JOURNAL TRANSCRIPT
CE: Namrta; JCM/201754; Total nos of Pages: 6;
JCM 201754
Original article
Prognostic role of aldosterone in patients with acute coronary syndrome: short and medium term follow-up Mignano Antoninoa,b,c, Pitruzzella Valentinaa,b,c, Arnone Gasparea,b,c,, Arnone M. Teresaa,b,c,, Rotolo Antoninoa,b,c, Assennato Pasqualea,b,c, Novo Giuseppinaa,b,c, Corrado Eglea,b,c and Novo Salvatorea,b,c Aims Different researches showed a correlation between aldosterone, atherosclerosis and ischemia in the last decade. Evidence exist about relationship between high levels of aldosterone and augmented risk of cardiovascular diseases, like hypertension, cardiac failure, coronary artery disease and stroke. The objective of this study was to determine the prognostic role of aldosterone in patients with myocardial infarction. Methods Population of the study includes 96 consecutive patients admitted in our Department for ST-elevated and non-ST-elevated myocardial infarction from June 2009 to March 2012. Plasmatic aldosterone levels were dosed at admission in hospital in all patients. A 2 years prospective follow-up was performed and fatal events and nonfatal events like reinfarction, congestive heart failure and arrhythmias were recorded. Results Aldosterone levels at admission were associated with incidence of congestive heart failure (P U 0.02), ventricular arrhythmias (P U 0.01) and all complications (P U 0.003) after 1-month follow-up. Moreover, high aldosterone levels gave important information at medium term (24 W 6 months). Specifically, aldosterone was a predictive variable of reinfarction (P < 0.0001), congestive heart failure (P < 0.0001) and adverse events (P U 0.0002). The logistic regression analysis confirmed these results and showed that aldosterone may be predictive of adverse
Introduction The first study that clarified the role of aldosterone in myocardial infarction has been conducted by Beygui et al.1 who analyzed the relationship between plasma aldosterone and outcome of patients with ST elevation myocardial infarction (STEMI) and without left ventricular dysfunction or heart failure. The study enrolled 356 patients, undergoing Percutaneous Coronary Intervention (PCI) for STEMI, who were divided in four quartiles and monitored for 6 months. Results of the study showed that higher levels of aldosterone were associated with higher incidence of ventricular fibrillation (P ¼ 0.02), heart failure (P ¼ 0.005) and cardiovascular death (P ¼ 0.03) during hospital stay.
Division of Nuclear Medicine of ‘‘Civico Benfratelli, G. Di Cristina’’ Hospital, Palermo - Italy. 1558-2027 ß 2013 Italian Federation of Cardiology
events at medium term follow-up [OR 1.1 (1.03–1.15); 95% confidence interval, P U 0.02]. Conclusion These data show a strong and significant correlation between aldosterone plasmatic levels at admission for myocardial infarction and fatal and nonfatal adverse events. Aldosterone appears a main marker of adverse clinical outcome according with literature. These data suggest necessity to identify if antialdosteronic drugs treatment, applied acutely in patients with aldosterone elevation, can influence favorably prognosis of patients with myocardial infarction. J Cardiovasc Med 2013, 14:000–000 Keywords: acute coronary syndrome, aldosterone, arrhythmias, failure, heart, myocardial infarction a Division of Cardiology, Department of Internal and Specialist Medicine and Cardiovascular Diseases, bPostgraduate School of Cardiology and cCentre for the Diagnosis of Preclinical and Multifocal Atherosclerosis and for Cardiovascular Prevention Division of Cardiology, University Hospital ‘P. Giaccone’, of the University of Palermo, Palermo, Italy
Correspondence to Novo Salvatore, MD, Division of Cardiology, Department of Internal and Specialist Medicine and Cardiovascular Diseases, University Hospital ‘P. Giaccone’, of the University of Palermo, Via del Vespro 129– 90127–Palermo, Italy Tel: +091 655 43 01, 3356889090; fax: +091 655 43 01; e-mail:
[email protected] Received 9 February 2013 Revised 17 April 2013 Accepted 24 May 2013
Moreover, patients of the highest quartile had worse outcome at 6 months than patients with lower levels of aldosterone independently from age, heart failure and successful reperfusion. Subsequently, the same group conducted a new study to determine the effect of spironolactone in patients with STEMI, showing that antialdosteronic drugs provide a lower incidence of arrhythmias and cardiac arrest.2 According to Beygui et al. data, Palmer et al.3 reported that aldosterone levels correlate with long-term mortality of patients with AMI. The study recruited 546 patients with STEMI or non-STEMI and without postinfarction heart failure. Over 80% of patients had non-STEMI and follow-up was 5 years. These data, therefore, confirm results of Beygui et al. extending conclusions to the larger group of non-STEMI patients who were more than 80% DOI:10.2459/JCM.0b013e328364129c
AQ2
CE: Namrta; JCM/201754; Total nos of Pages: 6;
JCM 201754
2 Journal of Cardiovascular Medicine 2013, Vol 00 No 00
of the total cohort. In addiction, levels of plasma aldosterone were elevated beyond the normal range in only a small percentage of patients suggesting that higher concentration of plasma aldosterone, within the normal range, may have an important impact on longterm survival.
All patients underwent to accurate medical history, objective clinical examination, standard ECG, echocardiography, samples for specific myocardial enzymes, blood glucose, total cholesterol, low density lipids (LDL), high density lipids (HDL), triglycerides, creatinine, BUN, serum electrolytes, AST levels, ALT levels, coagulation.
Finally, the LURIC study, that considered a large cohort of normotensive and hypertensive patients with and without coronary artery disease, heart failure and acute coronary syndrome, demonstrated that higher levels of plasma aldosterone, although within the normal range, correlate with overall and cardiovascular mortality.4
Left ventricular ejection fraction (LVEF), end-systolic volume, end-diastolic volume were evaluate with transthoracic echocardiography. Echocardiographic evaluation will performed with echocardiography ‘Acuson Sequoia’. Chamber dimension, LVEF and systolic function, valve function and morphology, pattern Doppler and diastolic function were assessed with conventional echocardiography. LVEF was measured by modified biplane Simpson method.
A recent meta-analysis, which considered 19 randomized controlled trials and a total of 10 807 patients, confirmed the negative effect of aldosterone in patients with chronic heart failure and IMA, reporting a 20% reduction in allcause mortality in patients treated with mineralocorticoid receptor antagonists.5 Primary objective of our study was to evaluate relation between plasmatic aldosterone levels at hospital admission and mortality (for cardiovascular disease or for all causes) and complications incidence (reinfarction, ventricular fibrillation, left ventricular insufficiency) at short term (less than 30 days after hospitalization) and at medium term (24 6 months) in patients admitted for myocardial infarction in our Operative Unit of Cardiology of University Hospital ‘Paolo Giaccone’ of Palermo. In addiction our study wanted evaluate efficacy of spironolactone on fatal and nonfatal adverse events reduction.
Materials and methods AQ3
The study included patients of every sex that were admitted for ST elevated and Non-ST-elevated myocardial infarction from June 2009 to March 2012 in our Operative Unit of Cardiology and that underwent to coronarography. Diagnosis of STEMI was made, according to the current guidelines, in those patients referred to our division for a typical chest pain lasting more than 20 min and with a persistent ST-elevation reflecting an acute and total occlusion of the artery responsible for the myocardial infarction.6 A diagnosis of non-STEMI was made, always according to the current guidelines, in patients referred for typical chest pain but without a persistent ST elevation, when a positive value of troponin was found.7 Exclusion criteria of the study were: potassium saver diuretics treatment before myocardial infarction, severe renal failure (creatinine >2.5 mg%), potassium levels more than 5 mmol/l, respiratory insufficiency, severe hepatic disease, malignant neoplasia or terminal cachexia, active infective diseases, mental disorders or linguistic barriers, that impeded adequate comprehension and collaboration.
Plasmatic aldosterone was dosed at admission in hospital in all patients by a commercial radioimmunoassay kit (ALDO-RIACT, Schering AG, Berlin, Germany). Considered normal range was 8–172 pg/ml. Data about coronary anatomy, stent or bypass presence and about drugs that were administered during cardiac catheterization (heparin, aspirin, clopidogrel, abciximab) were recorded in every patient. TIMI flow grade was evaluated in patients that underwent to angioplasty. Observation period of our prospective study lasted 24 months and, for medium term follow-up, information about fatal and nonfatal adverse events were recorded contacting patients to conduct a clinical examination or, if it was not possible, contacting them, their relatives or their medical doctors with telephonic interviews. Recorded data were about cardiovascular and noncardiovascular death and further hospitalizations for cardiovascular reasons (reinfarction, congestive heart failure and arrhythmias). Data management and statistical analysis
Statistical analysis was affected using Statview program (Abacus Concepts Inc.). Mean and SD were calculated for numeric variables and differences were obtained between groups by Student’s t test. Prevalence of clinical and laboratory variables and difference between groups were calculated by x2 statistical test. Considered significant statistic level was P < 0.05.
Results Three hundred and fifty-six patients were admitted in our intensive unit of cardiology with diagnosis of acute coronary syndrome from June 2009 to March 2012. Ninety-six patients with myocardial infarction that underwent to coronarography were recruited, 70 with ST-elevated myocardial infarction diagnosis and 26 with non-ST-elevated myocardial infarction diagnosis. All patients were informed at moment of enrollment about protocol and did consent to study participation. Median age of participants was 65 years, 57% was men and 57%
AQ4
AQ5
CE: Namrta; JCM/201754; Total nos of Pages: 6;
JCM 201754
Aldosterone in acute coronary syndrome patients Antonino et al. 3
had familiar history for myocardial infarction. Regarding other principal cardiovascular risks, 69.7% presented hypertension before myocardial infarction, diabetes mellitus type 2 was present in 29.2%, dyslipidemia in 33.3%, obesity in 33.7% and smoke in 40.6%. Basal characteristics of our population showed moderatehigh risk patients with myocardial infarction, 31% with age at least 75 years, 23% with history of acute myocardial infarction, 42.7% with anterior or anterior-septal or anterior-lateral acute myocardial infarction. Median levels of aldosterone in our population was 71.3 pg/ml. Mean ejection fraction of left ventricle at transthoracic echocardiography was 50%. In particular 40.5% of patients showed a normal ejection fraction (EF) and only 18.2% showed systolic dysfunction of left ventricle, defined to EF less than 40% presence. All patients underwent to coronary and ventricular catheterization that showed an involvement of one vessel in 51.6% of cases, an involvement of two vessels in 24.2% and a multivessel involvement in 24.2% of patients. Only in 2.5% of cases a full spontaneous reperfusion happened. Ninety percent of patients were treated with primary PCI and coronary stent application, with a successful reperfusion in 95% of patients. Remaining 5% of patients needed an aortic-coronary bypass. Patients that underwent to aortic-coronary bypass were 10.4% in all. Global population was divided in three groups in accord with plasmatic aldosterone levels tertiles. Every tertile was defined by aldosterone levels 19.0 or less (I), from 19.1 to 66.0 (II), at least 66.1 pg/ml (III). AQ8
Table 1
Comparing recorded data during echocardiographic examination, there were not any statistically significant differences between tertiles, considering ejection fraction, end-systolic volume and end-diastolic volume. At last, first and second tertiles were more frequently associated, but not significantly, with a less severe coronary disease, contrary to third tertile. During hospital stay only two deaths occurred after ventricular. These complications occurred during hospital stay: cardiogenic shock in 2.1%, congestive heart failure in 11.46%, reinfarction in 3.1%, ventricular fibrillation in 4.2% and atrial fibrillation in 8.3% of patients. Cardiogenic shock, ventricular fibrillation and death occurred only in patients of the third tertile. Cardiac heart failure kept a higher frequency in the higher tertile (21.9%) than in the second tertile (12.5%); re-infarction occurred in 6.25% of cases of third tertile and in 3.1% of the second tertile, and minor arrhythmias (atrial fibrillation, supraventricular tachycardia and atrial tachycardia) occurred more frequent in the third and in the second tertile (9.4%, respectively) than in the first one (6.25%). The rates of in-hospital events in different groups, according to the baseline tertiles of plasma aldosterone levels, showed an almost stepwise increase in rates of
Basal characteristics in agreement with plasmatic aldosterone levels tertiles
Variables Age Male sex (%) Previous AMIb (%) Hypertension (%) Diabetes (%) Smokers (%) Dyslipidemia (%) BMI (kg/m2), mean SD SBP (mmHg), mean SD DBP (mmHg), mean SD Ejection fraction (%), mean SD AMI location (%) Anterior wall Inferior wall Lateral wall Angiographic characteristics,% 1 vessel 2 vessels Multivessel Aldosterone (pg/ml), mean SD Troponine (ng/ml) mean SD C Reactive protein (pg/ml), mean SD Fibrinogen (mg/dl), mean SD Triglycerides (mg/dl), mean SD Total cholesterol (mg/dl), mean SD LDLc (mg/dl), mean SD HDLd (mg/dl), mean SD a
Patients treated with antialdosteronic drugs and standard therapy were 30 and they were distributed in plasmatic aldosterone levels tertiles: specifically nine in I tertile, 10 in II tertile and 11 in III tertile. Comparison between clinical characteristics of every tertile of patients is reported in Table 1.
Tertile 1
Tertile 2
Tertile 3
P Nsa 0.02 Ns 0.02 Ns 0008 Ns Ns Ns Ns Ns Ns
62 17 56 22 62.5 28 53 28.1 26.4 4.5 129 20 77 12 50 8
67 14 41 22 87.5 28 18.7 40.6 28.9 5.4 144 20 81 13 50 10
64 13 75 25 59.4 31 50 31.5 27.4 6.6 137 26 80 12 48 9
37.5 53 9.4
43.75 34.4 25
50 34.4 15.6
25 34.4 15.6 11.8 5.0 34.2 33 2.1 2.9 339 122 136.8 73 176,3 38 105.8 36 41.4 13
40.6 9.3 31.2 35.5 12.4 21.3 27 2 2.5 381 90 108.8 40 173.7 39 103.6 33 52.1 20.7
28 28.1 25 167 95 40.3 69 2.6 3.5 378 89 143 67 189 46 117 43 43.8 14
Ns
Ns, NOT significant. b AMI, acute myocardial infarction. c LDL, low density lipids. d HDL, high density lipids.