Aortic stiffness—Is kynurenic acid a novel marker? Cross-sectional study in patients with persistent atrial fibrillation

Abstract

Objective Although a number of modifiable and non-modifiable causes were implicated in arterial stiffness, its pathogenesis remains elusive, and very little is known about aortic elasticity in supraventricular arrhythmias. The potential role of disturbed kynurenine metabolism in the pathogenesis of cardiovascular disease has been recently suggested. Thus, we studied the correlations of aortic stiffness and echocardiographic parameters with biochemical markers and serum level of kynurenic acid (KYNA), an endothelial derivative of tryptophan, formed along the kynurenine pathway, among patients with atrial fibrillation (AF). Methods Study cohort comprised 100 patients with persistent AF (43 females/57 males). Arterial stiffness index (ASI), structural and functional indices of left atrium (LA) and left ventricle (LV) were evaluated electrocardiographically. Biochemical analyses included the measurements of serum KYNA (HPLC) and of the selected markers of lipids and glucose metabolism, thyroid status, kidney function, inflammation and coagulation. Results KYNA (β = 0.389, P = 0.029), homocysteine (β = 0.256, P = 0.40), total cholesterol (β = 0.814; P = 0.044), LDL (β = 0.663; P = 0.44), TSH (β = 0.262, P = 0.02), fT 3 (β =-0.333, P = 0.009), fT 4 (β =-0.275, P = 0.043) and creatinine (β = 0.374, P = 0.043) were independently correlated with ASI. ASI was also independently associated with LV end-systolic diameter (LVEDd; β = 1.751, P = 0.045), midwall fractional shortening (mFS; β =-1.266, P = 0.007), ratio mFS/end-systolic stress (mFS/ESS; β =-0.235, P = 0.026), LV shortening fraction (FS; β =-0.254, P = 0.017), and LA volume index (LAVI; β = 0.944, P = 0.022).

Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

“…Although 3-HAA was elevated in advanced atherosclerosis and correlated with decreased ankle-brachial index, it did not show increased odd ratio for advanced atherosclerosis ( 73 ). In atrial fibrillation increased KYNA was associated with raised aortic stiffness ( 90 ), but KYNA was not correlated with carotid intima-media thickness in chronic kidney disease ( 49 , 81 ).…”

Effects of Kynurenic Acid on the Rat Aorta Ischemia—Reperfusion Model: Pharmacological Characterization and Proteomic Profiling

“…However, its presence in the periphery is poorly studied, being reported in the heart, kidneys, liver, and endothelium [ 4 , 5 , 31 ]. Hypoglycemia and anoxia are factors that control the KYNA levels in serum, when produced by the endothelium [ 5 , 32 ].…”

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke

“…The PAr-index has been associated with future stroke in a population study [ 18 ] but has never been studied in a stroke population nor in the context of stroke recurrence. The role of KA in stroke recurrence is not clear, but KA has been found to be associated with coronary events [ 39 , 40 ] and aortic stiffness, which in turn is associated with atrial fibrillation [ 41 ]. In a recent study, Baumgarten et al found that the branch of the kynurenine pathway, leading to the formation of KA, was downregulated in atherosclerotic plaques, and this downregulation was associated with an increased risk of cerebrovascular events [ 19 ].…”