Received on October 5, 2008
Accepted on March 19, 2009

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Neopterin as a Predictor of Total and Cardiovascular Mortality in Individuals Undergoing Angiography in the Ludwigshafen Risk and Cardiovascular Health Study

¹ Synlab Centre of Laboratory Diagnostics Heidelberg, Heidelberg, Germany, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
² Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Austria
³ Division of Endocrinology, Department of Medicine, Ulm University, Germany
⁴ Cardiology Group Frankfurt-Sachsenhausen, Frankfurt, Germany
⁵ Synlab Centre of Laboratory Diagnostics Heidelberg, Heidelberg, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria, and Department of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany

^* To whom correspondence should be addressed. E-mail: tanja.grammer{at}synlab.de.

BACKGROUND: Neopterin is produced upon activation of the cell-mediated immune response, and may be a novel risk marker for adverse outcomes resulting from coronary artery disease.

METHODS: We measured neopterin in 1801 study participants with and 511 without angiographic coronary artery disease. Rates of death were determined after a median follow-up of 8.0 years.

RESULTS: Estimated glomerular filtration rate and N-terminal pro-B–type natriuretic peptide (NT-proBNP) were the strongest predictors of neopterin. Neopterin was positively related to age and inversely related to LDL cholesterol, HDL cholesterol, and triglycerides. Use of lipid-lowering drugs lowered neopterin. Sex, body mass index, diabetes mellitus, hypertension, smoking status, Friesinger coronary score, and clinical instability at presentation were not associated with neopterin. Unlike C-reactive protein, neopterin was not increased in unstable angina pectoris, non–ST–elevation myocardial infarction, or ST-elevation myocardial infarction. In the third and fourth quartiles of neopterin, unadjusted hazard ratios for death from any cause were 1.94 (95% CI 1.44–2.61) and 3.32 (95% CI 2.53–4.30) compared to individuals in the first quartile, whereas hazard ratios for death from cardiovascular causes were 2.14 (95% CI 1.44–3.18) and 3.84 (95% CI 2.67–5.52), respectively. Neopterin remained predictive of total and cardiovascular mortality after adjusting for sex, age, body mass index, type 2 diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol, triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical status at presentation, but NT-proBNP substantially weakened this association.

CONCLUSIONS: Neopterin is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease.