Prediction of Ischemic Stroke

from Coronary Plaques Ping CHAI Senior Consultant Department of Cardiology National University Heart Centre, Singapore Ping_Chai@nuhs.edu.sg

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.