Authors

• Josip Anđelo Borovac — Medicinski fakultet Sveučilišta u Splitu, Split, Hrvatska — ORCID: 0000-0002-4878-8146
• Joško Božić — Medicinski fakultet Sveučilišta u Splitu, Split, Hrvatska — ORCID: 0000-0003-1634-0635
• Daniela Šupe Domić — Klinički bolnički centar Split, Split, Hrvatska — ORCID: 0000-0002-5584-3182
• Zora Sušilović Grabovac — Klinički bolnički centar Split, Split, Hrvatska — ORCID: 0000-0001-9999-7557
• Duška Glavaš — Medicinski fakultet Sveučilišta u Splitu, Split, Hrvatska — ORCID: 0000-0003-2649-0936

Abstract

**Introduction**: Heart failure (HF) is a syndrome characterized by the activation of the complex cascade of neurohumoral mechanisms in order to maintain cardiac output. (1) Previous studies have shown that activation of a sympathetic nervous system (SNS) is more pronounced in patients with ischemic cardiomyopathy (IC) compared to those with non-ischemic cardiomyopathy (NIC). (2, 3) On the other hand, catestatin is a pleiotropic endogenous peptide that inhibits nicotinic receptor-mediated catecholamine release into the circulation and, therefore, exhibits inhibitory action on SNS activity. The main goal of the study was to determine and compare circulating catestatin levels among HF patients with IC and NIC. **Patients and Methods**: This study included a total of 38 patients admitted to the University Hospital Centre Split during the March-June of 2018 with an acute decompensation of HF determined by the current diagnostic criteria for HF laid out in the European Society of Cardiology guidelines from 2016. Patients with the acute coronary syndrome and/or infectious disease were excluded. Serum levels of catestatin were determined by the enzyme-linked immunosorbent assay (ELISA). **Results**: Twenty-one (55%) patient had IC while 17 (45%) had NIC. Both groups did not significantly differ in baseline anthropometric, clinical and echocardiographic parameters as well as medication intake (**Table 1**). Almost all patients were in NYHA III or IV class regarding the functional classification of HF (N=36, 95%). Patients with IC had significantly higher mean NYHA degree compared to NIC patients (3.4±0.6 vs. 3.1±0.4, p=0.039). Serum catestatin levels did not significantly differ between women and men (18.9 vs. 15.7 ng/mL, p=0.570). HF patients with IC had more than 2-fold higher catestatin serum levels compared to HF patients with NIC (22.8±20 vs. 10.6±8.5 ng/mL, p=0.025) (**Figure 1**). Catestatin showed positive significant correlation with NT-proBNP in a total sample of patients, independent of sex, age, body mass index and estimated glomerular filtration rate (r=0.516, p2) | 31.1 ± 5.6 | 28.9 ± 3.9 | 0.178 | | BSA (Mosteller, m2) | 2.1 ± 0.19 | 2.1 ± 0.18 | 0.904 | | Systolic BP (mmHg) | 135 ± 24 | 138.1 ± 26 | 0.705 | | Diastolic BP (mmHg) | 83.5 ± 10 | 83.1 ± 12 | 0.909 | | Mean NYHA class | 3.1 ± 0.4 | 3.4 ± 0.6 | 0.039 | | Urea (mmol/L) | 11.6 ± 7.1 | 13.3 ± 7.4 | 0.499 | | eGFR CKD-EPI (mL/min/1.73 m2) | 60.7 ± 26.1 | 48.4 ± 25 | 0.145 | | NT-proBNP (pg/mL) | 8205 ± 6638 | 9858 ± 7783 | 0.746 | | CRP (mg/L) | 23.4 ± 17.6 | 18.6 ± 20.4 | 0.628 | | Glucose, fasting (mmol/L) | 8.4 ± 3.1 | 10.3 ± 4.4 | 0.134 | | LVEF (biplane Simpson, %) | 35 ± 15 | 37 ± 14 | 0.697 | | LVEDd (mm) | 61.4 ± 8.9 | 61.1 ± 8.8 | 0.894 | | LVESd (mm) | 48 ± 11.2 | 47.1 ± 12.8 | 0.843 | | LA diameter (mm) | 50.9 ± 8.8 | 51.3 ± 8.1 | 0.884 | | **Comorbidities (%)** | | | | | Arterial hypertension | 15 (88.2%) | 21 (100%) | 0.106 | | Diabetes mellitus | 4 (23.5%) | 10 (47.6%) | 0.126 | | Atrial fibrillation | 9 (52.9%) | 12 (57.1%) | 0.796 | | Dyslipidemia | 12 (70.6%) | 13 (61.9%) | 0.575 | | History of stroke or TIA | 2 (11.8%) | 3 (14.3%) | 0.819 | | Peripheral artery disease | 5 (29.4%) | 3 (14.3%) | 0.255 | | COPD | 4 (23.5%) | 2 (9.5%) | 0.239 | | **Medication use (%)** | | | | | Aspirin | 5 (41.2%) | 13 (61.9%) | 0.393 | | ACE-I or ARB | 14 (82.4%) | 15 (71.4%) | 0.431 | | Beta-blocker | 15 (88.2%) | 19 (90.5%) | 0.823 | | Diuretics | 17 (100%) | 20 (95.2%) | 0.362 | | Calcium channel blocker | 3 (17.6%) | 3 (14.3%) | 0.778 | | Statins | 6 (35.3%) | 10 (47.6%) | 0.444 | [†] **Abbreviations: ACE-I**-angiotensin-converting-enzyme inhibitor; **ARB**-angiotensin II receptor blocker; **BMI**-body mass index; **BP**-blood pressure; **BSA**-body surface area; **COPD**-chronic obstructive pulmonary disease; **CRP**-C-reactive protein; **LA**-left atrium; **LVEDd**-left ventricular end-diastolic diameter; **LVEF**-left ventricular ejection fraction; **LVESd**-left ventricular end-systolic diameter; **eGFR**-estimated glomerular filtration rate; **NT-proBNP**-N-terminal prohormone of brain natriuretic peptide; **NYHA**-New York Heart Association functional classification of heart failure; **TIA**-transient ischemic attack. FIGURE 1. Difference in mean catestatin serum level (ng/mL) between heart failure patients with ischemic and non-ischemic cardiomyopathy. **Conclusion**: Significantly increased circulating catestatin levels in HF patients with ischemic etiology of the disease might indirectly reflect an increased neurohumoral activation in this population, as well as ventricular pressure overload.

Keywords

heart failure, catestatin, neurohumoral activation

DOI

Literature

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