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

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.

A tennis-based health program for middle-aged men who are at risk for heart disease

“…Although, the reduction of neopterin levels have been associated with reduction in CVD risk [29], we did not observed changes in this measurement, but we did observe a significant decrease in plasma carbonylated proteins after the tennis training. This reduction in peripheral oxidant stress may be associated with an exercise-induced up-regulation of the antioxidant system [30].…”

Neopterin as a biomarker of immune response in cancer patients

“…Acute myocardial infarction is also accompanied by a marked rise in urinary neopterin concentrations (55). Similarly to cancer or HIV-1 infection, high neopterin concentrations predict mortality for atherosclerosis or its complications (56,57).…”

Comparison of performance of composite biomarkers of inflammatory response in determining the prognosis of breast cancer patients

“…Similarly to cancer, atherosclerosis is accompanied by inflammatory response. Neopterin and PBC-derived ratios have also been reported to represent biomarkers of atherosclerosis and complications accompanying atherosclerosis and to predict the risk of related events [7,[29][30][31][32][33][34][35]. Surprisingly, only limited information is currently available with regard to a correlation or comparison between PBC-derived ratios and other biomarkers of inflammatory response [41,42].…”

“…Urinary or serum neopterin concentrations are elevated in a wide range of disorders, including, among others, malignant neoplasms, infectious disorders, transplant rejections, autoimmune diseases or complications of atherosclerosis [3][4][5][6][7][8][9][10]. An association of increased neopterin concentrations with poor prognosis has been reported in patients with different cancers [6,[11][12][13][14].…”