IMPACT OF ANTICOAGULANT THERAPY ON THE INDICATORS OF ARTERIAL STIFFNESS AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ATRIAL FIBRILLATION AFTER CARDIOEMBOLIC STROKE

Objective: to investigate the impact of anticoagulant therapy on the indicators of arterial stiffness and endothelial dysfunction (ED) in patients with atrial fibrillation (AF) after cardioembolic stroke (CES).

Patients and methods. The investigation enrolled 93 patients with AF after CES. The patients were divided into two groups: a study group in which all patients (n=48) received anticoagulants and a comparison group (n=45) in which the patients did not take anticoagulants, although the latter had been prescribed. The follow-up duration was 180.5±5.5 days. During this time the patients visited their doctors twice: the first visit was at baseline, the second one was after 24 weeks.

All the patients underwent three-dimensional sphygmography. The levels of glucose, creatinine, total cholesterol, high-density lipoproteins, and triglycerides were determined. The markers of endothelial function, such as von Willebrand factor, plasminogen, antithrombin III,  and tissue plasminogen activator inhibitor-1, were estimated.

Results. All the patients in the study and comparison groups had a higher comorbidity index of obvious somatic pathology. The patients from both groups showed changes in all cardiac morphometric and functional parameters. It was noted that after 6 months of a follow-up, there was a statistically significant positive trend in the indicators of arterial stiffness in the patients taking anticoagulants. The study group showed a significant correlation of blood pressure with the argumentation index. The 6-month follow-up revealed a strong correlation between the cardioankle vascular index and all the indicators of ED in the study group. After 24 weeks, in both groups there were 12 (12.9%) deaths: 3 (6.25%) and 8 (17.8%) in the study and comparison groups, respectively.

Conclusion. The findings suggest that in patients with AF after CES, the indicators of arterial stiffness and endothelial function tend to improve during anticoagulant therapy.

1. Kannel WB, Wolf PA, Benjamin EJ, et al. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based stimates. Am J Cardiol. 1998 Oct 16;82(8A):2N-9N.

2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010 Nov 4;363(19):1875-6. doi: 10.1056/NEJMc1007378.

3. Manesh R, Patel D, Kenneth W, et al. And the ROCKET AF Steering Committee for the ROCKET AF Investigators Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.

4. Granger CB, Alexander JH, McMurray JJ. For the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.

5. Chen LY, Foo DC, Wong RC, et al. Increased carotid intima-media hickness and arterial stiffness are associated with lone atrial fibrillation. Int J Cardiol. 2013 Oct 3;168(3):3132-4. doi: 10.1016/j.ijcard.2013.04.034. Epub 2013 Apr 25.

6. Larstorp AC, Ariansen I, Gjesdal K, et al. Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy the losartan intervention for endpoint (LIFE) reduction in hypertension study. Hypertension. 2012Aug;60(2):347-53. doi: 10.1161/HYPERTENSIONAHA.112.195032. Epub 2012 Jul 2.

7. Proietti M, Calvieri C, Malatino L, et al. Relationship between carotid intima-media thickness and non valvular atrial fibrillation type. Atherosclerosis. 2015 Feb;238(2):350-5. doi: 10.1016/j.atherosclerosis.2014.12.022. Epub 2014 Dec 20.

8. Болевич СБ, Войнов ВА. Молекулярные механизмы в патологии человека: Руководство для врачей. Москва: МИА; 2012. 208 c. [Bolevich SB, Voinov VA. Molekulyarnye mekhanizmy v patologii cheloveka: Rukovodstvo dlya vrachei [Molecular mechanisms in human pathology: a Guide for physicians]. Moscow: MIA; 2012. 208 p.]

9. Gronewold J, Hermann DM, Lehmann N, et al. Recall Study Investigative Group: Anklebrachial index predicts stroke in the general population in addition to classical risk factors. Atherosclerosis. 2014 Apr;233(2):545-50. doi: 10.1016/j.atherosclerosis.2014.01.044. Epub 2014 Jan 29.

10. Gutierrez J, Marshall RS, Lazar RM. Indirect measures of arterial stiffness and cognitive performance in individuals without traditional vascular risk factors or disease. JAMA Neurol. 2015 Mar;72(3):309-15. doi: 10.1001/jamaneurol.2014.3873.

11. Saji N, Kimura K, Yagita Y, et al. Comparison of arteriosclerotic indicators in patients with ischemic stroke: ankle-brachial index, brachial-ankle pulse wave velocity, and cardio-ankle vascular index. Hypertens Res. 2015 May;38(5):323-8. doi: 10.1038/hr.2015.8. Epub 2015 Feb 26.

12. Saji N, Kimura K, Yagita Y, et al. Deep cerebral microbleeds and chronic kidney disease in patients with acute lacunar infarcts. J Stroke Cerebrovasc Dis. 2015 Nov;24(11): 2572-9. doi: 10.1016/j.jstrokecerebrovasdis.2015.07.010. Epub 2015 Aug 29.

13. Chen SC, Lee WH, Hsu PC, et al. Association of Brachial-Ankle Pulse Wave Velocity With Cardiovascular Events in Atrial Fibrillation. Am J Hypertens. 2016 Mar;29(3): 348-56. doi: 10.1093/ajh/hpv124. Epub 2015 Aug 13.

14. Shirai K, Utino J, Otsuka K, et al. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb. 2006 Apr;13(2):101-7.

15. Saji N, Sato T, Sakuta K, et al. Chronic kidney disease is an independent predictor of adverse clinical outcomes in patients with recent small subcortical infarcts. Cerebrovasc Dis Extra. 2014 Aug 1;4(2):174-81. doi: 10.1159/000365565. eCollection 2014.

16. Fazekas F, Kleinert R, Offenbacher H, et al. The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol. 1991 Sep-Oct;12(5):915-21.

17. Shimizu Y, Nakazato M, Sekita T, et al. Association of arterial stiffness and diabetes with triglycerides-to-HDL cholesterol ratio for Japanese men: The Nagasaki Islands Study. Atherosclerosis. 2013 Jun;228(2):491-5. doi: 10.1016/j.atherosclerosis.2013.03.021. Epub 2013 Apr 1.

18. Wen W, Luo R, Tang X, et al. Age-related progression of arterial stiffness and its elevated positive association with blood pressure in healthy people. Atherosclerosis. 2015 Jan;238(1):147-52. doi: 10.1016/j.atherosclerosis.2014.10.089. Epub 2014 Nov 29.

19. Милягин ВА, Милягина ИВ, Пурыгина МА и др. Метод объемной сфигмографии на аппарате VaSera VS-1500. Методические рекомендации. Смоленск; 2014. 30 c. [Milyagin VA, Milyagina IV, Purygina MA, et al. Metod ob"emnoi sfigmografii na apparate VaSera VS-1500. Metodicheskie rekomendatsii [The method of volumetric sphygmography on the device VaSera VS-1500. Guidelines]. Smolensk; 2014. 30 p.]

20. Золотовская ИА, Давыдкин ИЛ, Дупляков ДВ. Эффективность терапевтической программы обучения пациентов с фибрилляцией предсердий, перенесших инсульт в режиме реального анализа данных. Кардиология: новости, мнения, обучение. 2016;(2):40-6. [Zolotovskaya IA, Davydkin IL, Duplyakov DV. The efficiency of therapeutic training of patients with atrial fibrillation who have had a stroke in real data analysis. Kardiologiya: novosti, mneniya, obuchenie. 2016;(2):40-6. (In Russ.)].

21. Давыдкин ИЛ, Золотовская ИА. Возможности снижения риска повторного инсульта у пациентов с фибрилляцией предсердий. Российский кардиологический журнал. 2015;(6):87-93. [Davydkin IL, Zolotovskaya IA. The possibility of reducing the risk of recurrent stroke in patients with atrial fibrillation. Rossiiskii kardiologicheskii zhurnal. 2015;(6):87-93. (In Russ.)].