Background:

Despite the improved understanding of modifiable risk factors linked to cardiovascular diseases (CVD) and established pharmacological interventions, patients are still at risk for recurring events. Chronic subclinical inflammation is sought to play a key role in this residual risk and identification of new potential markers is expected to improve prediction of future CVD events. Dual-specificity phosphatase 1 (DUSP1) was reported to play a pivotal role in CVD as a major negative modulator of MAPKs inflammatory signaling pathways. Our aim is to evaluate circulating DUSP1 levels in confirmed CVD patients and their matched controls as compared to oxLDL and hsCRP as well as its relation with classical CVD markers.

Methods:

Matched human cases (208) to their control (152) and their related anthropometric, and clinical metabolic data were extracted from The Kuwait Diabetes Epidemiology Program (KDEP), cohort at Dasman Diabetes Institute (DDI) to estimate the prevalence of obesity, metabolic syndrome and Type 2 Diabetes among the expatriate population of Kuwait. Analytical measurements for circulating plasma levels of DUSP1, oxLDL, and hsCRP were determined using human ELISA kits.

Results:

DUSP1 plasma levels were significantly higher and oxLDL levels were significantly lower in cases. (p<0.05) whereas hsCRP levels were statistically comparable in both groups. In cases, DUSP1 correlated negatively with HDL as we previously showed in non-diabetic obese subjects. With regards to hsCRP and as expected, there was a positive correlation in both groups with anthropometric parameters of adiposity. Least square mean of DUSP1 was significantly higher in cases (p<0.001) whereas oxLDL were decreased in this group. Moreover, least square mean of FBG was significantly higher in the patients while LDL and TC were significantly lower. Multivariate logistic regression analysis showed that DUSP1 is independently associated with CVD as reflected by a 2-fold increase of CVD risk with increased levels of DUSP1 whereas oxLDL and hsCRP were not associated.

Discussion:

Circulating DUSP1 might be a good predictor of chronic subclinical inflammation and residual risks in CVD patients whereas oxLDL might be considered for predicting CVD events in apparently healthy individuals.

Circulating DUSP1 as potential marker for residual inflammation in human subjects with cardiovascular diseases