was reported after adjustment for age, gender, and traditional cardiovascular risk factors (general linear model, p for trend: 0.03). In conclusion, our data shows an association between low protein Z levels and the occurrence of PAD. These findings provide evidence for the role of protein Z in the pathogenesis of the atherosclerotic disease.

Keywords

Protein Z - peripheral arterial disease - atherosclerosis
 

  • References

  • 1 Han X, Fiehler R, Broze Jr. GJ. Isolation of a protein Z-dependent plasma protease inhibitor. Proc Natl Acad Sci USA 1998; 95: 9250-9255.
    CrossrefPubMedGoogle Scholar
  • 2 Koren-Michowitz M, Eting E, Rahimi-Levene N. et al. Protein Z levels and central retinal vein or artery occlusion. Eur J Haematol 2005; 75: 401-405.
    CrossrefPubMedGoogle Scholar
  • 3 Paidas MJ, Ku D-H, Lee M-J. et al. Protein Z, protein S levels are lower in patients with thrombophilia and subsequent pregnancy complications. J Thromb Haemost 2005; 3: 497-501.
    CrossrefPubMedGoogle Scholar
  • 4 Greten J, Kreis I, Liliensiek B. et al. Localisation of protein Z in vascular lesions of patients with atherosclerosis. Vasa 1998; 27: 144-148.
    PubMedGoogle Scholar
  • 5 McQuillan A, Eikelboom J, Hankey G. et al. Protein Z in ischemic stroke and its etiologic subtypes. Stroke 2003; 34: 2415-2419.
    CrossrefPubMedGoogle Scholar
  • 6 Vasse M, Guegan-Massardier E, Borg JY. et al. Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet 2001; 357: 933-934.
    CrossrefPubMedGoogle Scholar
  • 7 Heeb MJ, Paganini-Hill A, Griffin JH. et al. Low protein Z levels and risk of ischemic stroke: differences by diabetes status and gender. Blood Cells Mol Dis 2002; 29: 139-144.
    CrossrefPubMedGoogle Scholar
  • 8 Heeb MJ, Fisher M, Paganini-Hill A. Association of low protein Z levels with ischemic stroke in young women. Thromb Haemost 2007; 97: 495-496.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Fedi S, Sofi F, Brogi D. et al. Low protein Z plasma levels are independently associated with acute coronary syndromes. Thromb Haemost 2003; 90: 1173-1178.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Sofi F, Cesari F, Vigiani S. et al. Protein Z levels in different phases of activity of coronary atherosclerosis. J Thromb Haemost 2005; 3: 2254-2258.
    CrossrefPubMedGoogle Scholar
  • 11 Morange PE, Juhan-Vague I. and the PRIME study group. Protein Z plasma levels are not associated with the risk of coronary heart disease: the PRIME study. J Thromb Haemost 2004; 2: 2050-2051.
    CrossrefPubMedGoogle Scholar
  • 12 Refaai MA, Ahn C, Lu L. et al. Protein Z and ZPI levels and cardiovascular events. J Thromb Haemost 2006; 4: 1628-1629.
    CrossrefPubMedGoogle Scholar
  • 13 Greenland P, Abrams J, Aurigemma GP. et al. Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: non-invasive tests of atherosclerosis burden. Writing Group III, Circulation 2000; 101: E16-22.
    PubMedGoogle Scholar
  • 14 Practice guidelines for primary care physicians: 2003 ESH/ESC Hypertension guidelines.. ESH/ESC hypertension guidelines committee. Hypertension 2003; 21: 1779-1186.
    CrossrefPubMedGoogle Scholar
  • 15 Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adult (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
    PubMedGoogle Scholar
  • 16 Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26: 5-20.
    CrossrefPubMedGoogle Scholar