Oxidative stress is a hallmark of chronic kidney disease (CKD) and this alteration is strongly implicated in left ventricular hypertrophy (LVH) and in LV dysfunction in experimental models. However, evidence implicating oxidative stress in alterations of LV mass and function in CKD is limited.
We resorted to the strongest genetic biomarker of paraxonase (PON-1) activity, the Q192R polymorphism in the PON-1 gene, to unbiasedly assess (Mendelian randomization) the cross-sectional and longitudinal (mixed linear modelling) associations between this gene-variant and LV mass and function in a cohort of 206 patients (age: 65 + 12 yrs and 50% males) with CKD of various severity who repeatedly underwent to echocardiographic study over a follow up of 3 years
The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoprastanes levels (P=0.03) and was dose-dependently related in a direct fashion with LV Mass Index (LVMI) (QQ: 131.4±42.6g/m2; RQ: 147.7±51.1g/m2; RR:167.3±41.9g/m2; P= 0.001)) and in an inverse fashion with systolic function (Ejection Fraction, LVEF) (QQ: 79±12%; RQ: 69±9%; RR: 65±10% P= 0.02). Furthermore, on longitudinal observation this gene polymorphism associated with the evolution of the same echocardiographic indicators [LVMI: 13.40g/m2 per risk allele (95% CI: 4.17 to 22.62) P=0.005; LVEF: -2.96% per risk allele (95% CI: -4.62 to -1.29%) P=0.001]. Multivariate analyses did not modify these associations.
In CKD patients the R allele of the Q192R polymorphism in the PON-1 gene is dose-dependently related to increased LV mass and decreased systolic function and is associated with the longitudinal evolution of these cardiac alterations. These results support a causal role of oxidative stress in LV structure and function in CKD patients.
