Abstract
Introduction. Chronic heart failure (CHF) is a complex clinical syndrome associated with high mortality rates. The presence of type 2 diabetes mellitus (DM) is an independent unfavourable prognostic factor in heart failure patients. Chronic heart failure and type 2 diabetes mellitus are closely inter-related conditions through different pathological mechanisms, including platelet activation. The presence of DM in CHF patients can dramatically increase platelet dysfunction. The problem is much complicated by high level of aspirin resistance in diabetic patients. The prevalence of aspirin resistance in CHF with DM has never been studied.The aim of our research was to estimate the prevalence of aspirin resistance in heart failure patients with type 2 diabetes mellitus and to clarify platelets` abnormalities according to glycemic control status.Materials and methods. The criteria for study inclusion were: a more than 1-year documented history of CHF due to coronary artery disease, sinus rhythm, type 2 diabetes mellitus, no change in medication for > 3 months, daily aspirin use 100 mg > 6 months. All patients had previous history of myocardial infarction. Exclusion criteria were: type 1 DM, patients with type 2 DM on insulin therapy and/or thiazolidinediones, major bleedings in anamnesis, chronic renal failure, chronic obstructive pulmonary disease, autoimmune diseases, significant liver failure, cancer. We studied 65 patients with heart failure and type 2 diabetes mellitus (mean age 62±8 years). The control population comprised 35 heart failure patients without diabetes mellitus (mean age 60±9 years). Platelet function was evaluated using standard light transmission aggregometry. Aspirin resistance was defined by known criteria: ≥ 70% ADP- and ≥ 40% epinephrine-induced aggregation. Measurements of CD41, CD41a, CD61 and CD62P were carried out by fluorescent microscopy study. The plasma levels of soluble P-selectin and soluble CD40L were measured by ELISA assays.Results. Age, sex, severity of CHF, left ventricular ejection fraction (LVEF), estimated glomerular filtration rate and cardiovascular treatment were comparable between three groups. Hypertension rate was slightly frequent in patients with CHF and decompensated DM. The patients with CHF and decompensated DM had higher fasting plasma glucose, HbA1cand HOMA-IR levels. The duration of the diabetes was similar. Glucose lowering treatment on admission was comparable between groups. The rate of aspirin resistance was tend to be higher in patients with CHF and DM (by ADP-induced aggregation: 23.1% in diabetic patients vs. 14.3% in non-diabetic patients, P=0.43; by epinephrine-induced aggregation: 36.9% in diabetic patients vs. 31.4% in non-diabetic patients, P=0.66), but the difference was not statistically significant. The compensation of DM didn’t influence on aspirin resistance rate also. The compensation of DM didn’t influence on aspirin resistance rate also. No significant changes in platelets’ parameters were observed between CHF patients without DM and patients with CHF and compensated DM. In contrast, the patients with CHF and decompensated DM presented higher platelet surface CD62P, CD41, CD41a and CD61 expression in comparison to CHF patients without DM. The patients with CHF and HbA1c of more than 7 % showed also higher plasma P-selectin and higher platelet surface CD41 and CD61 expression compared with CHF patients with HbA1c of less than 7 %. Plasma sP-selectin correlated positively with FPG, insulin, C-peptide and HOMA-IR. Platelet surface P-selectin correlated only with C-peptide. Both IIb and IIIa glycoprotein receptors correlated with HbA1c. Conclusions. The rate of aspirin resistance varies from 23 to 37% in patients with chronic heart failure and type 2 diabetes mellitus depending on tests used. Platelet reactivity is associated with glycemic control status in heart failure diabetic patients on long-term aspirin therapy.
Highlights
The aim of our study was to estimate the prevalence of aspirin resistance in heart failure patients with type 2 diabetes mellitus and to clarify plateletsabnormalities according to glycemic control status
The aim of this study was to estimate the prevalence of aspirin resistance in Chronic heart failure (CHF) patients with diabetes mellitus (DM) and to clarify platelet function abnormalities according to glycemic control status
Baseline characteristics of study population spectively recruited 65 patients with CHF and DM and 35 related to diabetes patients with CHF without DM, whose baseline characteristics are shown in table 1
Summary
We studied 65 patients with heart failure and type 2 diabetes mellitus. Platelet function was evaluated using standard light transmission aggregometry. Measurements of CD41, CD41a, CD61 and CD62P were carried out by fluorescent microscopy study. The plasma levels of soluble P-selectin and soluble CD40L were measured by ELISA assays. 23.1 % were aspirin-resistant by ADP-induced platelet aggregation test and 36.1 % after the use of epinephrine-induced platelet aggregation test. The poor glycemic control in patients with chronic heart failure was associated with high plasma P-selectin level and high CD41 and CD61 expression
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