Advertisement

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP

  • C. Jublanc
    Correspondence
    Corresponding author. Tel.: +33-1-42-17-78-41; fax: +33-1-42-17-78-53.
    Affiliations
    Department of Endocrinology, Group Hospitalier la Pitié-Salpétrière, Hôpital Pitié-Salpétrière, AP-HP, 47-83 Boulevard de l’Hôpital 75651, Paris Cedex 13, France

    INSERM Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), Hôpital Pitié-Salpétrière, Paris, France
    Search for articles by this author
  • E. Bruckert
    Affiliations
    Department of Endocrinology, Group Hospitalier la Pitié-Salpétrière, Hôpital Pitié-Salpétrière, AP-HP, 47-83 Boulevard de l’Hôpital 75651, Paris Cedex 13, France

    INSERM Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), Hôpital Pitié-Salpétrière, Paris, France
    Search for articles by this author
  • P. Giral
    Affiliations
    Department of Endocrinology, Group Hospitalier la Pitié-Salpétrière, Hôpital Pitié-Salpétrière, AP-HP, 47-83 Boulevard de l’Hôpital 75651, Paris Cedex 13, France

    INSERM Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), Hôpital Pitié-Salpétrière, Paris, France
    Search for articles by this author
  • M.J. Chapman
    Affiliations
    INSERM Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), Hôpital Pitié-Salpétrière, Paris, France
    Search for articles by this author
  • L. Leenhardt
    Affiliations
    Department of Nuclear Medicine, Hôpital Pitié-Salpétrière, Paris, France
    Search for articles by this author
  • V. Carreau
    Affiliations
    Department of Endocrinology, Group Hospitalier la Pitié-Salpétrière, Hôpital Pitié-Salpétrière, AP-HP, 47-83 Boulevard de l’Hôpital 75651, Paris Cedex 13, France
    Search for articles by this author
  • G. Turpin
    Affiliations
    Department of Endocrinology, Group Hospitalier la Pitié-Salpétrière, Hôpital Pitié-Salpétrière, AP-HP, 47-83 Boulevard de l’Hôpital 75651, Paris Cedex 13, France
    Search for articles by this author

      Abstract

      The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=−0.13, P=0.02). Significant correlations between FT4 levels and age (r=−0.16, P=0.003), glycemia (r=−0.14, P=0.01), and fibrinogen (r=−0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04 mg/l versus 1.77 mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.
      In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hak A.E.
        • Pols H.A.
        • Visser T.J.
        • Drexhage H.A.
        • Hofman A.
        • Witteman J.C.
        Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.
        Ann. Int. Med. 2000; 132: 270-278
        • McDermott M.T.
        • Ridgway E.C.
        Subclinical hypothyroidism is mild thyroid failure and should be treated.
        J. Clin. Endocrinol. Metab. 2001; 86: 4585-4590
        • Klein I.
        • Ojamaa K.
        Thyroid hormone and the cardiovascular system.
        N. Engl. J. Med. 2001; 344: 501-509
        • Packard C.J.
        • Shepherd J.
        • Lindsay G.M.
        • Gaw A.
        • Taskinen M.R.
        Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-B metabolism in hypothyroidism.
        J. Clin. Endocrinol. Metab. 1993; 76: 1209-1216
        • Chadarevian R.
        • Bruckert E.
        • Leenhardt L.
        • Giral P.
        • Ankri A.
        • Turpin G.
        Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism.
        J. Clin. Endocrinol. Metab. 2001; 86: 732-737
        • Diekman M.J.
        • van der Put N.M.
        • Blom H.J.
        • Tijssen J.G.
        • Wiersinga W.M.
        Determinants of changes in plasma homocysteine in hyperthyroidism and hypothyroidism.
        Clin. Endocrinol. (Oxford). 2001; 54: 197-204
        • Christ-Crain M.
        • Mejer C.
        • Guglielmetti M.
        • Huber P.
        • Riesen W.
        • Staub J.
        • et al.
        Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial.
        Atherosclerosis. 2003; 166: 379-386
        • Chadarevian R.
        • Bruckert E.
        • Giral P.
        • Turpin G.
        Relationship between thyroid hormones and fibrinogen levels.
        Blood Coagul. Fibrinolysis. 1999; 10: 481-486
        • Bruckert E.
        • Giral P.
        • Chadarevian R.
        • Turpin G.
        Low free-thyroxine levels are a risk factor for subclinical atherosclerosis in euthyroid hyperlipidemic patients.
        J. Cardiovasc. Risk. 1999; 6: 327-331
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • Buring J.E.
        • Cook N.R.
        Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
        N. Engl. J. Med. 2002; 347: 1557-1565
        • Nieuwenhuizen W.
        Biochemistry and measurement of fibrinogen.
        Eur. Heart J. 1995; 16: 6-10
        • Ansell B.J.
        • Watson K.E.
        • Weiss R.E.
        • Fonarow G.C.
        hsCRP and HDL effects of statin trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels. A clinical investigation.
        Heart Dis. 2003; 5: 2-7
        • Van de Ree M.A.
        • Huisman M.V.
        • Princen H.M.
        • Meinders A.E.
        • Kluft C.
        Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus.
        Atherosclerosis. 2003; 166: 129-135
        • Jialal I.
        • Stein D.
        • Balis D.
        • Grundy S.M.
        • Adams-Huet B.
        • Devaraj S.
        Effect of hydroxymethyl glutaryl coenzyme A reductase inhibitor therapy on high sensitive C-reactive protein levels.
        Circulation. 2001; 103: 1933-1935
        • Pradhan A.D.
        • Manson J.E.
        • Rossouw J.E.
        • Siscovick D.
        • Mouton C.
        • Rifai N.
        • et al.
        Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative Observational Study.
        JAMA. 2002; 288: 980-987
        • Primatesta P.
        • Falaschetti E.
        • Poulter N.R.
        Influence of hormone replacement therapy on C-reactive protein: population-based data.
        J Cardiovasc. Risk. 2003; 10: 57-60
        • Ridker P.M.
        • Hennekens C.H.
        • Rifai N.
        • Buring J.E.
        • Manson J.E.
        Hormone replacement therapy and increased plasma concentration of C-reactive protein.
        Circulation. 1999; 100: 713-716
        • Ridker P.M.
        Clinical application of C-reactive protein for cardiovascular disease detection and prevention.
        Circulation. 2003; 107: 363-369
        • Magyar M.T.
        • Szikszai Z.
        • Balla J.
        • Valikovics A.
        • Kappelmayer J.
        • Imre S.
        • et al.
        Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers.
        Stroke. 2003; 34: 58-63
        • Knudsen N.
        • Bulow I.
        • Laurberg P.
        • Perrild H.
        • Ovesen L.
        • Jorgensen T.
        High occurrence of thyroid multinodularity and low occurrence of subclinical hypothyroidism among tobacco smokers in a large population study.
        J. Endocrinol. 2002; 175: 571-576
        • Vestergaard P.
        Smoking and thyroid disorders. A meta-analysis.
        Eur. J. Endocrinol. 2002; 146: 153-161
        • Mejer C.
        • Trittibach P.
        • Guglielmetti M.
        • Staub J.J.
        • Muller B.
        Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey.
        BMJ. 2003; 326: 311-312