Skip to main content

Advertisement

SpringerLink
Log in

Hyperuricemia is associated with an increased prevalence of paroxysmal atrial fibrillation in patients with type 2 diabetes referred for clinically indicated 24-h Holter monitoring

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Several studies have reported an association between hyperuricemia and increased risk of permanent atrial fibrillation (AF) in patients with and without type 2 diabetes mellitus (T2DM). Currently, no published data are available on the relationship between hyperuricemia and risk of paroxysmal AF.

Methods

We retrospectively evaluated 245 T2DM outpatients without pre-existing AF, cancer, cirrhosis and end-stage renal disease, who underwent a 24-h ECG-Holter monitoring for various clinical indications. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of paroxysmal AF was confirmed in affected individuals on the basis of 24-h ECG-Holter monitoring by experienced cardiologists.

Results

Hyperuricemia was observed in 59 (24.1%) patients, whereas paroxysmal AF was found in 11 (4.5%) patients. The prevalence of paroxysmal AF was higher in patients with hyperuricemia than in those without hyperuricemia (10.2 vs. 2.7%, p = 0.026). Logistic regression analysis showed that hyperuricemia was associated with an increased risk of prevalent paroxysmal AF. This association remained significant even after adjustment for age, metabolic syndrome and chronic kidney disease (adjusted-odds ratio 4.01, 95% CI 1.08–14.9; p = 0.039). Similar results were found when we used serum uric acid levels as a continuous measure.

Conclusions

This study shows for the first time that hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM. These findings may partly explain the increased risk of permanent atrial fibrillation and cardiovascular death observed among patients with hyperuricemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

APC:

Atrial premature complex

AF:

Atrial fibrillation

BMI:

Body mass index

CKD:

Chronic kidney disease

COPD:

Chronic obstructive pulmonary disease

IHD:

Ischemic heart disease

MDRD:

Modification of diet in renal disease

PVC:

Premature ventricular complex

SVT:

Supraventricular tachycardia

T2DM:

Type 2 diabetes mellitus

VHD:

Valvular heart disease

VT:

Ventricular tachyarrhythmia

References

  1. Culleton BF, Larson MG, Kannel WB, Levy D (1999) Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med 131:7–13

    Article  CAS  PubMed  Google Scholar 

  2. Feig DI, Kang D-H, Johnson RJ (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zoppini G, Targher G, Bonora E (2011) The role of serum uric acid in cardiovascular disease in type 2 diabetic and non-diabetic subjects. A narrative review. J Endocrinol Invest 34:881–886

    Article  CAS  PubMed  Google Scholar 

  4. De Giorgi A, Fabbian F, Pala M, Tiseo R, Parisi C, Misurati E, Manfredini R (2015) Uric acid: friend or foe? Uric acid and cognitive function “Gout kills more wise men than simple”. Eur Rev Med Pharmacol Sci 19:640–646

    PubMed  Google Scholar 

  5. Veronese N, Carraro S, Bano G, Trevisan C, Solmi M, Luchini C, Manzato E, Caccialanza R, Sergi G, Nicetto D, Cereda E (2016) Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta-analysis. Eur J Clin Invest 46:920–930

    Article  CAS  PubMed  Google Scholar 

  6. Maharani N, Kuwabara M, Hisatome I (2016) Hyperuricemia and atrial fibrillation. Int Heart J 57:395–399

    Article  PubMed  Google Scholar 

  7. Tamariz L, Hernandez F, Bush A, Palacio A, Hare JM (2014) Association between serum uric acid and atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm 11:1102–1108

    Article  PubMed  Google Scholar 

  8. Liu T, Zhang X, Korantzopoulos P, Wang S, Li G (2011) Uric acid levels and atrial fibrillation in hypertensive patients. Intern Med 50:799–803

    Article  CAS  PubMed  Google Scholar 

  9. Suzuki S, Sagara K, Otsuka T, Matsuno S, Funada R, Uejima T, Oikawa Y, Koike A, Nagashima K, Kirigaya H, Yajima J, Sawada H, Aizawa T, Yamashita T (2012) Gender-specific relationship between serum uric acid level and atrial fibrillation prevalence. Circ J 76:607–611

    Article  CAS  PubMed  Google Scholar 

  10. Chao TF, Hung CL, Chen SJ, Wang KL, Chen TJ, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Chen SA (2013) The association between hyperuricemia, left atrial size and new-onset atrial fibrillation. Int J Cardiol 168:4027–4032

    Article  PubMed  Google Scholar 

  11. Xu X, Du N, Wang R, Wang Y, Cai S (2015) Hyperuricemia is independently associated with increased risk of atrial fibrillation: a meta-analysis of cohort studies. Int J Cardiol 184:699–702

    Article  PubMed  Google Scholar 

  12. Kuwabara M, Niwa K, Nishihara S, Nishi Y, Takahashi O, Kario K, Yamamoto K, Yamashita T, Hisatome I (2017) Hyperuricemia is an independent competing risk factor for atrial fibrillation. Int J Cardiol 231:137–142

    Article  PubMed  Google Scholar 

  13. Chuang SY, Wu CC, Hsu PF, Chia-Yu Chen R, Liu WL, Hsu YY, Pan WH (2014) Hyperuricemia and incident atrial fibrillation in a normotensive elderly population in Taiwan. Nutr Metab Cardiovasc Dis 24:1020–1026

    Article  CAS  PubMed  Google Scholar 

  14. Mantovani A, Rigolon R, Pichiri I, Pernigo M, Bergamini C, Zoppini G, Bonora E, Targher G (2016) Hyperuricemia is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes. J Endocrinol Invest 39:159–167

    Article  CAS  PubMed  Google Scholar 

  15. Valbusa F, Bertolini L, Bonapace S, Zenari L, Zoppini G, Arcaro G, Byrne CD, Targher G (2013) Relation of elevated serum uric acid levels to incidence of atrial fibrillation in patients with type 2 diabetes mellitus. Am J Cardiol 112:499–504

    Article  CAS  PubMed  Google Scholar 

  16. Tamariz L, Agarwal S, Soliman EZ, Chamberlain AM, Prineas R, Folsom AR, Ambrose M, Alonso A (2011) Association of serum uric acid with incident atrial fibrillation (from the atherosclerosis risk in communities [ARIC] study). Am J Cardiol 108:1272–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rahman F, Kwan GF, Benjamin EJ (2014) Global epidemiology of atrial fibrillation. Nat Rev Cardiol 11:639–654

    Article  PubMed  Google Scholar 

  18. Healey JS, Oldgren J, Ezekowitz M, Zhu J, Pais P, Wang J, Commerford P, Jansky P, Avezum A, Sigamani A, Demasceno A, Reilly P, Grinvalds A, Nakamya J, Aje A, Almahmeed W, Moriarty A, Wallentin L, Yusuf S (2016) Connolly SJ; RE-LY Atrial Fibrillation Registry and Cohort Study Investigators. Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study. Lancet 388:1161–1169

    Article  PubMed  Google Scholar 

  19. Lip GY, Fauchier L, Freedman SB, Van Gelder I, Natale A, Gianni C, Nattel S, Potpara T, Rienstra M, Tse HF, Lane DA (2016) Atrial fibrillation. Nat Rev Dis Primers 2:16016

    Article  PubMed  Google Scholar 

  20. Banerjee A, Taillandier S, Olesen JB, Lane DA, Lallemand B, Lip GY, Fauchier L (2013) Pattern of atrial fibrillation and risk of outcomes: the Loire Valley Atrial Fibrillation Project. Int J Cardiol 167:2682–2687

    Article  PubMed  Google Scholar 

  21. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) Modification of diet in renal disease study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470

    Article  CAS  PubMed  Google Scholar 

  22. Sattar N, Gaw A, Scherbakova O, Ford I, O’Reilly DS, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J (2003) Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 108:414–419

    Article  CAS  PubMed  Google Scholar 

  23. Girman CJ, Rhodes T, Mercuri M, 4S Group and the AFCAPS/TexCAPS Research Group et al (2004) The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 93:136–141

    Article  CAS  PubMed  Google Scholar 

  24. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace 18:1609–1678

    Article  PubMed  Google Scholar 

  25. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekvål TM, Spaulding C, Van Veldhuisen DJ, Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) (2015) 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Europace 17:1601–1687

    PubMed  Google Scholar 

  26. Ling LH, Kistler PM, Kalman JM, Schilling RJ, Hunter RJ (2016) Comorbidity of atrial fibrillation and heart failure. Nat Rev Cardiol 13:131–147

    Article  CAS  PubMed  Google Scholar 

  27. Fabritz L, Guasch E, Antoniades C, Bardinet I, Benninger G, Betts TR, Brand E, Breithardt G, Bucklar-Suchankova G, Camm AJ, Cartlidge D, Casadei B, Chua WW, Crijns HJ, Deeks J, Hatem S, Hidden-Lucet F, Kääb S, Maniadakis N, Martin S, Mont L, Reinecke H, Sinner MF, Schotten U, Southwood T, Stoll M, Vardas P, Wakili R, West A, Ziegler A, Kirchhof P (2016) Expert consensus document: defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment. Nat Rev Cardiol 13:230–237

    Article  CAS  PubMed  Google Scholar 

  28. Khosla U, Zharikov S, Finch J, Nakagawa T, Roncal C, Mu W, Kratova K, Block E, Prabhakar S, Johnson R (2005) Hyperuricemia induces endothelial dysfunction. Kidney Int 67:1739–1742

    Article  PubMed  Google Scholar 

  29. Berry CE, Hare JM (2004) Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 555:589–606

    Article  CAS  PubMed  Google Scholar 

  30. Kato M, Hisatome I, Tomikura Y, Kotani K, Kinugawa T, Ogino K, Ishida K, Igawa O, Shigemasa C, Somers V (2005) Status of endothelial dependent vasodilatation in patients with hyperuricemia. Am J Cardiol 96:1576–1578

    Article  CAS  PubMed  Google Scholar 

  31. Perez-Ruiz F, Becker MA (2015) Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease. Curr Med Res Opin 2:9–14

    Article  Google Scholar 

  32. Li N, Dobrev D (2017) Hyperuricemia: a causal player or a bystander linking inflammatory signaling and atrial fibrillation? Int J Cardiol 231:177–178

    Article  PubMed  Google Scholar 

  33. El khoury N, Mathieu S, Fiset C (2014) Interleukin-1β reduces L-type Ca2+ current through protein kinase Cϵ activation in mouse heart. J Biol Chem 289:21896–21908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sonmez O, Ertem FU, Vatankulu MA, Erdongan E, Tasal A, Kucukbuzcu S, Goktekin O (2014) Novel fibro-inflammation markers in assessing left atrial remodeling in non-valvular atrial fibrillation. Med Sci Monit 20:463–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nattel S, Harada M (2014) Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol 63:2335–2345

    Article  PubMed  Google Scholar 

  36. Hu YF, Chen YJ, Lin YJ, Chen SA (2015) Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol 12:230–243

    Article  CAS  PubMed  Google Scholar 

  37. Wu N, Xu B, Xiang Y, Wu L, Zhang Y, Ma X, Tong S, Shu M, Song Z, Li Y, Zhong L (2013) Association of inflammatory factors with occurrence and recurrence of atrial fibrillation: a meta-analysis. Int J Cardiol 169:62–72

    Article  PubMed  Google Scholar 

  38. Nattel S, Dobrev D (2016) Electrophysiological and molecular mechanisms of paroxysmal atrial fibrillation. Nat Rev Cardiol 13:575–590

    Article  CAS  PubMed  Google Scholar 

  39. Douen AG, Pageau N, Medic S (2008) Serial electrocardiographic assessments significantly improve detection of atrial fibrillation 2.6-fold in patients with acute stroke. Stroke 39:480–482

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale A. Stefani, 1, 37126, Verona, Italy

    A. Mantovani, R. Rigolon, A. Civettini, G. Zoppini, E. Bonora & G. Targher

  2. Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    B. Bolzan & G. Morani

  3. Division of Cardiology, “Sacro Cuore” Hospital, Negrar, VR, Italy

    S. Bonapace & C. Dugo

Authors
  1. A. Mantovani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Rigolon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Civettini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Bolzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Morani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Bonapace
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Dugo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Zoppini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Bonora
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G. Targher
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AM and GT conceived and designed the study. RR, AC, BB, GM, CD and SB researched data and reviewed/edited the manuscript. GZ and EB contributed to discussion and reviewed/edited the manuscript. AM and GT analyzed the data and wrote the manuscript draft. AM is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data.

Corresponding author

Correspondence to A. Mantovani.

Ethics declarations

Conflict of interest

The authors have no potential conflicts of interest to disclose.

Ethical approval

The local ethics committee approved the study protocol.

Informed consent

The ethics committee exempted our research from the informed consent requirement because we only accessed retrospectively a de-identified database for the purpose of data analysis.

Funding

GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 77 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mantovani, A., Rigolon, R., Civettini, A. et al. Hyperuricemia is associated with an increased prevalence of paroxysmal atrial fibrillation in patients with type 2 diabetes referred for clinically indicated 24-h Holter monitoring. J Endocrinol Invest 41, 223–231 (2018). https://doi.org/10.1007/s40618-017-0729-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0729-4

Keywords

Search

Navigation