Skip to main content
Top
Published in: Cardiovascular Drugs and Therapy 3/2012

01-06-2012

Obesity, Inflammation and Brachial Artery Flow-Mediated Dilatation: Therapeutic Targets in Patients with Microvascular Angina (Cardiac Syndrome X)

Authors: Peter Ong, Ramyya Sivanathan, Gabor Borgulya, Mukhtar Bizrah, Yassir Iqbal, Joycelyn Andoh, David Gaze, Juan Carlos Kaski

Published in: Cardiovascular Drugs and Therapy | Issue 3/2012

Login to get access

Abstract

Background

The pathophysiology of microvascular angina (cardiac syndrome X, CSX), (effort-induced angina, a positive response to exercise stress testing and angiographically normal coronary arteries) has not been fully elucidated. Various pathogenic mechanisms have been proposed, amongst which coronary microvascular dysfunction features prominently. Management of patients with microvascular angina is often challenging as a substantial number of patients does not respond to conventional anti-anginal therapy. In this study, we sought to assess the association between brachial artery FMD, high-sensitive C-reactive protein (hs-CRP) and cardiovascular risk factors including obesity in patients with cardiac syndrome X.

Methods and results

Thirty-four consecutive CSX patients (29 female, mean age 60 ± 9 years) were recruited from a specialised CSX clinic. Twelve asymptomatic subjects (10 female, mean age 51 ± 12 years) with comparable cardiovascular risk factor profile served as controls. All participants underwent standardized computer-assisted FMD measurements and assessment of hs-CRP concentrations at study entry. Body mass index (BMI), used as a general measure of obesity was calculated as weight (kilograms) divided by height (meters squared). Compared to controls, CSX patients had significantly higher hs-CRP concentrations (p = 0.003) and impaired FMD (p < 0.01). Moreover, among the CSX patients, a correlation between FMD and hs-CRP (r = −0.66, p < 0.01), FMD and BMI (r = 0.377, p = 0.028), and hs-CRP and BMI (r = −0.372, p = 0.030) was found.

Conclusion

Impaired brachial artery FMD is significantly associated with elevated hs-CRP concentrations and BMI in patients with CSX. The results support the concept that low-grade inflammation and obesity may promote vascular dysfunction in these patients representing therapeutic targets for future research investigations.
Literature
1.
go back to reference Kaski JC. Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation. 2004;109:568–72.PubMedCrossRef Kaski JC. Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation. 2004;109:568–72.PubMedCrossRef
2.
go back to reference Maseri A, Crea F, Kaski JC, Crake T. Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol. 1991;17:499–506.PubMedCrossRef Maseri A, Crea F, Kaski JC, Crake T. Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol. 1991;17:499–506.PubMedCrossRef
4.
go back to reference Lanza GA. Cardiac syndrome X: a critical overview and future perspectives. Heart. 2007;93:159–66.PubMedCrossRef Lanza GA. Cardiac syndrome X: a critical overview and future perspectives. Heart. 2007;93:159–66.PubMedCrossRef
5.
go back to reference Lekakis JP, Papamichael CM, Vemmos CN, Voutsas AA, Stamatelopoulos SF, Moulopoulos SD. Peripheral vascular endothelial dysfunction in patients with angina pectoris and normal coronary arteriograms. J Am Coll Cardiol. 1998;31:541–6.PubMedCrossRef Lekakis JP, Papamichael CM, Vemmos CN, Voutsas AA, Stamatelopoulos SF, Moulopoulos SD. Peripheral vascular endothelial dysfunction in patients with angina pectoris and normal coronary arteriograms. J Am Coll Cardiol. 1998;31:541–6.PubMedCrossRef
6.
go back to reference Masci PG, Laclaustra M, Lara JG, Kaski JC. Brachial artery flow-mediated dilation and myocardial perfusion in patients with cardiac syndrome X. Am J Cardiol. 2005;95:1478–80.PubMedCrossRef Masci PG, Laclaustra M, Lara JG, Kaski JC. Brachial artery flow-mediated dilation and myocardial perfusion in patients with cardiac syndrome X. Am J Cardiol. 2005;95:1478–80.PubMedCrossRef
7.
8.
go back to reference Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–9.PubMedCrossRef Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–9.PubMedCrossRef
9.
go back to reference Sidhu JS, Newey VR, Nassiri DK, Kaski JC. A rapid and reproducible on line automated technique to determine endothelial function. Heart. 2002;88:289–92.PubMedCrossRef Sidhu JS, Newey VR, Nassiri DK, Kaski JC. A rapid and reproducible on line automated technique to determine endothelial function. Heart. 2002;88:289–92.PubMedCrossRef
10.
go back to reference Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108:2993–9.PubMedCrossRef Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108:2993–9.PubMedCrossRef
11.
go back to reference Lanza GA, Crea F. Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation. 2010;121:2317–25.PubMedCrossRef Lanza GA, Crea F. Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation. 2010;121:2317–25.PubMedCrossRef
12.
go back to reference Arroyo-Espliguero R, Mollichelli N, Avanzas P, Zouridakis E, Newey VR, Nassiri DK, Kaski JC. Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. Eur Heart J. 2003;24:2006–11.PubMedCrossRef Arroyo-Espliguero R, Mollichelli N, Avanzas P, Zouridakis E, Newey VR, Nassiri DK, Kaski JC. Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. Eur Heart J. 2003;24:2006–11.PubMedCrossRef
13.
go back to reference López-Jiménez F, Cortés-Bergoderi M. Update: systemic diseases and the cardiovascular system (i): obesity and the heart. Rev Esp Cardiol. 2011;64:140–9.PubMedCrossRef López-Jiménez F, Cortés-Bergoderi M. Update: systemic diseases and the cardiovascular system (i): obesity and the heart. Rev Esp Cardiol. 2011;64:140–9.PubMedCrossRef
14.
go back to reference Al-Tahami BA, Bee YT, Ismail AA, Rasool AH. Impaired microvascular endothelial function in relatively young obese humans is associated with altered metabolic and inflammatory markers. Clin Hemorheol Microcirc. 2011;47:87–97.PubMed Al-Tahami BA, Bee YT, Ismail AA, Rasool AH. Impaired microvascular endothelial function in relatively young obese humans is associated with altered metabolic and inflammatory markers. Clin Hemorheol Microcirc. 2011;47:87–97.PubMed
15.
go back to reference De Rosa S, Cirillo P, Pacileo M, Di Palma V, Paglia A, Chiariello M. Leptin stimulated C-reactive protein production by human coronary artery endothelial cells. J Vasc Res. 2009;46:609–17.PubMedCrossRef De Rosa S, Cirillo P, Pacileo M, Di Palma V, Paglia A, Chiariello M. Leptin stimulated C-reactive protein production by human coronary artery endothelial cells. J Vasc Res. 2009;46:609–17.PubMedCrossRef
16.
go back to reference Khera A, Vega GL, Das SR, et al. Sex differences in the relationship between C-reactive protein and body fat. J Clin Endocrinol Metab. 2009;94:3251–8.PubMedCrossRef Khera A, Vega GL, Das SR, et al. Sex differences in the relationship between C-reactive protein and body fat. J Clin Endocrinol Metab. 2009;94:3251–8.PubMedCrossRef
17.
go back to reference Gentile M, Panico S, Rubba F, et al. Obesity, overweight, and weight gain over adult life are main determinants of elevated hs-CRP in a cohort of Mediterranean women. Eur J Clin Nutr. 2010;64:873–8.PubMedCrossRef Gentile M, Panico S, Rubba F, et al. Obesity, overweight, and weight gain over adult life are main determinants of elevated hs-CRP in a cohort of Mediterranean women. Eur J Clin Nutr. 2010;64:873–8.PubMedCrossRef
18.
go back to reference Bagi Z, Feher A, Cassuto J. Microvascular responsiveness in obesity: implications for therapeutic intervention. Br J Pharmacol. 2012;165:544–60.PubMedCrossRef Bagi Z, Feher A, Cassuto J. Microvascular responsiveness in obesity: implications for therapeutic intervention. Br J Pharmacol. 2012;165:544–60.PubMedCrossRef
19.
go back to reference Teragawa H, Fukuda Y, Matsuda K, et al. Relation between C reactive protein concentrations and coronary microvascular endothelial function. Heart. 2004;90:750–4.PubMedCrossRef Teragawa H, Fukuda Y, Matsuda K, et al. Relation between C reactive protein concentrations and coronary microvascular endothelial function. Heart. 2004;90:750–4.PubMedCrossRef
20.
go back to reference Atmaca Y, Ozdol C, Turhan S, Vurgun K, Duzen V, Erol C. The association of elevated white blood cell count and C-reactive protein with endothelial dysfunction in cardiac syndrome X. Acta Cardiol. 2008;63:723–8.PubMedCrossRef Atmaca Y, Ozdol C, Turhan S, Vurgun K, Duzen V, Erol C. The association of elevated white blood cell count and C-reactive protein with endothelial dysfunction in cardiac syndrome X. Acta Cardiol. 2008;63:723–8.PubMedCrossRef
21.
go back to reference Sakr SA, Abbas TM, Amer MZ, et al. Microvascular angina. The possible role of inflammation, uric acid, and endothelial dysfunction. Int Heart J. 2009;50:407–19.PubMedCrossRef Sakr SA, Abbas TM, Amer MZ, et al. Microvascular angina. The possible role of inflammation, uric acid, and endothelial dysfunction. Int Heart J. 2009;50:407–19.PubMedCrossRef
23.
go back to reference Kayikcioglu M, Payzin S, Yavuzgil O, Kultursay H, Can LH, Soydan I. Benefits of statin treatment in cardiac syndrome-X1. Eur Heart J. 2003;24:1999–2005.PubMedCrossRef Kayikcioglu M, Payzin S, Yavuzgil O, Kultursay H, Can LH, Soydan I. Benefits of statin treatment in cardiac syndrome-X1. Eur Heart J. 2003;24:1999–2005.PubMedCrossRef
24.
go back to reference Pauly DF, Johnson BD, Anderson RD, Handberg EM, Smith KM, Cooper-DeHoff RM, Sopko G, Sharaf BM, Kelsey SF, Merz CN, Pepine CJ. In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: a double-blind randomized study from the National Heart, Lung and Blood Institute Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J. 2011;162:678–84.PubMedCrossRef Pauly DF, Johnson BD, Anderson RD, Handberg EM, Smith KM, Cooper-DeHoff RM, Sopko G, Sharaf BM, Kelsey SF, Merz CN, Pepine CJ. In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: a double-blind randomized study from the National Heart, Lung and Blood Institute Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J. 2011;162:678–84.PubMedCrossRef
25.
go back to reference Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344–50.PubMedCrossRef Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344–50.PubMedCrossRef
26.
go back to reference Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc. Imaging. 2011;4:514–22. Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc. Imaging. 2011;4:514–22.
27.
go back to reference Charakida M, Masi S, Lüscher TF, Kastelein JJ, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010;31:2854–61.PubMedCrossRef Charakida M, Masi S, Lüscher TF, Kastelein JJ, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010;31:2854–61.PubMedCrossRef
Metadata
Title
Obesity, Inflammation and Brachial Artery Flow-Mediated Dilatation: Therapeutic Targets in Patients with Microvascular Angina (Cardiac Syndrome X)
Authors
Peter Ong
Ramyya Sivanathan
Gabor Borgulya
Mukhtar Bizrah
Yassir Iqbal
Joycelyn Andoh
David Gaze
Juan Carlos Kaski
Publication date
01-06-2012
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 3/2012
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-012-6382-4

Other articles of this Issue 3/2012

Cardiovascular Drugs and Therapy 3/2012 Go to the issue