Role of inflammatory and sympathetic activation in anxiety and depression interaction with myocardial infarction
Authors:
Company:
1- Research Institute for Complex Issues of Cardiovascular Diseases Siberian Branch of the Russian Academy of
Medical Sciences;
2Kemerovo State Medical Academy of Ministry of Health of the Russian Federation
For citation: Lebedeva NB, Barbarash OL. Role of inflammatory and sympathetic activation in anxiety and depression interaction with myocardial infarction. Kreativnaya kardiologiya. 2013; 2: 27-34 (in Russian)
Keywords: depression myocardial infarction autonomic imbalance inflammation
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Objective. To examine the relationships of subclinical inflammation biomarkers, autonomic imbalance and anxiety and depressive syndromes in patients with myocardial infarction (MI).
Material and Methods. 106 patients with ST-segment elevation MI, mean age 61.4±1.6 years, were enrolled. At days 5–7 the heart rate variability was assessed, plasma inflammatory biomarker concentrations (interleukins IL-1β, IL-6, IL-8, IL-10, interferon γ (INFγ), tumor necrosis factor alpha (TNFγ)) were measured by ELISA and psychometric testing using the Zung Self-Rating Depression scales, State-Trait Anxiety Inventory (Spielberger-Hanin) was done. The data were analyzed using the Statistica 6.0 software package (StatSoft).
Results. Patients with depression and increased levels of state and trait anxiety had significantly higher CRP and INFγ plasma concentrations as compared to those without depression or anxiety symptoms. Depression was associated with significantly higher concentrations of inflammatory cytokines IL-1β (72.2±1.3 pg/ml vs 49.5±7.7 in patients without depression, p=0.08), IL-8 (104.5±4.4 pg/ml vs 43.8±1.2, respectively, p=0.009) and reduced anti-inflammatory IL-10 (1.0±0.2 pg/ml vs 2.1±0.4; p=0.01), as well as with the sympathetic nervous system activation, as assessed with the SDNN. In the group of patients with myocardial infarction, who had a marked increase in the sympathetic nervous system activity (SDNN less 70 ms), the levels of IL-1β, IL-8, TNFα and INFγ were significantly higher as compared to those in patients with the normal SDNN values. Indeed, IL-1β levels were 164.5 (152, 174) and 108 (96, 110), respectively, IL-6 levels: 4.48 (2.2, 6.3) and 3.44 (2.4, 4.9) IL-8: 81.3 (76, 92) and 41 (28, 51); TNFFα levels: 37.4 (28.6, 44.4) and 2.63 (1.9, 4.3); INFγ 94.9 (91, 101.2) and 21.6 (18.3, 23), p<0.001 in all cases. The resulting differences did not depend on the severity of myocardial infarction.
Conclusion. The presence of myocardial infarction in patients with sub-acute symptoms of depression and increased anxiety is associated with more severe inflammatory and sympathetic activation, which may explain a well-known adverse prognostic role of anxiety and depression syndrome in MI.
1. Carney R.M. Depression and late mortality after myocardial infarction in the enhancing recovery in coronary heart disease
(ENRICHD) study. Psychosom. Med. 2004; 66: 466–74.
2. Frasure-Smith N., Lesperance F. Reflections on depression as a cardiac risk factors. Psychosom. Med. 2005; 67: 19–25.
3. Carney R.M., Freedland K.E. Depression in patients with coronary heart disease. Am. J. Med. 2008; 121: 20–7.
4. Hermann N., Sing-Manoux A., Shipley M. Do psychological factors affect inflammation and incident coronary heart disease.
Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1398.
5. Biasucci L.M. CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public
health practice: clinical use of inflammatory markers in patients with cardiovascular diseases: a background paper. Circulation. 2004;
110: 560–7.
6. Carney R.M., Freedland K.E., Veith R.C. Depression, the autonomic nervous system and coronary heart disease. Psychosom. Med.
2005; 67 (1): 29–33.
7. Chiappelli M., Tampieri C., Tumini T. et al. Interleukin-6 gene polymorphism in age-dependent risk factor for myocardial infarction
in men. Int. J. Immunogenet. 2005; 32: 349–53.
8. Shimbo K.W., Davidson D.C., Haas V. et al. Negative impact of depression on outcomes in patients with coronary artery disease:
mechanisms, treatment considerations, and future directions. Thromb. Haemost. 2005; 3: 897–908.
9. Guinjoan S.M., De Guevara M.S., Correa C. et al. Cardiac parasympathetic dysfunction related to depression in older adults with
acute coronary syndromes. J. Psychosom. Res. 2004; 56: 83–8.
10. La Rovere M.T., Pinna G.D., Maestri R. et al. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart
failure patients. Circulation. 2003; 107: 565–70
11. Empana J., Sykes D., Luc M. Contributions of depressive mood and circulation inflammatory markers to coronary heart disease in
healthy European men. Circulation. 2005; 111: 2299–305.
12. Loppnow H., Libby P. Proliferating or interleukin-1 activated human vascular smooth muscle cells secrete copious interleukin-6.
J. Clin. Invest. 1990; 85: 731–8.
13. Howren M.B., Lamkin D.M., Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom.
Med. 2009; 71: 171–86.
14. Hansson G.K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 2005; 352: 1685–96.
15. Otake H., Shite J., Shinke T. et al. Relation between plasma adiponectin, high-sensitivity C-reactive protein, and coronary plaque
components in patients with acute coronary syndrome. Am. J. Cardiol. 2008; 101: 1–7.
16. Stewart J.C., Janicki-Deverts D., Muldoon M.F. Depressive symptoms moderate the influence of hostility on serum interleukin-6 and
C-reactive protein. Psychosom. Med. 2008; 70: 197–204.
17. Panagiotakos A.B., Pitsavos C., Chrysohoou C. et al. Inflammation, coagulation, and depressive symptomatology in cardiovascular
disease-free people; the ATTICA study. Eur. Heart J. 2004. 25: 492–9.
18. Li J.J., Guo Y.L., Yang Y.J. Enhancing anti-inflammatory cytokine IL-10 may be beneficial for acute coronary syndrome. Med.
Hypotheses. 2005; 65 (1): 103–6.
19. Gold P.W., Wong M.L., Goldstein D.S. et al. Cardiac implications of increased arterial entry and reversible 24-h central and peripheral
norepinephrine levels in melancholia. Proc. Natl. Acad. Sci. USA. 2005; 102: 8303–8.
20. Otte C., Neylan T.C., Pipkin S.S. et al. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with
coronary disease: findings from the heart and soul study. Am. J. Psychiatry. 2005; 162: 2139–45.
21. Camm A.J., Pratt C.M., Schwartz P.J. et al. Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled
trial of azimilide using heart rate variability for risk stratification. Circulation. 2004; 109: 990–6.
Abstract
ИSummary. Ischemic heart disease as well as anxiety and depressive disorders are the diseases that are closely linked by common risk factors and pathogenic mechanisms, such as hyperactivity of the hypothalamic-pituitary-adrenal system, autonomic imbalance, platelet pathology and inflammation.Objective. To examine the relationships of subclinical inflammation biomarkers, autonomic imbalance and anxiety and depressive syndromes in patients with myocardial infarction (MI).
Material and Methods. 106 patients with ST-segment elevation MI, mean age 61.4±1.6 years, were enrolled. At days 5–7 the heart rate variability was assessed, plasma inflammatory biomarker concentrations (interleukins IL-1β, IL-6, IL-8, IL-10, interferon γ (INFγ), tumor necrosis factor alpha (TNFγ)) were measured by ELISA and psychometric testing using the Zung Self-Rating Depression scales, State-Trait Anxiety Inventory (Spielberger-Hanin) was done. The data were analyzed using the Statistica 6.0 software package (StatSoft).
Results. Patients with depression and increased levels of state and trait anxiety had significantly higher CRP and INFγ plasma concentrations as compared to those without depression or anxiety symptoms. Depression was associated with significantly higher concentrations of inflammatory cytokines IL-1β (72.2±1.3 pg/ml vs 49.5±7.7 in patients without depression, p=0.08), IL-8 (104.5±4.4 pg/ml vs 43.8±1.2, respectively, p=0.009) and reduced anti-inflammatory IL-10 (1.0±0.2 pg/ml vs 2.1±0.4; p=0.01), as well as with the sympathetic nervous system activation, as assessed with the SDNN. In the group of patients with myocardial infarction, who had a marked increase in the sympathetic nervous system activity (SDNN less 70 ms), the levels of IL-1β, IL-8, TNFα and INFγ were significantly higher as compared to those in patients with the normal SDNN values. Indeed, IL-1β levels were 164.5 (152, 174) and 108 (96, 110), respectively, IL-6 levels: 4.48 (2.2, 6.3) and 3.44 (2.4, 4.9) IL-8: 81.3 (76, 92) and 41 (28, 51); TNFFα levels: 37.4 (28.6, 44.4) and 2.63 (1.9, 4.3); INFγ 94.9 (91, 101.2) and 21.6 (18.3, 23), p<0.001 in all cases. The resulting differences did not depend on the severity of myocardial infarction.
Conclusion. The presence of myocardial infarction in patients with sub-acute symptoms of depression and increased anxiety is associated with more severe inflammatory and sympathetic activation, which may explain a well-known adverse prognostic role of anxiety and depression syndrome in MI.
References
Литература/References1. Carney R.M. Depression and late mortality after myocardial infarction in the enhancing recovery in coronary heart disease
(ENRICHD) study. Psychosom. Med. 2004; 66: 466–74.
2. Frasure-Smith N., Lesperance F. Reflections on depression as a cardiac risk factors. Psychosom. Med. 2005; 67: 19–25.
3. Carney R.M., Freedland K.E. Depression in patients with coronary heart disease. Am. J. Med. 2008; 121: 20–7.
4. Hermann N., Sing-Manoux A., Shipley M. Do psychological factors affect inflammation and incident coronary heart disease.
Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1398.
5. Biasucci L.M. CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public
health practice: clinical use of inflammatory markers in patients with cardiovascular diseases: a background paper. Circulation. 2004;
110: 560–7.
6. Carney R.M., Freedland K.E., Veith R.C. Depression, the autonomic nervous system and coronary heart disease. Psychosom. Med.
2005; 67 (1): 29–33.
7. Chiappelli M., Tampieri C., Tumini T. et al. Interleukin-6 gene polymorphism in age-dependent risk factor for myocardial infarction
in men. Int. J. Immunogenet. 2005; 32: 349–53.
8. Shimbo K.W., Davidson D.C., Haas V. et al. Negative impact of depression on outcomes in patients with coronary artery disease:
mechanisms, treatment considerations, and future directions. Thromb. Haemost. 2005; 3: 897–908.
9. Guinjoan S.M., De Guevara M.S., Correa C. et al. Cardiac parasympathetic dysfunction related to depression in older adults with
acute coronary syndromes. J. Psychosom. Res. 2004; 56: 83–8.
10. La Rovere M.T., Pinna G.D., Maestri R. et al. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart
failure patients. Circulation. 2003; 107: 565–70
11. Empana J., Sykes D., Luc M. Contributions of depressive mood and circulation inflammatory markers to coronary heart disease in
healthy European men. Circulation. 2005; 111: 2299–305.
12. Loppnow H., Libby P. Proliferating or interleukin-1 activated human vascular smooth muscle cells secrete copious interleukin-6.
J. Clin. Invest. 1990; 85: 731–8.
13. Howren M.B., Lamkin D.M., Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom.
Med. 2009; 71: 171–86.
14. Hansson G.K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 2005; 352: 1685–96.
15. Otake H., Shite J., Shinke T. et al. Relation between plasma adiponectin, high-sensitivity C-reactive protein, and coronary plaque
components in patients with acute coronary syndrome. Am. J. Cardiol. 2008; 101: 1–7.
16. Stewart J.C., Janicki-Deverts D., Muldoon M.F. Depressive symptoms moderate the influence of hostility on serum interleukin-6 and
C-reactive protein. Psychosom. Med. 2008; 70: 197–204.
17. Panagiotakos A.B., Pitsavos C., Chrysohoou C. et al. Inflammation, coagulation, and depressive symptomatology in cardiovascular
disease-free people; the ATTICA study. Eur. Heart J. 2004. 25: 492–9.
18. Li J.J., Guo Y.L., Yang Y.J. Enhancing anti-inflammatory cytokine IL-10 may be beneficial for acute coronary syndrome. Med.
Hypotheses. 2005; 65 (1): 103–6.
19. Gold P.W., Wong M.L., Goldstein D.S. et al. Cardiac implications of increased arterial entry and reversible 24-h central and peripheral
norepinephrine levels in melancholia. Proc. Natl. Acad. Sci. USA. 2005; 102: 8303–8.
20. Otte C., Neylan T.C., Pipkin S.S. et al. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with
coronary disease: findings from the heart and soul study. Am. J. Psychiatry. 2005; 162: 2139–45.
21. Camm A.J., Pratt C.M., Schwartz P.J. et al. Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled
trial of azimilide using heart rate variability for risk stratification. Circulation. 2004; 109: 990–6.
