Insuficiência cardíaca após síndrome coronária aguda: identificar para melhor tratar!

INTRODUCTION: The development of heart failure (HF) following acute coronary syndromes (ACS) significantly worsens short- and long-term prognosis. The present study aimed to identify clinical characteristics, detectable at admission for ACS, that could predict HF development during hospitalization, and to evaluate its impact on in-hospital mortality. METHODS: This was a retrospective cohort study that included 601 patients consecutively admitted with ACS. Demographic, clinical and laboratory data at admission were collected and HF was defined as maximum Killip class II or III. Logistic regression analysis was performed to identify independent predictors of HF and, additionally, in-hospital death. RESULTS: 29.3% of the population developed HF, mostly older patients (69.52+/-11.9 years vs. 61.81+/-12.4 years, p<0.0001), women, hypertensive, diabetic and non-smokers. On admission, this subgroup of patients presented with higher heart rate and glycemia, and lower glomerular filtration rate (eGFR) and hemoglobin. The percentage of patients with left ventricular systolic dysfunction (LVSD) was significantly higher in the group of patients with HF (74.4% versus 48.7%, p<0.0001); however, no significant differences were found in the type of ACS or its location. In the present study, we found that patients with HF were stratified less invasively (less likely to undergo cardiac catheterization or percutaneous coronary intervention). The development of HF was associated with longer hospitalization and higher in-hospital mortality (7.4% versus 2.1%, p=0.004) on univariate analysis, but not on multivariate analysis. On multivariate analysis, only age (OR=1.04; 95% CI 1.02-1.06), diabetes mellitus (OR=1.77; 95% CI 1.05-2.96), glycemia (OR=1.05; 95% CI 1.01-1.08), eGFR <60 ml/min/1.73m2 (OR=2.90, 95% CI 1.73- 4.84), heart rate (OR=1.03, 95% CI 1.02-1.04) and LVSD (OR=2.48, 95% CI 1.59-3.85) were independent predictors of HF. CONCLUSIONS: HF is a frequent complication in ACS and is associated with higher in-hospital mortality. Identifying risk of HF development on admission, through easily acquired clinical characteristics (older age, diabetes and/or elevated glycemia, renal failure and higher heart rate), will certainly influence immediate therapeutic choices and permit an individualized approach to each patient

Admission glycemia: a predictor of death after acute coronary syndrome in non-diabetic patients?

BACKGROUND: Previous studies have demonstrated that acute phase hyperglycemia is associated with increased in-hospital mortality in diabetic patients admitted with acute coronary syndrome (ACS), but this has not been clearly demonstrated in non-diabetic patients. The present study was designed to determine whether admission hyperglycemia (AG) is an independent predictor of in-hospital and six-month mortality after ACS in non-diabetic patients. METHODS: This was a retrospective cohort study of 426 non-diabetic patients consecutively admitted with ACS. The patients were stratified into quartile groups according to AG, which was also analyzed as a continuous variable. Vital status was obtained at six-month follow-up in 96.8% of the patients surviving hospitalization. Logistic regression analysis was used to identify independent predictors of in-hospital and six-month death. RESULTS: Of the 426 patients included in the study (age 62.6 years+/-13.1, 77% male), 22 (5.4%) patients died during hospitalization and 20 (5.2% of the patients surviving hospitalization) within six months of ACS. Mean AG was 134.89 mg/dl+/-51.95. The higher the AG, the more probable was presentation with ST-segment elevation ACS (STEMI), anterior STEMI, higher heart rate, Killip class higher than one (KK >1), higher serum creatinine and greater risk of in-hospital and six-month death. In multivariate analysis, only age (OR=1.10; 95% CI 1.04-1.17), STEMI (OR=3.02; 95% CI 1.07-8.50), AG (OR=1.073; 95% CI 1.004-1.146), serum creatinine (OR=1.10; 95% CI 1.009-1.204) and KK >1 on admission (OR=4.65; 95% CI 1.59-13.52) were independently associated with in-hospital death. Age (OR=1.07; 95% CI 1.03-1.12), serum creatinine (OR=1.09; 95% CI 1.01-1.18) and in-hospital development of heart failure (OR=2.34; 95% CI 1.07-5.10) were independently associated with higher risk of death within six months of ACS. CONCLUSIONS: AG is an independent predictive factor of in-hospital death after ACS in non-diabetic patients. Although it did not show an independent association with higher risk of six-month death, AG appears to contribute to it, since the risk is greater the higher the AG. Its predictive value may have been blunted by the insufficient power of the sample and/or by the time interval between acquisition of AG and the evaluated endpoint

Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome

INTRODUCTION: Clopidogrel is an antiplatelet agent converted to its active metabolite by cytochrome P-450 isoenzymes. Numerous drugs are known to inhibit P-450 isoenzymes, including proton pump inhibitors (PPIs), which are often associated with aspirin and clopidogrel to prevent adverse gastrointestinal effects. In vitro studies first showed that PPIs reduced the antiplatelet effect of clopidogrel, while recent clinical studies have raised concerns that the addition of a PPI to clopidogrel in acute coronary syndrome (ACS) patients could actually increase the risk of recurrent cardiovascular events. OBJECTIVE: The aim of this study was to evaluate whether the prescription of a PPI conferred a worse prognosis in patients discharged with aspirin and clopidogrel treatment after ACS. METHODS: A total of 876 patients admitted with ACS and discharged with aspirin and clopidogrel, with a planned duration of at least six months, from January 2004 to March 2008, were reviewed. Patients were classified in two groups according to whether or not a PPI was prescribed at discharge. The PPIs considered were those mainly metabolized by cytochrome P-450 2C19. We excluded patients with insufficient information available on either prescription or clinical records that could allow clearly confirm or exclude exposure to a PPI. Primary end points were six-month all-cause mortality and the composite of death, myocardial infarction and unstable angina at six months. RESULTS: Of the 802 patients considered for further analysis, 274 (34.2%) individuals were medicated with a PPI in addition to dual antiplatelet therapy. Patients taking PPIs were older, more often had renal insufficiency and less often had a history of coronary revascularization and smoking. They more often presented with Killip class >I and lower hemoglobin concentration on admission. There were no significant differences between the two groups in terms of medical treatment (during hospital stay and at discharge) or invasive procedures. By multivariate analysis, independent and positive predictors of PPI prescription were older age and lower hemoglobin concentration on admission. Patients taking PPIs had a slightly higher prevalence of six-month mortality (6.5% vs. 3.9%) and of the composite end point (12.9% vs. 9.2%), although without statistical significance. By multivariate analysis including potential confounding variables, the prescription of a PPI on top of aspirin and clopidogrel was still n ot associated with a worse prognosis. CONCLUSIONS: In the present study, PPI precription in addition to aspirin and clopidogrel after ACS was not associated with a worse six-month prognosis

Frequency and Pattern of Heteroplasmy in the Complete Human Mitochondrial Genome

Determining the levels of human mitochondrial heteroplasmy is of utmost importance in several fields. In spite of this, there are currently few published works that have focused on this issue. In order to increase the knowledge of mitochondrial DNA (mtDNA) heteroplasmy, the main goal of this work is to investigate the frequency and the mutational spectrum of heteroplasmy in the human mtDNA genome. To address this, a set of nine primer pairs designed to avoid co-amplification of nuclear DNA (nDNA) sequences of mitochondrial origin (NUMTs) was used to amplify the mitochondrial genome in 101 individuals. The analysed individuals represent a collection with a balanced representation of genders and mtDNA haplogroup distribution, similar to that of a Western European population. The results show that the frequency of heteroplasmic individuals exceeds 61%. The frequency of point heteroplasmy is 28.7%, with a widespread distribution across the entire mtDNA. In addition, an excess of transitions in heteroplasmy were detected, suggesting that genetic drift and/or selection may be acting to reduce its frequency at population level. In fact, heteroplasmy at highly stable positions might have a greater impact on the viability of mitochondria, suggesting that purifying selection must be operating to prevent their fixation within individuals. This study analyses the frequency of heteroplasmy in a healthy population, carrying out an evolutionary analysis of the detected changes and providing a new perspective with important consequences in medical, evolutionary and forensic fields

Targeted Delivery of Sildenafil for Inhibiting Pulmonary Vascular Remodeling

Pulmonary arterial hypertension is a fatal lung disease caused by the progressive remodeling of small pulmonary arteries (PAs). Sildenafil can prevent the remodeling of PAs, but conventional sildenafil formulations have shown limited treatment efficacy for their poor accumulation in PAs. Here, glucuronic acid (GlcA)-modified liposomes (GlcA-Lips) were developed to improve the delivery of sildenafil to aberrant over-proliferative PA smooth muscle cells via targeting the GLUT-1 (glucose transport-1), and, therefore, inhibiting the remodeling of PAs in a monocrotaline-induced PA hypertension model. GlcA-Lips encapsulating sildenafil (GlcA-sildenafil-Lips) had a size of 90 nm and a pH-sensitive drug release pattern. Immunostaining assay indicated the overexpression of GLUT-1 in PA smooth muscle cells. Cellular uptake studies showed a 1-fold increase of GlcA-Lips uptake by PA smooth muscle cells and pharmacokinetics and biodistribution experiments indicated longer blood circulation time of GlcA-Lips and increased ability to target PAs by 1-fold after 8 hours administration. Two-week treatment indicated GlcA-sildenafil-Lips significantly inhibited the remodeling of PAs, with a 32% reduction in the PA pressure, a 41% decrease in the medial thickening, and a 44% reduction of the right ventricle cardiomyocyte hypertrophy, and improved survival rate. Immunohistochemical analysis showed enhanced expression of caspase-3, after administration of GlcA-sildenafil-Lips, and reduced expression of P-ERK1/2 (phosphorylated ERK1/2) and HK-2 (hexokinase-2), and increased level of eNOS (endothelial nitric oxide synthase) and cyclic GMP (cGMP). In conclusion, targeted delivery of sildenafil to PA smooth muscle cells with GlcA-Lips could effectively inhibit the remodeling of PAs in the monocrotaline-induced PA hypertension

Water-induced modulation of Helicobacter pylori virulence properties

While the influence of water in Helicobacter pylori culturability and membrane integrity has been extensively studied, there are little data concerning the effect of this environment on virulence properties. Therefore, we studied the culturability of water-exposed H. pylori and determined whether there was any relation with the bacterium’s ability to adhere, produce functional components of pathogenicity and induce inflammation and alterations in apoptosis in an experimental model of human gastric epithelial cells. H. pylori partially retained the ability to adhere to epithelial cells even after complete loss of culturability. However, the microorganism is no longer effective in eliciting in vitro host cell inflammation and apoptosis, possibly due to the non-functionality of the cag type IV secretion system. These H. pylori-induced host cell responses, which are lost along with culturability, are known to increase epithelial cell turnover and, consequently, could have a deleterious effect on the initial H. pylori colonisation process. The fact that adhesion is maintained by H. pylori to the detriment of other factors involved in later infection stages appears to point to a modulation of the physiology of the pathogen after water exposure and might provide the microorganism with the necessary means to, at least transiently, colonise the human stomach.FCT (SFRH/BD/24579/2005) (to NMG