ARTYKUŁ ORYGINALNY / ORYGINAL ARTICLE

Platelet count and volume indices in patients with contrast-induced acute kidney injury and acute myocardial infarction treated invasively

Paweł Francuz1, Jacek Kowalczyk1, Ryszard Swoboda2, Katarzyna Przybylska-Siedlecka1, Monika Kozieł1, Tomasz Podolecki1, Andrzej Świątkowski1, Radosław Lenarczyk1, Beata Średniawa1, Zbigniew Kalarus1

1Department of Cardiology, Congenital Heart Diseases, and Electrotherapy, Medical University of Silesia, Silesian Centre for Heart Diseases, Zabrze, Poland
2Medical University of Silesia, Katowice, Poland

Address for correspondence:
Paweł Francuz, MD, Department of Cardiology, Congenital Heart Diseases, and Electrotherapy, Medical University of Silesia, Silesian Centre for Heart Diseases,
ul. Curie-Sklodowskiej 9, 41–800 Zabrze, Poland, e-mail: pawel.francuz@wp.pl
Received: 12.09.2014 Accepted: 22.01.2015 Available as AoP: 06.03.2015

Abstract Background: The aetiology of contrast-induced acute kidney injury (CI-AKI) is not well understood. We hypothesised that the pathophysiology of CI-AKI and impaired coronary reperfusion (IR), observed after invasive treatment of acute myocardial infarction (AMI), could be similar and might be related to platelet count (PC) and platelet volume indices (PVI). Aim: To evaluate the relation between PC, PVI, IR, and CI-AKI in patients with AMI treated invasively.

Methods: A single-centre study evaluated 607 consecutive AMI-patients treated invasively. Comparative analyses were performed between patients with CI-AKI and without CI-AKI for the total study population (CI-AKI, n = 156; 25.7% vs. nCI-AKI, n = 451; 74.3%), for patients with diabetes mellitus (CI-AKI-DM, n = 56; 9.2% vs. nCI-AKI-DM, n = 123; 20.3%), and for patients with baseline kidney dysfunction (CI-AKI-BKD, n = 31; 5.1% vs. nCI-AKI-BKD, n = 67; 11.0%). Subjects with IR, who developed CI-AKI, were compared to the remaining patients with respect to platelet parameters (CI-AKI-IR, n = 47; 7.7% vs. controls, n = 560; 92.3%). For total population, as well as studied subgroups, multivariate logistic regression analyses were performed to reveal independent factors associated with CI-AKI. The results of the models were reported as odds ratios (OR) and 95% confidence intervals (95% CI).

Results: PC was higher in CI-AKI-DM-patients (224.8 ± 62.8 × 109/L vs. 197.9 ± 63.3 × 109/L; p = 0.014) and in CI-AKI-BKD-patients (248.9 ± 86.5 × 109/L vs. 202.5 ± 59.3 × 109/L; p = 0.004) than in appropriate controls. Within the studied groups, there were no differences between CI-AKI and nCI-AKI patients with respect to PVI. Comparing CI-AKI-IR-patients with controls, no differences in PC or PVI were found. IR was observed more often in CI-AKI-patients than in nCI-AKI-patients only among diabetics (48.2% vs. 27.6%; p = 0.008). Increase in admission PC was independently associated with CI-AKI in patients with diabetes (per one unit increase OR 1.006; CI 1.0–1.01; p = 0.04) as well as with baseline kidney dysfunction (per one unit increase OR 1.01; CI 1,0–1,02; p = 0.02).

Conclusions: Any similarities in the pathophysiology of CI-AKI and IR were not reflected in platelet parameters. CI-AKI development was not related to PVI; however, higher PC was an independent risk factor for CI-AKI in patients with diabetes or baseline kidney dysfunction. Key words: acute myocardial infarction, contrast-induced acute kidney injury, diabetes mellitus, platelet count, platelet volume indices Kardiol Pol 2015; 73, 7: 520–526

INTRODUCTION

Contrast-induced acute kidney injury (CI-AKI) or contrast-induced nephropathy (CIN) occurrence is associated with worse prognosis in patients after acute myocardial infarction (AMI). However, the pathophysiology of the disease is still not known and no completely successful prevention or treatment has been proposed. The potential cause of CI-AKI is temporary renal vasoconstriction with subsequent return of blood flow and reperfusion injury [1]. Similarly, one of the types of reperfusion injury is the “no-reflow” or “slow flow” phenomenon associated with percutaneous coronary interventions (PCI). Platelets have a crucial role in acute coronary syndromes (ACS) and might be implicated in no-reflow through microvascular obstruction by platelet aggregates and release of platelet-derived vasoactive and chemotactic mediators [2–4]. It has been demonstrated that high mean platelet volume was an independent predictor of impaired coronary reperfusion (IR). Larger, more active platelets were associated with intravascular plugging on an epicardial and myocardial level despite revascularisation of the infarct-related artery [3]. Larger platelets were also associated with larger myocardial infarct size and greater presence of microvascular obstruction, as well as poor pre- and post-interventional flow on epicardial and myocardial levels [5–7]. In a recently published study it was shown that increased platelet distribution width (PDW) was independently associated with CIN occurrence in patients with ACS [8].

We hypothesised that the pathophysiology of CI-AKI and IR, observed after invasive treatment of AMI, could be similar, related to platelets, and reflected in platelet count (PC) and platelet volume indices (PVI). Therefore, the aim of the presented work was to assess the relation between PC, PVI, IR, and CI-AKI in AMI-patients treated invasively. To date, there has not been any data published on this subject.

METHODS

Data acquisition

The clinical data from all AMI-patients treated with PCI were collected and prospectively recorded in a computerised database as part of a single-centre AMI registry. The recorded data included demographics, laboratory values, presence of concomitant diseases, characteristics of AMI, clinical assessment of diabetes, angiographic findings, and revascularisation procedure.

Selection of patients

The total study population consisted of 607 consecutive patients referred to our department because of AMI and treated invasively between January 2004 and December 2005. Clinical AMI criteria evaluated on admission were: chest pain persisting > 20 min, ST segment elevation of at least 0.1 mV in two or more contiguous electrocardiographic leads, or non-diagnostic electrocardiogram with enzymatic confirmation of AMI.

Comparative analyses were performed between patients with CI-AKI and without CI-AKI for the total study population (CI-AKI, n = 156; 25.7% vs. nCI-AKI, n = 451; 74.3%), for patients with diabetes mellitus (CI-AKI-DM, n = 56; 9.2% vs. nCI-AKI-DM, n = 123; 20.3%), and for patients with baseline kidney dysfunction (CI-AKI-BKD, n = 31; 5.1% vs. nCI-AKI-BKD, n = 67; 11.0%). Subjects with IR, who developed CI-AKI, were compared to the remaining patients (CI-AKI-IR, n = 47; 7.7% vs. controls, n = 560; 92.3%).

CI-AKI was defined as a rise in serum creatinine of at least 26.5 μmol/L (0.3 mg/dL) within 48 h after contrast exposure, or at least a 50% increase from the baseline value during index hospital stay [9, 10]. IR was defined as the lack of Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 and/or lack of TIMI myocardial perfusion grade (MPG) 3 — the lack of optimal coronary and microvasculature flow despite no flow-limiting residual stenosis after PCI [2–4].

Baseline kidney dysfunction (BKD) was defined as estimated glomerular filtration rate (eGRF) < 60 mL/min/1.73 m2. The eGFR was calculated using the serum creatinine value on admission before catheterisation, according to the abbreviated Modification of Diet in Renal Disease Study Group Equation proposed by the National Kidney Foundation [11]. Diabetes mellitus (DM) was diagnosed based on European Society of Cardiology and European Association for the Study of Diabetes criteria [12].

Ethics

All clinical data were obtained as a result of the diagnostic procedures and therapy, which were in accordance with the guidelines for myocardial infarction. All patients provided informed, written consent for hospitalisation, invasive treatment, and use of their data for research purposes. The study protocol was in line with ethical standards and was approved by the Institutional Review Board.

Catheterisation protocol and treatment

An invasive cardiologist and two technicians were on in-hospital duty 24 h a day. All patients before coronary angiography received a single dose of oral aspirin (300 mg), 300–600 mg of clopidogrel just before PCI, and 100 U/kg of intravenous heparin (additional boluses were given as appropriate to achieve activated clotting time > 250 ms). In all patients, coronary angiography and PCI of infarct-related artery were performed immediately after admission using standard techniques. The goal of PCI was to restore TIMI flow grade 3 with residual stenosis lower than 30%, which denotes a successful procedure. After PCI of infarct-related artery, TIMI flow grade and TIMI MPG were evaluated by the operator based on his visual assessment [13]. After the intervention, all patients received 75–150 mg of aspirin daily indefinitely, 75 mg of clopidogrel daily, as well as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins, if these agents had not been contraindicated.

Laboratory methods

Venous peripheral blood samples for the PC and PVI measurement were drawn on admission and analysed on an automated cell counter. Blood samples were taken into standardised tubes containing dipotassium ethylenedinitro tetraacetic acid (EDTA) and stored at room temperature. All measurements were performed within 30 minutes of blood collection.

Statistical analysis

Continuous parameters were expressed as means with standard deviations unless otherwise specified, and categorical variables were presented as numbers and percentages. Comparative analysis between groups was performed using the t-Student test for continuous variables and the χ2 or Fisher’s exact test, as appropriate, for dichotomous parameters. For total population as well as studied subgroups, multivariate logistic regression analyses were performed to reveal independent factors associated with CI-AKI. The results of the models were reported as odds ratios (OR) and 95% confidence intervals (95% CI). All tests were double-sided. P values < 0.05 were considered statistically significant. All analyses were performed using the software package Statistica (version 6.1, StatSoft Inc., Tulsa, OK, USA).

RESULTS

In the total study population patients with CI-AKI, when compared to subjects without CI-AKI, were significantly older, more often presented with hypertension, DM, ejection fraction < 35%, cardiogenic shock (CS) on admission, had higher uric acid and serum creatinine concentrations on admission. There were no differences between compared groups with respect to admission PC and PVI. The incidence of IR was similar in both groups. Detailed baseline characteristics for the total study population are shown in Table 1.

Table 1. Comparative analysis of demographics, and clinical and laboratory data between patients developing CI-AKI and patients without CI-AKI, in all subjects with acute myocardial infarction (n = 607)

	CI-AKI (n = 156)	nCI-AKI (n = 451)	P
Age [years] Male Hypertension Hyperlipidaemia Diabetes mellitus Creatinine on admission [µmol/L] Baseline kidney dysfunction Uric acid [µmol/L] Cardiogenic shock on admission Ejection fraction < 35% Multivessel coronary artery disease TIMI < 3 and/or MPG < 3 after PCI of IRA Contrast media volume [mL] Platelet count [× 109/L] Mean platelet volume [fL] Platelet volume distribution width [fL] Platelet large cell ratio [%]	64.1 ± 10.5 111 (71.2%) 92 (59.0%) 95 (60.9%) 56 (35.9%) 95.1 ± 75.0 31 (19.9%) 387.8 ± 143.9 22 (14.1%) 31 (19.9%) 104 (66.7) 54 (34.6) 224.8 ± 87.9 218.0 ± 64.8 11.4 ± 1.1 13.8 ± 2.3 36.2 ± 8.9	60.8 ± 11.1 325 (72.1%) 223 (49.4%) 292 (64.7%) 123 (27.3%) 85.1 ± 26.1 67 (14.9%) 331.3 ± 98.2 20 (4.4%) 46 (10.2%) 274 (60.8) 131 (29.0) 219.6 ± 69.7 207.6 ± 65.6 11.3 ± 1.0 13.7 ± 2.1 35.5 ± 8.2	0.001 0.829 0.039 0.400 0.043 0.016 0.144 < 0.001 < 0.001 0.002 0.190 0.191 0.454 0.107 0.442 0.616 0.449
Values presented as mean ± standard deviation or percentage of subjects; CI-AKI — contrast induced acute kidney injury; IRA — infarct-related artery; MPG — myocardial perfusion grade; nCI-AKI — no contrast induced acute kidney injury; PCI — percutaneous coronary intervention; TIMI — Thrombolysis In Myocardial Infarction

Within the DM group, CI-AKI-patients were significantly older, showed higher serum uric acid and creatinine concentrations on admission, more often presented with CS on admission, TIMI flow < 3, and/or MPG < 3 after PCI of infarct-related artery when compared to patients without CI-AKI. Among diabetics, in CI-AKI subjects, IR occurrence was almost two-fold higher than in nCI-AKI patients. More­over, CI-AKI subjects showed higher PC. No differences in PVI were observed between the compared groups. Detailed baseline characteristics for subjects with DM are shown in Table 2.

Table 2. Comparative analysis of demographic, clinical, and laboratory data between patients developing CI-AKI and patients without CI-AKI among subjects with diabetes mellitus (n = 179)

	CI-AKI (n = 56)	nCI-AKI (n = 123)	P
Age [years] Male Hypertension Hyperlipidaemia Creatinine on admission [µmol/L] Baseline kidney dysfunction Uric acid [µmol/L] Cardiogenic shock on admission Ejection fraction < 35% Multivessel coronary artery disease TIMI < 3 and/or MPG < 3 after PCI of IRA Contrast media volume [mL] Platelet count [× 109/L] Mean platelet volume [fL] Platelet volume distribution width [fL] Platelet large cell ratio [%]	69.1 ± 7.8 37 (66.1%) 40 (71.4%) 30 (53.6%) 106.0 ± 76.6 21 (37.5%) 443.3 ± 176.8 14 (25.0%) 11 (19.6%) 43 (76.8%) 27 (48.2%) 228.7 ± 93.5 224.8 ± 62.8 11.4 ± 1.2 13.8 ± 2.4 36.6 ± 9.4	66.0 ± 8.9 70 (56.9%) 86 (69.9%) 79 (64.2%) 90.0 ± 34.9 17 (24.4%) 368.7 ± 120.4 4 (3.3%) 16 (13.0%) 86 (69.9%) 34 (27.6%) 223.2 ± 86.4 197.9 ± 63.3 11.5 ± 1.0 14.2 ± 2.3 37.0 ± 7.8	0.027 0.245 0.839 0.180 0.048 0.074 0.002 < 0.001 0.254 0.341 0.008 0.701 0.014 0.661 0.307 0.730
Abbreviations as in Table 1

Among subjects with BKD, CI-AKI-patients more often presented with CS on admission, ejection fraction < 35%, DM, and showed higher serum uric acid and creatinine concentrations on admission, when compared to patients without CI-AKI. Moreover, CI-AKI subjects showed higher PC. No differences in PVI were observed between the compared groups. The incidence of IR after the intervention was similar in both groups. Detailed baseline characteristics for subjects with BKD are shown in Table 3.

Table 3. Comparative analysis of demographic, clinical and laboratory data between patients developing CI-AKI and patients without CI-AKI among subjects with baseline kidney dysfunction (n = 98)

	CI-AKI (n = 31)	nCI-AKI (n = 67)	P
Age [years] Male Hypertension Hyperlipidaemia Diabetes mellitus Creatinine on admission [µmol/L] Uric acid [µmol/L] Cardiogenic shock on admission Ejection fraction < 35% Multivessel coronary artery disease TIMI < 3 and/or MPG < 3 after PCI of IRA Contrast media volume [mL] Platelet count [× 109/L] Mean platelet volume [fL] Platelet volume distribution width [fL] Platelet large cell ratio [%]	68.9 ± 10.8 20 (64.5%) 23 (74.2%) 16 (50.0%) 21 (67.7%) 177.5±138.4 515.9 ± 189.3 11 (35.5%) 8 (25.8%) 25 (80.6%) 14 (45.2%) 217.9 ± 82.3 248.9 ± 86.5 11.3 ± 0.9 13.6 ± 1.6 36.2 ± 7.3	67.7 ± 8.5 34 (50.7%) 39 (58.2%) 39 (58.2%) 30 (44.8%) 125.4±37.7 411.0 ± 124.0 10 (14.9%) 7 (10.4%) 45 (67.2%) 23 (34.3%) 211.6 ± 79.2 202.5 ± 59.3 11.4 ± 1.1 13.9 ± 2.2 36.7 ± 8.3	0.559 0.202 0.123 0.449 0.037 0.005 0.003 0.023 0.052 0.175 0.309 0.718 0.004 0.663 0.528 0.810
Abbreviations as in Table 1

The comparative analysis between subjects who developed IR and CI-AKI and controls did not reveal any significant differences in relation to admission PC and PVI (Table 4).

Table 4. Comparative analysis of platelet parameters in patients developing contrast-induced acute kidney injury and impaired coronary reperfusion (CI-AKI-IR) with control group

	CI-AKI-IR (n = 47)	Controls (n = 560)	P
Platelet count [× 109/L] Mean platelet volume [fL] Platelet volume distribution width [fL] Platelet large cell ratio [%]	217.4 ± 65.8 11.2 ± 1.2 13.6 ± 2.5 35.2 ± 9.6	209.5 ± 65.5 11.3 ± 1.0 13.7 ± 2.2 35.7 ± 8.2	0.440 0.734 0.675 0.687
Values presented as mean ± standard deviation.

Independent risk factors associated with CI-AKI within the total study population were: CS on admission (OR 3.94; CI 1.66–9.38; p = 0.002), ejection fraction at discharge (OR 0.96 per 1% increase; CI 0.94–0.98; p = 0.002), PC on admission was not independently associated with CI-AKI, only trend towards higher risk of CI-AKI was observed. Independent factors associated with CI-AKI in patients with DM were: age (OR 1.05; CI 1.0–1.09; p = 0.04), CS on admission (OR 10.0; CI 2.60–38.5; p < 0.001), and PC on admission (per one unit increase OR 1.006; CI 1.0–1.01; p = 0.04). Independent factors associated with CI-AKI in patients with BKD were: CS on admission (OR 6.36; CI 1.2–33.75; p = 0.03) and PC on admission (per one unit increase OR 1.01; CI 1.0–1.02; p = 0.02).

Similar analyses were performed to identify independent predictors of no-reflow; however, no platelet-related risk factors for no-reflow were found in the study population or in the analysed subgroups.

DISCUSSION

This work demonstrated that in the studied groups of AMI patients, contrast-induced nephropathy occurrence was not associated with admission PVI. Higher PC was observed in CI-AKI subjects with diabetes or BKD. Moreover, an increase in admission PC was an independent risk factor for CI-AKI development. This association had not been found in prior studies.

Published studies showed that larger, more active platelets play a role in the “no reflow” phenomenon. We hypothesised that platelets with more prothrombotic potential, responsible for coronary vascular plugging observed in no reflow, could also cause CI-AKI in a similar manner. However, in patients with CI-AKI and IR after invasive treatment, no associations with platelet parameters were found. Therefore, any similarities in the pathogenesis of these two diseases are not reflected in PC or in PVI.

In the presented study, patients who developed contrast-induced nephropathy had more often well-established CI-AKI risk factors than nCI-AKI controls — CS, diabetes, worse baseline renal function, and older age [10, 13]. CS was the most important independent risk factor for CI-AKI in the total study population and analysed subgroups. Higher PC in subjects with DM or baseline kidney dysfunction, who developed CI-AKI, had been also observed in patients with longer diabetes duration complicated with diabetic nephropathy [14] or insulin resistance [15], in women with metabolic syndrome [16]. The obtained data indicated that the coexistence of renal dysfunction and diabetes was associated with increased PC, but sex differences were not confirmed. In a recently published study by Sahin et al. [8] it was shown that an increase in PDW was independently associated with CI-AKI occurrence, an observation not found in the presented study. The investigated population in Sahin’s study consisted of patients with more favourable clinical presentation of ACS, presumably without patients with CS. Moreover, the incidence of AMI as well as frequency of invasive treatment was not shown. Therefore, different results relating to PDW could be caused by different platelet activation in different presentations of ACS. Platelet count was not analysed in Sahin’s study [8].

Limitations of the study

This study was designed as a prospective single-centre observational analysis, which could potentially have biased the results. The study groups were relatively small.

CONCLUSIONS

Considering the results, the authors concluded that the pathophysiology of CI-AKI seems to be different to that of IR. Any similarities in the pathophysiology of CI-AKI and IR were not reflected in platelet parameters. CI-AKI development was not related to PVI; however, higher PC was an independent risk factor for CI-AKI in patients with BKD or diabetes.

Conflict of interest: Radosław Lenarczyk — consultant fees: Medtronic, Biotronik, St. Jude Medical, speaker fees: Boehringer Ingelheim; Beata Średniawa — consultant fees: Medtronic Bakken Research Center, Bristol Myers Squibb, Pfizer, speaker fees: Boehringer Ingelheim, Servier, MSD, Adamed, Berlin Chemie, Sandoz, Reynolds Medical; Zbigniew Kalarus — speaker fees: Pfizer, Novonordisk, Eli Lilly, Boehringer Ingelheim, scientific conferences and congresses sponsorship: St. Jude Medical, Servier, Medtronic, consultant fees: Boehringer Ingelheim.

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