Renal dysfunction increases the risk of ischemic stroke and embolism in AF

Zeng W, Sun X, Tang K.
Stroke 2014; November 25; doi: 10.1161/STROKEAHA.114.006881

Background

Atrial fibrillation (AF) and Chronic Kidney Disease (CKD) are comorbid conditions [1-3], each of which has been related to an increased risk of stroke [4,5]. AF per se evokes a hypercoagulable state [6], whereas CKD without AF is associated with a prothrombotic state, including endothelial damage, abnormalities in coagulation factors, inflammation [7-10], and neurohormonal deficits mediated by the renin–angiotensin–aldosterone system  [11]. Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular AF.
The present meta-analysis addresses the relation between CKD and the risk of thromboembolic events in non-valvular AF. This pooled meta-analysis included 18 studies with a total of 538 479 patients and 41.719 incident thromboembolic events.

Main results

• AF patients with estimated glomerular filtration rate (eGFR) <60 mL/min (compared with AF patients with eGFR ≥60 mL/min) were at a significantly increased risk for thromboembolic events (relative risk: 1.62; 95% CI: 1.40–1.87; P<0.001).
• The annual rate of thromboembolic events increased by 0.41% (95% CI: 0.17%–0.65%) for every 10 mL/min decrease in renal function.
• The addition of renal impairment to CHADS2 yielded a slight improvement of the stratification of stroke risk, which was not the case for CHADS2-CKD and CHA2DS2-VASc scores.

Conclusions

After accounting for other known thromboembolic risk factors, renal dysfunction increased the risk of ischemic stroke and systemic embolism in patients with nonvalvular AF. Adding renal dysfunction to the CHADS2 score yielded a small but statistically significant improvement in risk discrimination. CKD may contribute to an increased risk of ischemic stroke and other thromboembolic events in patients with AF by augmenting the underlying prothrombotic state. Further studies are warranted to clarify whether there is additive predictive value of CKD being incorporated in clinical scores such as the CHA2DS2-VASc or whether the current components already sufficiently relate to renal dysfunction.

Find this article on Pubmed

References

1. Go AS, Fang MC, Udaltsova N, et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation. 2009;119:1363–1369.
2. Soliman EZ, Prineas RJ, Go AS, et al. Chronic kidney disease and prevalent atrial fibrillation: the Chronic Renal Insufficiency Cohort (CRIC). Am Heart J. 2010;159:1102–1107.
3. Baber U, Howard VJ, Halperin JL, et al. Association of chronic kidney disease with atrial fibrillation among adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Circ Arrhythm Electrophysiol. 2011;4:26–32.
4. Albertsen IE, Rasmussen LH, Overvad TF, et al. Risk of stroke or systemic embolism in atrial fibrillation patients treated with warfarin: a systematic review and meta-analysis. Stroke. 2013;44:1329–1336.
5. Kokubo Y, Nakamura S, Okamura T, et al. Relationship between blood pressure category and incidence of stroke and myocardial infarction in an urban Japanese population with and without
chronic kidney disease: the Suita Study. Stroke. 2009;40:2674–2679.
6. Lip GY, Lim HS. Atrial fibrillation and stroke prevention. Lancet Neurol 2007;6:981–993.
7. Reinecke H, Brand E, Mesters R, et al. Dilemmas in the management of atrial fibrillation in chronic kidney disease. J Am Soc Nephrol. 2009;20:705–711.
8. Tomura S, Nakamura Y, Doi M, et al. Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis. 1996;27:848–854.
9. Shlipak MG, Fried LF, Crump C, et al. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation. 2003;107:87–92.
10. Muntner P, Hamm LL, Kusek JW, et al. The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease. Ann Intern Med. 2004;140:9–17.
11. Miyazaki-Anzai S, Masuda M, Demos-Davies KM, et al. Endoplasmic reticulum stress effector
CCAAT/enhancer-binding protein homologous protein (CHOP) regulates chronic kidney disease-induced vascular calcification. J Am Heart Assoc. 2014;3:e000949.