Background
A team from the University Medical Centre Groningen (NL) has used multiple Olink® Target 96 panels to identify proteins associated with metabolic syndrome (MetS) symptoms in heart failure (HF) patients. Patients with MetS are twice as likely to develop HF and adverse progression of MetS significantly influences the therapeutic management of HF, but the role of MetS in the pathophysiology of HF is poorly understood.
Outcome
363 unique proteins were measured to compare HF patients with and without MetS in a discovery cohort of 1103 HF patients (42% with MetS) and a validation cohort of 1433 HF patients (43% with MetS). MetS was defined as the presence of at least three of five criteria: central obesity, elevated serum triglycerides, reduced high-density lipoprotein cholesterol, insulin resistance and hypertension. 48 proteins were differentially expressed between MetS +/- HF subjects (43 were elevated, 5 decreased) in patients with metabolic syndrome, while in the validation cohort, 58 were elevated and 3 decreased. A total of 29 biomarkers were found to be elevated in both the discovery and validation cohorts. The most significantly elevated biomarkers in patients with metabolic syndrome from both cohorts were LEP, FABP4, IL1RN, TNFRSF11A & RET.
They then applied pathway analysis to these results, identifying 10 enriched pathways in the discovery cohort and 6 in the validation cohort, all of which were related to inflammation. One specific inflammatory pathway that was common to both cohorts was up-regulation of the natural killer cell-mediated cytotoxicity pathway. Combined with additional clinical data, the results suggest that MetS in HF is associated with biomarkers and pathways relating to obesity, lipid metabolism and immune responses underlying chronic inflammation.
