1. Postulated Association Between AF and Stroke
Atherosclerotic risk factors
Genetics?
Vascular inflammation and injury + fibrosis AF
Diastolic dysfunction
Atrial myopathy
Diminished LAA flow velocities
Primary
Secondary
Dilatation
Fibrosis
Endothelial dysfunction (atrial and vascular)
LA thrombus
Hypercoagulable state
Implications
AF precedes CVA
Elimination of AF may prevent CVA
LAA closure may prevent CVA
AF (marker of vascular disease burden)
Mechanical dysfunction
Electrical heterogeneity

2. Performance of Contemporary Risk Stratification Schemes
Low Intermediate High
Study
AFI, 94
SPAF, 95
CHADS2
CHADS2 revised
Framingham
NICE, 2006
ACC/AHA/ESC, 2006
ACCP, 2008
Birmingham, 2009
C statistic
0.573
0.549
0.561
0.586
0.638
0.598
0.571
0.606
Range
Lip: Chest, 2010

3. Role of CHADS2 and CHA2DS2-VASc Scores in Predictors of Adverse Events
Patients with/without AF
High-risk CV outpatients
Chan: Atherosclerosis, 2014
Patients with ACS
Chua: PLOSOne, 2014
Patients with AFib undergoing PCI
Puurenen: Thrombosis Res, 2014
Post-STEMI patients at risk risk of AF and stroke
Lau K-K: Cardology Journal, 2014
Risk of stroke late post CABG
Biancari: J Stroke and Cerebrovascular Dis, 2012

4. Risk Factors for Thromboembolic Events in Atrial Fibrillation Patients
Hazard ratio estimates
CHA2DS2-VASc Points
Age ≥75 years
(reference <65 years) 2
Age years
(reference <65 years) 1
Previous Ischemic Stroke 2
Female Gender 1
Vascular Disease 1
Hypertension 1
Diabetes Mellitus 1
History of heart failure 1
History of intracranial bleeding
Reference
Argulian: Am J Med, 2015

5. Annual stroke event rate (%)
140,420 patients
Swedish nationwide health registry
Exclusions
Valvular AF
Warfarin exposure
4 week quarantine period after diagnosis
JACC, 2015
Annual Event Rates
Annual stroke event rate (%)
CHA2DS2-VASc Score
+TIA
+Pulmonary Embolism
+Unspecified Stroke/+Systemic Embolism
Ischemic stroke only
“Tipping point”
1.7%/yr – Warfarin
0.9%/yr – NOAC

6. Annual Stroke Rates in Different Cohort Studies Patients With CHADS2-VASc of 1
2.75
2.55
Men
Women *
2.01
%/yr
0.9 **
0.5
Registry
Denmark*
Sweden**
Taiwan***
Ref
Oleson
BMJ 2011
Friberg
JACC 2015
Chao
JACC 2015
*Hospital admission and death due to TE
** Ischemic stroke only
*** Other thromboembolic events and TIA

7. Adherence to Warfarin and NOAC – Clinical Outcomes Insurance Administrative Claims Database (USA – 100 Million Enrollees Over 20 Yr Period)
64,661 pt
Stroke or Systemic Embolism
Warfarin
Dabigatran
Rivaroxatan
Apixiban
AF (OAC)
HR 3.36
HR 2.73 NS
Hazard ratio
Adherence (80 days covered by OAC)
Cumulative time off OACs (<1 wk as reference)
1 wk-1 mo
1-3 mo
3-6 mo
6 mo
43.2%
CHA2DS2 VASc 0, 1
CHA2DS2 VASc 2, 3
CHA2DS2 VASc 4
Noseworthy P (In Press)

8. Stroke or systemic embolism (%)
Outcomes in Patients With AF Stratified by CHA2DS2-VASc Score and hs-TnT 12,892 Patients ARISTOTLE Trial
Stroke and Systemic Embolism
Cardiac Death
hs-Troponin-T (ng/L)
≤1.5
>
>6.8-13
>13
hs-Troponin-T (ng/L)
≤1.5
>
>6.8-13
>13
Stroke or systemic embolism (%)
Cardiac death (%)
CHA2DS2VASc score
CHA2DS2VASc score
Hijazi: JACC

9. Biomarkers in AFib – Future Prospects
Prediction of treatment responses
Drugs
Ablation
Assessment of bleeding risk with new oral anticoagulants
Genetic markers for tailoring of warfarin dosage
Evolution of proteomics and understanding of biological systems of disease
New biomarkers
Understanding pathophysiology of AF
New drug targets
Allow early disease detection

10. Limitations of Risk Stratification Scores for Atrial Fibrillation
The AF population is very heterogeneous regarding stroke risk
Different classifications in measuring stroke rates lead to overestimates
Incorporation of other embolic episodes into determinants of stroke risk
Current risk stratification schema are based primarily upon clinical risk factors
Differential weight of individual risk factors
Performance varies according to baseline risk of stroke which is variable among populations ?
What will be the role of biomarkers and imaging