Advertisement

Long-term LDL-c lowering in heterozygous familial hypercholesterolemia normalizes carotid intima-media thickness

  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    S. Sivapalaratnam
    Correspondence
    Corresponding author. Tel.: +31 20 566 6396; fax: +31 20 5669343.
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    Department of Vascular Medicine, Academic Medical Centre, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the manuscript.
    L.L. van Loendersloot
    Footnotes
    1 These authors contributed equally to the manuscript.
    Affiliations
    Department of Vascular Medicine, Academic Medical Centre, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

    Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands
    Search for articles by this author
  • B.A. Hutten
    Affiliations
    Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands
    Search for articles by this author
  • J.J.P. Kastelein
    Affiliations
    Department of Vascular Medicine, Academic Medical Centre, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Search for articles by this author
  • M.D. Trip
    Affiliations
    Department of Vascular Medicine, Academic Medical Centre, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Search for articles by this author
  • E. de Groot
    Affiliations
    Department of Vascular Medicine, Academic Medical Centre, F4-159.2, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the manuscript.

      Abstract

      Objective

      We investigated the effectiveness of statins in daily practice in reducing the arterial wall thicknesses by comparing the carotid intima-media thickness (cIMT) between statin-treated familial hypercholesterolemia (FH) patients and their unaffected spouses.

      Methods

      FH subjects treated with LDL-c lowering medication for at least 5 years and their unaffected spouses were included in this observational study. Clinical data and carotid intima-media thickness (cIMT) as surrogate marker for atherosclerosis were acquired.

      Results

      In total 40 FH patients, age 48.4 ± 4.2 years, and their 40 unaffected spouses, age 47.4 ± 3.9 years, were included. Pre-treatment total cholesterol levels of FH patients were on average 9.3 ± 2.0 mmol/L. Treated FH patients and unaffected spouses exhibited similar LDL-c (3.8 ± 1.5 vs. 3.5 ± 1.1 mmol/L; p = 0.25) and total cholesterol levels (5.8 ± 1.6 vs. 5.6 ± 1.1 mmol/L; p = 0.56). Also, in a multivariate model cIMT adjusted for age and sex did not differ between affecteds and spouses (95% CI: −0.032 to 0.092 mm; p = 0.34).

      Conclusion

      Long-term statin treatment normalizes cIMT in severe FH patients and therefore it is likely that the extreme risk of cardiovascular disease in FH patients is significantly reduced by this therapy.

      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

        • Goldstein J.L.
        • Hobbs H.H.
        • Brown M.S.
        Familial hypercholesterolemia.
        in: Baudet A.L. Vogelstein B. Kinzler K. Atonarakis A. Ballabio A. The metabolic and molecular basis of inherited disease. McGrawHill, New York2007
        • Huijgen R.
        • Vissers M.N.
        • Defesche J.C.
        • Lansberg P.J.
        • Kastelein J.J.
        • Hutten B.A.
        Familial hypercholesterolemia: current treatment and advances in management.
        Expert Rev Cardiovasc Ther. 2008; : 567-581
        • van Aalst-Cohen E.S.
        • Jansen A.C.
        • Tanck M.W.
        • et al.
        Diagnosing familial hypercholesterolaemia: the relevance of genetic testing.
        Eur Heart J. 2006; : 2240-2246
        • Stone N.J.
        • Levy R.I.
        • Fredrickson D.S.
        • Verter J.
        Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia.
        Circulation. 1974; : 476-488
        • Slack J.
        Risks of ischaemic heart-disease in familial hyperlipoproteinaemic states.
        Lancet. 1969; : 1380-1382
        • Havel R.J.
        • Hunninghake D.B.
        • Illingworth D.R.
        • et al.
        Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study.
        Ann Intern Med. 1987; : 609-615
        • Smilde T.J.
        • van W.S.
        • Wollersheim H.
        • Trip M.D.
        • Kastelein J.J.
        • Stalenhoef A.F.
        Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.
        Lancet. 2001; : 577-581
        • de Sauvage Nolting P.R.
        • Buirma R.J.
        • Hutten B.A.
        • Kastelein J.J.
        Two-year efficacy and safety of simvastatin 80 mg in familial hypercholesterolemia (the Examination of Probands and Relatives in Statin Studies With Familial Hypercholesterolemia [ExPRESS FH]).
        Am J Cardiol. 2002; : 181-184
        • Neil A.
        • Cooper J.
        • Betteridge J.
        • et al.
        Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study.
        Eur Heart J. 2008; : 2625-2633
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; : 499-502
        • Groot de E.
        • Hovingh G.K.
        • Wiegman A.
        • et al.
        Measurement of arterial wall thickness as a surrogate marker for atherosclerosis.
        Circulation. 2004; : III33-III38
        • Groot de E.
        • Zwinderman A.H.
        • van der Steen A.F.
        • et al.
        Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study.
        Ultrasound Med Biol. 1998; : 825-832
        • Lorenz M.W.
        • Markus H.S.
        • Bots M.L.
        • Rosvall M.
        • Sitzer M.
        Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis.
        Circulation. 2007; : 459-467
        • Versmissen J.
        • Oosterveer D.M.
        • Yazdanpanah M.
        • et al.
        Efficacy of statins in familial hypercholesterolaemia: a long term cohort study.
        BMJ. 2008; : a2423
        • Espeland M.A.
        • O’Leary D.H.
        • Terry J.G.
        • et al.
        Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors.
        Curr Control Trials Cardiovasc Med. 2005; : 3
        • Kastelein J.J.
        • Akdim F.
        • Stroes E.S.
        • et al.
        Simvastatin with or without ezetimibe in familial hypercholesterolemia.
        N Engl J Med. 2008; : 1431-1443