International Journal of Impotence Research (2014), 1–3 & 2014 Macmillan Publishers Limited All rights reserved 0955-9930/14 www.nature.com/ijir
ORIGINAL ARTICLE
Assessment of Mean Platelet Volume in men with vasculogenic and nonvasculogenic erectile dysfunction H Ciftci1, K Gumus¸1, ˙I Yagmur1, S Sahabettin2, H Çelik3, E Yeni1, M Savas1 and M Gulum1 Mean platelet (PLT) activation has an important role in the development of vascular diseases. In this study, we aimed to investigate the PLT volume in patients with vasculogenic and nonvasculogenic erectile dysfunction (ED) and compare it with the control group. Mean PLT volume (MPV) levels were measured in 50 patients with vasculogenic ED, in 30 patients who developed ED after radical prostatectomy (nonvasculogenic) and in 40 healthy controls. Ages were similar between the three groups. The diagnosis of ED was based on detailed sexual history, physical examination, laboratory assessment and color Doppler ultrasonography and is defined as the inability to attain or maintain a penile erection that is sufficient for successful vaginal intercourse. The results are given as mean±s.d. of the mean. The mean age of the patients with vasculogenic ED, of patients with ED after radical prostatectomy and of the control group were 53.70±12.39 (range 24–77), 54.60±11.40 (range 43–61) and 53.85±9.5 (range 30–73), respectively (P ¼ 0.853). The MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with ED after radical prostatectomy and in control groups: 7.49±1.4, 6.43±1.19 and 6.85±1.2 for MPV and 262.97±68, 251.77±78 and 252.89±82 for PLT values, respectively (P ¼ 0.033). The MPV and PLT values were not statistically significant in postprostatectomy ED patients and in control groups (P ¼ 0.663). There was no significant difference among the three groups in terms of white blood cells and hemoglobin levels. PLT count and mean PLT volume were detected to be increased in patients with vasculogenic ED. This finding may suggest a role for PLT volume in the pathogenesis of vasculogenic ED. International Journal of Impotence Research advance online publication, 29 May 2014; doi:10.1038/ijir.2014.17
INTRODUCTION Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual intercourse.1 ED affects all age groups, with increased prevalence associated with advanced age, diabetes, vascular disease, psychiatric disorders and several major surgeries.2 In the etiology of ED, generally organic and psychogenic factors come together. However, if the penis is considered a specialized vascular bed, it is well known that vascular reasons dominate in the etiology of ED.3 Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin. ED in patients who underwent a vascular evaluation for vascular pathology can be classified as having arteriogenic ED, venogenic ED or mixed vasculogenic ED.4 A 2011 meta-analysis of 12 prospective cohort studies provided strong evidence that ED is indeed significantly and independently associated with an increased risk for not only cardiovascular disease but also coronary heart disease, stroke and all-cause mortality.5 Clearly, ED is now regarded as a major health problem for the increasingly healthy aging population. The suggestion from scientific research that the pathogenesis of ED is predominately a disease of vascular origin led us to investigate the association between platelet (PLT) volume (Mean PLT volume (MPV)) and ED to elucidate the etiopathogenesis of ED. MPV is an indicator of PLT activation, which has an important role in the pathophysiology of thrombosis and is measured as a part of the complete blood count. Higher MPV may be observed in vascular pathologies and may increase the risk for cardiovascular disease. In addition, higher MPV is observed in patients with
diabetes mellitus,6 hypertension, hypercholesterolemia, smoking and obesity,7–10 suggesting a common mechanism by which these factors may increase the risk for cardiovascular disease and vasculogenic ED. In this study, we aimed to investigate the association between PLT volume and vasculogenic ED and postprostatectomy ED in patients and compare with a control group.
MATERIALS AND METHODS The study protocol was approved by the Institutional ethics committee School of Medicine, Harran University, Turkey, and all individuals who participated in the study gave their informed consent. MPV levels were measured in 50 patients with vasculogenic ED and in 30 patients with postprostatectomy ED and not having vascular disease as well as in 40 healthy male volunteers who were sexually active, married and agematched and who had an ED domain score X26 by ?International Index of Erectile Function short form who comprised the control group. The diagnosis of ED was based on detailed sexual history, physical examination, laboratory assessment and color Doppler ultrasonography and is defined as the inability to attain or maintain a penile erection sufficient for successful vaginal intercourse. The severity of ED is classified as mild to severe, according to the International Index of Erectile Function. None of the subjects were using antiPLT or anticoagulant drugs. Patients with neurogenic, endocrinological, or psychogenic ED, who had undergone pelvic surgery or pelvic trauma or had other vascular risk factors for ED, such as diabetes, smoking or hypertension, recently diagnosed coronary artery disease or hematological disorder, active infectious disease, malignancy, immunological disease or renal and hepatic failure, were excluded. The severity of ED was classified as mild to severe, according to the International Index of Erectile Function.
1 Department of Urology, Harran University Medical School, Sanliurfa, Turkey; 2Department of Clinical Biochemistry, Harran University, Sanliurfa, Turkey and 3Department of Physiology, Gaziantep University, Gaziantep, Turkey. Correspondence: Professor H Ciftci, Department of Urology, Harrran University Medical School, TR-63100 Sanliurfa, Turkey. E-mail: [email protected] Received 22 January 2013; revised 19 October 2013; accepted 9 April 2014
Assessment of Mean Platelet Volume H Ciftci et al
2 Blood samples were drawn from the antecubital vein between 08.00 and 10.00 a.m. after an overnight fast. Blood samples were collected in dipotassium EDTA-containing tubes. All measurements were taken immediately after venipuncture to prevent in vitro PLT activation. The MPV parameters were measured by using commercially available assay kits (Abbott) with an autoanalyzer (Aeroset, Abbott, Burlington, MA, USA). The other biochemical analyses were determined by standard methods. Total blood count, including hemoglobin, white blood cell (WBC), and PLTs, and MPV parameters were measured in both groups. Statistical analysis was performed with SPSS 13.0 for Windows version 13.0 (SPSS Inc., Chicago, IL, USA). Intergroup comparisons were performed using the Mann– Whitney U test, and the Kruskal–Wallis test was used to assess the relationship between categorical variables in patient groups. Po0.05 was used as a threshold for statistical significance. Data were presented as means±s.d.
RESULTS The results are given as mean±s.d. of the mean. The mean age of patients with vasculogenic ED, of patients with ED after radical prostatectomy and of the control group was 53.70±12.39 (range 24–77), 5460±11.40 (range 43–61) and 53.85±9.5 (range 30–73), respectively (P ¼ 0.853). The MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with ED after radical prostatectomy and in the control group: 7.49±1.4, 6.43±1.19 and 6.85±1.2 for MPV and 262.97±68, 251.77±78 and 252.89±82 for PLT values, respectively (P ¼ 0.033). The MPV and PLT values were not statistically significant in patients with postprostatectomy ED and in control groups (P ¼ 0.663). There was no significant difference among the three groups in terms of white blood cells (WBCs) and hemoglobin level. The findings are shown in Table 1. The MPV values were not statistically significant in patients with severe ED according to the International Index of Erectile Function compared with patients with mild ED (P40.05).
DISCUSSION Vascular disease is the underlying cause of ED in the majority of cases.11 The risk factors for ED—hypertension, smoking, abnormal lipid profile, sedentary lifestyle, obesity, metabolic syndromes and diabetes—are also risk factors for coronary artery disease. ED, in turn, is an independent predictor of future cardiovascular events.12 Endothelial dysfunction has an integral role in cardiovascular and peripheral vascular disease because of the systemic and subclinical inflammatory response that is characteristic of atherosclerosis.13 Damage to the endothelium by cardiovascular risk factors affects not only the coronary arteries but also arteries throughout the body, including those of corpora cavernosa of the Table 1. Study parameters in vasculogenic erectile dysfunction patients, postprostatectomy erectile dysfunction patients and in healthy controls
Age IIEF MPV (fL) WBC Hgb (g/d/L) PLT (k/ul)
Vasculogenic (ED, no ¼ 50)
Postprostatectomy (ED, no ¼ 30)
Healthy control, (no ¼ 40)
P
53.70±12.39 12.8±04 7.49±1,4 6.59±1.12 14.21±1,15 262.97±68
54.60±11.40 11.2±12 6.43±1.19 6.70±1.20 13.40±1.33 251.77±78
53.85±9.5 27.51±1,6 6.85± 1.2 6.96±1.88 14.34±1.49 252.89±82
ns s s ns ns s
Abbreviations: ED, erectile dysfunction; Hgb, hemoglobin; IIEF, International Index of Erectile Function; MPV, mean platelet volume; ns, statistically nonsignificant; PLT, platelet; s, statistically significant; WBC, white blood cells. Values are presented as mean±s.d. S, Po0.05; t-test for independent samples.
International Journal of Impotence Research (2014), 1 – 3
penis.14 In fact, the vascular endothelium is not only a simple barrier but also a true organ that synthesizes and releases substances, and it acts in a paracrine and endocrine manner on vascular tone and PLT aggregation.15 The erectile response of the penis depends on the balance between vasoconstrictors and vasodilatory agents that affect contraction and relaxation of cavernosal smooth-muscle agents and thus regulate blood inflow and erection.16 Inman et al.17 suggested that ED shares the same risk factors as coronary artery disease, with endothelial dysfunction being an important underlying pathological change in both diseases. Other potential mechanisms involved in the development of endothelial dysfunction that can lead to ED and coronary artery disease include a dysfunctional L-arginine nitric oxide pathway, increased peripheral sympathetic activity, vascular structural alterations leading to decreased vascular dilatation capacity and increased specific inflammatory mediators.18,19 Montorsi et al.20 suggested that this phenomenon might be related to the caliber of the blood vessels. Whereas the penile artery has a diameter of 1–2 mm, the proximal left anterior descending coronary artery has a diameter of 3–4 mm. Thus, an equally sized atherosclerotic plaque developing in the smaller penile arteries would more likely compromise flow, presenting itself as an ED complaint much earlier than if the same amount of plaque had developed in the larger coronary artery, causing angina. The effect of increased PLT activity on vascular disorders has been noted in several studies.21 PLTs have a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation or apposition after plaque rupture. The MPV is a marker of PLT function, and large PLTs contain more dense granules and produce more thromboxane A2.10 In several studies, increased MPV has been noted with cardiovascular risk factors, such as smoking, diabetes, obesity, hypertension and hyperlipidemia.10 In subjects with established cardiovascular disease, elevated MPV may be a marker for adverse cardiovascular events. However, most studies found no significant association between increased PLT count and incidence of acute myocardial infarction, restenosis or long-term mortality.22,23 The study by Bozkur et al.24 found that the increase in MPV is independent of the disease and that the increase in varicocele grade is associated with higher MPV in varicocele patients. In light of this result, it is reported that the etiopathogenesis of varicocele may be associated with PLT activation and/or vascular endothelial cell injury. In our study, we found that the MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with postprostatectomy ED and in controls. Several studies have reported that increases in PLT volume are often associated with decreases in PLT count,25 perhaps as a result of small PLTs being consumed in order to maintain a constant PLT functional mass. Conversely, we have found that the PLT count and PLT volume both increase in vasculogenic ED patients compared with postprostatectomy ED patients and the control group. Similar to our study, in one study they found that PLT count and PLT volume both increase during stimulated thrombopoiesis, indicating that PLT count and volume may be regulated by independent mechanisms. They report that the relationship between MPV and PLT count is not completely understood.10 However, increased MPV levels are usually considered a vascular risk factor. In a recent study Stokes and Granger. reported the involvement of PLT activation along with leukocytes and vascular endothelial cells in vascular and microvascular dysfunction.26 In light of this information and as a result of our study, the etiopathogenesis of vasculogenic ED may be associated with PLT activation and/or vascular endothelial cell injury. We concluded that patients with vasculogenic ED have higher MPV values, indicating a tendency for PLT aggregation regardless of the etiology, when compared with postprostatectomy ED patients and controls. On the basis of the importance of the vascular component (endothelial dysfunction) in the pathophysiology of & 2014 Macmillan Publishers Limited
Assessment of Mean Platelet Volume H Ciftci et al
3 ED, this finding suggests a role for PLTs in the pathogenesis of vascular complications. However, further large-scale studies are required to clarify whether patients with vasculogenic ED having high MPV values are at greater risk for thromboembolism and may benefit from antiPLT therapy. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 National Institute of Health Consensus Development Panel on Impotence. Proceedings of a Conference held December 7–9, 1992, Bethesda. Maryland. JAMA 1993; 270: 83–90. 2 Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40-69 years old: longitudinal results from the Massachusetts male aging study. J Urol 2000; 163: 460–463. 3 Simonsen U, Garcia-Sacristan A, Prieto D. Penile arteries and erection. J Vasc Res 2002; 39: 283–303. 4 Tal R, Voelzke BB, Land S, Motarjem P, Munarriz R, Goldstein I et al. Vasculogenic erectile dysfunction in teenagers: a 5-year multi-institutional experience. BJU Int 2009; 103: 646–650. 5 Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J Am Coll Cardiol 2011; 58: 1378–1385. 6 Kamath S, Blann AD, Lip GY. Platelet activation: assessment and quantification. Eur Heart J 2001; 22: 1561–1571. 7 Yas¸ar AS, Bilen E, Yu¨ksel IO, Arslantas¸ U, Karakas¸ F, Kirbas¸ O et al. Association between admission mean platelet volume and coronary patency after thrombolytic therapy for acute myocardial infarction. Turk Kardiyol Dern Ars 2010; 38: 85–89. 8 Nadar S, Blann AD, Lip GY. Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipinebased antihypertensive therapy. Ann Med 2004; 36: 552–557. 9 Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract 2005; 59: 981–982. 10 Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 2010; 8: 148–156. 11 Mehta A, Miner M, Sigman M. Assessment of EndoPAT Scores in men with vasculogenic and non-vasculogenic erectile dysfunction. Int J Clin Pract 2013; 67: 46–51.
& 2014 Macmillan Publishers Limited
12 Vlachopoulos C, Ioakeimidis N, Terentes-Printzios D, Stefanadis C. The triad: erectile dysfunction—endothelial dysfunction—cardiovascular disease. Curr Pharm Des 2008; 14: 3700–3714. 13 Vlachopoulos C, Rokkas K, Ioakeimidis N, Stefanadis C. Inflammation, metabolic syndrome, erectile dysfunction, and coronary artery disease: common links. Eur Urol 2007; 52: 1590–1600. 14 Uslu N, Eren M, Gorgulu S, Alper AT, Orhan AL, Yildirim A et al. Left ventricular diastolic function and endothelial function in patients with erectile dysfunction. Am J Cardiol 2006; 97: 1785–1788. 15 Azadzoi KM, Master TA, Siroky MB. Effect of chronic ischemia on constitutive and inducible nitric oxide synthase expression in erectile tissue. J Androl 2004; 25: 382–388. 16 Solomon H, Man JW, Jackson G. Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator. Heart 2003; 89: 251–253. 17 Inman BA, Sauver JL, Jacobson DJ, McGree ME, Nehra A, Lieber MM et al. A population-based, longitudinal study of erectile dysfunction and future coronary artery disease. Mayo Clin Proc 2009; 84: 108–113. 18 Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol 2011; 165: 687–701. 19 Mittawae B, El-Nashaar AR, Fouda A, Magdy M, Shamloul R. Incidence of erectile dysfunction in 800 hypertensive patients: a multicenter Egyptian national study. Urology 2006; 67: 575–578. 20 Montorsi P, Montorsi F, Schulman CC. Is erectile dysfunction the ‘‘tip of the iceberg’’ of a systemic vascular disorder? Eur Urol 2003; 44: 352–354. 21 Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 2004; 103: 2096–2104. 22 Boos CJ, Balakrishnan B, Lip GY. The effects of coronary artery disease severity on time-dependent changes in platelet activation indices in stored whole blood. J Thromb Thrombolysis 2008; 25: 135–140. 23 Khandekar MM, Khurana AS, Deshmukh SD, Kakrani AL, Katdare AD, Inamdar AK. Platelet volume indices in patients with coronary artery disease and acute myocardial infarction: an Indian scenario. J Clin Pathol 2006; 59: 146–149. 24 Bozkurt Y, Soylemez H, Sancaktutar AA, Islamoglu Y, Kar A, Penbegul N et al. Relationship between mean platelet volume and varicocele: a preliminary study. Urology 2012; 79: 1048–1051. 25 Yang A, Pizzulli L, Luderitz B. Mean platelet volume as marker of restenosis after percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris. Thromb Res 2006; 117: 371–377. 26 Stokes KY, Granger DN. Platelets: A critical link between inflammationand microvascular dysfunction. J Physiol 2011; 590(Pt 5): 1023–1034.
International Journal of Impotence Research (2014), 1 – 3
ORIGINAL ARTICLE
Assessment of Mean Platelet Volume in men with vasculogenic and nonvasculogenic erectile dysfunction H Ciftci1, K Gumus¸1, ˙I Yagmur1, S Sahabettin2, H Çelik3, E Yeni1, M Savas1 and M Gulum1 Mean platelet (PLT) activation has an important role in the development of vascular diseases. In this study, we aimed to investigate the PLT volume in patients with vasculogenic and nonvasculogenic erectile dysfunction (ED) and compare it with the control group. Mean PLT volume (MPV) levels were measured in 50 patients with vasculogenic ED, in 30 patients who developed ED after radical prostatectomy (nonvasculogenic) and in 40 healthy controls. Ages were similar between the three groups. The diagnosis of ED was based on detailed sexual history, physical examination, laboratory assessment and color Doppler ultrasonography and is defined as the inability to attain or maintain a penile erection that is sufficient for successful vaginal intercourse. The results are given as mean±s.d. of the mean. The mean age of the patients with vasculogenic ED, of patients with ED after radical prostatectomy and of the control group were 53.70±12.39 (range 24–77), 54.60±11.40 (range 43–61) and 53.85±9.5 (range 30–73), respectively (P ¼ 0.853). The MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with ED after radical prostatectomy and in control groups: 7.49±1.4, 6.43±1.19 and 6.85±1.2 for MPV and 262.97±68, 251.77±78 and 252.89±82 for PLT values, respectively (P ¼ 0.033). The MPV and PLT values were not statistically significant in postprostatectomy ED patients and in control groups (P ¼ 0.663). There was no significant difference among the three groups in terms of white blood cells and hemoglobin levels. PLT count and mean PLT volume were detected to be increased in patients with vasculogenic ED. This finding may suggest a role for PLT volume in the pathogenesis of vasculogenic ED. International Journal of Impotence Research advance online publication, 29 May 2014; doi:10.1038/ijir.2014.17
INTRODUCTION Erectile dysfunction (ED) is defined as the consistent inability to obtain or maintain an erection for satisfactory sexual intercourse.1 ED affects all age groups, with increased prevalence associated with advanced age, diabetes, vascular disease, psychiatric disorders and several major surgeries.2 In the etiology of ED, generally organic and psychogenic factors come together. However, if the penis is considered a specialized vascular bed, it is well known that vascular reasons dominate in the etiology of ED.3 Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin. ED in patients who underwent a vascular evaluation for vascular pathology can be classified as having arteriogenic ED, venogenic ED or mixed vasculogenic ED.4 A 2011 meta-analysis of 12 prospective cohort studies provided strong evidence that ED is indeed significantly and independently associated with an increased risk for not only cardiovascular disease but also coronary heart disease, stroke and all-cause mortality.5 Clearly, ED is now regarded as a major health problem for the increasingly healthy aging population. The suggestion from scientific research that the pathogenesis of ED is predominately a disease of vascular origin led us to investigate the association between platelet (PLT) volume (Mean PLT volume (MPV)) and ED to elucidate the etiopathogenesis of ED. MPV is an indicator of PLT activation, which has an important role in the pathophysiology of thrombosis and is measured as a part of the complete blood count. Higher MPV may be observed in vascular pathologies and may increase the risk for cardiovascular disease. In addition, higher MPV is observed in patients with
diabetes mellitus,6 hypertension, hypercholesterolemia, smoking and obesity,7–10 suggesting a common mechanism by which these factors may increase the risk for cardiovascular disease and vasculogenic ED. In this study, we aimed to investigate the association between PLT volume and vasculogenic ED and postprostatectomy ED in patients and compare with a control group.
MATERIALS AND METHODS The study protocol was approved by the Institutional ethics committee School of Medicine, Harran University, Turkey, and all individuals who participated in the study gave their informed consent. MPV levels were measured in 50 patients with vasculogenic ED and in 30 patients with postprostatectomy ED and not having vascular disease as well as in 40 healthy male volunteers who were sexually active, married and agematched and who had an ED domain score X26 by ?International Index of Erectile Function short form who comprised the control group. The diagnosis of ED was based on detailed sexual history, physical examination, laboratory assessment and color Doppler ultrasonography and is defined as the inability to attain or maintain a penile erection sufficient for successful vaginal intercourse. The severity of ED is classified as mild to severe, according to the International Index of Erectile Function. None of the subjects were using antiPLT or anticoagulant drugs. Patients with neurogenic, endocrinological, or psychogenic ED, who had undergone pelvic surgery or pelvic trauma or had other vascular risk factors for ED, such as diabetes, smoking or hypertension, recently diagnosed coronary artery disease or hematological disorder, active infectious disease, malignancy, immunological disease or renal and hepatic failure, were excluded. The severity of ED was classified as mild to severe, according to the International Index of Erectile Function.
1 Department of Urology, Harran University Medical School, Sanliurfa, Turkey; 2Department of Clinical Biochemistry, Harran University, Sanliurfa, Turkey and 3Department of Physiology, Gaziantep University, Gaziantep, Turkey. Correspondence: Professor H Ciftci, Department of Urology, Harrran University Medical School, TR-63100 Sanliurfa, Turkey. E-mail: [email protected] Received 22 January 2013; revised 19 October 2013; accepted 9 April 2014
Assessment of Mean Platelet Volume H Ciftci et al
2 Blood samples were drawn from the antecubital vein between 08.00 and 10.00 a.m. after an overnight fast. Blood samples were collected in dipotassium EDTA-containing tubes. All measurements were taken immediately after venipuncture to prevent in vitro PLT activation. The MPV parameters were measured by using commercially available assay kits (Abbott) with an autoanalyzer (Aeroset, Abbott, Burlington, MA, USA). The other biochemical analyses were determined by standard methods. Total blood count, including hemoglobin, white blood cell (WBC), and PLTs, and MPV parameters were measured in both groups. Statistical analysis was performed with SPSS 13.0 for Windows version 13.0 (SPSS Inc., Chicago, IL, USA). Intergroup comparisons were performed using the Mann– Whitney U test, and the Kruskal–Wallis test was used to assess the relationship between categorical variables in patient groups. Po0.05 was used as a threshold for statistical significance. Data were presented as means±s.d.
RESULTS The results are given as mean±s.d. of the mean. The mean age of patients with vasculogenic ED, of patients with ED after radical prostatectomy and of the control group was 53.70±12.39 (range 24–77), 5460±11.40 (range 43–61) and 53.85±9.5 (range 30–73), respectively (P ¼ 0.853). The MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with ED after radical prostatectomy and in the control group: 7.49±1.4, 6.43±1.19 and 6.85±1.2 for MPV and 262.97±68, 251.77±78 and 252.89±82 for PLT values, respectively (P ¼ 0.033). The MPV and PLT values were not statistically significant in patients with postprostatectomy ED and in control groups (P ¼ 0.663). There was no significant difference among the three groups in terms of white blood cells (WBCs) and hemoglobin level. The findings are shown in Table 1. The MPV values were not statistically significant in patients with severe ED according to the International Index of Erectile Function compared with patients with mild ED (P40.05).
DISCUSSION Vascular disease is the underlying cause of ED in the majority of cases.11 The risk factors for ED—hypertension, smoking, abnormal lipid profile, sedentary lifestyle, obesity, metabolic syndromes and diabetes—are also risk factors for coronary artery disease. ED, in turn, is an independent predictor of future cardiovascular events.12 Endothelial dysfunction has an integral role in cardiovascular and peripheral vascular disease because of the systemic and subclinical inflammatory response that is characteristic of atherosclerosis.13 Damage to the endothelium by cardiovascular risk factors affects not only the coronary arteries but also arteries throughout the body, including those of corpora cavernosa of the Table 1. Study parameters in vasculogenic erectile dysfunction patients, postprostatectomy erectile dysfunction patients and in healthy controls
Age IIEF MPV (fL) WBC Hgb (g/d/L) PLT (k/ul)
Vasculogenic (ED, no ¼ 50)
Postprostatectomy (ED, no ¼ 30)
Healthy control, (no ¼ 40)
P
53.70±12.39 12.8±04 7.49±1,4 6.59±1.12 14.21±1,15 262.97±68
54.60±11.40 11.2±12 6.43±1.19 6.70±1.20 13.40±1.33 251.77±78
53.85±9.5 27.51±1,6 6.85± 1.2 6.96±1.88 14.34±1.49 252.89±82
ns s s ns ns s
Abbreviations: ED, erectile dysfunction; Hgb, hemoglobin; IIEF, International Index of Erectile Function; MPV, mean platelet volume; ns, statistically nonsignificant; PLT, platelet; s, statistically significant; WBC, white blood cells. Values are presented as mean±s.d. S, Po0.05; t-test for independent samples.
International Journal of Impotence Research (2014), 1 – 3
penis.14 In fact, the vascular endothelium is not only a simple barrier but also a true organ that synthesizes and releases substances, and it acts in a paracrine and endocrine manner on vascular tone and PLT aggregation.15 The erectile response of the penis depends on the balance between vasoconstrictors and vasodilatory agents that affect contraction and relaxation of cavernosal smooth-muscle agents and thus regulate blood inflow and erection.16 Inman et al.17 suggested that ED shares the same risk factors as coronary artery disease, with endothelial dysfunction being an important underlying pathological change in both diseases. Other potential mechanisms involved in the development of endothelial dysfunction that can lead to ED and coronary artery disease include a dysfunctional L-arginine nitric oxide pathway, increased peripheral sympathetic activity, vascular structural alterations leading to decreased vascular dilatation capacity and increased specific inflammatory mediators.18,19 Montorsi et al.20 suggested that this phenomenon might be related to the caliber of the blood vessels. Whereas the penile artery has a diameter of 1–2 mm, the proximal left anterior descending coronary artery has a diameter of 3–4 mm. Thus, an equally sized atherosclerotic plaque developing in the smaller penile arteries would more likely compromise flow, presenting itself as an ED complaint much earlier than if the same amount of plaque had developed in the larger coronary artery, causing angina. The effect of increased PLT activity on vascular disorders has been noted in several studies.21 PLTs have a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation or apposition after plaque rupture. The MPV is a marker of PLT function, and large PLTs contain more dense granules and produce more thromboxane A2.10 In several studies, increased MPV has been noted with cardiovascular risk factors, such as smoking, diabetes, obesity, hypertension and hyperlipidemia.10 In subjects with established cardiovascular disease, elevated MPV may be a marker for adverse cardiovascular events. However, most studies found no significant association between increased PLT count and incidence of acute myocardial infarction, restenosis or long-term mortality.22,23 The study by Bozkur et al.24 found that the increase in MPV is independent of the disease and that the increase in varicocele grade is associated with higher MPV in varicocele patients. In light of this result, it is reported that the etiopathogenesis of varicocele may be associated with PLT activation and/or vascular endothelial cell injury. In our study, we found that the MPV and PLT values were significantly higher in patients with vasculogenic ED than in patients with postprostatectomy ED and in controls. Several studies have reported that increases in PLT volume are often associated with decreases in PLT count,25 perhaps as a result of small PLTs being consumed in order to maintain a constant PLT functional mass. Conversely, we have found that the PLT count and PLT volume both increase in vasculogenic ED patients compared with postprostatectomy ED patients and the control group. Similar to our study, in one study they found that PLT count and PLT volume both increase during stimulated thrombopoiesis, indicating that PLT count and volume may be regulated by independent mechanisms. They report that the relationship between MPV and PLT count is not completely understood.10 However, increased MPV levels are usually considered a vascular risk factor. In a recent study Stokes and Granger. reported the involvement of PLT activation along with leukocytes and vascular endothelial cells in vascular and microvascular dysfunction.26 In light of this information and as a result of our study, the etiopathogenesis of vasculogenic ED may be associated with PLT activation and/or vascular endothelial cell injury. We concluded that patients with vasculogenic ED have higher MPV values, indicating a tendency for PLT aggregation regardless of the etiology, when compared with postprostatectomy ED patients and controls. On the basis of the importance of the vascular component (endothelial dysfunction) in the pathophysiology of & 2014 Macmillan Publishers Limited
Assessment of Mean Platelet Volume H Ciftci et al
3 ED, this finding suggests a role for PLTs in the pathogenesis of vascular complications. However, further large-scale studies are required to clarify whether patients with vasculogenic ED having high MPV values are at greater risk for thromboembolism and may benefit from antiPLT therapy. CONFLICT OF INTEREST The authors declare no conflict of interest.
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