Immune Activation and Inflammation in Patients with Cardiovascular Disease Are Associated with Higher Phenylalanine to Tyrosine Ratios : The Ludwigshafen Risk and Cardiovascular Health Study

Abstract EN

Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD).

Preferentially Th1-type cytokine interferon-γ stimulates neopterin production by GTP cychlohydrolase I (GCH-I) in parallel in monocyte-derived macrophages and dendritic cells.

In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary cofactor of amino acid hydroxylases like phenylalanine 4-hydroxylase (PAH).

Serum concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.

The phenylalanine to tyrosine ratio (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme activity.

Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did not differ between individuals with or without CAD (Welch's t-test: P = n.s.).

Higher neopterin and hsCRP concentrations were observed in CAD patients compared to controls (P<0.0001) and they correlated with Phe/Tyr (Spearman's rank correlation for neopterin: rs = 0.216 and hsCRP: rs = 0.122; both of P<0.0001) concentrations.

In conclusion, immune activation is associated with higher Phe/Tyr in CAD patients.

Data indicates subnormal PAH activity which might be involved in the precipitation of neuropsychiatric symptoms in patients.