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Incidence of cardiovascular disease in familial combined hyperlipidemia: A 15-year follow-up study

  • Jim Luijten
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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  • Marleen M.J. van Greevenbroek
    Affiliations
    Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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  • Nicolaas C. Schaper
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands

    Care and Public Health Research Institute (CAPHRI), Maastricht University, the Netherlands
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  • Steven J.R. Meex
    Affiliations
    Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
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  • Caroline van der Steen
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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  • Lisanne J. Meijer
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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  • Douwe de Boer
    Affiliations
    Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
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  • Jacqueline de Graaf
    Affiliations
    Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, the Netherlands
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  • Coen D.A. Stehouwer
    Affiliations
    Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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  • Martijn C.G.J. Brouwers
    Correspondence
    Corresponding author.
    Affiliations
    Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, the Netherlands
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      Highlights

      • Three quarters of familial combined hyperlipidemia (FCHL) patients receive lipid lowering treatment.
      • The 15-year incidence of cardiovascular disease is still very high in FCHL.
      • The SCORE risk factors do not fully account for the increased risk in FCHL.

      Abstract

      Background and aims

      Familial combined hyperlipidemia (FCHL) is a complex dyslipidemia associated with premature cardiovascular disease (CVD). The present study was conducted to 1) determine the incidence of CVD in FCHL in this era of protocolled, primary prevention; and 2) examine whether cardiovascular risk estimation based on the Systemic Coronary Risk Estimation (SCORE) chart, as proposed in the 2016 ESC/EAS guidelines for the management of dyslipidemia, is justified in FCHL.

      Methods

      FCHL patients, their normolipidemic (NL) relatives and spouses originally included in our baseline cohort in 1998–2005 (n = 596) were invited for a follow-up visit to determine the incidence of CVD, defined as (non-)fatal coronary artery disease, ischemic stroke and peripheral artery disease requiring invasive treatment.

      Results

      Follow-up data (median: 15 years) was acquired for 85% of the original cohort. The cumulative incidence of CVD was significantly higher in FCHL patients than in spouses (23.6% versus 4.7%; hazard ratio (HR): 5.4, 95%CI: 2.0–14.6; HR after adjustment for risk factors included in SCORE: 4.7, 95%CI: 1.6–13.8), but not in NL relatives compared to spouses (5.8% versus 4.7%). The SCORE chart tended to overestimate CVD risk in the spouses (observed [O]/expected [E] ratio:0.2, p = 0.01), but not in FCHL patients (O/E:1.3, p = 0.50).

      Conclusions

      Risk of primary CVD is still substantially increased in FCHL patients, despite preventive measures. The overestimation of CVD risk by the SCORE chart – a nowadays frequently observed phenomenon thanks to improved primary prevention – was not seen in FCHL. These results suggest that more aggressive treatment is justified to avoid excessive CVD in FCHL.

      Graphical abstract

      Keywords

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