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

Abstract

Abstract 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.