Defining Patients at Extremely High Risk for Coronary Artery Disease in Heterozygous Familial Hypercholesterolemia

  • Sugisawa Takako
    Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center.
  • Okamura Tomonori
    Department of Public Health and Preventive Medicine, Keio University.
  • Makino Hisashi
    Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center.
  • Watanabe Makoto
    Department of Preventive Cardiology, National Cerebral and Cardiovascular Center.
  • Kishimoto Ichiro
    Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center.
  • Miyamoto Yoshihiro
    Department of Preventive Cardiology, National Cerebral and Cardiovascular Center.
  • Iwamoto Noriyuki
    Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center.
  • Yamamoto Akira
    Health Care Facilities for the Aged, Minoh Life Plaza.
  • Yokoyama Shinji
    Food and Nutritional Sciences, College of Bioscience and Biotechnology, Chubu University.
  • Harada-Shiba Mariko
    Division of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center. Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute.

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Aim: Heterozygous patients with familial hypercholesterolemia (FH) are known to be associated with a high risk of coronary artery disease (CAD), which is a major determinant of their clinical outcome. The prognosis of heterozygous FH patients substantially varies, being dependent on the level of their CAD risk, and their therapeutic regimen should be individualized. We assessed critical levels of LDL-cholesterol (LDL-C) and Achilles tendon thickness (ATT) to identify heterozygous FH patients at “very high” risk for CAD.<BR>Methods: One hundred and nine heterozygous FH patients who had no history of CAD and had had their plasma lipid profile and ATT assessed before treatment were followed up until their first CAD event or 31 December 2010. Multivariable logistic regression models were used to analyze the correlation of LDL-C and/or ATT levels with the risk of developing CAD.<BR>Results: During the follow-up period, 21 of the 109 patients had a CAD event, diagnosed by coronary angiogram. Individuals in the highest tertile of LDL-C had a CAD risk 8.29-fold higher than those in the lowest tertile. Individuals in the highest tertile of the ATT group had a 7.82-fold higher CAD risk than those in the lowest tertile. Those who had either LDL-C ≥ 260 mg/dL or ATT ≥ 14.5 had a 23.94-fold higher CAD risk than those with LDL-C < 260 mg/dL and ATT <14.5 mm.<BR>Conclusions: In heterozygous FH patients, LDL-C 260 mg/dL or higher and/or ATT 14.5 mm or thicker are useful markers for extracting patients at “very high” risk for CAD.

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