Increased inflammatory markers in children with familial hypercholesterolaemia

被引:43
作者
Ueland, T [1 ]
Vissers, MN
Wiegman, A
Rodenburg, J
Hutten, B
Gullestad, L
Ose, L
Rifai, N
Ridker, PM
Kastelein, JJP
Aukrust, P
Semb, AG
机构
[1] Univ Oslo, Rikshosp, Endocrinol Sect, Dept Med, N-0027 Oslo, Norway
[2] Diakonhjemmet Hosp, Oslo, Norway
[3] Baerum Hosp, Baerum, Norway
[4] Acad Med Ctr, Amsterdam, Netherlands
[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA
关键词
atherogenesis; CRP; heterozygous familial hypercholesterolaemia; inflammation; neopterin;
D O I
10.1111/j.1365-2362.2006.01613.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20-40 mg qd) or placebo on plasma levels of those markers. Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.
引用
收藏
页码:147 / 152
页数:6
相关论文
共 30 条
[1]   Soluble CD40 ligand and platelets: Self-perpetuating pathogenic loop in thrombosis and inflammation? [J].
Aukrust, P ;
Damas, JK ;
Solum, NO .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 43 (12) :2326-2328
[2]   Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes [J].
Aukrust, P ;
Müller, F ;
Ueland, T ;
Berget, T ;
Aaser, E ;
Brunsvig, A ;
Solum, NO ;
Forfang, K ;
Froland, SS ;
Gullestad, L .
CIRCULATION, 1999, 100 (06) :614-620
[3]   Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia [J].
Garlichs, CD ;
John, S ;
Schmeisser, A ;
Eskafi, S ;
Stumpf, C ;
Karl, M ;
Goppelt-Struebe, M ;
Schmieder, R ;
Daniel, WG .
CIRCULATION, 2001, 104 (20) :2395-2400
[4]   Soluble CD40 ligand in acute coronary syndromes [J].
Heeschen, C ;
Dimmeler, S ;
Hamm, CW ;
van den Brand, MJ ;
Boersma, E ;
Zeiher, AM ;
Simoons, ML ;
CAPTURE Study Investigators .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (12) :1104-1111
[5]   Patients with familial hypercholesterolaemia show enhanced spontaneous chemokine release from peripheral blood mononuclear cells ex vivo - Dependency of xanthomas/xanthelasms, smoking and gender [J].
Holven, KB ;
Myhre, AM ;
Aukrust, P ;
Hagve, TA ;
Ose, L ;
Nenseter, MS .
EUROPEAN HEART JOURNAL, 2003, 24 (19) :1756-1762
[6]   Additive beneficial effects of Losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients [J].
Koh, KK ;
Quon, MJ ;
Han, SH ;
Chung, WJ ;
Ahn, JY ;
Seo, YH ;
Kang, MH ;
Ahn, TH ;
Choi, IS ;
Shin, EK .
CIRCULATION, 2004, 110 (24) :3687-3692
[7]   Statins as a newly recognized type of immunomodulator [J].
Kwak, B ;
Mulhaupt, F ;
Myit, S ;
Mach, F .
NATURE MEDICINE, 2000, 6 (12) :1399-1402
[8]   Inflammation and atherosclerosis [J].
Libby, P ;
Ridker, PM ;
Maseri, A .
CIRCULATION, 2002, 105 (09) :1135-1143
[9]  
Libby Peter, 2004, Am J Med, V116 Suppl 6A, p9S
[10]   A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia [J].
Marks, D ;
Thorogood, M ;
Neil, HAW ;
Humphries, SE .
ATHEROSCLEROSIS, 2003, 168 (01) :1-14