Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia

被引:72
作者
Chan, Dick C. [1 ]
Pang, Jing [1 ]
Hooper, Amanda J. [1 ,2 ,3 ]
Burnett, John R. [1 ,2 ,4 ]
Bell, Damon A. [1 ,2 ,4 ,5 ]
Bates, Timothy R. [1 ,4 ]
van Bockxmeer, Frank M. [2 ,6 ]
Watts, Gerald F. [1 ,4 ]
机构
[1] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia
[2] Royal Perth Hosp, Dept Clin Biochem, PathWest Lab, Perth, WA 6001, Australia
[3] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia
[4] Royal Perth Hosp, Cardiometab Serv, Lipid Disorders Clin, Perth, WA 6001, Australia
[5] St John God Pathol, Dept Clin Biochem, Osborne Pk, WA, Australia
[6] Univ Western Australia, Sch Surg, Perth, WA 6009, Australia
关键词
Familial hypercholesterolemia; Cardiovascular disease; Risk factors; LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN(A) ISOFORM SIZE; CARDIOVASCULAR RISK-FACTORS; CHRONIC KIDNEY-DISEASE; LDL RECEPTOR GENE; HEART-DISEASE; IN-VIVO; PLASMA; PROTEINURIA; MORTALITY;
D O I
10.1016/j.ijcard.2015.08.146
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Familial hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol and increased risk of premature coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] increases CAD in FH, although the independence of this association relative to other CAD risk factors remains unclear. In this study, we examined the association between Lp(a) and other cardiovascular risk factors and prevalent CAD in patients with FH. Methods: A cross-sectional study of 390 patients with genetically confirmed FH were studied. Clinical and biochemical parameters of FH patients with and without CAD were compared. Results: FH patients with CAD were older and more often male and had a higher prevalence of hypertension, smoking, diabetes, obesity, reduced eGFR, and elevated plasma Lp(a) and pre-treatment LDL-cholesterol and triglyceride (or low HDL-cholesterol) than FH patients without CAD (P < 0.05 for all). In univariate analyses, age, male gender, smoking, hypertension, reduced eGFR, diabetes, obesity, plasma creatinine, Lp(a) and pretreatment LDL-cholesterol, triglycerides and HDL-cholesterol levels were significant predictors of CAD in the FH patients (P < 0.05 for all). Elevated LDL-cholesterol, raised Lp(a), hypertension and reduced eGFR remained significant independent predictors of CAD (P b 0.05 for all) in FH after adjusting for other modifiable risk factors. Conclusions: Elevated Lp(a), hypertension and renal insufficiency are independent risk factors beyond elevated pretreatment LDL-cholesterol which predict CAD in patients with FH. In spite of the cross-sectional design of our study, we propose the need for identifying and managing these abnormalities to reduce excess CAD risk in FH patients. However, this proposal remains to be formally tested in a prospective study. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:633 / 638
页数:6
相关论文
共 46 条
[1]   Risk stratification of patients with familial hypercholesterolemia in a multi-ethnic cohort [J].
Allard, Matthew D. ;
Saeedi, Ramesh ;
Yousefi, Masoud ;
Frohlich, Jiri .
LIPIDS IN HEALTH AND DISEASE, 2014, 13
[2]   Cardiovascular disease in familial hypercholesterolaemia: Influence of low-density lipoprotein receptor mutation type and classic risk factors [J].
Alonso, R. ;
Mata, N. ;
Castillo, S. ;
Fuentes, F. ;
Saenz, P. ;
Muniz, O. ;
Galiana, J. ;
Figueras, R. ;
Diaz, J. L. ;
Gomez-Enterria, P. ;
Mauri, M. ;
Piedecausa, M. ;
Irigoyen, L. ;
Aguado, R. ;
Mata, P. .
ATHEROSCLEROSIS, 2008, 200 (02) :315-321
[3]   Lipoprotein(a) Levels in Familial Hypercholesterolemia An Important Predictor of Cardiovascular Disease Independent of the Type of LDL Receptor Mutation [J].
Alonso, Rodrigo .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2014, 63 (19) :1983-1989
[4]   Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: An Australian experience [J].
Bell, Damon A. ;
Pang, Jing ;
Burrows, Sally ;
Bates, Timothy R. ;
van Bockxmeer, Frank M. ;
Hooper, Amanda J. ;
O'Leary, Peter ;
Burnett, John R. ;
Watts, Gerald F. .
ATHEROSCLEROSIS, 2015, 239 (01) :93-100
[5]   Lipoprotein (a): gene genie [J].
Durrington, Paul N. ;
Schofield, Jonathan D. ;
Siahmansur, Tarza ;
Soran, Handrean .
CURRENT OPINION IN LIPIDOLOGY, 2014, 25 (04) :289-296
[6]   Apolipoprotein(a) inhibits the conversion of Glu-plasminogen to Lys-plasminogen: a novel mechanism for lipoprotein(a)-mediated inhibition of plasminogen activation [J].
Feric, N. T. ;
Boffa, M. B. ;
Johnston, S. M. ;
Koschinsky, M. L. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2008, 6 (12) :2113-2120
[7]   CORONARY-ARTERY DISEASE IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS WITH THE SAME LDL RECEPTOR GENE MUTATION [J].
FERRIERES, J ;
LAMBERT, J ;
LUSSIERCACAN, S ;
DAVIGNON, J .
CIRCULATION, 1995, 92 (03) :290-295
[8]   In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients [J].
Frischmann, M. E. ;
Kronenberg, F. ;
Trenkwalder, E. ;
Schaefer, J. R. ;
Schweer, H. ;
Dieplinger, B. ;
Koenig, P. ;
Ikewaki, K. ;
Dieplinger, H. .
KIDNEY INTERNATIONAL, 2007, 71 (10) :1036-1043
[9]  
Goldstein J., 2001, The metabolic and molecular bases of inherited disease, P2863
[10]   Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales [J].
Haralambos, K. ;
Whatley, S. D. ;
Edwards, R. ;
Gingell, R. ;
Townsend, D. ;
Ashfield-Watt, P. ;
Lansberg, P. ;
Datta, D. B. N. ;
McDowell, I. F. W. .
ATHEROSCLEROSIS, 2015, 240 (01) :190-196