Screening for Chronic Obstructive Pulmonary Disease in Patients With Acute Coronary Syndromes

BACKGROUND:

Acute coronary syndromes (ACS) and chronic obstructive pulmonary disease (COPD) are respectively the first and the fourth leading cause of death in Western countries. ACS and COPD shared several risk factor, in particular smoking habitus. Available data may be summarized as follows: i) ACS, and generally ischemic heart disease (IHD), are the most frequent comorbidity in COPD patients; ii) cardiac adverse events are the most frequent cause of hospitalization and/or death in COPD patients; iii) patients with ACS and concomitant COPD are at higher risk of mortality, re-infarction and heart failure (HF); iv) COPD is frequently undiagnosed in patients with IHD. At the best of our knowledge, no studies investigated the effectiveness and feasibility of screening procedures to early detect COPD in ACS patients. The identification of unrecognized COPD in ACS patients may permit an optimization of the treatment with an significant improvement in the outcome. Finally, it is well known that several biological processes are involved in the development and worsening of IHD-COPD comorbidity (e.g. inflammation, hypoxia, heightened platelet reactivity, endothelial dysfunction). Nevertheless, a complete evaluation of these processes is currently missing. A better characterization of these biological processes underlying the ACS-COPD comorbidity may significantly improve its management.

HYPOTHESIS and SIGNIFICANCE:

Based on previous studies in patients with stable IHD, we suppose that at least 30% of patients admitted to hospital for ACS have undiagnosed COPD. They represent a subgroup of patients at very high risk of death, reinfarction and heart failure. We hypothesize that the combined use of PEF and RHSQ (adapted version) in ACS patients (smokers or former smokers) before hospital discharge may discriminate those with undiagnosed COPD. The early diagnosis of COPD comorbidity may have important clinical implications. We speculate that early identification of undiagnosed COPD in ACS patients may permit a promptly treatment and improve outcomes. Finally, we suppose that the worst outcome observed in ACS patients with undiagnosed COPD as well as in patients with prior ACS and acute exacerbation of COPD is due to a specific pattern of alterations in platelet reactivity (PR), endothelial function (EF) and inflammation. Therefore, their characterization may lead to an improvement in the clinical management of these patients.

METHODS:

Blood samples: At the time of enrollment an aliquot (7-10 ml) of whole blood will be collected and stored for DNA and RNA extraction. Blood samples to obtain plasma (7-10 ml) and serum (7-10 ml) will be collected both at the timing of enrolment and at the time of spirometry.

Screening procedure: PEF and RHSQ (adapted version) will be administered by an independent combined team of cardiologist and pulmonologist before the hospital discharge. According to international guidelines, patients will be asked to perform 3 consecutive PEF measurements and the highest values will be recorded. A PEF value below 80% predicted will be considered predictive of impaired lung function. The RHSQ questionnaire will be performed as previously reported with a value >19 suggesting high probability of COPD.

Spirometry: spirometry test will be performed 50-70 days after hospital discharge (enrollment time).

Primary outcome of the study: the endpoint of the study is the diagnosis of COPD at spirometry. The aim of the study is to establish if the combined use of PEF and RHSQ questionnaire is able to early predict COPD diagnosis.

Clinical follow-up: a complete 1-year follow-up will be collected in each patient recording the occurrence of all adverse events and hospital admissions. All adverse events will be adjudicated by two independent reviewers blinded to screening and spirometry outcomes.

Biological parameters: several evaluations of inflammation, endothelial and platelet function markers will be performed in blood samples from patients. The principals are reported below: high sensitivity C-reactive protein, fibrinogen, interleukin (IL)-6, IL-1Ra, tumor necrosis factor (TNF)-alpha, platelet reactivity as assessed by light transmission aggregometry and VerifyNow system, ICAM and Bcl-2 and e-NOS (extracellular nitric oxide synthase) (in human umbilical vein endothelial cells that will be incubate with serum of patients), intracellular levels of reactive oxygen species.

Secondary outcomes: PEF, RHSQ, biological parameters and spirometry results will be related to clinical outcome.