Petr Ostadal

The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in the patients with unstable angina and non-Q-wave myocardial infarction

The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris (UAP) or non-Q-wave myocardial infarction (NQMI) can influence the serum level of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) 24 h later. Forty-four patients with rest chest pain and subendocardial ischemia on ECG were randomized to receive cerivastatin 0.3 mg at the time of admission (group C+) to standard therapy or to remain just on standard therapy (group C−). Blood samples for determination of troponin I (TI), CRP, IL-6 and IL-8 were collected at admission (entry level) and 24 h later (final level). Patients with non-physiological baseline levels of TI, as well as patients with progression to Q wave MI were excluded. All baseline, clinical and demographic data and final values of TI were comparable in the two groups. In patients treated with cerivastatin (group C+, n = 13) we observed decrease in the CRP level (−6.73 ± 3.93 mg/L); on the other hand, in group C− (n = 17) the CRP level increased (+7.92 ± 2.77 mg/L, p = 0.004). Similar differences were observed also in IL-6: in group C+ the level was significantly reduced as compared with the increase in group C− (−0.76 ± 0.52 vs. 4.58 ± 1.49 ng/L, p = 0.005). The level of IL-8 was not affected. Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI; this might positively influence their prognosis. Nevertheless, further studies are needed to support this hypothesis.

Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696].

BackgroundActivation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS.MethodsThe FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest.ConclusionThe primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUNDnThe role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 μmol/l), D--diabetes mellitus) scoring system.nnnMETHODSnAHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315).nnnRESULTSnMain outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001).nnnCONCLUSIONnThe AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

Positive Influence of Being Overweight/Obese on Long Term Survival in Patients Hospitalised Due to Acute Heart Failure

Background Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the “obesity paradox” on a large cohort with long-term follow-up are lacking. Methods Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5–25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. Results In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26–1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09–1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11–1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. Conclusion These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Acute heart failure registry from high-volume university hospital ED: comparing European and US data

BACKGROUNDnAcute heart failure (AHF) is associated with a poor prognosis.nnnOBJECTIVESnThe objectives of this study are to describe mechanisms of AHF and to identify the predictors for all-cause mortality by patients admitted for hospitalization by emergency departments (EDs) as well as to compare European and American data.nnnMETHODSnWe designed a prospective registry of consecutively admitted patients for AHF to a high-volume university hospital ED during a 1-year period (n=202; age, 75±11 years; 51% men; ejection fraction, 38%±15%).nnnRESULTSnThe major causes of AHF were coronary artery disease, often with concomitant mitral regurgitation, hypertension, or atrial fibrillation (>90% of cases). At admission, 24.9% of patients had preserved ejection fractions (>50%); and only 7.7% fulfilled the definition of diastolic AHF. The 30-day and long-term mortality (median follow-up, 793 days) were 20.3% and 31.0%, respectively. A low systolic blood pressure (P=.006), reduced ejection fraction (P=.044), and low serum hemoglobin level (P<.01) emerged as the strongest predictors of all-cause mortality. In patients with AHF without acute myocardial infarction (MI) (63.9%), prescription, at discharge, of statins (P<.05) was independently associated with all-cause mortality.nnnCONCLUSIONSnThe patients blood pressure, ejection fraction, and hemoglobin values, at admission, were identified as the strongest predictors of all-cause mortality. In AHF not triggered by acute MI, long-term use of statins may be associated with reduced survival. The prevalence of diastolic AHF is low. The American AHF population had similar baseline characteristics; needed fewer intensive care unit admissions; had a better 30 days of prognosis, lower incidence of MI, and de novo AHF diagnoses. In a similar subgroup, we observed similar incidences of inotropic support and mechanical ventilation. Our results could not be generalized to all patients with AHF admitted to US EDs.

Immediate effect of fluvastatin on lipid levels in acute coronary syndrome.

It is widely assumed that acute benefit of statin therapy is mediated especially by non-lipid effects. The immediate influence of statins on lipid levels in patients with acute coronary syndrome (ACS) is, however, not clear. A total of 64 consecutive patients with ACS were randomized at admission to fluvastatin 80xa0mg (Group 1, Nxa0=xa032) or standard therapy without statin (Group 2, Nxa0=xa032). The levels of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG) were examined at admission and after 24xa0h. Baseline characteristics were comparable in both groups. In Group 1, fluvastatin significantly decreased the levels of TC by 14.5%, LDL-C by 17.2%, and HDL-C by 10.0% (Pxa0<xa00.001); TG were not influenced. In Group 2 only marginal reductions in TC (by 4.1%, Pxa0=xa00.03) and HDL-C (by 7.5%, Pxa0<xa00.01) were detected; the levels of LDL-C and TG were not changed. As compared with Group 2, in Group 1 the final levels of TC (Pxa0=xa00.02) and LDL-C (Pxa0=xa00.01) were significantly lower. Fluvastatin therapy, when started at admission in patients with ACS, significantly reduces TC and LDL-C already after 24xa0h. We suggest that the lipid-lowering effect of statins in the therapy of ACS is probably as prompt as non-lipid effects.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial

The randomized clinical trial RELAX‐AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX‐AHF trial (relax‐comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax‐non‐comparable group), and finally with characteristics and outcomes of patients from the RELAX‐AHF trial.

Does Reperfusion Cause Any Injury to the Myocardium

Enormous effort has been made during the past three decades to explain the pathologic events which occur upon reperfusion of the previously ischemic heart in animals. Experimental studies have described potentially harmful effects of reperfusion, a phenomenon called “reperfusion injury”. It is based on the observations in different animals that some myocardial damage occurs upon reperfusion if it is not instituted within a certain time-period of the ischemic insult. Although reperfusion has been shown as the most efficient treatment strategy for acute myocardial infarction in humans, arrhythmias and myocardial depression (cardiac stunning) have been observed upon reperfusion in patients with acute myocardial infarction; these harmful effects are temporary. In fact, the hard-core evidence that reperfusion causes myocardial injury in human is lacking and this is primarily due to the fact that a host of drugs are administered before inducing reperfusion by angioplasty, thrombolytic therapy or coronary bypass surgery. The purpose of this article is to summarize the current knowledge regarding the relationship between reperfusion and reperfusion injury and their implications in clinical management. De spite abundant information concerning the reperfusion-related injury, it is not clear whether reperfusion causes further injury to the ischemia-damaged cardiomyocytes or it is the delayed effect of ischemia per se. In addition, modifications of the reperfusion conditions have not been shown to improve the long-term damage to the myocardium. Thus, some caution should be exercised in interpreting the data from animal experiments to human until long-term results on ischemia-reperfusion injury are available.

Prognostic Impact of Copeptin and Mid-Regional Pro-Adrenomedullin in Chronic Heart Failure with Regard to Comorbidities

The aim of the study is to evaluate the impact of new humoral substances: copeptin and mid- regional proadrenomedullin (MR-proADM) on one-year survival of patients with stable systolic chronic heart failure (CHF) and to compare them with AHEAD score assessing the comorbidities. The FAR NHL (FARmacology and NeuroHumoraL activation) registry is a database of patients with stable CHF (ejection fraction (EF) <50%) treated in specialized HF departments. AHEAD score is a simple bed-side mortality predictive model based on age and comorbidities. Primary endpoint after 1-year follow-up was: death or hospitalization for decompensation of HF or heart transplantation or LVAD implantation. To whole FAR NHL registry, a total amount of 1088 patients were included, in 552 of them the levels of copeptin and MR-proADM were available. Mean age was 65+12 years, mean EF was 31+9%. Patients without primary endpoint were assigned as group A (469 pts), those with the primary endpoint group B (83 pts). There were statistically significant differences between the groups in the levels of copeptin: group A median 15.9 pmol/l (3.4-50.9) vs group B 23.7 pmol/l(5.0-89.44) (p<0.001), MR-proADM: group A median 0.63 nmol/l(0.32-1.34) vs group B 0.74 nmol/l (0.4-1.94) (p<0.001). Relationship of AHEAD score to primary endpoint in the first year of follow-up was not significant, but within 24th month it reached statistical significance: p= 0.017. Patients with higher AHEAD score (more comorbidities) reached more often the primary end-point. The cutt-off value ≥ 23.7 for copeptin had 50.6% sensitivity and 73.3%. The cut –off value for MR-proADM ≥ 0.58 had higher sensitivity 79.5% and lower specificity 42.0%. For both humoral substances there was statistical significant difference for discrimination of patients with primary endpoint in lower AHEAD score groups. However, in the highest AHEAD score the level of these substances lost their predictive value.