This document discusses coronary heart disease in young adults. It finds that while most coronary disease occurs in older populations, 2-6% of acute coronary events occur in younger "premature" patients under 55 years old. Major risk factors for young adults include smoking, family history of early heart disease, male gender, and hyperlipidemia. Diagnostic tests may include electrocardiograms, stress tests, echocardiograms, CT angiograms, and calcium scoring. Aggressive risk factor modification including smoking cessation and statin therapy is important for prognosis. While short term outcomes of revascularization are good, long term mortality is still elevated compared to the general population.

1. NEW PERSPECTIVES OF
CORONARY HEART
DISEASE IN YOUNG
ADULTS
MBCHB(HON) MD FRCP FACC FESC FSCAI FAMS
DR STANLEY CHIA
CARDIOLOGIST
INTEVENTIONAL CARDIOLOGIST
ASIAN HEART & VASCULAR CENTRE

2. ISCHAEMIC HEART DISEASE IN
YOUNG ADULTS
• Cardiovascular disease is the leading cause of
death in the world
 2nd commonest cause of death and
hospitalization in Singapore
 80% of CVD due to coronary artery disease
• Large body of data and research on CAD, but...
little data on premature CAD or “young” MI

3. Socioeconomic
burden
Heart Attack
Patient’s
psychology
CORONARY DISEASE/MYOCARDIAL
INFARCTION IS MORE THAN LIFE AND DEATH
Ability to work
Impact on
family
Long-term
morbidity

4. 34 YEAR OLD MAN
• Breathless on exertion for several months
• Diabetes mellitus x10 years
• Recently diagnosed hypertension,
hyperlipidaemia
• Non-smoker
• Found to be in renal failure and heart
failure – Left ventricular ejection fraction
35%, moderately impaired

5. Severe left circumflex
artery stenosis
Severe left anterior
descending artery stenosis
Severe Double Vessel Disease

6. 25 YEAR OLD MAN
• Recent severe chest tightness
• Smoked 20 cigarettes/day
• Overweight
• Found to have elevated cholesterol levels
• Electrocardiogram showed evolved
inferior MI
• Cardiac Biomarkers were positive for MI

7. Severe left circumflex artery stenosis
Severe left anterior
descending artery stenosis
Occluded right coronary artery
Severe Triple Vessel Disease

8. “I’M YOUNG, I DON’T NEED TO
WORRY ABOUT HEART DISEASE"
Heart disease is more common
among older people …

10. DEFINITION OF “YOUNG”,
PREMATURE CAD/MI
• Definition of premature CAD varies in literature
from <35 to <55 years old
• Spectrum of terminology of young CAD:

11. EPIDEMIOLOGY OF “YOUNG”
CORONARY ARTERY DISEASE
• 10 year incidence: (Framingham Study)
• MI < 55 years: 51/1000 in men, 7.4/1000 in women
• CAD: men 30-34 yrs: 12.9/1000, women 35-44 yrs: 5.2/100
• Young patients account for 2-6% of all acute coronary events
• Gender: Median age of presentation in women is higher than
men. In Singapore, men have 4x greater risk then women for
age <65
• Ethnicity: South Asian “young” CAD prevalence ~5-10% (other
ethnic groups ~1-2%). Earlier onset: ~53 yr. Europeans ~63 yr.

12. RISK FACTORS
• The global INTERHEART study identified 9 risk
factors that account for >90% of MI
• Traditional CV risk factors apply to all ages
• Majority of “young” patients have at least one
identifying CV risk factor
• Higher prevalence of smoking, family history, male
gender, hyperlipidaemia
• Lower rates of prior CHD history, DM, Hypt
Yusuf, et al. Lancet 2004

13. Yusuf, et al. Lancet 2004
Lipids
Smoking
Diabetes
Alcohol
HEART ATTACK
RISK FACTORS
Lack of
Exercise
Lack of Fruits and
Vegetables
Hypertension
Abdominal
obesity
Psychosocial

14. SMOKING
• Probably most common and important
modifiable risk factor among “young” adults
• Stronger association of smoking with MI in
young pts (odds ratio 3.33 vs 2.44, Yusuf et al. 2004)
• Smoking rates among “young” MI ~51%-89%
• “Young” patients smoked more per day, but
fewer pack years prior to MI

15. FAMILY HISTORY
• Prevalence of FH 2-4 fold higher vs older patients
• 41-71% of “young” MI patients have family history
of heart disease (1st deg relative <55-60 years)
• Strong predictor of future acute coronary event
GENDER BIAS
• Vast majority in men ~79-95%
• Up to 90% of patients presenting with MI were men
• One potential reason that young women may experience
delays in prompt care

16. HYPERLIPIDAEMIA
• Traditional risk for CHD in all age group
• Association less robust than other risk factors
• Familial-combined hyperlipidaemia reported to
have relatively high prevalence up to 38%
• Young MI exhibit higher endogenous cholesterol
synthesis and higher non-HDL cholesterol
• ApoB/ApoA1 ratio strongly associated with MI,
especially in the “young” (odds ratio 4.35)

17. OTHER TRADITIONAL RISKS
• Diabetes mellitus Lower rates than older
• Hypertension patients with MI
• Diabetes mellitus: Increased risk for MI (odds ratio 8)
• Hypertension: Higher rate of untreated patients
• Higher BMI / Central obesity
 As prevalence of obesity increasing – potential
future epidemic!

18. OTHER RARE CAUSES
• Cocaine use
• Spontaneous coronary artery dissection (more common
in women, peripartum, idiopathic, atherosclerotic)
• Kawasaki disease
• Factor V Leiden
• Low levels of oestrogen
• Oral contraceptive pill
• Hyperhomocysteinaemia
Kawasaki disease

19. RARE RISK FACTORS –
GENETIC POLYMORPHISMS
• Cholesterol ester transfer protein (CETP) gene – significant
association with progression of atherosclerosis
• ApoE4 allele – homozygous individuals at risk of
hyperlipoproteinaemia
• MTHFR gene – homocysteinaemia
• Hepatic lipase – HDL metabolism
• Familial hypercholesterolaemia – mutations in LDL receptor
ApoB, PCSK9, ApoE gene

21. PATHOPHYSIOLOGY OF
“YOUNG CAD”
• 80% accounted by Conventional coronary
atherosclerotic disease
• 4% due to congenital coronary anatomy
• 5% due to embolic phenomenon
• 5% associated with coagulopathy
• 6% due to spasm, inflammatory disease,
radiation, trauma, substance abuse

22. CLINICAL PRESENTATION OF
“YOUNG MI”
• Presentation: Two-thirds NSTEMI, One-third STEMI
• Prodrome: Most have no previous angina, MI or CHF
• Only ~25% men had chest pain in prior 1 mth. Rate even
lower among women. Compared to 2/3 in older adults
• Extent of disease: Usually less extensive, usually single
vessel disease. Less than 10% Triple vessel disease
• Spontaneous coronary dissection – rare disease – but not
as infrequent in young women.

23. Spontaneous Coronary Dissection
Coronary Atherosclerosis
Coronary
Artery
Spasm

24. Severe left circumflex
artery stenosis
Post Left main-LAD-LCx
stenting
Left main dissection
Post aspiration

25. MANAGEMENT
• Guidelines-recommended therapies apply
-- Not age-dependent
• Risk factor modification is of utmost importance
• Smoking cessation – 1/3 relative risk reduction for
mortality as well as for recurrent events
• Young patients generally do well with revascularization
(Coronary stenting, bypass surgery as appropriate)

26. RISK REDUCTION WITH STATINS IN
PRIMARY AND SECONDARY PREVENTION

27. LEVEL OF
RISK
PRIMARY TARGET SECONDARY TARGET
VERY HIGH LDL-C <70 MG/DL (1.8 MMOL/L) OR ≥50%
↓ IF BASELINE 70−135 MG/DL (1.8−3.5
MMOL/L)
NON-HDL-C <100 MG/DL
(2.6 MMOL/L) OR APOB
<80 MG/DL
↓ IF BASELINE 100−200 MG/DL (1.8−3.5
MMOL/L)
HIGH LDL-C <100 MG/DL (2.6 MMOL/L) OR ≥50% NON-HDL-C <130 MG/DL
(3.4 MMOL/L) OR APOB
<100 MG/DL
MODERATE LDL-C <115 MG/DL (3.0 MMOL/L) NON-HDL-C <145 MG/DL
(3.8 MMOL/L)
LOW LDL-C <115 MG/DL (3.0 MMOL/L) NON-HDL-C <145 MG/DL
(3.8 MMOL/L)
LIPID TARGETS

28. LDL-C: low-density lipoprotein cholesterol; LDLR: low-density
lipoprotein receptors; PCSK9: proprotein convertase subtilisin-
like/kexin type 9; SREBP: sterol regulatory element binding protein
ROLE OF
PCSK9

30. CV
death,
MI,
stroke
Hosp
for
UA
or
Cor
Revasc
CV
death,
MI,
stroke
• Patients with atherosclerotic disease, LDL of 70 mg/dL
• Evolocumab on a background of statin therapy lowered LDL
cholesterol levels by 30 mg /dL (0.78 mmol/L)
• Further Reduced the risk of cardiovascular events.

31. PROGNOSIS POST-MI
• Both PCI and CABG are associated with excellent
Immediate and medium-term survival (at 5yrs)
• Short term mortality low compared to older adults
• However 5 years post-MI, drop in survival
• Long term mortality exceeds 15% at 7 years, and
25-29% at 15 years
• Compared to general population, mortality
increased by 74-fold
Barbash et al. Eur Heart J 1995
Fournier et al. Am J Cardiol 2004
Zimmermann et al. JACC 1995

32. PROGNOSIS
• Predictors for Mortality: Presence of heart failure,
ventricular arrhythmias, angina, re-infarction
• Strongest predictor of prognosis is left ventricular
ejection fraction
• LVEF <45% (Odds ratio 4.4. 95% CI 1.6-124)
• Obesity and smoking are also associated with
adverse outcomes – mortality and future acute
coronary events

33. PROGNOSIS
• Gender: Mortality of is 2x higher in women
than in men < 50 yrs
• Diabetes and Multi-vessel CAD: PCI had lower
event-free survival (revascularization, CVA, MI)
at 5 years
• Reduction of Health-related quality of life
• Angina
• Depression

34. WORKUP OF SUSPECTED YOUNG
CAD
• Description of symptoms – typical and atypical
• Conventional Risk factors – diabetes, BP, Lipids
• Family history – 1st degree relative, IHD, SCD
• Social habits – Smoking, drugs, exercise
• Further risk stratification
1. Electrocardiogram
2. Exercise stress test
3. Echocardiogram

35. COMMON SCREENING TESTS
1. Electrocardiogram (ECG)
2. Exercise Treadmill ECG Test
3. Stress Echocardiogram
4. Myocardial Perfusion Imaging
5. Computed Tomography Coronary Angiogram

36. 1. Electrocardiogram
2. Exercise Stress Test

37. 3. Echocardiogram
4. Myocardial Perfusion Scan

38. CT CoronaryAngiogram and
Calcium Scoring

39. ASSOCIATION OF CORONARY
CALCIUM WITH CHD AND DEATH IN
YOUNG ADULTS
• Individuals aged 32-46 years (n~3000+)
• Prospective community study, calcium score measured at
baseline and follow up 12.5 years
• Presence of any calcium was associated with 5-fold increased risk of
CHD events and 3-fold increased risk of CVD events
• Calcium score of >100 associated with early death (hazard ratio
3.7)
• Coronary calcium associated with risk of CAD, CVD, death
• Carr JJ, et al. JAMA Cardiol 2017;2:391-399

40. Carr JJ, et al. JAMA Cardiol 2017;2:391-399

41. • 4146 patients with stable chest pain
• Following exercise stress test, randomized to CT coronary
angiogram vs standard care (stress echo, nuclear
perfusion etc)
• Median follow-up 5 years – Death and non-fatal MI
The Scot-Heart Investigators. N Eng J Med 2018 Aug.

42. The Scot-Heart Investigators. N Eng J Med 2018 Aug.
• CTCA group had a lower 5-year event rate of death and
non-fatal MI vs standard care (2.3% vs 3.9%, HR 0.41-
0.84, P=0.004)
• Overall rates of angiogram, revascularization similar, but
more patients in CTCA group had preventive therapies
(aspirin, statins) and anti-anginal therapy.

43. SO HOW DID WE
MANAGE THE “BOY”
WITH TRIPLE VESSEL
CORONARY DISEASE?

44. Severe left anterior
descending artery stenosis
Occluded right coronary artery

45. Severe left circumflex artery stenosis

46. MORE IMPORTANTLY…
• Risk Factor control
• Smoking cessation
• Diet, weight loss, cardiac rehabilitation
• Chronic Anti-platelet therapy
• Aggressive lipid lowering
1. Statins
2. Ezetimibe
3. PCSK9 inhibitors

48. Mount Elizabeth Novena Specialist Centre
Mount Elizabeth Medical Centre
Gleneagles Medical Centre