Adenosine A2(A) receptor gene polymorphism (1976C > T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy

OBJECTIVES: Patients with non ischemic-dilated cardiomyopathy (DCM) are characterized by an activation of the adenosinergic system and reduced coronary flow reserve (CFR) evaluated by transthoracic Doppler echocardiography during vasodilator adenosinergic stress (dipyridamole administration). The aim of this study was to assess whether genetic polymorphisms (263C>T and 1976C>T) of the A2(A) receptor gene affect CFR response in patients with DCM. METHODS: We enrolled a group of 80 patients with DCM (55 male; age, 62±10.3 years) and 162 healthy volunteers (55 male; age, 45.1±9.5 years). Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was determined in DCM. A2(A) receptor genotyping was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism analysis. The expression of A2(A) protein and mRNA was also assessed in healthy controls. RESULTS: The genotype distribution of the 263C>T (P=0.5) and 1976C>T (P=0.8) polymorphisms was not significantly different between patients and controls. Patients with 1976TT genotype had significantly lower CFR value than 1976CC patients (2.3±0.7, 2.0±0.5 and 1.9±0.4, P<0.05 for CC, CT and TT genotypes, respectively). Controls who were heterozygous (P=0.02) or homozygous (P=0.001) for the T1976 allele showed a significant increase in A2(A) receptor protein. CONCLUSION: These data demonstrate that A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in patients with DCM, and support a direct consequences of this single nucleotide polymorphism for protein expression. Additional studies are needed to better define the functional role of this genetic variant as well as to clarify the potential clinical impact of genetics during pharmacological stress cardiac imaging

Increase in plasma levels of adenosine and adenine nucleotides after intravenous infusion of buflomedil in humans.

To clarify the mode of action of the vasoactive agent buflomedil, we evaluated plasma levels of adenosine and adenine nucleotides after intravenous (i.v.) infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil induced an increase of the same order of magnitude in plasma levels of adenosine and adenine nucleotides. Maximal adenosine increase (84%) was observed at the end of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55%, respectively) and of AMP (61%) were detected 10 and 5 min after discontinuation of infusion, respectively. Although the exact mode of action of buflomedil at the molecular level remains unclear, some indirect findings suggest that the increase in adenosine may be due to enhanced release rather than to inhibition of cell uptake. Because such activity of buflomedil consists of enhancement of physiologic mechanisms of vasodilation and tissue protection occurring in the course of ischemic events, new pharmacologic perspectives for the drug may arise

Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study

Background: Atrial fibrillation (AF) is associated with a substantial risk of thromboembolism and mortality, significantly reduced by oral anticoagulation. Adherence to guidelines may lower the risks for both all cause and cardiovascular (CV) deaths. Methods: Our objective was to evaluate if antithrombotic prophylaxis according to the 2012 European Society of Cardiology (ESC) guidelines is associated to a lower rate of adverse outcomes. Data were obtained from REPOSI; a prospective observational study enrolling inpatients aged 6565&nbsp;years. Patients enrolled in 2012 and 2014 discharged with an AF diagnosis were analysed. Results: Among 2535 patients, 558 (22.0&nbsp;%) were discharged with a diagnosis of AF. Based on ESC guidelines, 40.9&nbsp;% of patients were on guideline-adherent thromboprophylaxis, 6.8&nbsp;% were overtreated, and 52.3&nbsp;% were undertreated. Logistic analysis showed that increasing age (p&nbsp;=&nbsp;0.01), heart failure (p&nbsp;=&nbsp;0.04), coronary artery disease (p&nbsp;=&nbsp;0.013), peripheral arterial disease (p&nbsp;=&nbsp;0.03) and concomitant cancer (p&nbsp;=&nbsp;0.003) were associated with non-adherence to guidelines. Specifically, undertreatment was significantly associated with increasing age (p&nbsp;=&nbsp;0.001) and cancer (p&nbsp;&lt;&nbsp;0.001), and inversely associated with HF (p&nbsp;=&nbsp;0.023). AF patients who were guideline adherent had a lower rate of both all-cause death (p&nbsp;=&nbsp;0.007) and CV death (p&nbsp;=&nbsp;0.024) compared to those non-adherent. Kaplan\u2013Meier analysis showed that guideline-adherent patients had a lower cumulative risk for both all-cause (p&nbsp;=&nbsp;0.002) and CV deaths (p&nbsp;=&nbsp;0.011). On Cox regression analysis, guideline adherence was independently associated with a lower risk of all-cause and CV deaths (p&nbsp;=&nbsp;0.019 and p&nbsp;=&nbsp;0.006). Conclusions: Non-adherence to guidelines is highly prevalent among elderly AF patients, despite guideline-adherent treatment being independently associated with lower risk of all-cause and CV deaths. Efforts to improve guideline adherence would lead to better outcomes for elderly AF patients

Polypharmacy in older people: lessons from 10\ua0years of experience with the REPOSI\ua0register

As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and\ua0inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug\u2013drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI (REgistro POliterapie SIMI, Societ\ue0 Italiana di Medicina Interna) in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and, thus to avoid potentially inappropriate medications. The main findings of the register, that has accrued so far, 7005 older patients throughout a 10\ua0year period, are summarized herewith, with special emphasis on the main patterns of poor prescription appropriateness and related risks of adverse events

Mortality rate and risk factors for gastrointestinal bleeding in elderly patients

Background: Gastrointestinal bleeding (GIB) is burdened by high mortality rate that increases with aging. Elderly patients may be exposed to multiple risk factors for GIB. We aimed at defining the impact of GIB in elderly patients. Methods: Since 2008, samples of elderly patients (age 65 65 years) with multimorbidity admitted to 101 internal medicine wards across Italy have been prospectively enrolled and followed-up (REPOSI registry). Diagnoses of GIB, length of stay (LOS), mortality rate, and possible risk factors, including drugs, index of comorbidity (Cumulative Illness Rating Scale [CIRS]), polypharmacy, and chronic diseases were assessed. Adjusted multivariate logistic regression models were computed. Results: 3872 patients were included (mean age 79 \ub1 7.5 years, F:M ratio 1.1:1). GIB was reported in 120 patients (mean age 79.6 \ub1 7.3 years, F:M 0.9:1), with a crude prevalence of 3.1%. Upper GIB occurred in 72 patients (mean age 79.3 \ub1 7.6 years, F:M 0.8:1), lower GIB in 51 patients (mean age 79.4 \ub1 7.1 years, F:M 0.9:1), and both upper/lower GIB in 3 patients. Hemorrhagic gastritis/duodenitis and colonic diverticular disease were the most common causes. The LOS of patients with GIB was 11.7 \ub1 8.1 days, with a 3.3% in-hospital and a 9.4% 3-month mortality rates. Liver cirrhosis (OR 5.64; CI 2.51\u201312.65), non-ASA antiplatelet agents (OR 2.70; CI 1.23\u20135.90), and CIRS index of comorbidity &gt;3 (OR 2.41; CI 1.16\u20134.98) were associated with GIB (p &lt; 0.05). Conclusions: A high index of comorbidity is associated with high odds of GIB in elderly patients. The use of non-ASA antiplatelet agents should be discussed in patients with multimorbidity