Cardiovascular Status of Carriers of the Apolipoprotein A-I Milano Mutant

Abstract

Background —Carriers of the apolipoprotein A-I Milano (apoA-I M ) mutant present with very low plasma HDL cholesterol and moderate hypertriglyceridemia, apparently not leading to premature coronary heart disease. The objective of this study was to establish whether this high-risk lipid/lipoprotein profile is associated with structural changes in the carotid arteries and heart, indicative of preclinical atherosclerosis. Methods and Results —Twenty-one A-I M carriers were compared with age- and sex-matched control subjects from the same kindred and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HA). Structural changes in the carotid arteries were defined as the intima-media thickness (IMT) measured by B-mode ultrasound. HA subjects, both recruited among patients attending our Lipid Clinic and blood donors, showed significant thickening of the carotids (average IMT, 0.86±0.25 and 0.88±0.29 mm, respectively) compared with control subjects (average IMT, 0.64±0.12 mm); the apoA-I M carriers instead showed normal arterial thickness (average IMT, 0.63±0.10 mm). Moreover, a significantly higher prevalence of atherosclerotic plaques was found in patients and blood donors with HA (both 57%) compared with apoA-I M carriers (33%) and control subjects (21%). Echocardiographic findings and maximal treadmill ECG did not differ significantly between apoA-I M carriers and control subjects, apart from a slight increase in left ventricular end-diastolic dimension in the carriers. Conclusions —Despite severe HA, carriers of the apoA-I M mutant do not show structural changes in the arteries and heart, in contrast to HA subjects, who are characterized by a marked increase in carotid IMT and increased prevalence of atherosclerotic plaques.