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Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms.

Methods

The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200 ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133+/KDR+ endothelial progenitor cell (EPC) levels were measured by flow cytometry.

Results

Among healthy subjects, PR interval was inversely associated with FMD (R = −0.20, P = 0.015), but not with the level of circulating CD133+/KDR+ EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200 ms was more common compared with healthy subjects (45/348 (13 %) versus 4/150 (3 %), P < 0.001). PR interval was associated inversely with FMD (R = −0.14, P = 0.01) and positively with circulating CD133+/KDR+ EPC level (R = +0.14, P = 0.009). Circulating CD133+/KDR+ EPC level was significantly increased in patients with PR prolongation >200 ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10−3/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133+/KDR+ EPC by +0.002 (95 % confidence interval (CI) 0.000 to 0.004 (log, ×10−3/ml), P = 0.011) and depressed FMD (B = −0.014 %, 95 % CI −0.027 to −0.002, P = 0.026).

Conclusions

PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.

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References

  1. Epstein, A. E., DiMarco, J. P., Ellenbogen, K. A., et al. (2008). ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Journal of the American College of Cardiology, 51(21), e1–e62.

    Article  PubMed  Google Scholar 

  2. Bexton, R. S., & Camm, A. J. (1984). First degree atrioventricular block. European Heart Journal, 5(Suppl A), 107–109.

    Article  PubMed  Google Scholar 

  3. Perlman, L. V., Ostrander, L. D., Jr., Keller, J. B., et al. (1971). An epidemiologic study of first degree atrioventricular block in Tecumseh, Michigan. Chest, 59(1), 40–46.

    Article  PubMed  CAS  Google Scholar 

  4. Soliman, E. Z., Prineas, R. J., Case, L. D., et al. (2009). Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Stroke, 40(4), 1204–1211.

    Article  PubMed  Google Scholar 

  5. Cheng, S., Keyes, M. J., Larson, M. G., et al. (2009). Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. Journal of the American Medical Association, 301(24), 2571–2577.

    Article  PubMed  CAS  Google Scholar 

  6. Crisel, R. K., Farzaneh-Far, R., Na, B., et al. (2011). First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study. European Heart Journal, 32(15), 1875–1880.

    Article  PubMed  Google Scholar 

  7. Chan, Y. H., Siu, C. W., Yiu, K. H., et al. (2011). Abnormal vascular function in PR-interval prolongation. Clinical Cardiology, 34(10), 628–632.

    Article  PubMed  Google Scholar 

  8. Patti, G., Pasceri, V., Melfi, R., et al. (2005). Impaired flow-mediated dilation and risk of restenosis in patients undergoing coronary stent implantation. Circulation, 111(1), 70–75.

    Article  PubMed  Google Scholar 

  9. Chan, Y. H., Lau, K. K., Yiu, K. H., et al. (2008). Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke. European Heart Journal, 29(22), 2800–2807.

    Article  PubMed  CAS  Google Scholar 

  10. Chan, Y. H., Lau, K. K., Yiu, K. H., et al. (2007). Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden. American Journal of Clinical Nutrition, 86(4), 938–945.

    PubMed  CAS  Google Scholar 

  11. Chan, Y. H., Lam, T. H., Lau, K. K., et al. (2011). Dietary intake of phytoestrogen is associated with increased circulating endothelial progenitor cells in patients with cardiovascular disease. European Journal of Cardiovascular Prevention and Rehabilitation, 18(3), 360–368.

    Article  PubMed  Google Scholar 

  12. Yiu, Y. F., Chan, Y. H., Yiu, K. H., et al. (2011). Vitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 96(5), E830–E835.

    Article  PubMed  CAS  Google Scholar 

  13. Shimbo, D., Grahame-Clarke, C., Miyake, Y., et al. (2007). The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis, 192(1), 197–203.

    Article  PubMed  CAS  Google Scholar 

  14. Shantsila, E., Watson, T., & Lip, G. Y. (2007). Endothelial progenitor cells in cardiovascular disorders. Journal of the American College of Cardiology, 49(7), 741–752.

    Article  PubMed  CAS  Google Scholar 

  15. Dixen, U., Ravn, L., Soeby-Rasmussen, C., et al. (2007). Raised plasma aldosterone and natriuretic peptides in atrial fibrillation. Cardiology, 108(1), 35–39.

    Article  PubMed  CAS  Google Scholar 

  16. Goette, A., Hoffmanns, P., Enayati, W., et al. (2001). Effect of successful electrical cardioversion on serum aldosterone in patients with persistent atrial fibrillation. The American Journal of Cardiology, 88(8), 906–909. A8.

    Article  PubMed  CAS  Google Scholar 

  17. Wozakowska-Kaplon, B., Bartkowiak, R., & Janiszewska, G. (2010). A decrease in serum aldosterone level is associated with maintenance of sinus rhythm after successful cardioversion of atrial fibrillation. Pacing and Clinical Electrophysiology, 33(5), 561–565.

    Article  PubMed  Google Scholar 

  18. Hashikabe, Y., Suzuki, K., Jojima, T., et al. (2006). Aldosterone impairs vascular endothelial cell function. Journal of Cardiovascular Pharmacology, 47(4), 609–613.

    Article  PubMed  CAS  Google Scholar 

  19. Kotchen, T. A., Kotchen, J. M., Grim, C. E., et al. (2009). Aldosterone and alterations of hypertension-related vascular function in African Americans. American Journal of Hypertension, 22(3), 319–324.

    Article  PubMed  CAS  Google Scholar 

  20. Siragy, H. M. (2010). Improving vascular function in hypertension: potential benefits of combination therapy with amlodipine and renin-angiotensin-aldosterone system blockers. Journal of Hypertension, 28(1), 2–8.

    Article  PubMed  CAS  Google Scholar 

  21. Schneider, M. P., Hua, T. A., Bohm, M., et al. (2010). Prevention of atrial fibrillation by renin-angiotensin system inhibition a meta-analysis. Journal of the American College of Cardiology, 55(21), 2299–2307.

    Article  PubMed  Google Scholar 

  22. Yang, Z., Xia, W. H., Zhang, Y. Y., et al. (2012). Shear stress-induced activation of Tie2-dependent signaling pathway enhances reendothelialization capacity of early endothelial progenitor cells. Journal of Molecular and Cellular Cardiology, 52(5), 1155–1163.

    Article  PubMed  CAS  Google Scholar 

  23. Watson, T., Shantsila, E., Blann, A., et al. (2010). Circulating progenitor cells in patients with atrial fibrillation and their relation with serum markers of inflammation and angiogenesis. Thrombosis and Haemostasis, 104(2), 327–334.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by the CRCG Small Project Funding of the University of Hong Kong (project no. 200907176063) and the Sun Chieh Yeh Heart Foundation, Hong Kong.

Conflict of interest

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, The University of Hong Kong, Rm 1928, Block K, Queen Mary Hospital, Hong Kong SAR, China

    Yap-Hang Chan, Chung-Wah Siu, Kai-Hang Yiu, Yuen-Fung Yiu, Chu-Pak Lau & Hung-Fat Tse

  2. School of Public Health, The University of Hong Kong, Hong Kong SAR, China

    Yap-Hang Chan & Tai-Hing Lam

  3. Research Center of Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, Hong Kong SAR, China

    Chung-Wah Siu & Hung-Fat Tse

  4. Division of Neurology, Department of Medicine, University of Hong Kong, Hong Kong SAR, China

    Kui-Kai Lau

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  1. Yap-Hang Chan
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  2. Chung-Wah Siu
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  4. Yuen-Fung Yiu
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Correspondence to Hung-Fat Tse.

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Chan, YH., Siu, CW., Yiu, KH. et al. Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients. J Interv Card Electrophysiol 37, 55–61 (2013). https://doi.org/10.1007/s10840-012-9777-z

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  • DOI: https://doi.org/10.1007/s10840-012-9777-z

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