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, PhDAssistant Professor

Medical School of Chinese PLAPhysician, Cardiovascular Medicine

PLA General HospitalBeijing, China

2015 ESC Congress-Registry I Atrial Fibrillation session

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

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):e29-322Zhao D, et al. Stroke. 2008 Jun;39(6):1668-74

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

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

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

Data resource

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

Results

Number Patient-yearsTotal individuals 425,600 1,864,232

Non-AF population 424,720 1,859,589

AF population 880 4,643

Ischaemic stroke 13,242 64,834

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

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

Baseline characteristics

Stroke incidence (per 100 person-years, 95% CI) stratified by

CHA2DS2-VASc score in non-AF and AF populations

Ischemic stroke as classified by CHA2DS2-VASc

scores

With increasing CHA2DS2-VASc scores, ischaemic stroke increased in both non-AF and AF populations

With increasing CHA2DS2-VASc scores, ischaemic stroke increased in both non-AF and AF populations

Ischemic stroke (n=13242) CHA2DS2-VASc Non-AF (n=424720) AF (n=880) 0 0.31 (0.29-0.32) 0.39 (0.11-1.40) 1 0.59 (0.57-0.60) 0.19 (0.06-0.55) 2 1.30 (1.25-1.34) 1.35 (0.79-2.30) 3 1.61 (1.55-1.67) 1.77 (1.14-2.75) 4 1.86 (1.71-2.02) 2.89 (1.62-5.10) 5 3.17 (2.48-4.04) 4.23 (1.45-11.70) Total 0.35 (0.34-0.35) 1.11 (0.84-1.45) p value for trend <0.001 <0.001

* 95% CI: confidential interval

Stroke and CHA2DS2-VASc scores

For patients age ≥75, there was no significant difference in mean CHA2DS2-VASc score between the non-AF and AF

population

* Compared between non-AF and AF individuals. SD: Standard deviation

CHA2DS2-VASc scores in the elderly

CHA2DS2-VASc scores in non-AF and AF individuals in relation to age group

Age Whole population

(n= 425600)

Non-AF (n=424720)

AF (n=880)

P*

<65, n=348431 (mean, SD)

0.69(0.66) 0.68(0.66) 1.07(0.76) <0.001

65-74, n=56952 (mean, SD)

2.34(0.88) 2.34(0.88) 2.68(0.97) <0.001

≥ 75, n=20217 (mean, SD)

2.66(0.63) 2.65(0.63) 2.77(0.74) 0.086

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

*

*

*

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 CHA2DS2-VASc

= 5

AF population: CHA2DS2-VASc score

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

Non-AF population (n=424720) Risk factors Hazard ratio 95% CI P value Dilated cardiomyopathy 4.00 1.00-16.01 0.048 Myocardial infarction 2.93 1.53-5.64 0.001 Age ≥ 75 years 2.77 2.67-2.87 <0.001 Hypertension 1.70 1.63-1.78 <0.001 Vascular disease 1.70 1.52-1.90 <0.001 Hyperlipidemia 1.52 1.36-1.69 <0.001 Diabetic 1.28 1.17-1.39 <0.001 Female 1.18 1.14-1.22 <0.001 Renal dysfunction 1.10 0.82-1.47 0.532 Heart failure 0.83 0.54-1.28 0.413 AF population (n=880) Risk factors Hazard ratio 95% CI P value Hyperlipidemia 5.32 1.83-15.45 0.002 Hypertension 3.30 1.83-5.95 <0.001 Diabetic 3.07 1.29-7.34 0.011 Vascular disease 2.80 0.65-11.99 0.165 Age ≥ 75 years 2.78 1.53-5.06 0.001 Female 1.18 0.65-2.11 0.584 Renal dysfunction 1.01 0.13-7.67 0.99 Heart failure 0.42 0.06-3.13 0.399 Myocardial infarction* - - 0.994 Dilated cardiomyopathy* - - 0.978

* 95% CI: confidential interval.

Risk factors for ischaemic stroke

Cumulative hazard of ischaemic stroke associated with CHA2DS2-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 CHA2DS2-VASc score ≥2

Conclusions Multiple risk factors raise ischaemic stroke risk in non-AF patients,

comparable to that for AF in the elderly

CHA2DS2-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

• 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

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 Guo1; Hao Wang1; Yingchun Tian4; Yutang Wang1; Gregory Y. H. Lip1,2,3

1Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China; 2University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK; 3Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Department of Gerontology, Second People’s Hospital, Yunnan Province, China

Thromb Haemostat 2015 http://dx.doi.org/10.1160/TH15-07-0577

2015 ESC Congress-Registry I Atrial Fibrillation session