International Journal of Cardiology 172 (2014) e159–e161
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Increased mean platelet volume in patients with coronary artery disease and its seasonal variation Satoshi Kurisu ⁎, Noriaki Watanabe, Hiroki Ikenaga, Takashi Shimonaga, Tadanao Higaki, Toshitaka Iwasaki, Naoya Mitsuba, Ken Ishibashi, Yoshihiro Dohi, Yasuki Kihara Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
a r t i c l e
i n f o
Article history: Received 7 October 2013 Accepted 22 December 2013 Available online 28 December 2013 Keywords: Platelet Hematology Season
Increased morbidity and mortality from cardiovascular disease in winter have been recognized in countries at high latitudes. In general, this phenomenon is thought to correlate with changes in environmental temperature [1]. Previous studies have shown seasonal variation in blood pressure, fibrinogen or hemostatic factors [2]. However, little is known about how platelet activity changes in association with season. Mean platelet volume (MPV) is a well-established marker of platelet activation, and it increases in stroke or acute myocardial infarction [3,4]. In the current study, we compared MPV between patients with coronary artery disease (CAD) treated with optimal medical therapy and control subjects. We also assessed whether seasonal variation in MPV was found in patients with CAD. The study population consisted of 36 patients with CAD and 36 ageand sex-matched control subjects in whom MPV was measured in spring (March to May). CAD was defined as N75% stenosis in one or more vessels, prior myocardial infarction or prior coronary intervention. In patients with CAD, measurements of MPV were carried out on 4 occasions: in spring (March to May); summer (June to August); autumn (September to November); and winter (December to February). Medications in patients with CAD were unchanged during the follow-up period. Patients with evidence of heart failure, renal failure (serum creatinine N 2 mg/dl), hepatic disease, hematological disease, autoimmune disease, cancer, thrombocytopenia and systematic inflammatory conditions were excluded in this study. MPV was measured in a
⁎ Corresponding author at: 1-2-3, Kasumi-cho, Minami-ku,4, Hiroshima 734-8551, Japan. Tel.: +81 82 257 5540; fax: +81 82 257 1569. E-mail address: [email protected] (S. Kurisu). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.071
blood sample collected in tripotassium EDTA tubes within 30 min to prevent EDTA-induced swelling. An automatic blood counter was used for whole blood counts. Statistical analysis between patients with CAD and control subjects was performed with chi-square and Student's t-tests. Analysis of variance was used to determine the difference in MPV among the seasons. All data are expressed as mean ± SD. Differences were considered significant if the p value was b0.05. Clinical characteristics of 36 patients with CAD and 36 control subjects are shown in Table 1. Patients with CAD had diabetes, prior myocardial infarction or prior coronary intervention more frequently compared to control subjects. Also, patients with CAD were treated with angiotensin-converting enzyme inhibitors, beta blockers, statins, aspirin and oral hypoglycemic agents more frequently compared to control subjects. There was no significant difference in white blood cell count or hemoglobin between the 2 groups. Compared to control subjects, platelet count was significantly lower (17.4 ± 3.5 × 104/μl vs 21.2 ± 3.7 × 104/μl, p b 0.01), and MPV was significantly larger in patients with CAD (10.16 ± 0.80 fl vs 9.67 ± 0.51 fl, p b 0.01). Time course of platelet count and MPV in patients with CAD is shown in Fig. 1. There was no significant difference in platelet count and MPV among the seasons. The current study demonstrated the following: 1) MPV was larger in patients with CAD compared to control subjects; and 2) seasonal variation of MPV was not found in patients with CAD treated with optimal medical therapy. Platelets are heterogeneous in size, density and reactivity. Compared to smaller ones, larger platelets have more granules, aggregate more rapidly with collagen, have higher thromboxane A2 and express more glycoprotein IIb/IIIa receptor. MPV is a well-established indicator of platelet activation which is central to the processes in the pathophysiology of CAD. We found that MPV was larger in patients with CAD compared to control subjects, which was consistent with previous report [5]. Increased MPV has also been shown in conditions such as hypertension, insulin resistance or diabetes [6]. These are also risk factors for CAD. On the other hand, aspirin appears not to affect MPV, either in vitro or in vivo [7,8]. In the current study, patients with CAD had diabetes more frequently compared to control subjects, which might contribute to the increased MPV in patients with CAD at least in part. It is well known that mortality from cardiovascular disease is higher in winter and cold weather than in summer [9]. Therefore, it is of great interest whether seasonal variation of platelet count or MPV is found on a parallel with seasonal change in the incidence of cardiovascular
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S. Kurisu et al. / International Journal of Cardiology 172 (2014) e159–e161
Table 1 Clinical characteristics of patients with coronary artery disease and control subjects.
Age (years) Male gender Hypertension Diabetes Prior myocardial infarction Prior coronary intervention Medications Angiotensin-converting enzyme inhibitors Angiotensin II type1 receptor blockers Beta blockers Calcium channel blockers Statins Aspirin Oral hypoglycemic agents Serum creatinine (mg/dl) Low-density lipoprotein cholesterol (mg/dl) High-density lipoprotein cholesterol (mg/dl) Hemoglobin A1C (%) White blood cell count (×103) Hemoglobin (g/dl) Platelet count (×104/μl) Mean platelet volume (fl)
Patients with coronary artery disease (n = 36)
Control subjects (n = 36)
p value
72.8 ± 8.7 31 (86%) 27 (75%) 18 (50%) 17 (47%) 34 (94%)
72.8 ± 9.3 31 (86%) 28 (78%) 4 (11%) 0 (0%) 0 (0%)
ns ns ns p b 0.01 p b 0.01 p b 0.01
7 (19%) 18 (50%) 21 (58%) 15 (42%) 34 (94%) 36 (100%) 15 (42%) 0.95 ± 0.28 91.3 ± 22.5 58.1 ± 12.1 6.62 ± 1.09 5.90 ± 1.12 13.9 ± 1.4 17.4 ± 3.5 10.16 ± 0.80
0 (0%) 23 (64%) 3 (8%) 15 (42%) 5 (14%) 0 (0%) 3 (8%) 0.95 ± 0.28 121.7 ± 20.6 58.0 ± 14.5 5.93 ± 0.41 6.06 ± 1.69 14.2 ± 5.8 21.2 ± 3.7 9.67 ± 0.51
pb ns pb ns pb pb pb ns pb ns pb ns ns pb pb
disease. Several studies in Europe showed seasonal variation of MPV and fibrinogen together with their association with climatic data in healthy subjects. Crawford et al. reported that peak MPV and fibrinogen were found in May and June, respectively, but no significant variation in platelet count was found [10]. On the other hand, in the current study, there was no significant seasonal variation in platelet count or MPV in patients with CAD treated with optimal medical therapy. Our results were inconsistent with those in healthy subjects. One possible explanation was that patients with CAD often had multiple conditions associated with increased MPV compared to healthy subjects. They might
0.01 0.01 0.01 0.01 0.01 0.01 0.01
0.01 0.01
contribute to persistent increase and lack of seasonal variation in MPV throughout the year. Another possible explanation was that our patients were treated with optimal medical therapy including angiotensinconverting enzyme inhibitors, angiotensin II type 1 receptor blockers, beta blockers or statins, although no data are available concerning favorable effects of these agents on MPV at present. Further studies are necessary to clarify whether the seasonal response in MPV in patients with CAD is different from that in healthy subjects. There are several limitations in the current study. First, we did not assess platelet activation using different methods such as optical
Fig. 1. Time course of platelet count (upper panel) and mean platelet volume (lower panel) in patients with coronary artery disease. There was no significant difference in platelet count and mean platelet volume among the seasons. Data are shown as mean (SD).
S. Kurisu et al. / International Journal of Cardiology 172 (2014) e159–e161
aggregometry, platelet function analyzer, platelet reactivity test or platelet aggregate ratio, flow cytometry or thromboxane B2 generation. However, it is noteworthy that MPV is a simple and wellestablished marker of platelet activation, not requiring an advanced or expensive technology. Second, we did not have climatic data including ambient temperature or core body temperature, and could not assess their relations to MPV. Finally, the small sample size is a major limitation and a larger study should be performed to confirm our findings. In conclusion, MPV increased in patients with CAD, and it did not change in association with season. References [1] Pan WH, Li LA, Tsai MJ. Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly Chinese. Lancet 1995;345:353–5.
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[2] Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435–9. [3] O'Malley T, Langhorne P, Elton RA, Stewart C. Platelet size in stroke patients. Stroke 1995;26:995–9. [4] Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991;338:1409–11. [5] Ekici B, Erkan AF, Alhan A, Sayin I, Ayli M, Töre HF. Is mean platelet volume associated with the angiographic severity of coronary artery disease? Kardiol Pol 2013;71:832–8. [6] Papanas N, Symeonidis G, Maltezos E, et al. Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2004;15:475–8. [7] Erhart S, Beer JH, Reinhart WH. Influence of aspirin on platelet count and volume in humans. Acta Haematol 1999;101:140–4. [8] Colkesen Y, Coskun I, Muderrisoglu H. The effect of aspirin on mean platelet volume in patients with paroxysmal atrial fibrillation. Platelets 2013;24:263–6. [9] Kloner RA, Poole WK, Perritt RL. When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases. Circulation 1999;100:1630–4. [10] Crawford VL, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age Ageing 2003;32:661–5.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Increased mean platelet volume in patients with coronary artery disease and its seasonal variation Satoshi Kurisu ⁎, Noriaki Watanabe, Hiroki Ikenaga, Takashi Shimonaga, Tadanao Higaki, Toshitaka Iwasaki, Naoya Mitsuba, Ken Ishibashi, Yoshihiro Dohi, Yasuki Kihara Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
a r t i c l e
i n f o
Article history: Received 7 October 2013 Accepted 22 December 2013 Available online 28 December 2013 Keywords: Platelet Hematology Season
Increased morbidity and mortality from cardiovascular disease in winter have been recognized in countries at high latitudes. In general, this phenomenon is thought to correlate with changes in environmental temperature [1]. Previous studies have shown seasonal variation in blood pressure, fibrinogen or hemostatic factors [2]. However, little is known about how platelet activity changes in association with season. Mean platelet volume (MPV) is a well-established marker of platelet activation, and it increases in stroke or acute myocardial infarction [3,4]. In the current study, we compared MPV between patients with coronary artery disease (CAD) treated with optimal medical therapy and control subjects. We also assessed whether seasonal variation in MPV was found in patients with CAD. The study population consisted of 36 patients with CAD and 36 ageand sex-matched control subjects in whom MPV was measured in spring (March to May). CAD was defined as N75% stenosis in one or more vessels, prior myocardial infarction or prior coronary intervention. In patients with CAD, measurements of MPV were carried out on 4 occasions: in spring (March to May); summer (June to August); autumn (September to November); and winter (December to February). Medications in patients with CAD were unchanged during the follow-up period. Patients with evidence of heart failure, renal failure (serum creatinine N 2 mg/dl), hepatic disease, hematological disease, autoimmune disease, cancer, thrombocytopenia and systematic inflammatory conditions were excluded in this study. MPV was measured in a
⁎ Corresponding author at: 1-2-3, Kasumi-cho, Minami-ku,4, Hiroshima 734-8551, Japan. Tel.: +81 82 257 5540; fax: +81 82 257 1569. E-mail address: [email protected] (S. Kurisu). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.071
blood sample collected in tripotassium EDTA tubes within 30 min to prevent EDTA-induced swelling. An automatic blood counter was used for whole blood counts. Statistical analysis between patients with CAD and control subjects was performed with chi-square and Student's t-tests. Analysis of variance was used to determine the difference in MPV among the seasons. All data are expressed as mean ± SD. Differences were considered significant if the p value was b0.05. Clinical characteristics of 36 patients with CAD and 36 control subjects are shown in Table 1. Patients with CAD had diabetes, prior myocardial infarction or prior coronary intervention more frequently compared to control subjects. Also, patients with CAD were treated with angiotensin-converting enzyme inhibitors, beta blockers, statins, aspirin and oral hypoglycemic agents more frequently compared to control subjects. There was no significant difference in white blood cell count or hemoglobin between the 2 groups. Compared to control subjects, platelet count was significantly lower (17.4 ± 3.5 × 104/μl vs 21.2 ± 3.7 × 104/μl, p b 0.01), and MPV was significantly larger in patients with CAD (10.16 ± 0.80 fl vs 9.67 ± 0.51 fl, p b 0.01). Time course of platelet count and MPV in patients with CAD is shown in Fig. 1. There was no significant difference in platelet count and MPV among the seasons. The current study demonstrated the following: 1) MPV was larger in patients with CAD compared to control subjects; and 2) seasonal variation of MPV was not found in patients with CAD treated with optimal medical therapy. Platelets are heterogeneous in size, density and reactivity. Compared to smaller ones, larger platelets have more granules, aggregate more rapidly with collagen, have higher thromboxane A2 and express more glycoprotein IIb/IIIa receptor. MPV is a well-established indicator of platelet activation which is central to the processes in the pathophysiology of CAD. We found that MPV was larger in patients with CAD compared to control subjects, which was consistent with previous report [5]. Increased MPV has also been shown in conditions such as hypertension, insulin resistance or diabetes [6]. These are also risk factors for CAD. On the other hand, aspirin appears not to affect MPV, either in vitro or in vivo [7,8]. In the current study, patients with CAD had diabetes more frequently compared to control subjects, which might contribute to the increased MPV in patients with CAD at least in part. It is well known that mortality from cardiovascular disease is higher in winter and cold weather than in summer [9]. Therefore, it is of great interest whether seasonal variation of platelet count or MPV is found on a parallel with seasonal change in the incidence of cardiovascular
e160
S. Kurisu et al. / International Journal of Cardiology 172 (2014) e159–e161
Table 1 Clinical characteristics of patients with coronary artery disease and control subjects.
Age (years) Male gender Hypertension Diabetes Prior myocardial infarction Prior coronary intervention Medications Angiotensin-converting enzyme inhibitors Angiotensin II type1 receptor blockers Beta blockers Calcium channel blockers Statins Aspirin Oral hypoglycemic agents Serum creatinine (mg/dl) Low-density lipoprotein cholesterol (mg/dl) High-density lipoprotein cholesterol (mg/dl) Hemoglobin A1C (%) White blood cell count (×103) Hemoglobin (g/dl) Platelet count (×104/μl) Mean platelet volume (fl)
Patients with coronary artery disease (n = 36)
Control subjects (n = 36)
p value
72.8 ± 8.7 31 (86%) 27 (75%) 18 (50%) 17 (47%) 34 (94%)
72.8 ± 9.3 31 (86%) 28 (78%) 4 (11%) 0 (0%) 0 (0%)
ns ns ns p b 0.01 p b 0.01 p b 0.01
7 (19%) 18 (50%) 21 (58%) 15 (42%) 34 (94%) 36 (100%) 15 (42%) 0.95 ± 0.28 91.3 ± 22.5 58.1 ± 12.1 6.62 ± 1.09 5.90 ± 1.12 13.9 ± 1.4 17.4 ± 3.5 10.16 ± 0.80
0 (0%) 23 (64%) 3 (8%) 15 (42%) 5 (14%) 0 (0%) 3 (8%) 0.95 ± 0.28 121.7 ± 20.6 58.0 ± 14.5 5.93 ± 0.41 6.06 ± 1.69 14.2 ± 5.8 21.2 ± 3.7 9.67 ± 0.51
pb ns pb ns pb pb pb ns pb ns pb ns ns pb pb
disease. Several studies in Europe showed seasonal variation of MPV and fibrinogen together with their association with climatic data in healthy subjects. Crawford et al. reported that peak MPV and fibrinogen were found in May and June, respectively, but no significant variation in platelet count was found [10]. On the other hand, in the current study, there was no significant seasonal variation in platelet count or MPV in patients with CAD treated with optimal medical therapy. Our results were inconsistent with those in healthy subjects. One possible explanation was that patients with CAD often had multiple conditions associated with increased MPV compared to healthy subjects. They might
0.01 0.01 0.01 0.01 0.01 0.01 0.01
0.01 0.01
contribute to persistent increase and lack of seasonal variation in MPV throughout the year. Another possible explanation was that our patients were treated with optimal medical therapy including angiotensinconverting enzyme inhibitors, angiotensin II type 1 receptor blockers, beta blockers or statins, although no data are available concerning favorable effects of these agents on MPV at present. Further studies are necessary to clarify whether the seasonal response in MPV in patients with CAD is different from that in healthy subjects. There are several limitations in the current study. First, we did not assess platelet activation using different methods such as optical
Fig. 1. Time course of platelet count (upper panel) and mean platelet volume (lower panel) in patients with coronary artery disease. There was no significant difference in platelet count and mean platelet volume among the seasons. Data are shown as mean (SD).
S. Kurisu et al. / International Journal of Cardiology 172 (2014) e159–e161
aggregometry, platelet function analyzer, platelet reactivity test or platelet aggregate ratio, flow cytometry or thromboxane B2 generation. However, it is noteworthy that MPV is a simple and wellestablished marker of platelet activation, not requiring an advanced or expensive technology. Second, we did not have climatic data including ambient temperature or core body temperature, and could not assess their relations to MPV. Finally, the small sample size is a major limitation and a larger study should be performed to confirm our findings. In conclusion, MPV increased in patients with CAD, and it did not change in association with season. References [1] Pan WH, Li LA, Tsai MJ. Temperature extremes and mortality from coronary heart disease and cerebral infarction in elderly Chinese. Lancet 1995;345:353–5.
e161
[2] Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435–9. [3] O'Malley T, Langhorne P, Elton RA, Stewart C. Platelet size in stroke patients. Stroke 1995;26:995–9. [4] Martin JF, Bath PM, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991;338:1409–11. [5] Ekici B, Erkan AF, Alhan A, Sayin I, Ayli M, Töre HF. Is mean platelet volume associated with the angiographic severity of coronary artery disease? Kardiol Pol 2013;71:832–8. [6] Papanas N, Symeonidis G, Maltezos E, et al. Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2004;15:475–8. [7] Erhart S, Beer JH, Reinhart WH. Influence of aspirin on platelet count and volume in humans. Acta Haematol 1999;101:140–4. [8] Colkesen Y, Coskun I, Muderrisoglu H. The effect of aspirin on mean platelet volume in patients with paroxysmal atrial fibrillation. Platelets 2013;24:263–6. [9] Kloner RA, Poole WK, Perritt RL. When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases. Circulation 1999;100:1630–4. [10] Crawford VL, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age Ageing 2003;32:661–5.
