Current Knowledge of Selected Cardiovascular Biomarkers in Pediatrics: Kidney Injury Molecule-1, Salusin-α and -β, Uromodulin, and Adropin

Cardiovascular diseases are the leading cause of morbidity and mortality in the modern world. Their common denominator is atherosclerosis, a process beginning in childhood. In pediatrics, the aim of preventive measures is to recognize children and adolescents at risk for accelerated atherosclerosis and possible premature cardiovascular events in adulthood. Several diagnostic procedures and biomarkers are available for cardiovascular risk assessment in adults. However, reliable markers in pediatrics are still insufficiently studied. In this contribution, we discuss five potential biomarkers of particular interest: kidney injury molecule-1, salusin-α and -β, uromodulin, and adropin. Studies regarding the pediatric population are scarce, but they support the evidence from studies in the adult population. These markers might entail both a prognostic and a therapeutic interest.

Synergistic Effect of 3′,4′-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus

The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.

Cardiovascular Biomarkers and Diastolic Dysfunction in Patients With Chronic Chagas Cardiomyopathy

Background: Chronic Chagas Cardiomyopathy is a unique form of cardiomyopathy, with a significantly higher mortality risk than other heart failure etiologies. Diastolic dysfunction (DD) plays an important role in the prognosis of CCM; however, the value of serum biomarkers in identifying and stratifying DD has been poorly studied in this context. We aimed to analyze the correlation of six biochemical markers with diastolic function echocardiographic markers and DD diagnosis in patients with CCM.Methods: Cross-sectional study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high-sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Tissue Doppler imaging was used to measure echocardiographic parameters indicating DD. Multivariate logistic regression models adjusted by age, sex, BMI, and NYHA classification were used to evaluate the association between the biomarkers and DD.Results: From the total patients included (55% male with a median age of 62 years), 38% had a preserved LVEF, but only 14% had a normal global longitudinal strain. Moreover, 64% had a diagnosis of diastolic dysfunction, with most of the patients showing a restrictive pattern (n = 28). The median levels of all biomarkers (except for sST2) were significantly higher in the group of patients with DD. Higher levels of natural log-transformed NTproBNP (per 1-unit increase, OR = 3.41, p < 0.001), Hs-cTnT (per 1-unit increase, OR = 3.24, p = 0.001), NGAL (per 1-unit increase, OR = 5.24, p =0.003), and Cys-C (per 1-unit increase, OR = 22.26, p = 0.008) were associated with increased odds of having diastolic dysfunction in the multivariate analyses. Finally, NT-proBNP had the highest AUC value (88.54) for discriminating DD presence.Conclusion: Cardiovascular biomarkers represent valuable tools for diastolic dysfunction assessment in the context of CCM. Additional studies focusing mainly on patients with HFpEF are required to validate the performance of these cardiovascular biomarkers in CCM, allowing for an optimal assessment of this unique population.

Dynamic changes of cardiovascular biomarkers after ablation for atrial fibrillation: observations from AXAFA-AFNET5

Background The dynamic changes and stability of blood biomarkers over time and after treatment are not well known. In this study, we describe changes in 12 centrally quantified known and novel cardiovascular biomarkers, prior to and 3 months after ablation for atrial fibrillation (AF). Purpose In patients enrolled in the AXAFA-AFNET5 trial, we 1) characterised changes in 12 biomarker levels pre and post-ablation, 2) ascertained if biomarker changes are consistent between males and females, and 3) identified biomarkers which predict recurrent AF post-ablation. Methods and results Of the 674 patients who were recruited and randomised, 633 received the study drug and underwent ablation. Peripheral blood samples were available for 488 patients at baseline and 434 at 3 months follow-up (median age [Q1, Q3] 64 [58, 70] years; 34% female). Between baseline (BL) and follow-up (FU), paired comparisons revealed that 3 biomarkers decreased, ANG2 (median [Q1, Q3] BL 2.185 [1.711, 3.115], FU 1.827 [1.457, 2.297] ng/mL, p<0.001), BMP10 (BL 2.056 [1.810, 2.380], FU 1.986 [1.757, 2.260] ng/mL, p<0.001), and NTproBNP (BL 2.219 [0.858, 5.731] per 100pg/mL, p<0.001), while 1 biomarker increased, FABP3 (BL 2.911 [2.425, 3.508], FU 2.911 [2.462, 3.521], p=0.005). The remaining 8 biomarkers remained unchanged. Significant differences in ANG2, BMP10, NTproBNP and FABP3 were driven by patients who remained arrhythmia free at follow-up whereas biomarker levels remained unchanged in 121 patients who experienced recurrent AF (39%; Figure). Change scores were mainly consistent between males and females, however, CRP decreased significantly more in females. Recurrent AF episodes were not different between males and females (p=0.319). Cox proportional hazards model assessed the relationship of individual biomarkers at baseline for predicting recurrent AF. Elevated ANG2 (hazard ratio, HR per ng/mL [95% confidence interval] 1.214 [1.113, 1.325]), BMP10 (HR per ng/mL 1.516 [1.039, 2.214]), and NTproBNP (HR per 100 pg/mL 1.050 [1.025, 1.076]) significantly predicted increased risk for recurrent AF, after adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, stroke, heart failure, ablation type (PVI, PVI and other, other), ablation energy (radiofrequency, cryoablation, other), and treatment arm. Conclusion In this study, most cardiovascular biomarkers are unchanged after ablation for AF, however, ANG2, BMP10, and NTproBNP decreased at follow-up. These effects are driven by patients who remained arrhythmia free and could potentially reflect improvement in vascular (ANG2), endothelial (BMP10), and myocardial load (NTproBNP) parameters post-ablation. This outcome corresponds with the observation that elevated levels of these biomarkers at baseline predict recurrent AF at 3 months. Both males and females demonstrate similar changes in biomarker profiles and benefit equally from ablation for AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK (German Centre for Cardiovascular Research) and BMBF (German Ministry of Education and Research) to AFNET.Additional support from European Union [grant agreement No. 633196 (CATCH ME)]. Biomarker changes

Routine advanced echocardiography in the evaluation of cardiovascular sequelae of COVID19 survivors with elevated cardiovascular biomarkers

Background COVID19 has been related to elevated CVB and biventricular dysfunction during hospitalization. However, it is unknown whether patients with biomarker elevation exhibit long-lasting abnormalities in cardiac function. Purpose To determine, using advanced echocardiography, the prevalence and type of cardiovascular sequelae after COVID19 infection with marked elevation of cardiovascular biomarkers (CVB), and their prognostic implications. Methods All patients admitted from March 1st to May 25th, 2020 to a tertiary referral hospital were included. Patients with cardiovascular disease antecedent, death during admission, or the first 30 days after discharge were excluded. Patients with hs-TnI >45 ng/L, NT-proBNP >300 pg/ml, and D-dimer >8000 ng/ml were separated based on each CVB elevation and matched with COVID controls (three biomarkers within the normal range) based on intensive care requirements and age. Results From a total of 2025 hospitalized COVID19 patients, 80 patients with significantly elevated CVB and 29 controls were finally included. No differences in baseline characteristics were observed among groups, but elevated CVB patients were sicker. Follow-up echocardiograms showed no differences among groups regarding LVEF or RV diameters, but TAPSE was lower if hs-TnI or D-dimer were elevated. Hs-TnI patients also had lower global myocardial work and global longitudinal strain. The presence of an abnormal echocardiogram was more frequent in the elevated CVB group compared to controls (23.8 vs 10.3%, P=0.123) but mainly associated with mild abnormalities in deformation parameters. Management did not change in any case and no major cardiovascular events except deep vein thrombosis occurred after a median follow-up of 7 months (Figure 1). Conclusions Minimal abnormalities in cardiac structure and function are observed in COVID19 survivors without previous cardiovascular diseases who presented a significant CVB rise at admission, with no impact on patient management or short-term prognosis. These results do not support a routine screening program after discharge in this population. FUNDunding Acknowledgement Type of funding sources: None. Figure 1