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Efflusso di colesterolo e malattia cardiovascolare nell’ipercolesterolemia familiare

L'efficacia della terapia volta a ridurre il livello del colesterolo LDL è stata dimostrata anche per l'ipercolesterolemia familiare. Rimane però ancora alto nella maggior parte dei casi il rischio residuo, anche perché il raggiungimento degli obiettivi terapeutici è difficilmente raggiungibile. Ma possono esserci altre cause e tra queste, Ogura e Coll. hanno puntato l'attenzione sui meccanismi di efflusso del colesterolo, ipotizzando che ad un difetto della rimozione del colesterolo si possa, almeno in parte, attribuire la responsabilità della persistenza di un rischio cardiovascolare elevato. I risultati del loro studio sembrano dar loro ragione. La capacità di efflusso del colesterolo è in effetti risultata ridotta nel pazienti con ipercolesterolemia familiare eterozigote che avevano sofferto di un evento cardiovascolare, rispetto a coloro che non avevano avuto eventi. La ridotta capacità di efflusso era inoltre associata alla presenza di arco corneale, xantoma del tendine di Achille e spessore medio-intimale della carotide.

Association Between Cholesterol Efflux Capacity and Atherosclerotic Cardiovascular Disease in Patients With Familial Hypercholesterolemia

Ogura M, Hori M, Harada-Shiba M

Arterioscler Thromb Vasc Biol 2016;36:181-188

OBJECTIVE: Patients with familial hypercholesterolemia (FH) are at high risk for premature atherosclerotic cardiovascular disease (ASCVD), especially because of long-term exposure to high low-density lipoprotein cholesterol levels. It has been reported that low-density lipoprotein-lowering therapy delays the onset of ASCVD. However, it still remains difficult to prevent it. Therefore, novel biomarkers and therapeutic targets are necessary to evaluate and prevent atherosclerosis in FH. The aim of this study was to investigate associations of cholesterol efflux capacity with the presence of ASCVD and clinical features in patients with heterozygous FH.
APPROACH AND RESULTS: We measured cholesterol efflux capacity in 227 patients with heterozygous FH under pharmaceutical treatment. Seventy-six (33.5%) of them were known to have ASCVD. In a logistic-regression analysis adjusted for risk factors, increased efflux capacity was associated with decreased risk of ASCVD even after the addition of high-density lipoprotein cholesterol level as a covariate (odds ratio per 1-SD increase, 0.95; 95% confidence interval, 0.90-0.99; P<0.05). Decreased cholesterol efflux capacity was associated with the presence of corneal arcus after adjusting for age and sex. In addition, inverse relationships between cholesterol efflux capacity and Achilles tendon thickness, as well as carotid intima-media thickness, were observed after adjustment for age, sex, and traditional cardiovascular risk factors.
CONCLUSIONS: Cholesterol efflux capacity was independently and inversely associated with the presence of ASCVD in heterozygous FH. In view of residual risks after treatment with statins, cholesterol efflux capacity might be a novel biomarker and a therapeutic target for preventing atherosclerosis in patients with FH.

Arterioscler Thromb Vasc Biol 2016;36:181-188