| Abstract | Background: During acute myocardial infarction, phosphorylated TnI levels, Ca2+ sensitivity and ATPase activity are decreased in the myocardium, and the elevation in Ca2+ levels activates protease I (calpain I), leading to the proteolytic degradation of troponins. Concurrently, hypoxia enhanced the expression of hypoxia inducible factor 1 alpha (HIF-1a) increasing the level of apelin, which limits infarct size, and improves myocardial function. -----
Methods: In this prospective observational study, 100 consecutive patients meeting the following criteria were included: continuous chest pain lasting > 30 min, an electrocardiogram (ECG) with ST-segment elevation (measured at the J-point) ≥ 2.5 mm in men < 40 years, ≥ 2 mm in men ≥ 40 years, or ≥ 1.5mm in women in leads V2-V3 and/or ≥ 1mm in other leads [in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB)], rise of specific biomarkers such as troponin I and the MB fraction of creatine kinase (CKMB), and patients who underwent reperfusion therapy. The levels of apelin-12, creatine kinase (CK), the MB fraction of creatine kinase (CKMB), troponin I, NT-proBNP, CRP, triglycerides, LDL and HDL cholesterol, and other routine laboratory parameters are measured. In particular, we evaluated the levels of apelin-12 and troponin I on the first and seventh days after reperfusion therapy in all patients. -----
Results: There was variability in apelin values on the first day (Kruskal-Wallis test) relative to segmental wall motion abnormalities (SWMAs) (p=0.046) and on the seventh day relative to different numbers of coronary lesions and stenoses (p<0.001). Based on the Mann-Whitney test, the relationship between apelin-12 and the final TIMI grade flow in the acute phase of myocardial infarction was statistically significant (p=0.001). Apelin-12 was inversely correlated with troponin I levels (Spearman’s correlation = −0.40) with a p value <0.001. There was variability in the apelin values on the seventh day (Kruskal-Wallis test) based on major adverse cardiac events (MACE) (p = 0.012). Using ROC curve analyses, a cut-off value of >2.2 for the association of apelin with MACE was determined, and the AUC was 0.71 (95% CI, 0.58–0.84). Survival analysis using the Kaplan-Meier method showed a lower rate of MACE among patients with apelin levels >2.2 (p = 0.002), and the ROC curve analysis showed a statistically significant difference in the area under the curve (p = 0.004). Pearson’s correlation between apelin-12 and creatine kinase-MB on the first day in patients without reperfusion injury was characterized with a p value <0.003, while between apelin-12 and NT-proBNP on the seventh day in patients without reperfusion injury p value was -0.042. -----
Conclusion: The increase level of apelin during acute phase of myocardial infarction indicate a protective effect from reperfusion injury while low level of apelin during non-acute phase of myocardial infarction is found to be inversely associated with number of coronary stenoses. Apelin-12 influences troponin I levels in the acute phase of STEMI, whereas during the non-acute phase, low apelin levels were associated with high rate of MACE. In STEMI patients undergoing reperfusion therapy, apelin-12 was associated with creatine kinase-MB depending reperfusion injury determining role of apelin in creatine kinase system. |
| Abstract (english) | Uvod: Razina fosforiliranog troponina I, osjetljivost Ca2+ i aktivnost ATP-aze snižena je u miokardu tijekom akutnog infarkta miokarda. Porast razine Ca2+ aktivira proteazu I (kalpain I) koja proteolizom razgrađuje troponine. Istovremeno, hipoksija potiče ekspresiju hipoksijom induciranog faktora 1 alfa (HIF-1a) koji potiče porast razine apelina. Apelin ograničava veličinu infarkta i poboljšava funkciju miokarda. -----
Metode: U ovu prospektivnu opservacijsku studiju bilo je uključeno 100 uzastopnih bolesnika koji su ispunjavali sljedeće kriterije: neprekinuta bol u prsima u trajanju > 30 min, elevacija ST-spojnice u elektrokardiogramu (EKG) (mjerena od J-točke) ≥ 2.5 mm u muškaraca < 40 godina, ≥ 2 mm u muškaraca ≥ 40 godina ili ≥ 1.5 mm u žena u odvodima V2-V3 i/ili ≥ 1mm u drugim odvodima (uz odsutnost hipertrofije lijeve klijetke ili bloka lijeve grane), porast specifičnih biomarkera poput troponina I, MB frakcije kreatin kinaze (CKMB), i bolesnici koji su bili podvrgnuti reperfuzijskoj terapiji. Mjerena je razina apelina-12, kreatin kinaze (CK), MB frakcije kreatin kinaze (CKMB), troponina I, NT-proBNP, CRP, triglicerida, LDL i HDL kolesterola te rutinskih laboratorijskih parametara. Posebna pozornost data je na mjerenje razine apelina-12 i troponina I prvi i sedmi dan nakon reperfuzijske terapije kod svih bolesnika. -----
Rezultati: Pronađena je varijabilnost u razini apelina prvog dana (Kruskal-Walisov test) relativna u odnosu na segmentalne abnormalnosti gibanja stijenke (SWMAs) (p=0.046) i sedmog dana relativna u odnosu na različiti broj koronarnih lezija i stenoza (p<0.001). Prema Mann-Whitneyevom testu, povezanost uzmeđu apelina-12 i konačnog stupnja TIMI protoka u akutnoj fazi infarkta miokarda bila je statistički značajna (p=0.001). Razina apelina-12 bila je obrnuto proporcionalna razini troponina (Spearmanova korelacija =-0.40) sa p-vrijednosti <0.001. Postojala je varijabilnost u razini apelina sedmog dana (Kruskal-Waslisov test) temeljena na pojavi velikih neželjenih kardijalnih događaja (MACE) (p=0.012). Koristeći ROC krivulju, granična vrijednost testa vrijednosti od > 2.2 bila je određena za povezanost apelina s MACE, a površina ispod krivulje (AUC) bila je 0.71 (95% interval podudarnosti CI, 0.58-0.84). Analiza preživljenja (koristeći Kaplan-Meierovu metodu) pokazala je nižu stopu MACE u bolesnika s razinom apelina > 2.2 (p=0.002), a ROC krivulja je pokazala statistički značajnu razliku u površini ispod krivulje (p=0.004). Pearsonova korelacija između apelina-12 i kreatin kinaze-MB prvog dana u bolesnika bez reperfuzijske ozljede bila je okarakterizirana sa p-vrijednosti <0.003, dok je p-vrijednost korelacije između apelina 12 i NT-proBNP-a sedmog dana u bolesnika bez reperfuzijske ozljede bila -0.042. -----
Zaključak: Porast razine apelina tijekon akutne faze infarkta miokarda ukazuje na protektivni učinak na reperfuzijsku ozljedu dok je niska razina apelina tijekom neakutne faze infarkta miokarda u obrnuto proporcionalnoj vezi s brojem koronarnih stenoza. Apelin-12 utječe na razinu troponina I u akutnoj fazi STEMI-ja, dok su tijekom neakutne faze, niske razine apelina povezane s većom pojavnosti MACE-a u razdoblju od 12 mjeseci praćenja. U bolesnika sa STEMI-jem koji su podvrgnuti reperfuzijskoj terapiji, apelin-12 je povezan s kreatin kinazom-MB ovisno o reperfuzijskoj ozljedi koja određuje ulogu apelina u sustavu kreatin kinaze. |
