Background/Purpose

Psoriatic diseases are systemic inflammatory joint and skin disorders associated with increased cardiovascular (CV) morbidity.  Paraoxonase (PON) and Arylesterase (ARYL) are antioxidant enzymatic proteins associated with High Density Lipoproteins (HDL).   These levels have been associated with providing systemic protection against HDL and LDL lipid peroxidation and promoting the atheroprotective properties.  Previously reports show PON/ARYL levels are significantly reduced in RA and SLE. While it is known that the risk for CV disease is elevated in patients with psoriatic disease relative to the general population, we believe this is the first report between serum PON/Aryl levels and risk of coronary heart disease (CHD) using Framingham risk score (FRS) in Psoriasis (PsO) and Psoriatic Arthritis (PsA) patients. We sought to compare the prevalence of FRS and the levels of related biomarkers in patients with PsO and PsA. 

Methods:

We performed a cross sectional study of 289 patients (age 49(+/-13.2), 51% males) with PsO and PsA from our Cardiometabolic Outcome Measures in Psoriatic Arthritis Study (COMPASS), a longitudinal cohort with a focus on cardiovascular health from 2011-2014. Baseline serum PON/ARYL levels were obtained from our cohort (N = 238, PsA 57%, PsO, 43%).  The disease cohorts were each further subdivided into 3 groups based on their FRS; FRS <10% (low risk, PsA/PsO  n=111/76), 10-20% (intermediate risk, PsA/PsO n=17/23) and FRS ≥ 20% (high risk group, PsA/PsO n=8/3), respectively. Analysis of variance (ANOVA) was used to compare mean serum levels across FRS categories (Kruskal-Wallis for comparison of medians).  Odds ratios (OR) and 95% confidence interval from logistic regression were computed to show the association of PON/Aryl levels to increased CV risk (FRS ≥ 20%). P values < 0.05 are considered statistically significant.

Results:

A statistically significant inverse relationship between the mean levels of serum Aryl activity (126.8 ± 29.0, 117.9 ± 37.3, 86.6 ± 19.4 µmol/min/mL, p = 0.001) and the levels of increasing CHD risk were found in PsA patients .  A similarly strong inverse relationship between serum PON activity (median: 667.0, 544.0, 268.0 nmol/min/mL, P = 0.051) and increasing levels of CHD risk also existed in the PsA population. There was no significant relationship between both PON (p=0.45) and Aryl (p=0.19) compared to FRS in the PsO population.

Baseline PON and Aryl were significantly associated with FRS≥20% (natural-log transformed PON OR: 0.19 (0.05, 0.69), p=0.01; Aryl OR: 0.95 (0.92, 0.98), p=0.002).  No significant associations with PON/Aryl and increased CV risk were found within the PsO population.

Conclusion: Exposure of increased burden of inflammation (PsA>PsO>controls) is associated with more severe CV risk in patients with PsA. This association may be mediated by novel biomarkers for dysfunctional HDL. The stronger relationship between FRS and PON/Aryl activity levels in the PsA patients is hypothesized to be due to the greater level of systemic inflammatory disease and oxidative stress. Given the early onset of PsA (before the age of 40), this test can potentially provide an incremental benefit to assess CV risk.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/exploring-the-association-of-serum-paraoxonase-and-arylesterase-activities-with-cardiovascular-risk-in-psoriasis-and-psoriatic-arthritis/