PCSK9 and lipoprotein (a) levels are two predictors of coronary artery calcification in asymptomatic patients with familial hypercholesterolemia.
We aimed to assess whether elevated PCSK9 and lipoprotein (a) [Lp(a)] levels associate with coronary artery calcification (CAC), a good marker of atherosclerosis burden, in asymptomatic familial hypercholesterolemia.



We selected 161 molecularly defined FH patients treated with stable doses of statins for more than a year. CAC was measured using the Agatston method and quantified as categorical variable. Fasting plasma samples were collected and analyzed for lipids and lipoproteins. PCSK9 was measured by ELISA, Lp(a) and apolipoprotein (a) concentrations by inmunoturbidimetry and LC-MS/MS, respectively.



Circulating PCSK9 levels were significantly reduced in patients without CAC (n = 63), compared to those with CAC (n = 99). Patients with the highest CAC scores (above 100) had the highest levels of circulating PCSK9 and Lp(a). In multivariable regression analyses, the main predictors for a positive CAC score was age and sex followed by circulating PCSK9 and Lp(a) levels.



In statin treated asymptomatic FH patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease.
Spanish Familial Hypercholesterolemia Foundation, Madrid, Spain; Department of Nutrition, Clínica Las Condes, Santiago, Chile.
Rodrigo
R
Alonso
Spanish Familial Hypercholesterolemia Foundation, Madrid, Spain.
Pedro
P
Mata
Internal Medicine Department, Hospital Virgen del Rocío, Sevilla, Spain.
Ovidio
O
Muñiz
IMIBIC Hospital Universitario Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, Cordoba, Spain.
Francisco
F
Fuentes-Jimenez
Internal Medicine Department, Hospital Avente y Lago, A Coruña, Spain.
Jose Luis
JL
Díaz
Lipid Clinic Endocrinology Service Clinic Hospital, Barcelona, Spain.
Daniel
D
Zambón
Department of Radiology, IIS-Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Marta
M
Tomás
Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquimica y Biologia Molecular, Universidad del Pais Vasco, Bilbao, Spain.
Cesar
C
Martin
Inra UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France.
Thomas
T
Moyon
Inra UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France.
Mikaël
M
Croyal
Inra UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France.
Aurélie
A
Thedrez
Inra UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France; Inserm UMR 1188, Sainte Clotilde, France; Université de la Réunion, Faculté de Médecine, Saint-Denis, France; CHU de la Réunion, Saint-Denis, France. Electronic address: gilles.lambert@univ-reunion.fr.
Gilles
G
Lambert
D000328:Adult; D000368:Aged; D002114:Calcinosis / Q000097:blood*; D002118:Calcium / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D000071449:Proprotein Convertase 9 / Q000097:blood*; D014057:Tomography, X-Ray Computed
D017270:Lipoprotein(a); C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D002118:Calcium
Coronary artery calcification; Hypercholesterolemia; Lipids and lipoprotein metabolism