Elevated lipoprotein(a) does not cause low-grade inflammation despite causal association with aortic valve stenosis and myocardial infarction: A study of 100 578 individuals from the general population

Journal of Clinical Endocrinology and Metabolism

Volumn 100, Issue 7, 2015, Pages 2690-2699

  Langsted, Anne ^a,c   Varbo, Anette ^a,c   Kamstrup, Pia R ^a,c   Nordestgaard, Børge G ^a,b,c  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b FREDERIKSBERG HOSPITAL   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; LIPOPROTEIN A;

ADULT; AGED; AORTA VALVE STENOSIS; ARTICLE; CARDIOVASCULAR RISK; DISEASE ASSOCIATION; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE; HAZARD RATIO; HEART INFARCTION; HUMAN; INFLAMMATION; KIV 2 GENE; LIPOPROTEIN BLOOD LEVEL; LPA GENE; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SINGLE NUCLEOTIDE POLYMORPHISM; AORTIC VALVE STENOSIS; BLOOD; COHORT ANALYSIS; DENMARK; GENETIC PREDISPOSITION; GENETICS; MENDELIAN RANDOMIZATION ANALYSIS; METABOLISM; MIDDLE AGED; MYOCARDIAL INFARCTION; RISK FACTOR;

AGED; AORTIC VALVE STENOSIS; C-REACTIVE PROTEIN; COHORT STUDIES; DENMARK; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; INFLAMMATION; LIPOPROTEIN(A); MALE; MENDELIAN RANDOMIZATION ANALYSIS; MIDDLE AGED; MYOCARDIAL INFARCTION; RISK FACTORS;

EID: 84941029258     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2015-1096     Document Type: Article

References (43)

1. Utermann G. Lipoprotein(a). In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:2753-2787.
2. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. Eur Heart J. 2010;31: 2844-2853.
3. Kronenberg F, Utermann G. Lipoprotein(a): Resurrected by genetics. J Intern Med. 2013;273:6-30.
4. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503-512.
5. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein( a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63:470-477.
6. Kamstrup PR, Tybjærg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331-2339.
7. Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361:2518-2528.
8. Tsimikas S, Brilakis ES, Miller ER, et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. NEngl J Med. 2005; 353:46-57.
9. Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: Mechanistic insights from animal models. Clin Biochem. 2004;37:333-343.
10. CapliceNM,Panetta C, Peterson TE, et al. Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: A novel link between lipoproteins and thrombosis. Blood. 2001;98:2980-2987.
11. Deb A, Caplice NM. Lipoprotein(a): New insights into mechanisms of atherogenesis and thrombosis. Clin Cardiol. 2004;27:258-264.
12. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol. 2012;32:1732-1741.
13. BrownMS,Goldstein JL. Plasma lipoproteins: Teaching old dogmas new tricks. Nature. 1987;330:113-114.
14. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey S mith G. Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133-1163.
15. Zacho J, Tybjærg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008;359:1897-1908.
16. Varbo A, Benn M, Tybjærg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427-436.
17. Nordestgaard BG, Benn M, Schnohr P, Tybjærg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299-308.
18. Kamstrup PR, Benn M, Tybjærg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: The Copenhagen City Heart Study. Circulation. 2008;117:176-184.
19. Seman LJ, Breckenridge WC. Isolation and partial characterization of apolipoprotein (a) from human lipoprotein (a). Biochem Cell Biol. 1986;64:999-1009.
20. Varbo A, Benn M, Tybjærg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013;128:1298-1309.
21. Benn M, Tybjærg-Hansen A, McCarthy MI, Jensen GB, Grande P, Nordestgaard BG. Nonfasting glucose, ischemic heart disease, and myocardial infarction: A Mendelian randomization study. J Am Coll Cardiol. 2012;59:2356-2365.
22. Goldstein JK, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill;2001:2863-2913.
23. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: Consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34:3478-3490a.
24. Edelberg JM, Gonzalez-Gronow M, Pizzo SV. Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator. Thromb Res. 1990;57:155-162.
25. Loscalzo J, WeinfeldM,FlessGM,ScanuAM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis. 1990;10: 240-245.
26. Simon DI, Fless GM, Scanu AM, Loscalzo J. Tissue-type plasminogen activator binds to and is inhibited by surface-bound lipoprotein( a) and low-density lipoprotein. Biochemistry. 1991;30:6671-6677.
27. Yano Y, Shimokawa K, Okada Y, Noma A. Immunolocalization of lipoprotein(a) in wounded tissues. J Histochem Cytochem. 1997; 45:559-568.
28. Nielsen LB, Stender S, Kjeldsen K, Nordestgaard BG. Specific accumulation of lipoprotein(a) in balloon-injured rabbit aorta in vivo. Circ Res. 1996;78:615-626.
29. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685-1695.
30. Zacho J, Tybjærg-Hansen A, Nordestgaard BG. C-reactive protein and risk of venous thromboembolism in the general population. Arterioscler Thromb Vasc Biol. 2010;30:1672-1678.
31. van Aken BE, den Heijer M, Bos GM, van Deventer SJ, Reitsma PH. Recurrent venous thrombosis and markers of inflammation. Thromb Haemost. 2000;83:536-539.
32. Mohler ER, Sheridan MJ, Nichols R, Harvey WP, Waller BF. Development and progression of aortic valve stenosis: Atherosclerosis risk factors-A causal relationship? A clinical morphologic study. Clin Cardiol. 1991;14:995-999.
33. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD. Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994;90:844-853.
34. Galante A, Pietroiusti A, Vellini M, et al. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol. 2001;38:1078-1082.
35. Gerber IL, Stewart RA, Hammett CJ, et al. Effect of aortic valve replacement on c-reactive protein in nonrheumatic aortic stenosis. Am J Cardiol. 2003;92:1129-1132.
36. Novaro GM, Katz R, Aviles RJ, et al. Clinical factors, but not Creactive protein, predict progression of calcific aortic-valve disease: The Cardiovascular Health Study. J Am Coll Cardiol. 2007;50: 1992-1998.
37. Dursunoglu D, Evrengül H, Polat B, et al. Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: Serum levels and relationship to inflammation. Rheumatol Int. 2005;25:241-245.
38. Wang J, Hu B, Kong L, Cai H, Zhang C. Native, oxidized lipoprotein( a) and lipoprotein(a) immune complex in patients with active and inactive rheumatoid arthritis: Plasma concentrations and relationship to inflammation. Clin Chim Acta. 2008;390:67-71.
39. Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999;55:648-658.
40. Slunga L, Johnson O, Dahlén GH, Eriksson S. Lipoprotein(a) and acute-phase proteins in acute myocardial infarction. Scand J Clin Lab Invest. 1992;52:95-101.
41. Noma A, Abe A, Maeda S, et al. Lp(a): An acute-phase reactant? Chem Phys Lipids. 1994;67-68:411-417.
42. Cobbaert C, Kesteloot H. Serum lipoprotein(a) levels in racially different populations. Am J Epidemiol. 1992;136:441-449.
43. Utermann G. Genetic architecture and evolution of the lipoprotein( a) trait. Curr Opin Lipidol. 1999;10:133-141.