Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients

Camilla Hage (1) , Erik Michaelsson (2) , Bengt Kull (2) , Tasso Miliotis (2) , Sara Svedlund (3) , Cecilia Linde (1) , Erwan Donal (4, 5) , Jean-Claude Daubert (4, 5) , Li-Ming Gan (3) , Lars H. Lund (1)

1 Karolinska Institutet [Stockholm]
2 AstraZeneca
3 GU - Göteborgs Universitet = University of Gothenburg
4 CIC-IT Rennes
5 LTSI - Laboratoire Traitement du Signal et de l'Image

Aims In heart failure (HF) with preserved ejection fraction (HFpEF), microvascular inflammation is proposed as an underlying mechanism. Myeloperoxidase (MPO) is associated with vascular dysfunction and prognosis in congestive HF. Methods and results MPO, MPO-related biomarkers, and echocardiography were assessed in 86 patients, 4-8 weeks after presentation with acute HF (EF >= 45%), and in 46 healthy controls. Patients were followed up for median 579 days (Q1;Q3 276;1178) regarding the composite endpoint all-cause mortality or HF hospitalization. Patients were 73 years old, 51% were female, EF was 64% (Q1;Q3 58;68), E/e ' was ratio 10.8 (8.3;14.0), and left atrial volume index (LAVI) was 43 mL/m(2) (38;52). Controls were 60 (57;62) years old (vs. patients; P < 0.001), 24% were female (P = 0.005), and left ventricular EF was 63% (59;66; P = 0.790). MPO was increased in HFpEF compared with controls, 101 (81;132) vs. 86 (74;101 ng/mL, P = 0.015), as was uric acid 369 (314;439) vs. 289 (252;328 mu mol/L, P < 0.001), calprotectin, asymmetric dimethyl arginine (ADMA), and symmetric dimethyl arginine (SDMA), while arginine was decreased. MPO correlated with uric acid (r = 0.26; P = 0.016). In patients with E/e ' > 14, uric acid and SDMA were elevated (421 vs. 344 mu M, P = 0.012; 0.54 vs. 0.47 mu M, P = 0.039, respectively), and MPO was 121 vs. 98 ng/mL (P = 0.090). The ratios of arginine/ADMA (112 vs. 162; P < 0.001) and ADMA/SDMA (1.36 vs. 1.17; P = 0.002) were decreased in HFpEF patients, suggesting reduced NO availability and increased enzymatic clearance of ADMA, respectively. Uric acid independently predicted the endpoint [hazard ratio (HR) 3.76 (95% CI 1.19-11.85; P = 0.024)] but not MPO [HR 1.48 (95% CI 0.70-3.14; P = 0.304)] or the other biomarkers. Conclusions In HFpEF, MPO-dependent oxidative stress reflected by uric acid and calprotectin is increased, and SDMA is associated with diastolic dysfunction and uric acid with outcome. This suggests microvascular neutrophil involvement mirroring endothelial dysfunction, a central component of the HFpEF syndrome and a potential treatment target.

Mots clés: Endothelial dysfunction; Heart failure with preserved ejection fraction; Microvascular inflammation; Myeloperoxidase; Prognosis

Domaines: Ingénierie biomédicale

Camilla Hage, Erik Michaelsson, Bengt Kull, Tasso Miliotis, Sara Svedlund, et al.. Myeloperoxidase and related biomarkers are suggestive footprints of endothelial microvascular inflammation in HFpEF patients. ESC Heart Failure, 2020, 7 (4), pp.1534-1546. ⟨10.1002/ehf2.12700⟩. ⟨hal-02735847⟩