Risk Of Combined Endpoint Research Articles

THE ASSOCIATIONS OF β-ADRENORECEPTORS GENES POLYMORPHISMS WITH THE COURSE OF HEART FAILURE AND WITH THE LOW TRIIODOTHYRONINE SYNDROME (LITERATURE REVIEW AND OWN OBSERVATIONS)E

The systematization of literature data on the associations of β-adrenoreceptors (β-AR) genes polymorphisms with the course of heart failure (HF) and with the development of low triiodothyronine syndrome (LT3S), and the results of our own study were presented. The study of associations of β-AR system genes polymorphisms with the clinical outcome of HF and the effectiveness of β-adrenoblockers (β-AB) has been continued. It has been demonstrated that carrier state of the A allele of the Ser49Gly (c.145A > G) polymorphism of the b1-AR gene leads to a decrease in the risk of combined end point. At the same time, the carrier state of the G allele of the Gln27Glu (c.79C> G) polymorphism of the b2-AR gene increases the risk of combined end point. Administration of bisoprolol at a dose of > 5 mg leads to a reduction of the risk of the combined endpoint, provided the G/A genotype of the Ser49Gly (c.145A > G) polymorphism of the β1-AR gene is present. The use of bisoprolol at this dose also reduces the risk of re-hospitalisation and combined endpoint, provided the homozygous genotype (C/C) of the Gln27Glu (c.79C > G) polymorphism of the β2-AR gene is present. The probability of the low triiodothyronine syndrome increases with the homozygous G/G genotype of the Gln27Glu polymorphism of the β2-AR gene and in the presence of the C/T polymorphism of the Serβ75 GNβ3 gene. The genotype C/G of the Gln27Glu polymorphism of the β2-AR gene is associated with a decreased risk of LT3S.

The association of polymorphisms of ­β-adrenoreception genes with the course of heart failure

Objective — to study the relationship of β-adrenoreception gene polymorphisms with the course of heart failure.Materials and methods. The study involved 285 patients with heart failure against the background of post­infarction cardiosclerosis included. The genotyping was performed using 4 polymorphisms (Gly389Arg of the β1­-adrenoreceptors gene, Ser49Gly of the β1-adrenoreceptors gene, Gln27Glu of the β2­-adrenoreceptors gene and Ser275 of the β3­-subunit of G-­protein gene) using the polymerase chain reaction. Over the two-years follow up period, from 285 patients, 81 (28.4 %) had re­hospitalization or outpatient intravenous administration of the loop diuretics due to HF decompensation. During this period, 18 patients died (6.3 %). 93 patients (32.6 %) had a combined endpoint. The genetic and epidemio­lo­gical analysis was carried out using the SNPStats program.Results and discussion. The allele A of a Ser49Gly polymorphism (c.145A > G) of a β1­-adrenoreception gene is associated with a reduced risk of combined endpoint in patients with a heart failure (OR = 0.52 (0.28—0.96), p = 0.032, dominant model and OR = 0.51 (0.28—0.92), p = 0.02, in the log-­additive inheritance model). This allele of a Ser49Gly polymorphism (c.145A > G) of a β1­-adrenoreceptor gene is also associated with a decrease in the frequency of rehospita­lization (OR = 0.50 (0.26—0.95), p = 0.028, the dominant model and OR = 0.49 (0.26—0.92), p = 0.019, for the log-ad­­di­tive model). The allele G of Gln27Glu polymorphism (c.79C > G) of a β2-adrenergic receptor gene increases the risk of a combined endpoint in patients with a heart failure (OR = 1.76 (1.04—2.96), p = 0.032, the dominant model of inheri­tance and OR = 1,75 (1.06—2.90), p = 0.029, for an over­dominant model). No significant effect of the Gly389Arg polymorphism (c.1165G > C) of the β1­-adrenergic receptor gene and the Ser275 polymorphism (c.79C > G) of the β3-­subunit of the G­-protein on the course of heart failure was revealed.Conclusions. The obtained results allow to conclude that peculiarities of the heart failure course may have associations with the genetic differences in the pathways of β-adrenoreception.

Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial infarction

The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.

High residual platelet reactivity during dual antiplatelet therapy, found by optical aggregometry and the rate of atherothrombotic complications after coronary artery stenting in patients with ischemic heart disease in clinical practice

Aim. To study the prevalence of high residual platelet reactivity (HRPR) during the dual antiplatelet therapy (DAT) with acetylsalicylic acid (ASA) and clopidogrel by optical aggregometry in patients with ischemic heart disease (IHD) after percutaneous transluminal coronary angioplasty (PTCA) in clinical practice, as well as to determine its value for the prediction of clinical course and outcome of disease. Material and methods. Patients after PTCA and during DAT were included into the study. Evaluation of the functional activity of platelets by optical aggregometry was performed in all patients at baseline. Resistance to ASA, clopidogrel and DAT were detected. Endpoints included cases of repeated atherothrombotic events (sudden cardiac death, myocardial infarction, unstable angina, ischemic stroke, stent thrombosis). Adherence to therapy was evaluated by Morisky-Green test. Results. 97 patients were included into the final analysis. The risk of myocardial infarction or unstable angina pectoris in the ASA-resistant patients was significantly higher than this in the DAT-sensitive patients [relative risk (RR)=7.68; 95% confidence interval (CI) 2.8-20.54; p=0.045]. Maximum RR for stent thrombosis was in clopidogrel-resistant (RR=7.1; 95% CI 1.41-35.82; p=0.0485) and DAT-resistant patients (RR=12.8; 95% CI 4.5-36.38; p=0.0491), compared with patients with a sensitivity to antiplatelet therapy. DAT-resistance was associated with a higher RR of the combined endpoint, compared with the sensitivity to antiplatelet therapy (RR=10.24; 95% CI 3.96-26.5; p=0.046]), and have a tendency to association with increased risk of combined endpoint compared with isolated ASA-resistance (RR=1.3; 95% CI 0.68-2.6; p=0.081). Conclusion. HRPR during DAT is common in clinical practice in patients with ischemic heart disease after PTCA. Routine use of optical aggregometry in DAT may help to identify patients with an increased risk of thrombotic events in the postoperative period and to assign them an alternative antiplatelet therapy.

Prognostic significance of dilated inferior vena cava in advanced decompensated heart failure.

Dilated inferior vena cava (IVC) is prevalent among patients with heart failure (HF), but whether its presence predicts worsening renal function (WRF) or adverse outcomes is unclear. This cohort study analyzed patients with left ventricular ejection fraction <40 % and repeated hospitalizations (≥2 times) for HF between August 2009 and August 2011. The study endpoints were death and HF re-hospitalization. Among baseline parameters, IVC diameter was the most powerful predictor for the development of WRF (area under the curve = 0.795, cut-off value = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized for HF and 14 patients (19 %) died. The event rates were significantly greater in the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re-hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the risk of combined end-points was increased in patients with aging, elevated blood urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the development of WRF and could be a predictor for adverse outcomes.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Prognostic value of combining high sensitive troponin T and N-terminal pro B-type natriuretic peptide in chest pain patients with no persistent ST-elevation

The aim was to examine whether high sensitive troponin T (Hs-TnT) is better than conventional troponins to risk stratify chest pain patients, in particular when applying early serial measurements or combining with natriuretic peptides. Samples were obtained on admission and after 2h in 231 chest pain patients who were followed for a median time of 22months. Troponin levels were determined by Hs-TnT, conventional TnT (Roche Diagnostics) and troponin I (Beckman Coulter) assays. N-terminal pro B-type natriuretic peptide (NT-proBNP) was determined by the assay from Roche Diagnostics. The combined endpoint was death, MI or heart failure. When predefined decision limits were used, Hs-TnT (14ng/L), TnT (0.04μg/L), and TnI (0.06μg/L) identified 63%, 46%, and 52% of the patients with positive troponin. In those with negative TnT, Hs-TnT identified 36 patients of whom 19% had subsequent events. In those with negative TnI, Hs-TnT identified 26 patients of whom 23% had subsequent events. After adjusting for differences in baseline characteristics, both Hs-TnT and NT-proBNP were independently associated with short-term (3months) risk of combined endpoint and long-term risk of death or MI. By combining Hs-TnT and NT-proBNP patients could be divided into low-, intermediate- and high-risk groups.

Enlarged Left Atrium Is a Simple and Strong Predictor of Poor Prognosis in Patients after Myocardial Infarction

Patients after myocardial infarction (MI) differ according to the extend of myocardial damage and prognosis. Diastolic function impairment may have great impact on development of heart failure and outcomes. We evaluated the prognostic value of various echocardiographic measurements in 18-month and 3-year observation after MI. 60 patients after MI (44 male, mean age 60 +/- 11) were examined by transthoracic echocardiography with the assessment of wide spectrum of parameters. Mortality and combined end points (cardiac deaths and heart failure exacerbation) were assessed after 18-month and 3-year observation and groups with and without end points were compared. Optimal cutoff values were estimated by receiver operating characteristic (ROC) analysis and resulting Kaplan-Meier curves were compared. After 18 months, 11 deaths occurred and 20 subjects experienced hospitalization caused by heart failure exacerbation. Although the group with cardiac events showed a greater enlargement of the left ventricle and lower ejection fraction, the highest relative risk of poor outcome (RR = 5.0) was related to the left atrial enlargement above 44 mm. Although restrictive or pseudonormal inflows were connected with 2.1 relative risk of combined end point, all patients with E deceleration time < or = 130 ms experienced heart failure exacerbation or death. Despite tissue Doppler and propagation parameters describing elevated end-diastolic pressure differed between groups with various outcomes in multivariate analysis, only enlarged left atrium was an independent predictor for both combined end point and cardiac death. Further 3-year follow-up solely confirmed the role of above described predictors.

Incidence and Risk of Adverse Perioperative Events among Surgical Patients Taking Traditional Chinese Herbal Medicines

The use of traditional Chinese herbal medicines (TCHMs) among the presurgical population is widespread, but their impact on perioperative patient care is unclear. The authors estimated the incidence and risk of TCHM-related perioperative events. In a Hong Kong cohort study, 601 patients undergoing major elective surgery were asked about their Western medicine and TCHM use in the 2 weeks before surgery. Unanticipated perioperative events were noted by attending anesthesiologists, blinded to patients' use of specific TCHMs. Modified Poisson regression models were used to obtain the relative risk of combined endpoints of perioperative events associated with TCHM use. Of the 601 patients, 483 patients (80%) took self-prescribed TCHM, and 47 (8%) took TCHM by prescription (with or without self-prescribed TCHM) in the 2 weeks before surgery. The crude incidences of any combined endpoints of preoperative, intraoperative, and postoperative events were 23% (95% confidence interval, 19-26%), 74% (95% confidence interval, 71-78%), and 63% (95% confidence interval, 59-66%), respectively. Compared with nonusers, patients who took TCHM by prescription were more likely to have a preoperative event (adjusted relative risk, 2.21; 95% confidence interval, 1.14-4.29). The authors present four case reports to highlight the effect of TCHM by prescription on prolonged activated partial thromboplastin time and hypokalemia in the preoperative period. In contrast, there was no significant association between the use of any type of TCHM and the occurrence of either intraoperative or postoperative events. The use of TCHM by prescription near the time of surgery should be discouraged because of the increased risk of adverse events in the preoperative period.