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

Abstract

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.

• Authors: Masatsune Ogura, Mika Hori, Mariko Harada-Shiba
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 36 Issue 1 Pg. 181-8 (Jan 2016) ISSN: 1524-4636 [Electronic] United States
• PMID: 26543100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Biomarkers
• Cholesterol, HDL
• LDLR protein, human
• Receptors, LDL
• PCSK9 protein, human
• Proprotein Convertase 9
• Proprotein Convertases
• Serine Endopeptidases

Topics

• Achilles Tendon (diagnostic imaging)
• Adult
• Aged
• Arcus Senilis (blood, etiology, genetics)
• Asymptomatic Diseases
• Atherosclerosis (blood, diagnosis, etiology, genetics)
• Biomarkers (blood)
• Carotid Artery Diseases (blood, etiology, genetics)
• Carotid Intima-Media Thickness
• Cholesterol, HDL (blood)
• Cross-Sectional Studies
• Female
• Genetic Predisposition to Disease
• Heterozygote
• Humans
• Hyperlipoproteinemia Type II (blood, diagnosis, genetics)
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Mutation
• Odds Ratio
• Phenotype
• Proprotein Convertase 9
• Proprotein Convertases (genetics)
• Radiography
• Receptors, LDL (genetics)
• Serine Endopeptidases (genetics)