#1550 Incident hypertension: immune biomarkers and vascular phenotypes

Abstract

Abstract Background and Aims Blood pressure (BP) regulation is mediated by cardiac, vascular, endocrine, renal, and immune system interactions. Hence, hypertension may exist as different phenotypic variants, with different clinical features and susceptibility to target organ damage. We aimed to analyse the circulating protein biomarker ‘signature’ of: 1) untreated hypertension; 2) hypertensive phenotypes identified by arterial and blood pressure parameters. Method 61 patients with hypertension, and 61 controls were assessed using 24hr ambulatory BP monitoring; endothelial function, arterial stiffness, carotid intima-media thickness (CIMT), and cardiovascular variability [1]. Circulating protein biomarkers analysed using Olink® Inflammation plasma biomarker panel, reported as NPX (Normalized Protein eXpression), in Log2 scale. Results 34 biomarkers dominated by cytokines and chemokines differed between normotensive and hypertensive subjects (Fig. 1), though failed to meet Bonferroni-adjusted threshold. Inflammatory biomarkers correlated with BP and arterial stiffness, BP variability, and CIMT, but not endothelial function. Associations were concordant across systolic and diastolic BP; TPP1, CCL7, CCL11, and CCL21 positively correlating; IL18R1, and KYNU negatively. These relationships were more pronounced in hypertensive subgroup, 85 biomarkers correlating including CD molecules (CD200R1, CD22, CD58, CD6, CD70) and cytokines (IL-5, IL-11, IL-15, IL-18, IL-32, IL-1RL2, IL-22RA1, IL-5RA). HGF, AGE, and CCL21 showed greatest between group differences and correlated with multiple BP or vascular parameters. Systolic nocturnal dipping demonstrated negative correlation with biomarkers relating to immune cell interactions and cellular adhesion (CTRC, EPHA1, LGALS4, SIT1, SMOC, IL-18 and TNFSF11). Machine learning techniques identified three phenotypes of hypertension, ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ [1]. Sixteen of the 85 correlating biomarkers also differed between these phenotypic groups: Conclusion Hypertension is linked to alterations in circulating immune biomarkers. Multiple biomarkers correlated with both arterial stiffness and BP parameters. Some biomarkers are only correlated in the hypertensive group. Many also relate to nocturnal dipping, and differed across the hypertension endotypes. HGF is a promising biomarker for BP and arterial function; warranting further validation.