Consequences of Cholesteryl Ester Transfer Protein Inhibition in Patients With Familial Hypoalphalipoproteinemia

To the Editor: A large proportion of clinical events cannot be prevented during statin therapy, which calls for novel drug targets to further improve cardiovascular outcome. In particular, HDL-increasing strategies hold great promise. The impact of decreased HDL-C on cardiovascular disease (CVD)-related morbidity and mortality has been sharply delineated in individuals affected by familial hypoalphalipoproteinemia (FHA).1 HDL exerts multiple antiatherogenic actions beyond its role in reverse cholesterol transport, comprising antiinflammatory, antioxidative, and direct vascular effects.2 Whereas current strategies to raise HDL-C are limited, novel CETP-inhibitors are capable of mediating significant HDL-C elevation.3,4 Therefore, we evaluated the effects of CETP inhibition on lipid metabolism and markers of oxidation in subjects with FHA. Subjects were recruited from a Dutch population-based study to identify genes that control HDL-C levels,1 meeting the following criteria: (1) plasma HDL-C level below 10th percentile for age and sex; (2) absence of secondary lipid disorders; and (3) high likelihood of inherited low HDL (defined as HDL-C below 10th percentile in at least one first-degree family member). Nineteen FHA patients (13 men and 6 women; mean±SD age: 42.9±13.9 years), all free of overt macrovascular disease, were enrolled in the study. In 9 of these subjects the underlying defect was defined: heterozygosity for an apolipoprotein A-I (L178P) mutation,1 whereas in the remainder this genetic defect was excluded. The study protocol was approved …