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TRANSCRIPT
Prediction of Ischemic Stroke
from Coronary Plaques Ping CHAI Senior Consultant Department of Cardiology National University Heart Centre, Singapore [email protected]
6th Asian Preventive Cardiology & Cardiac Rehabilitation Conference
Disclosure
• I have no conflict of interest to declare.
Lecture Outline
• Association of coronary heart disease and ischaemic stroke.
• Predicting stroke risk with atherosclerotic cardiovascular risk factors.
• Predicting stroke risk after myocardial infarction.
• Association of coronary plaques with ischaemic stroke.
What is the link between
coronary artery disease and
ischaemic stroke?
Atherosclerosis
• A systemic, progressive, proliferative, inflammatory and degenerative disease involving multiple arterial beds.
• Major manifestations of atherosclerosis:
– Coronary heart disease (myocardial infarction, angina pectoris, heart failure and coronary death)
– Cerebrovascular disease (fatal and non-fatal stroke, transient ischaemic attack)
– Peripheral artery disease
– Aortic atherosclerotic disease including thoracic and abdominal aortic aneurysm
Coronary Heart Disease (CHD) versus
Ischaemic Stroke (IS)
• Worldwide, an estimated 17.5 million people died from cardiovascular diseases in 2012, representing 31% of all global deaths.
• Of these deaths, an estimated 7.4 million were due to CHD and 6.7 million were due to stroke.
• Globally, age-standardized AMI incidence in all ages decreased from 1990 to 2010, from 222.7 to 195.3 per 100,000 in males and from 136.3 to 115.0 in females.
• However, age-standardized stroke incidence in all ages remained unchanged from 250.6 per 100,000 in 1990 to 258 per 100,000 in 2010.
http://www.who.int/mediacentre/factsheets/fs317/en Moran AE, et al. Circulation. 2014;129:1493-1501 Feigin VL, et al. Lancet 2014; 383: 245–55
Coronary Heart Disease (CHD) versus
Ischaemic Stroke (IS)
• Atherosclerosis accounts for >90% of CHD events but only 20% to 40% of IS.
• CHD and IS share a number of risk factors and some, but not all aetiopathogenic features.
• Cardiovascular risk factors may play different roles in overall risk of both conditions.
• Incidence of CHD highest in 5th to 6th decade of life, and decrease later on.
• Incidence of stroke increases progressively with age.
Conforto AB, et al. http://dx.doi.org/10.1590/0004-282X20130028 Soler EP, Ruiz VC. Current Cardiology Reviews, 2010, 6, 138-149
Effects of Cardiovascular Risk Factors
on CHD & IS Risk • INTERHEART Study: 12461 cases of new MI & 14637 controls in 52 countries.
• INTERSTROKE Study: 13447 cases of 1st acute stroke (77% IS) & 13472 controls in 32 countries.
Yusuf S, et al. Lancet 2004; 364: 937–52 O’Donnell MJ, et al. Lancet 2016; 388: 761–75
Risk Factor INTERHEART Adjusted for age, sex, smoking
INTERSTROKE (Ischaemic stroke)
OR (99%CI) PAR (99%CI) OR (99%CI) PAR (99%CI)
Smoking 2.27 (2.11-2.44) 36.4% (33.9-39.0) 1.93 (1.69-2.21) 15.1% (12.8-17.8)
Hypertension 2.48 (2.30-2.68) 23.4% (21.7-25.1) 2.78 (2.5-3.1) 45.7% (42.4-49.0)
Diabetes 3.08 (2.77-3.42) 12.3% (11.2-13.5) 1.33 (1.18-1.50) 7.5% (5.0-11.1)
Psychosocial 2.51 (2.15-2.93) 28.8% (22.6-35.8) 1.98 (1.56-2.52) 15.1% (10.3-21.5)
Exercise 0.72 (0.65-0.79) 25.5% (20.1-31.8) 0.63 (0.53-0.74) 33.4% (24.2-44.0)
Alcohol intake 0.79 (0.73-0.86) 13.9% (9.3-20.2) 2.14 (1.62-2.82) 4.6% (2.0-10.0)
OR: Odds ratio PAR: Population attributable risk
Effects of Cardiovascular Risk Factors
on CHD & Stroke Risk
Nguyen HN, et al. Circ J 2013; 77: 2851 – 2859
Can we predict stroke risk
from cardiovascular risk
factors?
Framingham Stroke Risk Score
Wolf PA, et al. Stroke 1991;22:312-318)
ARIC Stroke Risk Calculator
Atherosclerotic Cardiovascular
Risk Prediction
Atherosclerotic Cardiovascular
Risk Prediction
Is there an association between
stroke and coronary heart
disease?
Association Between Stroke and
Coronary Heart Disease
Gongora-Rivera F, et al. Stroke. 2007;38:1203-1210
Increased Incidence of Stroke after
Acute Myocardial Infarction
Witt BJ, et al. Am J Med 2006;119:e1-e9
Increased Risk of Ischaemic Stroke
after Myocardial Infarction
Sundboll J, et al. Stroke. 2016;47:1727-1733
• 258,806 patients with a first-time inpatient diagnosis of MI compared with a sex- and age-matched cohort of 1,244,773 individuals from Danish medical registries.
• Ischaemic stroke risk 30-fold in first 30 days after MI and 3-fold during 31 to 365 days. • Cumulative ischaemic stroke risk after 1 to 30 years was 12.6%.
Stroke Associated with Unrecognized
Myocardial Infarction
Barbier CE, et al. (J Am Coll Cardiol 2011;58:1372–7
• Cerebral MRI and cardiac late-enhancement MRI were performed on 394 randomly selected 75-year-old subjects (188 women, 206 men), subsample of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.
• Clinically recognized myocardial infarctions (RMI) were found in 21 (5%) and unrecognized myocardial infarctions (UMI) in 120 subjects (30%).
Mortality Rate After Ischaemic Stroke
Post Myocardial Infarction
Brammas A, et al. Stroke 2013;44:3050–5
• 173,233 unselected patients with AMI were collected from Swedish registry 1998-2008. • Analyzed 1-year mortality data for AMI with and without ischaemic stroke. • 1-year mortality was 36.5% for AMI with stroke and 18.3% for AMI without stroke.
Can we predict stroke risk
after myocardial infarction?
Stroke Risk Prediction After Acute Coronary
Syndrome (ACS) Using CHADS2 Score
Poci D, et al. Chest 2012;141:1431–40
a. Adjusted for all clinical variables except those 5 included in the CHADS2 score and LVEF, thrombolysis, primary PCI, other PCI/CABG, and medication at discharge.
b. Per unit increase in the original six-graded CHADS2 score.
Ischaemic Stroke Risk Prediction After MI
Using Modified R-CHA2DS2-VASc Score
Barra S, et al. Thromb Res 2013;132:293–9
Prediction of Ischaemic Stroke After MI
Using Modified R-CHA2DS2-VASc Score
Barra S, et al. Thromb Res 2013;132:293–9
R-CHA2DS2-VASc Score
Category ≤2 3-4 5-7 ≥8 Gamma for trend P
STROKE
Incidence 1.4% 3.8% 5.1% 13.6% 0.525 <0.001
ALL-CAUSE MORTALITY
Incidence 2.4% 12.1% 23.1% 52.2% 0.721 <0.001
STROKE + ALL-CAUSE MORTALITY
Incidence 3.6% 15.3% 26.9% 59.7% 0.705 <0.001
Observational retrospective single-centre cohort study including 1711 patients admitted with MI and discharged alive
Ischaemic Stroke Risk Prediction after
ACS Using 6-Month GRACE Score
Alvarez-Alvarez B D, et al. Open Heart 2014;1:e000123. doi:10.1136
Ischaemic Stroke Risk Prediction after
ACS Using 6-Month GRACE Score
Alvarez-Alvarez B D, et al. Open Heart 2014;1:e000123. doi:10.1136
Kaplan-Meier curves illustrating survival according to GRACE risk scores. Green: low risk, yellow: moderate risk and red: high risk.
High risk
Moderate risk
Low risk
Does coronary artery disease
predict ischaemic stroke?
Severity of Carotid Artery Stenosis Correlates
with Extent of Coronary Artery Disease
Steinvil A, et al. Am Coll Cardiol 2011;57:779–83
Coronary Artery Disease is Prevalent in
Patients with Ischaemic Stroke
Amarenco P, et al. Stroke. 2011;42:22-29
315 patients with no known coronary heart disease underwent coronary angiography a median of 8 days (IQR, 6 –11) after ischaemic stroke onset.
Stroke Equivalent to Coronary
Heart Disease
Can we non-invasively
diagnose coronary artery
disease and predict ischaemic
stroke risk?
Coronary Artery Calcium (CAC) Score on
Cardiac CT for CVD Risk Assessment
Budoff MJ, et al. J Am Coll Cardiol 2007;49:1860–70 Erbel R, et al. Cardiovasc Med 2015;18(3):75–82
CAC Score
• 25,253 asymptomatic subjects referred for CAC to assess CV risk.
• Mean follow-up of 6.8± 3 years. • Death rate was 2%.
Utility of Coronary Artery Calcium
(CAC) in CVD Risk Assessment
Yeboah J, et al. J Am Coll Cardiol 2016;67:139–47
Stroke is Associated with Coronary
Artery Calcium (CAC)
Vliegenthart R, et al. Stroke. 2002;33:462-465
CAC is an Independent Stroke
Predictor
Hermann DM, et al. Stroke. 2013;44:1008-1013
• 4180 subjects from the Heinz Nixdorf Recall study (45–75 years of age; 47.1% men) without previous stroke, CHD, or MI.
• Evaluated for stroke events over 94.9± 19.4 months..
• CAC determined by EBCT.
• 92 incident strokes occurred (82 ischemic, 10 haemorrhagic).
FRS: Framingham Risk Score
CAC is an Independent Predictor of
Cerebrovascular Events (CVE)
Gibson AO, et al. J Am Coll Cardiol Img 2014;7:1108–15
• 6779 asymptomatic subjects without prior CHD or stroke from the MESA study (61.9± 10.2 years of age; 47.4% men)
• Evaluated for incident cerebrovascular events over 9.5± 2.4 years.
• CAC determined by either EBCT or MDCT.
• 234 (3.5%) CVE occurred (180 strokes, 67 TIAs).
• CAC categories: ‒ 1st: CAC=0 ‒ 2nd: CAC=1-100 ‒ 3rd: CAC=101-400 ‒ 4th: CAC>400
FSRS: Framingham Stroke Risk Score
Association of CAC & Other Imaging
Parameters with Stroke Risk
Jain A, et al. Circ Cardiovasc Imaging. 2011;4:8-15
Model 1: ‒ Adjusted for
traditional risk factors.
Model 2: ‒ Adjusted for
traditional risk factors as well as imaging-derived measures (CAC, IMT, LV mass, and LV mass/volume) in the same model.
Comparison of CAC with Carotid Plaque
Parameters for Stroke Risk Prediction
Gepner AD, et al. Circ Cardiovasc Imaging. 2015;8:e002262
• 6779 MESA participants, mean age 62.2 years • 49.9% had CAC, and 46.7% had carotid plaque • After 9.5 years (mean), 538 CVD events, 388 CHD events, and 196 stroke/TIA
CAC and Risk of Dementia
Kuller LH, et al. J Am Coll Cardiol 2016;67:1013–22
Time to dementia from the initial CAC measurement was 7.1± 1.6 years for those with CAC scores of 0 versus 5.2± 3.3 years for those with CAC scores >400.
Incorporating CAC into CV Risk
Prediction
Does not predict stroke risk!
Ischaemic Stroke Risk Increased in
Patients with Obstructive CAD on CT
Lin CK, et al. SAGE Open Medicine 2: 2050312114533535
• Retrospective review of 1518 coronary CT angiogram reports.
• Patients divided into groups with obstructive (≥50% stenosis), non-obstructive (<50% stenosis) and no CAD.
• Median follow-up period of 22 months.
• Subsequent major adverse CV events and ischaemic stroke rates studied.
The incidence of ischaemic stroke was 3.8% in patients with obstructive CAD on CCTA compared to 0.4% in those with no CAD (p < 0.001).
Take Home Message
Both coronary artery disease and ischaemic stroke are manifestations of the same systemic atherosclerotic disease.
High prevalence of CAD in stroke patients.
After myocardial infarction, risk of stroke is increased and carries a poor prognosis.
Coronary artery calcium score and plaque characteristics on CT appear promising for predicting stroke risk.
More research needs to be conducted to further refine the utility of coronary plaques for stroke prediction.