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The Influence of Haemoglobin A1c Levels on Platelet Aggregation and Platelet Turnover in Patients with Coronary Artery Disease Treated with Aspirin.

Neergaard-Petersen S, Hvas AM, Grove EL, Larsen SB, Gregersen S, Kristensen SD - PLoS ONE (2015)

Bottom Line: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events.Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.These associations were mainly evident in non-diabetic and prediabetic CAD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT

Background: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes.

Methods: In this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c ≥5.7-6.4% [39-47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.

Results: CAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients.

Conclusions: CAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively, though weakly, with increased platelet aggregation, platelet turnover and platelet activation.

No MeSH data available.


Related in: MedlinePlus

Platelet aggregation.Platelet aggregation in patients with coronary artery disease; 307 patients without diabetes (HbA1c < 5.7%) and 303 patients with prediabetes (HbA1c 5.7–6.4%). Platelet aggregation induced by A) arachidonic acid and B) collagen as agonists using Multiplate Analyzer. Median and interquartile ranges are indicated.
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pone.0132629.g001: Platelet aggregation.Platelet aggregation in patients with coronary artery disease; 307 patients without diabetes (HbA1c < 5.7%) and 303 patients with prediabetes (HbA1c 5.7–6.4%). Platelet aggregation induced by A) arachidonic acid and B) collagen as agonists using Multiplate Analyzer. Median and interquartile ranges are indicated.

Mentions: Among patients naive to antidiabetic treatment, CAD patients with prediabetes had significantly increased levels of platelet aggregation evaluated by AA (p = 0.04) and collagen (p = 0.02) as compared with non-diabetic patients (Fig 1). Using the VerifyNow Aspirin assay there was non-significantly higher level of platelet aggregation in prediabetic CAD patients than in non-diabetic patients (434 ± 35 vs. 429 ± 33 ARU, p = 0.12). Platelet count was significantly increased in prediabetic patients (232 (199; 267) vs. 221 (191; 255) x 109/L, p = 0.02), but there was no difference in levels of soluble P-selectin (73 ± 26 vs. 72 ± 24 ng/mL; p = 0.49) compared with the non-diabetic group. Prediabetic patients had numerically higher platelet turnover compared with non-diabetic patients evaluated by IPC (6.0 (4.5; 8.0) vs. 5.7 (4.2; 7.6) x 109/L, p = 0.17), but the values were similar as regards IPF (2.6 (1.9; 3.5) vs. 2.5 (1.9; 3.5) %, p = 0.93) or MPV (10.9 ± 0.9 vs. 10.9 ± 0.8 fL, p = 0.82). When adjusting for platelet count alone as well in combination with age and gender, the influence of prediabetes on platelet aggregation (p-values >0.07), soluble P-selectin (p-values >0.97) and immature platelets (p-values >0.24) became/remained non-significant. Based on differences in demographic data in Table 2 between non-diabetic and prediabetic CAD patients, the influence of prediabetes on platelet aggregation and platelet turnover was investigated in a multivariate regression model including age, sex, smoking, body mass index, previous myocardial infarction, haemoglobin, kidney function, HbA1c, platelet count and treatment with proton pump inhibitors. When adjusting for these variables, prediabetes did not significantly influence platelet aggregation or platelet turnover (p-values > 0.05), while platelet count remained an independent determinant of AA- and collagen-induced platelet aggregation, P-selectin and parameters of platelet turnover including IPC, IPF and MPV (p-values < 0.05).


The Influence of Haemoglobin A1c Levels on Platelet Aggregation and Platelet Turnover in Patients with Coronary Artery Disease Treated with Aspirin.

Neergaard-Petersen S, Hvas AM, Grove EL, Larsen SB, Gregersen S, Kristensen SD - PLoS ONE (2015)

Platelet aggregation.Platelet aggregation in patients with coronary artery disease; 307 patients without diabetes (HbA1c < 5.7%) and 303 patients with prediabetes (HbA1c 5.7–6.4%). Platelet aggregation induced by A) arachidonic acid and B) collagen as agonists using Multiplate Analyzer. Median and interquartile ranges are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493028&req=5

pone.0132629.g001: Platelet aggregation.Platelet aggregation in patients with coronary artery disease; 307 patients without diabetes (HbA1c < 5.7%) and 303 patients with prediabetes (HbA1c 5.7–6.4%). Platelet aggregation induced by A) arachidonic acid and B) collagen as agonists using Multiplate Analyzer. Median and interquartile ranges are indicated.
Mentions: Among patients naive to antidiabetic treatment, CAD patients with prediabetes had significantly increased levels of platelet aggregation evaluated by AA (p = 0.04) and collagen (p = 0.02) as compared with non-diabetic patients (Fig 1). Using the VerifyNow Aspirin assay there was non-significantly higher level of platelet aggregation in prediabetic CAD patients than in non-diabetic patients (434 ± 35 vs. 429 ± 33 ARU, p = 0.12). Platelet count was significantly increased in prediabetic patients (232 (199; 267) vs. 221 (191; 255) x 109/L, p = 0.02), but there was no difference in levels of soluble P-selectin (73 ± 26 vs. 72 ± 24 ng/mL; p = 0.49) compared with the non-diabetic group. Prediabetic patients had numerically higher platelet turnover compared with non-diabetic patients evaluated by IPC (6.0 (4.5; 8.0) vs. 5.7 (4.2; 7.6) x 109/L, p = 0.17), but the values were similar as regards IPF (2.6 (1.9; 3.5) vs. 2.5 (1.9; 3.5) %, p = 0.93) or MPV (10.9 ± 0.9 vs. 10.9 ± 0.8 fL, p = 0.82). When adjusting for platelet count alone as well in combination with age and gender, the influence of prediabetes on platelet aggregation (p-values >0.07), soluble P-selectin (p-values >0.97) and immature platelets (p-values >0.24) became/remained non-significant. Based on differences in demographic data in Table 2 between non-diabetic and prediabetic CAD patients, the influence of prediabetes on platelet aggregation and platelet turnover was investigated in a multivariate regression model including age, sex, smoking, body mass index, previous myocardial infarction, haemoglobin, kidney function, HbA1c, platelet count and treatment with proton pump inhibitors. When adjusting for these variables, prediabetes did not significantly influence platelet aggregation or platelet turnover (p-values > 0.05), while platelet count remained an independent determinant of AA- and collagen-induced platelet aggregation, P-selectin and parameters of platelet turnover including IPC, IPF and MPV (p-values < 0.05).

Bottom Line: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events.Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.These associations were mainly evident in non-diabetic and prediabetic CAD patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT

Background: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes.

Methods: In this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c ≥5.7-6.4% [39-47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.

Results: CAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients.

Conclusions: CAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively, though weakly, with increased platelet aggregation, platelet turnover and platelet activation.

No MeSH data available.


Related in: MedlinePlus