Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study.
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.


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.
Sirtori
C R
CR
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Milan, Italy. cesare.sirtori@unimi.it
Calabresi
L
L
Franceschini
G
G
Baldassarre
D
D
Amato
M
M
Johansson
J
J
Salvetti
M
M
Monteduro
C
C
Zulli
R
R
Muiesan
M L
ML
Agabiti-Rosei
E
E
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D002302:Cardiac Output / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004452:Echocardiography; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006579:Heterozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D008297:Male; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; C080631:apolipoprotein A-I Milano; D002784:Cholesterol