Rodrigo Alonso1, Pedro Mata2, Ovidio Muñiz3, Francisco Fuentes-Jimenez4, Jose Luis Díaz5, Daniel Zambón6, Marta Tomás7, Cesar Martin8, Thomas Moyon9, Mikaël Croyal9, Aurélie Thedrez9, Gilles Lambert10. 1. Spanish Familial Hypercholesterolemia Foundation, Madrid, Spain; Department of Nutrition, Clínica Las Condes, Santiago, Chile. 2. Spanish Familial Hypercholesterolemia Foundation, Madrid, Spain. 3. Internal Medicine Department, Hospital Virgen del Rocío, Sevilla, Spain. 4. IMIBIC Hospital Universitario Reina Sofia, Universidad de Cordoba, Cordoba, Spain; CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, Cordoba, Spain. 5. Internal Medicine Department, Hospital Avente y Lago, A Coruña, Spain. 6. Lipid Clinic Endocrinology Service Clinic Hospital, Barcelona, Spain. 7. Department of Radiology, IIS-Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. 8. Unidad de Biofísica (CSIC, UPV/EHU) and Departamento de Bioquimica y Biologia Molecular, Universidad del Pais Vasco, Bilbao, Spain. 9. Inra UMR 1280, Université de Nantes, Faculté de Médecine, Nantes, France. 10. 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.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: We selected 161 molecularly defined FHpatients 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. RESULTS: 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. CONCLUSIONS: In statin treated asymptomatic FHpatients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease.
Authors: Brian T Steffen; George Thanassoulis; Daniel Duprez; James H Stein; Amy B Karger; Mathew C Tattersall; Joel D Kaufman; Weihua Guan; Michael Y Tsai Journal: Arterioscler Thromb Vasc Biol Date: 2019-03 Impact factor: 8.311
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