METHODS: The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary
Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients.
RESULTS:
Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had
LDL-C <100 mg/dL accounted for 12.3% and those with CAD who had attained the target (
LDL-C <70 mg/dL) in the
secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age >40, heterozygous FH score >20,
hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum
HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with
statin alone, statin+ezetimibe, statin+resin, or statin+probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-
drug combination (statin+ezetimibe+resin or statin+ezetimibe+probucol) accounted for 7.5%.
Statins and
ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity
statins were mainly prescribed,
statin doses were much lower than those reported in Western countries. The addition of
ezetimibe resulted in ~20% reduction in serum
LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic
cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum
LDL-C and
triglyceride levels were not related to ASCVD events.
CONCLUSION: The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum
LDL-C was not achieved for primary and
secondary prevention of CAD, suggesting that a more aggressive
LDL-C lowering and appropriate management of residual risks are necessary.