Lipids and Lipoproteins in

Risk Prediction

Savvas Hadjiphilippou, BSc, MBBS*, Kausik K. Ray, BSc,

MBChB, MD, MPhil (Cantab)

PEMBIMBING
DR. JOEL HERBERT MANURUNG, SP.JP

DISUSUN
APRYANA DAMAYANTI AR
HERDYANA SILITONGA
SOPHIA L.PAA
 POIN KUNCI

 Low-density lipoprotein cholesterol (LDL-C) is

causal in the development of atherosclerotic
cardiovascular disease, and treatment has been
shown to improve coronary artery disease
mortality

 Studies measuring lipoprotein concentration using

nuclear magnetic resonance spectroscopy are
promising;
 Globally, ischemic heart disease remains the
leading cause of death .Decades of research have
demonstrated

pendahuluan
that the cholesterol cargo transported principally
by low-density lipoprotein (LDL) particles initiates
atherogenesis and is a causal factor in the
development of atherosclerotic cardiovascular
disease.

Although elevated total cholesterol

(TC) and low high-density lipoprotein cholesterol
(HDL-C) are associated with increased cardiovascular
risk, to this date given its proven causal nature,
lowering LDL cholesterol (LDL-C) has been
the main therapeutic target.

A meta-analysis quantified that a 1 mmol/

L reduction in LDL-C was associated with a 10%
reduction in all-cause mortality, a 20% reduction
in coronary artery disease–related mortality, and
a reduction of 21% to 23% in fatal and nonfatal
events.
(Fig. 1)
Cholesterol metabolism is a complex process
 TRADITIONAL LIPID RISK FACTORS
1. Non–High-Density Lipoprotein
Cholesterol a. Hazard ratios for risk of
major cardiovascular events
Non-HDL-C is the TC in atherogenic adjusted for established risk
lipoproteins after HDL-C has been factors.
subtracted and includes LDL, VLDL, IDL, b. Individual relationships
and Lp(a). between on-treatment levels
and major cardiovascular
(Table 1 )Adjusted hazard ratios for risk of events in TNT (Treating to
New Targets) trial and IDEAL
major cardiovascular events for individual (the Incremental Decrease in
lipids and lipoprotein markers. Events through Aggressive
Boekholdt Kastelein Ridker et Lipid Lowering) study.
et al,19 2012a et al,15
2008b
al,16 2005c Calculated by a Cox
LDL - C 1,13 1,15 1,62 proportional hazard model
with adjustment for the
Non-HDL- C 1,16 1,19 2,51
effects of study, age, and sex.
apoB100 1,14 1,19 2,50
c. Hazard ratios of future
apoB100/apo - 1,24 3,01 cardiovascular events among
A-I ratio
individuals in the extreme
TC/HDL - 1,21 3,81
ratio
quintiles of each measured
apoA - - 1,75 variable.
HDL- C - - 2,32
Triglycerides

Study of the relationship of triglycerides with coronary

heart disease :

The PROVE-IT TIMI 22 (The Pravastatin or Moreover, a population-based study by the

Atorvastatin
Emerging Risk Factors Collaboration (ERFC)
Evaluation and Infection Therapy–Thrombolysis in found
Myocardial Infarction 22) trial, demonstrated that that the association between TG levels and
low on-treatment TG levels (<1.69 mmol/L) were coronary
associated with reduced coronary heart disease artery disease risk was lost after adjusting
risk compared with higher TG levels (HR 0.73, for HDL-C, non-HDL-C, and standard risk
CI 0.62–0.87; P<.001). factors.

Remnant cholesterol is
Although currently no national dyslipidemia
the cholesterol found in TG-rich lipoproteins
guidelines recommend TG as a treatment
(VLDL, IDL) and TG levels are a surrogate
marker target because no randomized trials have
convincingly
of remnant cholesterol. A 1 mmol/L increase in
demonstrated benefit from TG lowering, they
remnant cholesterol is associated with a 2.8-fold
do still represent a good marker of increased
causal risk for ischemic heart disease cardiovascular
independent
risk.
of reduced HDL-C.
 High-Density Lipoprotein Cholesterol
The JUPITER trial analysis
demonstrated that residual
risk after aggressive statin
therapy is not related to
HDL-C concentrations
Further analysis of JUPITER
(The Justification for the Use of
Statins in Prevention: an
Intervention Trial Evaluating
Rosuvastatin) trial participants
with LDL-C less than 3.4 mmol/L
identified that this on-treatment
residual risk was likely to be
related to other lipid parameters,
such as apoB100 and VLDL.
Additionally, genetic
polymorphisms related to
HDL-C were not associated
with the risk of myocardial
infarction, suggesting that
raising HDL-C levels may
not reduce the risk of
myocardial infarction.
Total Cholesterol to High-Density
Lipoprotein Cholesterol Ratio

 The TC to HDL-C (TC/HDL-C) ratio does, however, have a

clearer association with cardiovascular risk.

 In an analysis of 32,826 subjects from the Nurses’ Health

Study, the TC/HDL-C ratio was found to be independently
associated with risk of coronary heart disease events among
postmenopausal women (relative risk [RR] 1.6). In addition,
the study suggested that the single TC/ HDL-C ratio may be
more useful than its separate values. Baseline TC/HDL-C ratio
was also predictive of coronary events in other studies and has
since been incorporated into many risk prediction tools.
 EMERGING RISK FACTORS
1. Apolipoproteins

 Apolipoproteins are proteins that bind  The association between apoB100

to lipids to form lipoproteins. Within and cardiovascular risk is
HDL, the main apolipoprotein is apoA-
I, whereas within LDL the main recognized within national
apolipoprotein is apoB100. guidance23,42,43 with treatment
targets (Table 2).
 ApoB100 is associated with the risk of
coronary heart disease independent of Table 2
other traditional risk factors. In the Air Secondary target levels for patients with a
Force/Texas Coronary Atherosclerosis Framingham Risk Score greater than 20%
ApoB100 Non-HDL- C
Prevention Study (AFCAPS /
TexCAPS) study, only apoB100 was a
predictor of cardiovascular risk both at Canada23 <0,0016 mmol/L <2,6 mmol/L
baseline and at 1-year follow-up,
whereas LDL-C was not (P<.001). European42 <0,0016 mmol/L <2,6 mmol/L

USA43 <0,0016 mmol/L <2,6 mmol/L

 Lipoprotein(a)

The Lp(a) gene is noted to be

the strongest monogenetic risk
factor for coronary artery
disease regardless of race

The RR for coronary heart

disease does not vary by sex,
non-HDL-C, or HDL-C,
suggesting that Lp(a) is an
independent risk factor for
coronary heart disease

In 2010, the EAS recommended screening for

elevated Lp(a) in individuals at intermediate or
high coronary heart disease risk,52 whereas
Canadia guidelines recommend the use of
Lp(a) in risk assessment of individuals at
intermediate risk or with a family history of
premature coronary artery
disease.
These can be measured using techniques such as:

Nuclear magnetic
Gel electrophoresis
resonance (NMR)

values
areexpressed as
particles per liter
Ultracentrifugation
(concentration)
ornanometers
Lipoprotein (particle size)
Particles
 SUMMARY

1. LDL-C as a causal factor in developing atherosclerotic

cardiovascular disease and evidence that despite reductions in
LDL-C residual risk remains, there has been an increasing
emphasis on identifying other lipids, apolipoproteins, and their
ratios to improve risk prediction

2. With the discovery and increasing use of other measures, such

as non-HDL-C and apoB100, coupled with techniques to
measure these, which are standardized and less influenced by
diet, there will undoubtedly be a drive to include these within
future risk prediction models after their cost-effectiveness over
traditional markers has been assessed.

3. Lipid particle concentration and size has sparked considerable

interest and, although there is an association with
cardiovascular risk, practical difficulties in using this for routine
clinical practice limits its use for now.
TERIMA KASIH