1. Multiple risk factors raise ischaemic stroke risk comparable to AF in the elderly: A large Chinese insurance analysis from 425,600 Chinese individuals without prior stroke Guo Yutao, MD, PhD Assistant Professor Medical School of Chinese PLA Physician, Cardiovascular Medicine PLA General Hospital Beijing, China 2015 ESC Congress-Registry I Atrial Fibrillation session

2. Declarations of Interest The study was supported by Chinese PLA Healthcare Foundation (13BJZ40), Beijing Natural Science Foundation (7142149), and National Natural Science Foundation of China (H2501) Ethic Approval Approval number: 13BJZ40 IRB: Medical Ethics Committee of PLA General Hospital Registry number of IRB by China Food and Drug Administration ： XZF20120145

3. Introduction US age-standardized death rates from CVD A stroke/40 seconds 1 stroke death/ 20 death Sino-MONICA-Beijing: Age standardized incidence rates of ischaemic stroke in population aged 25-74 years Mozaffarian D, et al. Circulation. 2015 Jan 27;131(4):e29-322 Zhao D, et al. Stroke. 2008 Jun;39(6):1668-74

4. Stroke is a major burden in elderly patients in China Elderly population Primary prevention China 75% of strokes occur in patients age ≥65 >76% of strokes are first events Stroke mortality in Asia is higher than in Europe or North America Kim JS. Int J Stroke. 2014 Oct; 9(7):856-7. Meschia JF, et al. Stroke. 2014 Dec; 45(12):3754-832. Mozaffarian D, et al. Circulation. 2015 Jan 27;131(4):e29-322

5. Objective To investigate incident ischaemic stroke in relation to age and increasing cardiovascular risk factor(s), and the incremental impact of AF on stroke rates To explore the risk factors for developing incident stokes in the general population without prior stroke Major risk factors (i.e. AF) for stroke have been identified, however, how AF incrementally contributes to the risk for ischaemic stroke with increasing age and multiple cardiovascular risk factors is unclear

6. Data resource

7. The accuracy and sensitivity of identifying AF using ICD codes has been tested in the large Chinese insurance dataset. Guo Y, et al. Chest. 2014 Jun 12. doi: 10.1378/chest.14-0321 Patient flow chart

8. Results NumberPatient-years Total individuals 425,600 1,864,232 Non-AF population 424,7201,859,589 AF population 8804,643 Ischaemic stroke 13,24264,834 Mean time to ischaemic stroke was 4.93 (standard deviation(SD) 3.44) years, with a median of 5 (IQR 1-8) years. The follow-up period Observational period

9. Baseline characteristics of the study population (n=425,600) Baseline characteristics

10. Stroke incidence (per 100 person-years, 95% CI) stratified by CHA 2 DS 2 -VASc score in non-AF and AF populations Ischemic stroke as classified by CHA 2 DS 2 -VASc scores With increasing CHA2DS2-VASc scores, ischaemic stroke increased in both non-AF and AF populations * 95% CI: confidential interval Stroke and CHA 2 DS 2 -VASc scores

11. For patients age ≥75, there was no significant difference in mean CHA 2 DS 2 - VASc score between the non-AF and AF population * Compared between non-AF and AF individuals. SD: Standard deviation CHA 2 DS 2 -VASc scores in the elderly CHA 2 DS 2 -VASc scores in non-AF and AF individuals in relation to age group

12. Comorbidities were defined as vascular disease (coronary artery disease, peripheral vascular disease), hypertension, diabetes, or heart failure Compared to non-AF, p<0.05. A: Rate of comorbidities in population aged <65 years. B: Rate of comorbidities in population aged 65 – 74 years. C: Rate of comorbidities in population aged ≥ 75 years. The AF population more commonly had multiple morbidities compared to the non-AF population, especially in the elderly Distribution of comorbidities in non-AF and AF The rate of comorbidities in non-AF and AF population stratified by age group * * *

13. 1 2 3 4 5 Stroke incidence in non-AF and AF population. The left X and Y axes show the stroke incidence in non-AF population associated with age and comorbidities, while the right X and Y axis showed the stroke incidence in AF population classified by CHA2DS2-VASc scores. Comorbidities were defined as vascular disease (coronary artery disease, peripheral vascular disease), hypertension, diabetic, or heart failure. Comorbidity=1: any one disease of the four comorbidities. Comorbidities ≥2 : two disease or above of the four comorbidities. Non-AF population aged over 75 years with multiple comorbidities had the highest risk for the incident stroke, similar to AF population with CHA 2 DS 2 -VASc = 5 AF population: CHA 2 DS 2 -VASc score

14. Multivariate analysis of risk factors for ischaemic stroke in non-AF population and AF population Hypertension, diabetic, age ≥75 years, and hyperlipidemia also predicted the occurrence of ischaemic stroke in the AF population Myocardial infarction, aged ≥75 years, hypertension, vascular disease, hyperlipidemia, diabetic, female, and dilated cardiomyopathy were the independent risk factors for ischaemic stroke in the non-AF population * 95% CI: confidential interval. Risk factors for ischaemic stroke

15. Cumulative hazard of ischaemic stroke associated with CHA 2 DS 2 -VASc scores in the non-AF and AF population. (a) Non-AF population (all p<0.001). (b) AF population (all p<0.01). HR: Hazard ratio, 95% CI: Confidential interval. A B High risk for ischaemic stroke increases with CHA 2 DS 2 -VASc score ≥2

16. Conclusions  Multiple risk factors raise ischaemic stroke risk in non-AF patients, comparable to that for AF in the elderly  CHA 2 DS 2 -VASc score shows the good predictive ability of ischaemic stoke in the ‘general’ population, AF and non-AF  Prevention strategies for stroke adapted to the changing risk profile of geographical difference are needed to reduce the stroke burden 2015 ESC Congress-Registry I Atrial Fibrillation session

17. Not “Specific" risk factor, but multiple risk factors contribute to stroke Not “Independent effect”, but concomitant effects of risk factors confer to stroke The key issue of stroke risk is not if the patient suffers AF or not, but the numbers of risk factors and the weight of these risk factors Take home message

18. Multiple risk factors and ischaemic stroke in the elderly Asian population with and without atrial fibrillation. An analysis of 425,600 Chinese individuals without prior stroke Yutao Guo 1 ; Hao Wang 1 ; Yingchun Tian 4 ; Yutang Wang 1 ; Gregory Y. H. Lip 1,2,3 1 Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China; 2 University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK; 3 Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4 Department of Gerontology, Second People’s Hospital, Yunnan Province, China Thromb Haemostat 2015 http://dx.doi.org/10.1160/TH15-07-0577

19. 2015 ESC Congress-Registry I Atrial Fibrillation session