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(Circulation. 2001;103:1949.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Cardiovascular Status of Carriers of the Apolipoprotein A-I_Milano Mutant

The Limone sul Garda Study

Cesare R. Sirtori, MD, PhD; Laura Calabresi, PhD; Guido Franceschini, PhD; Damiano Baldassarre, PhD; Mauro Amato, PhD; Jan Johansson, MD, PhD; Massimo Salvetti, MD; Cristina Monteduro, MD; Roberto Zulli, MD; Maria L. Muiesan, MD; Enrico Agabiti-Rosei, MD

From the Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Milan, Italy (C.R.S., L.C., G.F., D.B., M.A.); Esperion Therapeutics Inc, Ann Arbor, Mich (J.J.); and Cattedra di Semeiotica e Metodologia Medica, University of Brescia, Brescia, Italy (M.S., C.M., R.Z., M.L.M., E.A.).

Correspondence to Professor Cesare Sirtori, Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy. E-mail cesare.sirtori{at}unimi.it

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.

Key Words: lipoproteins • apolipoproteins • carotid arteries • intima-media thickening • heart diseases

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