- Email: [email protected]
Lack of depression effect on platelet activation in patients with heart failure
Psychiatry Research 129 (2004) 289 – 292 www.elsevier.com/locate/psychres
Brief report
Lack of depression effect on platelet activation in patients with heart failure Jagoda Pasica,*, Mark D. Sullivanb, Joan Russoa, Wayne L. Chandlerc, Wayne C. Levyd a
Department of Psychiatry and Behavioral Sciences, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Box 350896, Seattle, WA 98104-2499, USA b Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA c Department of Laboratory Medicine, University of Washington, Seattle, WA, USA d Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA, USA Received 10 April 2003; received in revised form 7 September 2004; accepted 21 September 2004
Abstract P-selectin is a marker of platelet activation. Previous studies have reported elevated P-selectin in patients with congestive heart failure (CHF) and depression as separate disorders. We examined if comorbid depression had an effect on platelet activation in CHF patients. Soluble (s)P-selectin was measured in 108 CHF patients; 24 with comorbid depression. There were no significant differences in age, cardiac parameters or (s)P-selectin levels between CHF-only patients and patients with comorbid depression. Our data show no group differences in P-selectin values, which suggests that comorbid depression has no additive effect on platelet activation in CHF patient. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: P-selectin; Endothelial processes; Atherosclerosis; Cytokines
1. Introduction Recently, it has been shown that depression is associated with a two-fold higher risk of developing congestive heart failure (CHF) among community elderly (Williams et al., 2002) and that hospitalized CHF patients with depression had twice the 12-month
* Corresponding author. Tel.: +1 206 731 2377; fax: +1 206 731 8615. E-mail address: [email protected] (J. Pasic).
mortality rates compared with non-depressed CHF patients (Jiang et al., 2001). The mechanism of underlying comorbid depression and heart disease is unknown. One hypothesis is that this is due to the disturbance in platelet activation. Platelet activation has been shown to be important in acute coronary syndromes (Blann et al., 1997; Parker et al., 2001), and there is now evidence suggesting that platelet activity is heightened in patients with CHF (Davis et al., 2000; O’Connor et al., 1999; Weikert et al., 2002). P-selectin (CD62P, GMP-140, PADGEM) is an adhesion molecule stored in the alpha granules of
0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.09.008
290
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
platelets. Upon platelet activation, P-selectin is translocated to the cell surface where it mediates the interaction with leukocytes and the adhesion of leukocytes to endothelial cells. The expression of Pselectin on the platelet surface has been used as a marker for platelet activation (Gurney et al., 2002). Elevated P-selectin levels have been found in patients with severe CHF, suggesting persistent platelet activation (O’Connor et al., 1999). Recent studies have demonstrated elevated plasma levels (Piletz et al., 2002) and increased expression (Walsh et al., 2002) of P-selectin in patients with major depression. However, there are no reports of using P-selectin to assess platelet activation in CHF patients and comorbid depression. The objective of this study is to examine if comorbid major depression or dysthymia had an effect on platelet activation in CHF patients.
2. Methods We studied 108 CHF patients with New York Heart Association (NYHA) functional classes II–IV and ejection fraction (EF) below 40% who were referred for cardiac transplantation. A written informed consent was obtained from all recruited patients. Twentyfour patients (22%) had comorbid major depression or dysthymic disorder, which was diagnosed by the PRIME-MD interview. Depression status was used to divide the patients into a CHF-only group and a CHF plus depression group. The Hamilton Depression Rating scale (HAM-D) was used to assess severity of depression symptoms. Blood samples were obtained for detection of plasma soluble (s)P-selectin by an enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Minneapolis, MN). After centrifugation of the whole blood–citrate mixture at +4 8C at 1800g for 15 min, the samples were stored at 70 8C until assay. A previous study by Gibbs et al. (2001) reported median (s)P-selectin values for CHF patients (43 ng/mL, range 33–60) and control subjects (33 ng/mL, range 29–39). The patients’ cardiac status was established by a heart failure cardiologist using the NYHA classification (classes II–IV), EF and 6-min walk test in all subjects, and a clinically performed Cardiopulmonary Exercise Test (CPET) peak oxygen consumption (n=72). Statistical analyses were done using t-tests,
chi-square tests, Fisher’s exact tests and partial Pearson correlations, controlling for age, gender and relevant medications.
3. Results Table 1 presents characteristics by patient groups. The two patient groups were similar in age, gender and years of education. Although there appeared to be a gender difference (16% vs. 33% women) between groups, the two-sided Fisher’s exact test was not significant ( P=0.77). The groups did not differ significantly in cardiac severity measured by NYHA class, EF or maximal oxygen consumption on the CPET test. Patients with CHF and depression walked for a significantly shorter time on a 6-min walk test than did the CHF-only patients. There was no significant difference between (s)P-selectin levels in CHF-only and CHF plus depression patients. HAM-D scores clearly separated the groups, with significantly higher HAM-D scores in CHF and depression than CHF-only groups. There were no significant correlations of (s)Pselectin with the demographic or cardiac variables. There were no significant correlations between Pselectin and HAM-D scores (r=0.10, P=0.65). Pselectin correlated with increased weight (r=0.22, Pb0.05), quantity of smoking (r=0.22, Pb0.01) and treatment with h-blockers (r=0.27, Pb0.05). All correlations were controlled for age, gender and relevant
Table 1 Patient characteristics and variables Variable (meanFS.D.)
CHF-only, n=84
CHF plus depression, n=24
t-test, P-value
Age (years) Gender (% women) Education (years) NYHA class EF% CPET O2-peak (ml/kg/min) 6-min walk test (m) HAM-D score (s)P-selectin (ng/ml)
53.7F1.1 16 14.7F0.4 2.7F0.7 30.0F1.0 17.2F0.6 (n=57) 1265F31 7.2F0.6 57.4F2.7
50.1F2.4 33 14.7F0.5 3.0F0.2 26.2F1.6 15.0F1.1 (n=15) 959F88 24.0F2.2 56.1F5.5
0.14 0.77a 0.98 0.09 0.71 0.08
a
Fisher’s exact test. *** Highly significant.
0.0001*** 0.0001*** 0.82
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
medications [aspirin, angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers]. There were no significant relationships of Pselectin and HAM-D scores in patients with (r=0.16) and without (r= 0.05) antidepressants, although the relationship seemed stronger in those receiving antidepressants.
4. Discussion This study reports cross-sectional comparison of (s)P-selectin levels in patients with CHF-only compared with patients with CHF plus major depression or dysthymia. Our data show no group differences in P-selectin values between patients with CHF-only compared with CHF and comorbid depression, suggesting that comorbid depression produced no additional platelet activation in CHF patients. Other studies have shown elevated levels of Pselectin in CHF (O’Connor et al., 1999) and depression (Piletz et al., 2002) as separate conditions. This is the first study addressing the platelet activation via Pselectin in CHF patients and comorbid depression. Our results do not support P-selectin as a useful marker in differentiating the effect of depression on platelet activation in comorbid heart failure patients. Another recent study challenges the diagnostic utility of platelet parameters as tools for the identification of platelet abnormalities for predicting clinical outcomes, or for monitoring antiplatelet strategies in heart failure patients. The study by Serebruany et al. (2002) reports that patients with heart failure who were enrolled in the EPCOT trial (Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure) exhibited substantial variability of platelet markers, including P-selectin. Their findings failed to demonstrate correlations of major clinical characteristics of heart failure, such as NYHA class, EF or etiology of CHF, with the platelet characteristics they investigated. The apparent lack of a depression effect on (s)Pselectin in CHF patients in this study could be due to the lack of correlation between platelet parameters and heart failure in conjunction with depression. One explanation is that (s)P-selectin in CHF and comorbid depression is involved in a dynamic vascular/endothelial process of atherogenesis, which happens through a
291
shear-induced platelet aggregation, the mediation of rolling of platelets on activated endothelial cells, and the interaction of platelets with neutrophils/monocytes and immunomodulation via cytokines. The magnitude of platelet activation may not have been captured by the measurement of P-selectin, due to its quick recruitment in the above processes. Another reason depression did not have the additional effect on P-selectin in CHF could be that either Pselectin expression itself or the platelet activation represents downstream effects of other, more primary abnormalities. The putative signaling and regulatory molecular processes that integrate multiple chemical/ neuronal/hormonal networks may be responsible for the dysfunction on many molecular levels; hence it is difficult to demonstrate an additive effect on P-selectin or platelet activation. Availability of age and gendercontrolled (s)P-selectin data from depressed individuals without heart disease using the same technique could help address this question. Correlations between P-selectin and increased weight, quantity of smoking and treatment with hblockers were the positive findings in this study. Increased weight is probably due to obesity and insulin resistance and not to volume excess, since the jugular venous pressure was low in most patients. One might speculate that P-selectin may be valuable in demonstrating the progression of CHF and/or in conjunction with depression. Cigarette smoking can damage the endothelium (Blann and McCollum, 1993) and platelets (Blache et al., 1992), which also suggests that P-selectin could be useful in monitoring endothelial-vascular processes. Some studies suggested an independent association between P-selectin and smoking (Demerath et al., 2001), and others showed no effect of acute smoking on platelet activation and adhesion molecules (Blann et al., 1998). An association of P-selectin and treatment with h-blockers may be explained by several hypotheses, including an indirect measure of disease progression, platelet activation and vascular effects of h-blockers. It has been reported that treatment with ACE inhibitors improved the prothrombotic state in CHF and that h-blockers were associated with elevated platelet counts (Gibbs et al., 2001) and enhanced platelet aggregation (Knight et al., 1997). Increased P-selectin is considered to be an indicator of current atherosclerosis, and a potential marker
292
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
of disease progression (Blake and Ridker, 2001). In this study, we report cross-sectional results on the effect of depression on P-selectin. Our main finding is that comorbid depression has no additive effect on platelet activation in CHF patients. Further analyses of longitudinal data might shed light on the value of Pselectin as a marker of disease progression and the effect of depression in CHF patients. Further studies are needed to determine if P-selectin can be used as a marker of the more complex interactions between endothelial-vascular-inflammatory processes in the pathogenesis of heart failure and whether these are pertinent to comorbid depression. Alternatively, the diagnostic utility of P-selectin as a marker of platelet activation and its clinical usefulness in heart failure patients with and without comorbid depression may be of limited value.
Acknowledgments This study was supported by the National Alliance for Research on Schizophrenia and Depression, the American Heart Association and the Charles A. Dana Foundation. Findings were presented in part at the XII World Congress of Psychiatry, Yokohama, Japan, August 24–29, 2002.
References Blache, D., Bouthillier, D., Davignon, J., 1992. Acute influence of smoking on platelet behavior, endothelium and plasma lipids and normalization by aspirin. Atherosclerosis 93, 179 – 188. Blake, G.J., Ridker, P.M., 2001. Novel clinical markers of vascular wall inflammation. Circulation Research 89, 763 – 771. Blann, A.D., McCollum, C.N., 1993. Adverse influence of cigarette smoking on the endothelium. Thrombosis and Haemostasis 70, 707 – 711. Blann, A.D., Faragher, E.B., McCollum, C.N., 1997. Increased soluble P-selectin following myocardial infarction: a new marker of the progression of atherosclerosis. Blood Coagulation and Fibrinolysis 8, 383 – 390. Blann, A.D., Kirkpatrick, U., Devine, C., Naser, S., McCollum, C.N., 1998. The influence of acute smoking on leucocytes, platelets and the endothelium. Atherosclerosis 141, 133 – 139. Davis, C.J., Gurbel, P.A., Gattis, W.A., Fuzaylov, S.Y., Nair, G.V., O’Connor, C.M., Serebruany, V.L., 2000. Hemostatic abnormalities in patients with congestive heart failure: diagnostic
significance and clinical challenge. International Journal of Cardiology 75, 15 – 21. Demerath, E., Towne, B., Blangero, J., Siervogel, R.M., 2001. The relationship of soluble ICAM-1, VCAM-1, P-selectin and Eselectin to cardiovascular disease risk factors in healthy men and women. Annals of Human Biology 28, 664 – 678. Gibbs, C.R., Blann, A.D., Watson, R.D.S., Lip, G.Y.H., 2001. Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm. Circulation 103, 1746 – 1751. Gurney, D., Lip, G.Y.H., Blann, A.D., 2002. A reliable plasma marker of platelet activation. American Journal of Hematology 70, 139 – 144. Jiang, J.W, Alexander, J., Christopher, E., Kuchibhatla, M., Gaulden, L.H., Cuffe, M.S., Blazing, M.A., Davenport, C., Califf, R.M., Krishnan, R.R., O’Connor, C.M., 2001. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure. Archives of Internal Medicine 161, 1849 – 1856. Knight, C.J., Panesar, M., Wilson, D.J., Chronos, N.A.F., Patel, D., Fox, K., Goodall, A.H., 1997. Different effects of calcium antagonists, nitrates, and beta-blockers on platelet function. Possible importance for the treatment of unstable angina. Circulation 95, 125 – 132. O’Connor, C.M., Gurbel, P.A., Serebruany, V., 1999. Usefulness of soluble and surface-bound P-selectin in detecting heightened platelet activity in patients with congestive heart failure. American Journal of Cardiology 83, 1345 – 1349. Parker III, C., Vita, J.A., Freedman, J.E., 2001. Soluble adhesion molecules and unstable coronary artery disease. Atherosclerosis 156, 417 – 424. Piletz, J.E., Zhu, H., Madakasira, S., Pazzaglia, P., Lindsay DeVane, C., Goldman, N., Halaris, A., 2002. Elevated P-selectin on platelets in depression: response to bupropion. Journal of Psychiatric Research 34, 397 – 404. Serebruany, V.L., McKenzie, M.E., Meister, A.F., Fuzaylov, S.Y., Gurbel, P.A., Atar, D., Gattis, W.A., O’Connor, C.M., 2002. Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the hemodyneR hemostatic analyzer. Pathophysiology of Haemostasis and Thrombosis 32, 8 – 15. Walsh, M.T., Dinan, T.G., Condren, R.M., Ryan, M., Kenny, D., 2002. Depression is associated with an increase in the expression of the platelet adhesion receptor glycoprotein Ib. Life Sciences 70, 3155 – 3165. Weikert, U., Kuhl, U., Schultheiss, H.P., Rauch, U., 2002. Platelet activation is increased in patients with cardiomyopathy: myocardial inflammation and platelet reactivity. Platelets 13, 487 – 491. Williams, S.A., Kasl, S.V., Heiat, A., Abramson, J.L., Krumholz, H.M., Vaccarino, V., 2002. Depression and risk of heart failure among the elderly: a prospective community-based study. Psychosomatic Medicine 64, 6 – 12.
Brief report
Lack of depression effect on platelet activation in patients with heart failure Jagoda Pasica,*, Mark D. Sullivanb, Joan Russoa, Wayne L. Chandlerc, Wayne C. Levyd a
Department of Psychiatry and Behavioral Sciences, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Box 350896, Seattle, WA 98104-2499, USA b Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA c Department of Laboratory Medicine, University of Washington, Seattle, WA, USA d Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA, USA Received 10 April 2003; received in revised form 7 September 2004; accepted 21 September 2004
Abstract P-selectin is a marker of platelet activation. Previous studies have reported elevated P-selectin in patients with congestive heart failure (CHF) and depression as separate disorders. We examined if comorbid depression had an effect on platelet activation in CHF patients. Soluble (s)P-selectin was measured in 108 CHF patients; 24 with comorbid depression. There were no significant differences in age, cardiac parameters or (s)P-selectin levels between CHF-only patients and patients with comorbid depression. Our data show no group differences in P-selectin values, which suggests that comorbid depression has no additive effect on platelet activation in CHF patient. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: P-selectin; Endothelial processes; Atherosclerosis; Cytokines
1. Introduction Recently, it has been shown that depression is associated with a two-fold higher risk of developing congestive heart failure (CHF) among community elderly (Williams et al., 2002) and that hospitalized CHF patients with depression had twice the 12-month
* Corresponding author. Tel.: +1 206 731 2377; fax: +1 206 731 8615. E-mail address: [email protected] (J. Pasic).
mortality rates compared with non-depressed CHF patients (Jiang et al., 2001). The mechanism of underlying comorbid depression and heart disease is unknown. One hypothesis is that this is due to the disturbance in platelet activation. Platelet activation has been shown to be important in acute coronary syndromes (Blann et al., 1997; Parker et al., 2001), and there is now evidence suggesting that platelet activity is heightened in patients with CHF (Davis et al., 2000; O’Connor et al., 1999; Weikert et al., 2002). P-selectin (CD62P, GMP-140, PADGEM) is an adhesion molecule stored in the alpha granules of
0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.09.008
290
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
platelets. Upon platelet activation, P-selectin is translocated to the cell surface where it mediates the interaction with leukocytes and the adhesion of leukocytes to endothelial cells. The expression of Pselectin on the platelet surface has been used as a marker for platelet activation (Gurney et al., 2002). Elevated P-selectin levels have been found in patients with severe CHF, suggesting persistent platelet activation (O’Connor et al., 1999). Recent studies have demonstrated elevated plasma levels (Piletz et al., 2002) and increased expression (Walsh et al., 2002) of P-selectin in patients with major depression. However, there are no reports of using P-selectin to assess platelet activation in CHF patients and comorbid depression. The objective of this study is to examine if comorbid major depression or dysthymia had an effect on platelet activation in CHF patients.
2. Methods We studied 108 CHF patients with New York Heart Association (NYHA) functional classes II–IV and ejection fraction (EF) below 40% who were referred for cardiac transplantation. A written informed consent was obtained from all recruited patients. Twentyfour patients (22%) had comorbid major depression or dysthymic disorder, which was diagnosed by the PRIME-MD interview. Depression status was used to divide the patients into a CHF-only group and a CHF plus depression group. The Hamilton Depression Rating scale (HAM-D) was used to assess severity of depression symptoms. Blood samples were obtained for detection of plasma soluble (s)P-selectin by an enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Minneapolis, MN). After centrifugation of the whole blood–citrate mixture at +4 8C at 1800g for 15 min, the samples were stored at 70 8C until assay. A previous study by Gibbs et al. (2001) reported median (s)P-selectin values for CHF patients (43 ng/mL, range 33–60) and control subjects (33 ng/mL, range 29–39). The patients’ cardiac status was established by a heart failure cardiologist using the NYHA classification (classes II–IV), EF and 6-min walk test in all subjects, and a clinically performed Cardiopulmonary Exercise Test (CPET) peak oxygen consumption (n=72). Statistical analyses were done using t-tests,
chi-square tests, Fisher’s exact tests and partial Pearson correlations, controlling for age, gender and relevant medications.
3. Results Table 1 presents characteristics by patient groups. The two patient groups were similar in age, gender and years of education. Although there appeared to be a gender difference (16% vs. 33% women) between groups, the two-sided Fisher’s exact test was not significant ( P=0.77). The groups did not differ significantly in cardiac severity measured by NYHA class, EF or maximal oxygen consumption on the CPET test. Patients with CHF and depression walked for a significantly shorter time on a 6-min walk test than did the CHF-only patients. There was no significant difference between (s)P-selectin levels in CHF-only and CHF plus depression patients. HAM-D scores clearly separated the groups, with significantly higher HAM-D scores in CHF and depression than CHF-only groups. There were no significant correlations of (s)Pselectin with the demographic or cardiac variables. There were no significant correlations between Pselectin and HAM-D scores (r=0.10, P=0.65). Pselectin correlated with increased weight (r=0.22, Pb0.05), quantity of smoking (r=0.22, Pb0.01) and treatment with h-blockers (r=0.27, Pb0.05). All correlations were controlled for age, gender and relevant
Table 1 Patient characteristics and variables Variable (meanFS.D.)
CHF-only, n=84
CHF plus depression, n=24
t-test, P-value
Age (years) Gender (% women) Education (years) NYHA class EF% CPET O2-peak (ml/kg/min) 6-min walk test (m) HAM-D score (s)P-selectin (ng/ml)
53.7F1.1 16 14.7F0.4 2.7F0.7 30.0F1.0 17.2F0.6 (n=57) 1265F31 7.2F0.6 57.4F2.7
50.1F2.4 33 14.7F0.5 3.0F0.2 26.2F1.6 15.0F1.1 (n=15) 959F88 24.0F2.2 56.1F5.5
0.14 0.77a 0.98 0.09 0.71 0.08
a
Fisher’s exact test. *** Highly significant.
0.0001*** 0.0001*** 0.82
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
medications [aspirin, angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers]. There were no significant relationships of Pselectin and HAM-D scores in patients with (r=0.16) and without (r= 0.05) antidepressants, although the relationship seemed stronger in those receiving antidepressants.
4. Discussion This study reports cross-sectional comparison of (s)P-selectin levels in patients with CHF-only compared with patients with CHF plus major depression or dysthymia. Our data show no group differences in P-selectin values between patients with CHF-only compared with CHF and comorbid depression, suggesting that comorbid depression produced no additional platelet activation in CHF patients. Other studies have shown elevated levels of Pselectin in CHF (O’Connor et al., 1999) and depression (Piletz et al., 2002) as separate conditions. This is the first study addressing the platelet activation via Pselectin in CHF patients and comorbid depression. Our results do not support P-selectin as a useful marker in differentiating the effect of depression on platelet activation in comorbid heart failure patients. Another recent study challenges the diagnostic utility of platelet parameters as tools for the identification of platelet abnormalities for predicting clinical outcomes, or for monitoring antiplatelet strategies in heart failure patients. The study by Serebruany et al. (2002) reports that patients with heart failure who were enrolled in the EPCOT trial (Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure) exhibited substantial variability of platelet markers, including P-selectin. Their findings failed to demonstrate correlations of major clinical characteristics of heart failure, such as NYHA class, EF or etiology of CHF, with the platelet characteristics they investigated. The apparent lack of a depression effect on (s)Pselectin in CHF patients in this study could be due to the lack of correlation between platelet parameters and heart failure in conjunction with depression. One explanation is that (s)P-selectin in CHF and comorbid depression is involved in a dynamic vascular/endothelial process of atherogenesis, which happens through a
291
shear-induced platelet aggregation, the mediation of rolling of platelets on activated endothelial cells, and the interaction of platelets with neutrophils/monocytes and immunomodulation via cytokines. The magnitude of platelet activation may not have been captured by the measurement of P-selectin, due to its quick recruitment in the above processes. Another reason depression did not have the additional effect on P-selectin in CHF could be that either Pselectin expression itself or the platelet activation represents downstream effects of other, more primary abnormalities. The putative signaling and regulatory molecular processes that integrate multiple chemical/ neuronal/hormonal networks may be responsible for the dysfunction on many molecular levels; hence it is difficult to demonstrate an additive effect on P-selectin or platelet activation. Availability of age and gendercontrolled (s)P-selectin data from depressed individuals without heart disease using the same technique could help address this question. Correlations between P-selectin and increased weight, quantity of smoking and treatment with hblockers were the positive findings in this study. Increased weight is probably due to obesity and insulin resistance and not to volume excess, since the jugular venous pressure was low in most patients. One might speculate that P-selectin may be valuable in demonstrating the progression of CHF and/or in conjunction with depression. Cigarette smoking can damage the endothelium (Blann and McCollum, 1993) and platelets (Blache et al., 1992), which also suggests that P-selectin could be useful in monitoring endothelial-vascular processes. Some studies suggested an independent association between P-selectin and smoking (Demerath et al., 2001), and others showed no effect of acute smoking on platelet activation and adhesion molecules (Blann et al., 1998). An association of P-selectin and treatment with h-blockers may be explained by several hypotheses, including an indirect measure of disease progression, platelet activation and vascular effects of h-blockers. It has been reported that treatment with ACE inhibitors improved the prothrombotic state in CHF and that h-blockers were associated with elevated platelet counts (Gibbs et al., 2001) and enhanced platelet aggregation (Knight et al., 1997). Increased P-selectin is considered to be an indicator of current atherosclerosis, and a potential marker
292
J. Pasic et al. / Psychiatry Research 129 (2004) 289–292
of disease progression (Blake and Ridker, 2001). In this study, we report cross-sectional results on the effect of depression on P-selectin. Our main finding is that comorbid depression has no additive effect on platelet activation in CHF patients. Further analyses of longitudinal data might shed light on the value of Pselectin as a marker of disease progression and the effect of depression in CHF patients. Further studies are needed to determine if P-selectin can be used as a marker of the more complex interactions between endothelial-vascular-inflammatory processes in the pathogenesis of heart failure and whether these are pertinent to comorbid depression. Alternatively, the diagnostic utility of P-selectin as a marker of platelet activation and its clinical usefulness in heart failure patients with and without comorbid depression may be of limited value.
Acknowledgments This study was supported by the National Alliance for Research on Schizophrenia and Depression, the American Heart Association and the Charles A. Dana Foundation. Findings were presented in part at the XII World Congress of Psychiatry, Yokohama, Japan, August 24–29, 2002.
References Blache, D., Bouthillier, D., Davignon, J., 1992. Acute influence of smoking on platelet behavior, endothelium and plasma lipids and normalization by aspirin. Atherosclerosis 93, 179 – 188. Blake, G.J., Ridker, P.M., 2001. Novel clinical markers of vascular wall inflammation. Circulation Research 89, 763 – 771. Blann, A.D., McCollum, C.N., 1993. Adverse influence of cigarette smoking on the endothelium. Thrombosis and Haemostasis 70, 707 – 711. Blann, A.D., Faragher, E.B., McCollum, C.N., 1997. Increased soluble P-selectin following myocardial infarction: a new marker of the progression of atherosclerosis. Blood Coagulation and Fibrinolysis 8, 383 – 390. Blann, A.D., Kirkpatrick, U., Devine, C., Naser, S., McCollum, C.N., 1998. The influence of acute smoking on leucocytes, platelets and the endothelium. Atherosclerosis 141, 133 – 139. Davis, C.J., Gurbel, P.A., Gattis, W.A., Fuzaylov, S.Y., Nair, G.V., O’Connor, C.M., Serebruany, V.L., 2000. Hemostatic abnormalities in patients with congestive heart failure: diagnostic
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