Plasma lipoprotein-associated phospholipase A2 levels in heart failure: association with mortality in the community.
OBJECTIVE
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a useful inflammatory marker of cardiovascular risk, yet little is known of its prognostic role in heart failure (HF). We evaluated the association of Lp-PLA2 with mortality in subjects with HF and assessed its incremental value for risk discrimination over established risk factors and biomarkers.


METHODS
Residents of Olmsted County, MN, diagnosed with HF between September 2003 and April 2007 (n=646, mean age 76 years, 51% women) were prospectively enrolled and followed-up. Plasma Lp-PLA2 levels were measured at baseline and evaluated along with known risk indicators.


RESULTS
Lp-PLA2 was positively associated with male gender and low-density lipoprotein cholesterol and inversely associated with statin use and diabetes. During follow-up (median 21 months), 213 deaths occurred. Elevated Lp-PLA2 was associated with an increased risk of mortality (hazard ratio (HR)=1.57; 95% confidence interval (CI): 1.03-2.37; P=0.035, per 1-unit increase in the log-transformed values). The relationship differed markedly by age (P(interaction)=0.003), with a strong association in patients under 80 years (covariate-adjusted HR=3.83; 95% CI: 1.93-7.61; P<0.001) and none in older ones (covariate-adjusted HR=0.82; 95% CI: 0.44-1.51; P=0.55). For the younger subjects, an improvement in the model's discriminatory power was obtained by adding Lp-PLA2 to established risk indicators and biomarkers (area under the receiver operating characteristic curve, 0.709-0.744, P(difference)=0.008).


CONCLUSIONS
In this community-based cohort of patients with HF, Lp-PLA2 was strongly and independently associated with mortality and contributed incrementally to risk discrimination in patients under 80 years of age.
Gerber
Yariv
Y
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, United States.
Dunlay
Shannon M
SM
Jaffe
Allan S
AS
McConnell
Joseph P
JP
Weston
Susan A
SA
Killian
Jill M
JM
Roger
Véronique L
VL
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
Circulation. 2003 Mar 25;107(11):1486-91
12654604
Lancet. 2007 Dec 1;370(9602):1829-39
18061058
N Engl J Med. 2000 Oct 19;343(16):1148-55
11036120
Radiology. 1983 Sep;148(3):839-43
6878708
Mayo Clin Proc. 2007 Aug;82(8):933-8
17673061
Atherosclerosis. 2000 Jun;150(2):413-9
10856534
Mayo Clin Proc. 1996 Mar;71(3):266-74
8594285
Circ Res. 2002 Nov 29;91(11):988-98
12456484
Arterioscler Thromb Vasc Biol. 2005 May;25(5):923-31
15731492
FEBS Lett. 2001 Sep 21;505(3):357-63
11576528
Arch Intern Med. 2005 Nov 28;165(21):2454-6
16314539
Atherosclerosis. 2007 Feb;190(2):388-96
16530769
J Biomed Inform. 2005 Apr;38(2):145-53
15797003
Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2909-17
10591668
Circulation. 2005 Sep 6;112(10):1428-34
16129801
Curr Opin Lipidol. 2003 Aug;14(4):347-52
12865731
Eur J Cardiovasc Prev Rehabil. 2007 Feb;14(1):3-11
17301621
JAMA. 1994 Nov 2;272(17):1335-40
7772105
N Engl J Med. 2004 Apr 1;350(14):1387-97
15070788
Arch Intern Med. 2006 Jul 10;166(13):1368-73
16832001
Circulation. 2004 Dec 21;110(25):e560-7
15611382
JAMA. 2004 Jul 21;292(3):344-50
15265849
Arch Intern Med. 2006 Oct 23;166(19):2073-80
17060536
Am J Epidemiol. 2004 May 1;159(9):882-90
15105181
J Am Geriatr Soc. 2005 Dec;53(12):2159-64
16398902
Circulation. 2007 May 29;115(21):2715-21
17502572
J Am Coll Cardiol. 1998 Jul;32(1):216-24
9669273
Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2517-22
16902161
Heart. 2004 Apr;90(4):464-70
15020532
Am Heart J. 2003 Aug;146(2):194-6
12891180
Circulation. 2003 Jan 28;107(3):499-511
12551878
Diabetes. 1979 Dec;28(12):1039-57
510803
Br Heart J. 1962 May;24:257-64
14454369
Am J Epidemiol. 1979 Apr;109(4):394-9
443238
Eur Heart J. 2005 Jan;26(2):137-44
15618069
Eur Heart J. 2006 Oct;27(19):2346-52
16952920
JAMA. 2006 Nov 8;296(18):2209-16
17090767
Bioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70
12643913
Circulation. 2005 Mar 1;111(8):980-7
15710755
Circulation. 2002 Mar 5;105(9):1135-43
11877368
Am J Epidemiol. 2004 Aug 1;160(3):259-69
15257999
Circulation. 2006 Oct 10;114(15):1557-60
17030701
Am Heart J. 2003 Jun;145(6):1094-101
12796768
J Am Coll Cardiol. 1993 Oct;22(4 Suppl A):6A-13A
8376698
Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):106-11
16239595
Am J Manag Care. 2007 Jun;13(6 Part 1):281-8
17567225
Mayo Clin Proc. 2007 Feb;82(2):159-65
17290721
Eur Heart J. 2005 Jan;26(1):65-9
15615801