Patients with low HDL-cholesterol caused by mutations in LCAT have increased arterial stiffness.
OBJECTIVE
Carriers of a functional mutation in LCAT, encoding lecithin:cholesterol acyl transferase, are exposed to lifelong low high-density lipoprotein cholesterol (HDL-c) levels. We investigated whether LCAT mutation carriers have increased arterial stiffness as a marker of cardiovascular disease and whether arterial stiffness was associated with carotid wall thickening.


METHODS
We assessed 45 carriers of LCAT mutations (mean age ± SD 46 ± 13 yrs) and 45 age-matched controls. Probands referred with established cardiovascular disease were excluded. We measured carotid-fermoral pulse wave velocity (PWV) and carotid artery wall thickening by ultrasound and 3.0 T magnetic resonance imaging.


RESULTS
In carriers, HDL-c was lower (32 ± 12 vs. 59 ± 16 mg/dl; p < 0.0001) and triglycerides were higher (median 116 [IQR 80-170] vs. 71 [IQR 53-89] mg/dl; p < 0.001) vs. controls. PWV was higher in carriers vs. controls (7.9 ± 2.0 m/s vs. 7.1 ± 1.6 m/s; p < 0.01). This difference retained significance in multivariate analysis including age, sex, mean arterial pressure and body mass index, and after exclusion of carriers and controls with cardiovascular disease. Both in carriers and controls, PWV was correlated with wall thickening of the carotid arteries as assessed by ultrasound (R 0.50, p < 0.001 for carriers and R 0.36, p < 0.04 for controls) and 3.0 T magnetic resonance imaging (R 0.54, p < 0.001 for carriers and R 0.58, p < 0.001 for controls).


CONCLUSIONS
Pulse wave velocity is increased in LCAT mutation carriers with low HDL-c and is associated with carotid wall thickening.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. b.vandenbogaard@amc.nl
Bas
B
van den Bogaard
Adriaan G
AG
Holleboom
Raphaël
R
Duivenvoorden
Barbara A
BA
Hutten
John J P
JJ
Kastelein
G Kees
GK
Hovingh
Jan Albert
JA
Kuivenhoven
Erik S G
ES
Stroes
Bert-Jan H
BJ
van den Born
D000328:Adult; D001011:Aorta / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics*; D063177:Pulse Wave Analysis; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D059289:Vascular Stiffness / Q000235:genetics
D015415:Biomarkers; D008076:Cholesterol, HDL; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase