AUTHOR=Reponen Elina J. , Dieset Ingrid , Tesli Martin , Mørch Ragni H. , Aas Monica , Vedal Trude S. J. , Haug Elisabeth , Drange Ole Kristian , Steen Nils Eiel , Hope Sigrun , Szabo Attila , Gohar Sherif M. , Wedervang-Resell Kirsten , Djurovic Srdjan , Melle Ingrid , Aukrust Pål , Andreassen Ole A. , Ueland Thor TITLE=Atherogenic Lipid Ratios Related to Myeloperoxidase and C-Reactive Protein Levels in Psychotic Disorders JOURNAL=Frontiers in Psychiatry VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00672 DOI=10.3389/fpsyt.2020.00672 ISSN=1664-0640 ABSTRACT=Background

Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.

Methods

As a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors.

Results

A markedly higher proportion (26%–31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses.

Conclusions

Our findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies.