Outpatient Registry REGION: Prospective Follow-up Data and Outcomes in Patients After Acute Cerebrovascular Accident

Aim. To estimate outcomes and risk of all-cause mortality, cardiovascular (CV) mortality, and non-fatal CV events in patients with a history of acute cerebrovascular accident (ACVA) according to data of outpatient prospective registries.

Material and methods. 986 patients with a history of ACVA (aged 70.6Ѓ}10.9 years; 56.8% women) were enrolled into the outpatient registry REGION-Ryazan, including the registry of patients with ACVA of any remoteness (ACVA-AR) – 511 (aged 70.4Ѓ}10.5 years; 58.5% women) and the registry of patients, visited outpatient clinics for the first time after ACVA (ACVA-FT) – 475 (aged 70.8Ѓ}11.3 years; 54.9% women). Outcomes, risk of all-cause and CV mortality, composite CV endpoint (CV death, nonfatal myocardial infarction and ACVA), hospitalizations due to CV diseases (CVD) were evaluated during 37 (17;52) months of follow-up period.

Results. 310 (31.2%) patients died during the follow-up. The most part of fatal outcomes (56.4%) was registered during the first year of follow-up, especially during the first 3 months (33.9%). Mortality among men (35.9%) was higher than among women (28.0%), р=0.008. 147 (28.8%) and 163 (34.3%) patients died in registries ACVA-AR and ACVA-FT, respectively (70.4% and 90.2% of fatal outcomes were from CV causes, respectively; р=0.04). The higher risk of death was associated with the following factors: age – hazard ratio (HR) 1.10 for each next year of age (95% confidence interval [95%CI] 1.09-1.12); sex (men) – HR 2.01 (95%CI 1.55-2.62); atrial fibrillation (AF) – HR 1.42 (95%CI 1,09-1,86); recurrent ACVA – HR 1.64 (95%CI 1.23-2.19); history of myocardial infarction (MI) – HR 1.45 (95%CI 1.09-1.93); low blood hemoglobin level – HR 2.44 (95%CI 1.59-3.79); heart rate ≥80 beats/min – HR 1.51 (95%CI 1.13-2.03); diabetes – HR 1.56 (95%CI 1.16-2.08); chronic obstructive pulmonary disease (COPD) – HR 1.89 (95%CI 1.34-2.66); no antihypertensive therapy in arterial hypertension – HR 2.03 (95%CI 1.42-2.88). The lower risk of death was associated with the following factors: prescription of ACE inhibitors (ACEI) – HR 0.60 (95%CI 0.42-0.85); angiotensin II receptor blockers (ARB) – HR 0.26 (95%CI 0.13-0.50), beta-blockers – HR 0.71 (95%CI 0.50-0.99); statins – HR 0.59 (95%CI 0.42-0.82). Factors, listed above, had significant association not only with all-cause mortality but also with CV mortality and composite CV endpoint. The higher rate of hospitalizations due to CVD was associated with younger age (incidence rate ratio [IRR] for 1 year 1.03; 95%CI 1.02-1.05; р<0.001), female sex (IRR 2.40; 95%CI 1.79-3.23; р<0.001), COPD (IRR 2.44; 95%CI 1.63-3.65; р<0.001) and heart rate ≥80 beats/min (IRR 1.51; 95%CI 1.12-2.04; р=0.007).

Conclusions. All-cause mortality in patients with a history of ACVA, enrolled in outpatient registry REGION, was 31.2% during 3-year follow-up. The proportion of CV death among the fatal cases was higher in the ACVA-FT registry than in ACVA-AR registry. The higher mortality rate was associated with the following factors: age, sex (male), recurrent ACVA, history of MI, diagnosis of AF, COPD and diabetes, low blood hemoglobin level, heart rate ≥80 beats/min, no antihypertensive therapy in arterial hypertension. The higher incidence of hospitalizations due to CVD was associated with younger age, sex (female), COPD and heart rate ≥80 beats/min. Prescription of ACEI, ARB, beta-blockers and statins was associated with lower risk of death and composite CV endpoint.

1. Benjamin E.J., Muntner P., Alonso A., et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019;139(10):e56-e528. DOI:10.1161/CIR.0000000000000659/

2. Skvortsova V.I., Shetova I.M., Kakorina E.P., et al. Reduction in stroke death rates through a package of measures to improve medical care for patients with vascular diseases in the Russian Federation. The Russian Journal of Preventive Medicine. 2018;21(1):4-10 (In Russ.) DOI:10.17116/profmed20182114-10.

3. Liao Y., Greenlund K.J., Croft J.B., et al. Factors explaining excess stroke prevalence in the US Stroke Belt. Stroke. 2009;40(10):3336-41. DOI:10.1161/STROKEAHA.109.561688.

4. Piepoli M.F., Hoes A.W., Agewall S., et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016:37;2315-81. DOI:10.1093/eurheartj/ehw106.

5. Kernan W.N., Ovbiagele B., Black H.R., et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. Stroke. 2014;45(7):2160-236. DOI:10.1161/STR.0000000000000024.

6. Boytsov S.A., Pogosova N.V, Drapkina O.M., et al. Cardiovascular prevention 2017. Russian national recommendations. Russ J Cardiol. 2018;23(6):7-122 (In Russ.) DOI:10.15829/15604071-2018-6-7-122.

7. Boytsov S.A., Martsevich S.Y., Kutishenko N.P., et al. Registers in cardiology: their principles, rules, and real-word potential. Cardiovascular Therapy and Prevention. 2013;12(1):4-9 (In Russ.) DOI:10.15829/1728-8800-2013-1-4-9.

8. Suvorov A.Y., Martsevich S.Y., Kutishenko N.P., et al. Evaluation of compliance with modern clinical recommendations of cardiovascular therapy aimed at improving outcomes in patients after a stroke (according to the LIS-2 registry). Rational Pharmacotherapy in Cardiology. 2015;11(3):247-52. (In Russ.) DOI:10.20996/1819-6446-2015-113-247-252.

9. Chugunova S.A., Nikolaeva T.Y., Kuzmina Z.M., et al. Stroke epidemiology in Yakutsk based on the population-based register in 2015. Far East Medical Journal. 2017;3:80-85. (In Russ.)

10. Boytsov S.A., Lukyanov M.M., Yakushin S.S., et al. The outpatient based registry RECVASA: prospective follow-up data, risk evluation and outcomes in cardiovascular patients. Cardiovascular Therapy and Prevention. 2015;14(1):53-62 (In Russ.) DOI:10.15829/1728-8800-2015-1-53-62.

11. Loukianov M.M., Yakushin S.S., Martsevich S.Y., et al. Cardiovascular Diseases and Drug Treatment in Patients with the History of Cerebral Stroke: Data of the Outpatient Registry REGION. Ration Pharmacother Cardiol. 2018;14(6):879-86 (In Russ.). DOI:10.20996/18196446-2018-14-6-879-886.

12. Martsevich S.Y., Kutishenko N.P., Lukyanov M.M., et al. The study Hospital register of patients with acute cerebrovascular accident (REGION): characteristics of patient and outcomes of hospital treatment. Cardiovascular Therapy and Prevention. 2018;17(6):32-8 (In Russ.). DOI:10.15829/1728-8800-2018-6-32-38.

13. Cabral N.L., Muller M., Franco S.C., et al. Three-year survival and recurrence after first-ever stroke: The Joinville stroke registry. BMC Neurol. 2015;15:70. DOI:10.1186/s12883-015-0317-1.

14. Elneihoum A.M., Goransson M.., Falke P, et al. Three-year survival and recurrence after stroke in Malmo, Sweden: an analysis of stroke registry data. Stroke. 1998;29:2114-17. DOI:10.1161/01.str.29.10.2114.

15. Phan H.T., Blizzard C.L., Reeves M.J., et al. Sex Differences in Long-Term Mortality After Stroke in the INSTRUCT (INternational STRoke oUtComes sTudy). Circ Cardiovasc Qual Outcomes. 2017;10:e003436. DOI:10.1161/CIRCOUTCOMES.116.003436.

16. Radisauskas R., Tamosiunas A., Kranciukaite-Butylkiniene D., et al. Long-term survival after stroke in Lithuania: Data from Kaunas population-based stroke registry. PLoS ONE. 2019;14(7):e0219392. DOI:10.1371/journal.pone.0219392.

17. Takashima N., Arima H., Kita Y., et al. Incidence, Management and Short-Term Outcome of Stroke in a General Population of 1,4 Million Japanese. Circ J. 2017;81:1636-46. DOI:10.1253/circj.CJ17-0177.

18. Andersen K.K., Olsen T.S. Social Inequality by Income in Shortand Long-Term Cause-Specific Mortality after Stroke. Journal of Stroke and Cerebrovascular Diseases. 2019;28(6):1529-36. DOI:10.1016/j.jstrokecerebrovasdis.2019.03.013.

19. Yusuf S., Islam S., Chow C.K., et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey. Lancet. 2011;378(9798):1231-43. DOI:10.1016/S01406736(11)61215-4.

20. Rector T.S., Vickrey B.G., Wickstrom S.L., et al. Occurrence of Secondary Ischemic Events Among Persons With Atherosclerotic Vascular Disease. Stroke. 2002;33:901-6 DOI:10.1161/hs0402.105246.

21. Emdin C.A., Rothwell P.M., Salimi-Khorshidi G., et al. Blood pressure and risk of vascular dementia: evidence from a primary care registry and a cohort study of transient ischemic attack and stroke. Stroke. 2016;47:1429-35 DOI:10.1161/STROKEAHA.116.012658.

22. Goldstein L.B., Amarenco P., Lamonte M., et al.; on behalf of the SPARCL Investigators. Relative effects of statin therapy on stroke and cardiovascular events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study. Stroke. 2008;39:2444-8. DOI:10.1161/STROKEAHA.107.513747.