TY - JOUR
T1 - Prognostic utility of neopterin and risk of heart failure hospitalization after an acute coronary syndrome
AU - Nazer, Babak
AU - Ray, Kausik K.
AU - Sloan, Sarah
AU - Scirica, Benjamin
AU - Morrow, David A.
AU - Cannon, Christopher P.
AU - Braunwald, Eugene
N1 - Funding Information:
Conflict of interest: K.K.R. has received unrestricted research grants from Pfizer, Sanofi, Solvay, BMS, and MSD, and has received honoraria for lectures, advisory boards, and consultancy from Pfizer, AstraZe-neca, Daiichi Sankyo, Lilly, MSD, Schering, Novartis, Roche, Servier, and IPSEN. B.S. has received consultant fees/honoraria from Gilead, Shionogi, and has conducted research and received research grants from Merck, AstraZeneca, Johnson & Johnson, Bayer, BristolMyers Squibb, Daiichi Sankyo, and Gilead. D.A.M. has received research grants from Dade Behring, Biosite and Roche Diagnostics, and honoraria for lecturing from Dade Behring. C.P.C. has received research grant support from AstraZeneca, Bristol-Myers Squibb, Merck, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin, Merck, Merck/Schering-Plough Partnership, Novartis, and Takeda, is clinical advisor and has equity holdings in Automedics Medical Systems, and has received honoraria for independent educational symposia from AstraZeneca and Pfizer. E.B. has received research support from Bristol-Myers Squibb, Merck, and AstraZeneca.
Funding Information:
K.K.R. was funded by a BHF Intermediate Fellowship. PROVE IT-TIMI 22 was funded by Bristol-Myers Squibb and Sankyo.
PY - 2011/6
Y1 - 2011/6
N2 - Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of heart failure (HF). The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and resultsAmong the subjects of Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial, 3946 had neopterin levels measured at study entry, on average 7 days after acute coronary syndrome (ACS). We assessed the relationship between neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (neopterin), the adjusted risk of HF increased by 34 [hazard ratio (HR) 1.34, CI 1.101.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors, C-reactive protein and brain natriuretic protein (BNP), the further addition of neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional biomarkers.
AB - Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of heart failure (HF). The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and resultsAmong the subjects of Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial, 3946 had neopterin levels measured at study entry, on average 7 days after acute coronary syndrome (ACS). We assessed the relationship between neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (neopterin), the adjusted risk of HF increased by 34 [hazard ratio (HR) 1.34, CI 1.101.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors, C-reactive protein and brain natriuretic protein (BNP), the further addition of neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional biomarkers.
KW - Biomarkers
KW - Heart failure
KW - Prognosis
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U2 - 10.1093/eurheartj/ehr032
DO - 10.1093/eurheartj/ehr032
M3 - Article
C2 - 21345849
AN - SCOPUS:79958145754
VL - 32
SP - 1390
EP - 1397
JO - European Heart Journal
JF - European Heart Journal
SN - 0195-668X
IS - 11
ER -