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Thromb Haemost 2003; 90(06): 1192-1197
DOI: 10.1160/TH03-01-0053
Vascular Development and Vessel Remodelling
Schattauer GmbH

Markers of endothelial activation and atherothrombosis in women with history of preeclampsia or gestational hypertension

Mark Vickers
1   Department of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland
,
Isobel Ford
1   Department of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland
,
Rona Morrison
1   Department of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland
,
Gordon Prescott
2   Department of Public Health, University of Aberdeen, Aberdeen, Scotland
,
Stuart Watson
2   Department of Public Health, University of Aberdeen, Aberdeen, Scotland
,
Philip Hannaford
4   Department of General Practice & Primary Care, University of Aberdeen, Aberdeen, Scotland
,
Cairns Smith
2   Department of Public Health, University of Aberdeen, Aberdeen, Scotland
,
Doris Campbell
3   Department of Obstetrics & Gynaecology, University of Aberdeen, Aberdeen, Scotland
,
Michael Greaves
1   Department of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland
› Author AffiliationsFinancial support: We thank the British Heart Foundation for funding the collection of blood samples and Tenovus who funded their laboratory analyses.
Further Information

Publication History

Received 27 January 2003

Accepted after resubmission 08 August 2003

Publication Date:
05 December 2017 (online)

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Summary

Women who have had preeclampsia (PE) or gestational hypertension (GH) exhibit relatively high rates of circulatory diseases. PE is a disease associated with inflammation and vascular endothelial dysfunction. We therefore hypothesised that women with a history of PE or GH might have abnormal levels of markers of endothelial activation or inflammation, reflecting either an innate predisposition to preeclampsia or changes induced by the eclamptic process. Levels of von Willebrand factor, fibrinogen and C-reactive protein were compared in 392 women with a history of PE between 1951 and 1970, 297 women with a history of GH and 163 matched controls. Although no significant differences between those with either PE or GH and controls were noted, subjects with a history of PE had significantly higher CRP values than those with GH. No significant differences were found when the three groups were compared for von Willebrand factor or fibrinogen. Overall, the data do not support our hypothesis.

In addition, our data document increasing von Willebrand factor levels increase with age, which may help explain the age dependent increase in venous or arterial thrombosis. Moderate alcohol consumption was also associated with lower levels of inflammatory markers.

Keywords

Preeclampsia - fibrinogen - von Willebrand factor - C-reactive protein - vascular endothelium
 

  • References

  • 1 Roberts JM, Cooper DW. Pathogenesis and genetics of preeclampsia. Lancet 2001; 357: 53-6.
    CrossrefPubMedGoogle Scholar
  • 2 Esplin MS, Fausett MB, Fraser A. et al. Paternal and maternal components of the predisposition to preeclampsia. NEJM 2001; 344: 867-72.
    CrossrefPubMedGoogle Scholar
  • 3 Higgins JR, de Swiet M. Blood pressure measurement and classification in pregnancy. Lancet 2001; 357: 131-5.
    CrossrefPubMedGoogle Scholar
  • 4 Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. In: Wynn R, ed. Obstetrics and Gynecology Annual 1979; 177-191.
    PubMedGoogle Scholar
  • 5 Pijnenborg R. et al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynae 1991; 986: 48-55.
    PubMedGoogle Scholar
  • 6 Taylor RN. et al. Selective effects of preeclamptic sera as human endothelial cell pro-coagulant protein expression. Am J Obst Gynecol 1991; 165: 1705-10.
    CrossrefPubMedGoogle Scholar
  • 7 Roberts JM. Endothelial dysfunction in preclampsia. Semin Reprod Endocrinol 1998; 16: 5-15.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Verhaar MC, Rabelink TJ. The endothelium: a gynecological and obstetric point of view. Eur J Obst Gyn & Reprod Biol 2001; 94: 180-5.
    PubMedGoogle Scholar
  • 9 Roberts JM, Taylor RN, Musci TJ. et al. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 1989; 161: 1200-4.
    CrossrefPubMedGoogle Scholar
  • 10 Krauss T. et al. Circulating endothelial cell adhesion molecules as diagnostic markers for the early identification of pregnant women at risk for development of preeclampsia. Am J Obst Gynecol 1997; 177: 443-9.
    CrossrefPubMedGoogle Scholar
  • 11 Sibai BM. Risk factors, pregnancy complications, and prevention of hypertensive disorders in women with pregravid diabetes mellitus. J Matern-Fetal Med 2000; 9: 62-5.
    PubMedGoogle Scholar
  • 12 Sugi T, Makino T. Autoantibodies to contact proteins in patients with recurrent pregnancy losses. J Reprod Immunol 2002; 53: 269-77.
    CrossrefPubMedGoogle Scholar
  • 13 Greaves M. Antiphospholipid antibodies and thrombosis. Lancet 1999; 353: 1348-53.
    CrossrefPubMedGoogle Scholar
  • 14 Chesley LC. et al. The familial factor in toxemia of pregnancy. Obst Gynecol 1968; 32: 303-11.
    PubMedGoogle Scholar
  • 15 Lachmeijer AM, Aarnoudse JE, ten Kate LP. et al. Concordance for pre-eclampsia in mono-zygous twins. Br J Obstet Gynecol 1998; 105: 1315-7.
    CrossrefPubMedGoogle Scholar
  • 16 Thornton JG, Macdonald AM. Twin mothers, pregnancy hypertension and pre-eclampsia. Br J Obstet Gynaecol 1999; 106: 570-5.
    CrossrefPubMedGoogle Scholar
  • 17 Ros HS, Lichtenstein P, Lipworth L. et al. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet 2000; 91: 256-60.
    CrossrefPubMedGoogle Scholar
  • 18 Chesley LC, Annitto JE, Cosgrove RA. The remote prognosis of eclamptic women. Sixth periodic report. Am J Obstet Gynecol 1976; 124: 446-59.
    CrossrefPubMedGoogle Scholar
  • 19 Fisher KA, Luger A, Spargo BH. et al. Hypertension in pregnancy: clinical-pathological correlations and remote prognosis. Medicine 1981; 60: 267-76.
    CrossrefPubMedGoogle Scholar
  • 20 Jonsdottir LS, Arngrimsson R, Geirsson RT. et al. Death rates from ischemic heart disease in women with a history of hypertension in pregnancy. Acta Obstet Gynecol Scand 1995; 74: 772-6.
    CrossrefPubMedGoogle Scholar
  • 21 Wilson BJ, Watson SM, Prescott GJ. et al. Hypertensive diseases of pregnancy and the risk of hypertension and stroke in later life. Br Med J 2003; 326: 845-9.
    CrossrefPubMedGoogle Scholar
  • 22 Fujimura Y, Titani K. ‘Structure and Func-tion of von Willebrand factor&rsquo. In Bloom AL, Forbes CD, Thomas DP. EGD Tuddenham -Haemostasis and Thrombosis, 3rd ed Edinburgh, UK: Chur-chill Livingstone; 379-96.
    Google Scholar
  • 23 Mannucci PM. Von Willebrand factor: a marker of endothelial damage?. Arterioscler, Thromb Vasc Biol 1998; 18: 1359-62.
    CrossrefPubMedGoogle Scholar
  • 24 Whincup PH, Danesh J, Walker M. et al. Von Willbebrand factor and coronary heart disease Prospective study and meta-analysis. Eur Heart J 2002; 23: 1764-70.
    CrossrefPubMedGoogle Scholar
  • 25 Kumari M, Marmot M, Brunner E. Social determinants of von Willebrand factor: the Whitehall II study. Arterioscler Thromb Vasc Biol 2000; 20: 1842-7.
    CrossrefPubMedGoogle Scholar
  • 26 Szalai AJ, van Ginkel FW, Dalrymple SA. et al. Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice. J Immunol 1998; 160: 5294-5299.
    PubMedGoogle Scholar
  • 27 Weinhold B, Bader A, Poli V. et al. Interleukin-6 is necessary, but not sufficient, for induction of the human C-reactive protein gene in vivo. Biochem J 1997; 325: 617-21.
    CrossrefPubMedGoogle Scholar
  • 28 Culley FJ, Bodman-Smith KB, Ferguson MA. et al. C-reactive protein binds to phosphory-lated carbohydrates. Glycobiology 2000; 10: 59-65.
    CrossrefPubMedGoogle Scholar
  • 29 Danesh J, Collins R, Appleby P. et al. Association of fibrinogen, C-reactive protein, albumin or leukocyte count with coronary heart disease: meta-analysis of prospective studies. JAMA 1998; 279: 1477-82.
    CrossrefPubMedGoogle Scholar
  • 30 Danesh J, Whincup P, Walker M. et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321: 199-204.
    CrossrefPubMedGoogle Scholar
  • 31 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165-8.
    CrossrefPubMedGoogle Scholar
  • 32 Redman CW, Sacks GP, Sargent IL. Preeclampsia, an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999; 180: 499-506.
    CrossrefPubMedGoogle Scholar
  • 33 Ray A. A SAF binding site in the promoter region of human gamma-fibrinogen gene functions as an Il-6 response element. J Immunol 2000; 165: 3411-17.
    CrossrefPubMedGoogle Scholar
  • 34 Hutchinson WL. et al. Immunoradiometric assay of circulating C-reactive proteins: age-related values in the adult general population. Clin Chem 2000; 46: 934-68.
    PubMedGoogle Scholar
  • 35 Thun MJ, Peto R, Lopez AD. et al. Alcohol consumption and mortality among middle aged and elderly US adults. NEJM 1997; 337: 1705-14.
    CrossrefPubMedGoogle Scholar
  • 36 Clausen T, Djurovic S, Brosstad FR. et al. Altered circulating levels of adhesion molecules at 18 weeks’ gestation among women with eventual preeclampsia: indicators of disturbed placentation in absence of evidence of endothelial dysfunction?. Am J Obstet Gynecol 2000; 182: 321-5.
    CrossrefPubMedGoogle Scholar
  • 37 Chambers JC, Fusi L, Malik IS. et al. Association of maternal endothelial dysfunction with preeclampsia. JAMA 2001; 285: 1607-12.
    CrossrefPubMedGoogle Scholar
  • 38 Mayosi BM, Vickers MA, Green FR. et al. Evidence of a quantitative trait locus for plasma fibrinogen from a family-based association study. Genescreen 2001; 1: 151-5.
    CrossrefPubMedGoogle Scholar
  • 39 Vickers MA. et al. Genotype at a promoter polymorphism of the interleukin-6 gene is associated with plasma C-reactive protein. Cardiovasc Res 2002; 53: 1029-34.
    CrossrefPubMedGoogle Scholar
  • 40 Ross R. Atherosclerosis – an inflammatory disease. NEJM 1999; 340: 115-26.
    CrossrefPubMedGoogle Scholar
  • 41 Grandone E. et al. Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or without proteinuria. Thromb Haemost 1999; 81: 349-52.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Morrison ER, Miedzybrodzka ZH, Campbell DM. et al. Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. Thromb Haemost 2002; 87: 779-85.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Kraaijenhagen RA. et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. NEJM 2000 343: 457-62.
    PubMedGoogle Scholar
  • 45 Kamphuisen PW, Lensen R, Houwing-Duistermaat JJ. et al. Heritability of elevated factor VIII antigen levels in factor V Leiden families with thrombophilia. Br J Haem 2000; 109: 519-22.
    CrossrefPubMedGoogle Scholar
  • 46 Kamphuisen PW, Rosendaal FR, Eikenboom JC. et al. Factor V antigen levels and venous thromobosis: risk profile, interaction with factor V Leiden and relation with factor VIII antigen levels. Arterioscler, Thromb Vasc Biol 2000; 20: 1382-6.
    CrossrefPubMedGoogle Scholar
  • 47 Imhof A, Froehlich M, Brenner H. et al. Effect of alcohol consumption on systemic markers of inflammation. Lancet 2001; 357: 763-7.
    CrossrefPubMedGoogle Scholar