Wayan Aryadana,

MD
Cardiac Intervensionist
 Introduction
• The determination of CAD risk is currently based on the
Framingham Risk Model and SCORE risk chart
• This model included traditional risk factors such as hypertension,
diabetes mellitus, smoking, high LDL levels, low HDL levels,
family history of premature CAD and age
• These traditional risk factors, however cannot explain the entire
risk for the incident of CAD
Traditional risk Factor
When to assess total CV risk?
 Age

• The absolute risk of CAD increases with age in both men an women
• This is caused by the accumulation of coronary atherosclerosis after
age 65
• Most new onset CAD occur after age 65
• It has been purposed that contribution of age may be a reflection of
the intensity and duration of exposure to other traditional CAD
risk factors
 Hypertension
• Hypertension is a potent risk
factor for CAD
• Hypertension prevalence is
increasing and treatment rates
remain poor
• Worldwide, hypertension
causes 7.6 million
premature deaths annually,
with 80% of this burden
occurring in low and middle-
income country
The relationship of systolic blood
pressure (BP) to subsequent risk
of coronary heart disease
mortality was evaluated in
>340,000 US men of 35–57 years
of age at the beginning of the
study and followed up for an
average of 11.6 years
 Smoking
• Other than advanced age, smoking is the single most important
risk
factor for coronary artery disease.
• Compared with nonsmokers, persons who consume 20 or more
cigarettes daily have a two- to threefold increase in total CHD
• Overall consumption rates in women now in excess of 20%
• Smoking cessation was found to reduce CHD mortality by
36% as compared with mortality in subjects who continued
smoking
 Smoking

Effect of smoking on CAD :

• Increased sympathetic tone
• Increase in blood pressure
• Reduction in myocardial oxygen supply
• Accelerating atherosclerosis process
• Enhance oxidation of low density Lipoprotein
• Impair endothelium-dependent coronary artery vasodilation
• Adverse hemostatic and inflammatory effects
 Diabetes Mellitus
• Patients with diabetes have two- to eightfold higher rates
of future cardiovascular events as compared with age- and ethnicity
matched nondiabetic individuals
• Diabetic patients have a greater atherosclerotic burden, both in the
major arteries and in microvascular tone
• In the Nurses Health Study, women who eventually developed type 2
diabetes had a threefold elevated relative risk of myocardial infarction
before the diagnosis of diabetes
 Absolute cardiovascular event
rates in randomized statin trials
• Interventions in large clinical trials to lower LDL cholesterol levels by
various approaches (e.g., bile acid–binding resins, intestinal bypass
surgery, statins) have shown a reduction in cardiovascular events.
Progression of atherosclerosis as
measured by intravascular ultrasound
 Framingham Risk Factors- level of
High Density Lipoprotein (HDL)
• Each increase of HDL cholesterol by 1 mg/dL is associated with a 2%
to 3% decrease in risk of total cardiovascular disease
• HDL could ferry cholesterol from the vessel wall, augmenting
peripheral catabolism of cholesterol
• HDL can also carry antioxidant enzymes that may reduce the levels of
oxidized phospholipids in atheromatous lesions, which could enhance
atherogenesis.
• There is of lack evidence that increasing HDL-C levels reduces risk.
Role of HDL-C and reverse
cholesterol transport
 Emerging risk factors for CAD

Coronary Artery C-Reactive Carotid Media

Lipoprotein (a)
Calcium Protein Intimal Thickness

Lipoprotein –
Homocysteine associated Leukocyte count
Phospholipase A2
 Coronary Artery Calcium
• Calcium content of the coronary arteries estimated from a radiographic
image by using 1 of several scoring systems
• The association between the presence of coronary artery
calcification (CAC) and risk of cardiovascular events has been
established for several year
• Increased coronary artery calcium is sensitive for the presence of
angiographically significant (50%) coronary stenosis
• its utility in standard practice remains unclear in asymptomatic individuals
• May be considered in individuals deemed to be intermediate risk based on
traditional risk factors, because this might lead to reclassification
 C-Reactive Protein
• A serum protein involved in immune and inflammatory responses
• Measured using -> Turbometric highly sensitive CRP assay
• Classified into :Low (<1 mg/L), intermediate (1–3 mg/L), and high (>3
mg/L)
• Elevated CRP levels were associated with an increased risk of CHD
events, independent of other traditional risk factors
• Statin therapy reduces CRP levels and that this reduction is
associated with slowed progression of atherosclerotic disease
• The cost-effectiveness of CRP screening is still being debated
 Lipoprotein (a)
• Multiple studies have suggested that Lp(a) excess seems to correlate
with CHD risk and increase in atherosclerotic burden
• Lp(a) excess has been shown in clinical trials to respond to treatment
with niacin
• The European Atherosclerosis Society Consensus Panel has recently
recommended screening for elevated Lp(a) in those at intermediate
or high CVD/CHD risk and suggested a desirable level of 50
mg/dL as a function of global cardiovascular risk, as well as use of
niacin for Lp(a) and CVD/CHD risk reduction
 Carotid Media Intima Thickness
• Thickness of the intima and media measured in common carotid,
carotid bifurcation, and internal carotid arteries
• Measured using -> High-resolution B-mode ultrasonography
• Hodis et al showed that an increase of 0.03 mm in CIMT was
associated with a relative risk for myocardial infarction (MI) or death
due to coronary cause of 2.2 (95% confidence interval, 1.4–3.6)
• No clear guidelines have been established with regard to the clinical
application of CIMT measurement
 Homocysteine
• An amino acid found in serum, produced in the liver from methionine
• Measured using-> ELISA, enzymatic, and other assays
• Plasma homocysteine has been identified as an independent risk
factor for coronary artery disease (CAD), stroke, peripheral arterial
disease, extracranial carotid arterial disease, aortic atherosclerosis
and deep vein thrombosis
• Mechanism including-> vascular injury, leukocyte recruitment,
smooth muscle cell proliferation and collagen accumulation
• Treatment of hyperhomocysteinemia has not been shown to have a
mortality benefit
 Lipoprotein-associated
Phospholipase A2
• Lp-PLA2 is a vascular-specific inflammatory enzyme
• Plasma Lp-PLA2 levels are significantly associated with changes in
coronary plaque load
• Darapladib is an Lp-PLA2 inhibitor than has been shown to reduce
serum makers of inflammation in patients already on statin
therapy
• It is has been shown to inhibit intraplaque compositional changes,
thus preventing necrotic core expansion.
 Leukocyte count
• The number of leukocytes in a given volume of blood
• Measured by -> Automated cell counters
• The total leukocyte count did not predict major CHD events
consistently
• The relationship between leukocyte count and
CHD events also varied with the timing of the assessment
of end points
Consideration of screening