BSR|ProfMa.

Cardiac Biomarkers
Luisa G. Daroy || August 11, 2017
Block #1

thrombogenic core to the blood causing the infarction.

TOPIC OUTLINE Trichrome stain was used, rendering luminal thrombus and
I. Biomarkers in Heart Disease intraplaque hemorrhage red and collagen blue. Panel B is a
A. Coronary Heart Disease high-power micrograph of the area in Panel A indicated by the
B. Atherosclerosis asterisk and shows that the contents of the atheromatous
C. Risk Prediction for CVD plaque have seeped through the gap in the cap into the lumen,
II. Biomarker Assay
III. Lipoprotein
suggesting that plaque rupture preceded thrombosis (the
A. Apolipoprotein B asterisk indicates cholesterol crystals)
IV. Inflammatory Markers
A. Myeloperoxidase
B. Lipoprotein-associated Phospholipase A2
C. High sensitivity C-reactive protein
D. Interleukin- 6
V. Other Markers
A. Plasma Fibrinogen
B. Cardiac Troponin- I
C. BNP
D. Cystatin C
VI. Clinical Impact
A. Translation from Lab to Clinic
B. Multi-biomarker approach
C. Prognostic Significance
VII. Biomarker for Cardiovascular Disease
A. Genomics and Cardiovascular Medicine Initiative
B. Genotyping ACE I/D Polymorphism
C. Association of AGT M235T with severe stenosis Figure 2. Participation of Inflammation in all stages of
D. Gene Polymorphisms and hypertension
VIII. References
atherosclerosis
IX. Quiz A: Leukocyte recruitment to the nascent atherosclerotic lesion.
PPT Audio Book Blood leukocytes adhere poorly to the normal endothelium.
When the endothelial monolayer becomes inflamed, it
I. BIOMARKERS IN HEART DISEASE expresses adhesion molecules that allow leukocytes to adhere.
Pro-inflammatory cytokines provide a chemotactic stimulus to
A. Coronary Heart Disease adherent leukocytes to migrate into the intima. B: Monocytes in
Major cause of death worldwide intima transform into macrophages, express scavenger
Atherosclerosis, the underlying cause (pathophysiology) of receptors, and engulf lipid particles, thus becoming the foam
CHD, starts early in life (you can be tested at puberty) and cells characteristic of atherosclerotic lesions. T lymphocytes
progresses slowly and silently for decades join macrophages in the intima during lesion evolution and
Clinical manifestation: myocardial infarction (MI), stroke, secrete cytokines and growth factors that can promote the
angina, or sudden death at ages 50-60 y/o (men) and 60-70 migration and proliferation of smooth muscle cells. C: T
y/o (women) lymphocytes also secrete cytokines that inhibit the production
Cholesterol screening used to identify individuals at risk of of collagen by smooth muscle cells and that stimulate
developing future coronary events. However, it fails to macrophages to express collagen-degrading enzymes. This
identify 50% of individuals who develop MI each year who weakens the fibrous cap that protects the blood from the
have either normal or moderately increased serum thrombogenic lipid core of the plaque. When the plaque
cholesterol levels ruptures, a thrombus forms that is responsible for most of the
acute complications of atherosclerosis

B. Atherosclerosis C. Risk Prediction for CVD

Not simply a disease of lipid deposits (not just on
cholesterol), rather, systemic inflammation also plays a role
in atherothrombotic inception & progression
Mononuclear cells, macrophages and T-lymphocytes are
prominent in atheromatous plaques in the arterial wall. The
shoulder region of the plaque where it tapers off to go to
the sides, is the most vulnerable site for rupture in acute
coronary syndromes, is heavily infiltrated with inflammatory
cells
Cytokines have been shown to increase in acute coronary
syndromes (ACS), even in the absence of myocardial
necrosiscause de novo (new) hepatic production of acute
phase reactants such as C-reactive protein
Figure 1. Atherosclerotic Lesion in a Human Artery
Panel A shows a cross-sectioned coronary artery from a
patient who died of a massive myocardial infarction. It contains
an occlusive thrombus superimposed on a lipid-rich
atherosclerotic plaque. The fibrous cap covering the lipid-rich
core has ruptured (area between the arrows), exposing the
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Risk prediction models for heart disease based on
demographic and clinical variables:
o Good performance on population basis. HOWEVER
o May misclassify some individuals
o May underestimate long-term CV risk
Traditional risk factors (primary risk factors) such as
cholesterol, hypertension, and smoking may have less
prognostic value in secondary prevention setting than for
primary prevention; this may result from the more aggressive
management of these risk factors and the relative
importance of heart disease severity as a risk factor for
recurrent events.
In patients with established Coronary Artery Disease (CAD),
biomarkers may have the ability to capture dynamic
pathophysiological processes that are not assessed with
standard clinical measurements, such as:
o Hemodynamic function
o Stability of atherosclerotic plaque
o Microvascular damage to the kidney
Whether these are uniquely predictive beyond traditional risk
factors and standard clinical information is not yet known
Biomarker-improved risk models:
o Several biomarkers independently predict CV events when
added individually to models containing traditional
demographic and clinical variables
o Multi-marker risk prediction models
Among persons with prevalent CAD, biomarkers reflecting
hemodynamic stress, kidney damage, and inflammation
added significant risk discrimination for CV events
Traditional risk factors:
o Demographic information (age, gender)
o Clinical variables (blood pressure, cholesterol levels,
diabetes, smoking status, etc.)
Blood-based biomarkers:
o Lipoproteins (Apolipoproteins, triglycerides, LDL, HDL)
o Inflammatory markers (C-reactive protein, interleukin-6)
o Coagulation Markers (fibrinogen)
o Cardiac troponin-1
o Brain Natriuretic Peptide (BNP)
o Cystatin C
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 BSR Cardiac Biomarkers
II. BIOMARKER ASSAYS A. Apolipoprotein B
Specimen Collection: Present on chylomicrons, very low- and intermediate-density
o Blood samples are drawn in the fasting state lipoproteins, lipoprotein (a) atherogenic particles
o Serum and plasma are tested immediately, or aliquoted Measure of atherogenicity of plasma and treatment target
and stored at -70C (at very low temperatures) May be a good predictor of residual CVD risk in a statin-
Clinical manifestation: myocardial infarction (MI), stroke, treated patient
angina, or sudden death at ages 50-60 y/o (men) and 60-70 <90 mg/dL for individuals with diabetes or 2 CVD risk factors
y/o (women) and <80 mg/dl in those with known CVD or diabetes with
Cholesterol screening used to identify individuals at risk of additional CVD risk factor. These are the cut-off points for
developing future coronary events. However, it fails to Apolipoprotein B
identify 50% of individuals who develop MI each year who Independent predictor of endothelial vasodilatory function,
have either normal or moderately increased serum
increased carotid IMT (intima medial thickness), and arterial
cholesterol levels
stiffness in health subjects, as well as patients with familial
combined hyperlipidemia. Good biomarker
Table 1. Assay Methods
Analyte Specimen Method Target Process
IV. INFLAMMATORY MARKERS
NT- Plasma, ECL Cardiac
proBNP Serum Immunoassay, Hormone A. Myeloperoxidase (MPO)
point of care May have a role in CVD protection
(POC) tests Stored in leukocyte granules and released with neutrophil
Cystatin C Serum Nephelometry Renal activation
Dysfunction and
CV Risk
B. Lipoprotein-associated Phospholipase A2 (Lp-LPA2)
Albumin 24-hr Nephelometry
urine Elevated levels are associated with CVD and increased risk
of ischemic stroke (after adjustment for conventional CVD
hsCRP Serum Integra and Inflammatory
risk factors)
extended range marker
assays Pro-inflammatory substance produced by monocytes,
lymphocytes, and mast cells
Apolipo- Atherogenecity
protein B 80% bound to LDL-C, and 20% to HDL-C
IL-6 Serum Quantikine Inflammatory
Immunoassay marker C. High-sensitivity C-reactive Protein (hsCRP)
Fibrinogen Plasma Clauss assay Coagulation Predictive of CVD events such as MI, ischemic stroke, CV
marker death, incident diabetes, incident hypertension
ECL- electrochemiluminescence Prognostic for peripheral arterial disease (PAD)
Nephelometry- measures turbidity An acute phase reactant that reflects low grade inflammation
Inflammatory marker produced primarily by liver in response
III. LIPOPROTEINS to cytokines: IL-1, IL-6 and TNF-
Local production of CRP by cells in atherosclerotic plaques
may also be possible
CRP level might reflect the vulnerability of the atheromatous
lesion and the likelihood of a plaque to rupture
At concentration >15ug/mL, CRP significantly reduced
endothelial progenitor cell (EPC), inhibited the expression of
EC- specific markers (Tie-2, EC-lectin, VE-cadherin)
significantly increased EPC apoptosis, and impaired EPC-
induced angiogenesis. This process interferes with the
renewal of your blood vessel through EPCs.
o EPC- marker of the health of blood vessels
EPC-induced angiogenesis is dependent of the presence of
NO CRP treatment causes decrease in endothelial NO
synthase mRNA expression by EPCs
Thus, CRP at concentration known to predict adverse
vascular outcomes directly inhibits EPC differentiation,
survival, and function, key components of angiogenesis and
the response to chronic ischemia
o High level of CRP interferes with the renewal of blood
Figure 3. Summary of the general pathways of lipoprotein vessels and repair
metabolism Rosiglitazone (PPAR agonist) inhibits the negative effects of
Low-density lipoprotein cholesterol (LDL-C): primary target CRP on EPC biology
of therapy; an indicator of hypercholesterolemia o Rosuvastatin is also considered a therapy for this type of
High-density lipoprotein cholesterol (HDL-C): childhood condition
levels perform as well as Apolipoprotein B in predicting hsCRP assays may need further standardization to address
subclinical atherosclerosis in adulthood population-based cutoff value
Apolipoprotein B: superior to LDL-C in predicting
atherosclerotic risk
Apo B/ApoA-1 ratio is associated with increased CAD

Figure 4. Atherogenic and anti-atherogenic lipoproteins. Figure 5. Bone Marrow-derived EPCs contribute to
Apo B, apolipoprotein B; Apo A-I, apolipoprotein A-I; postnatal neovascularization. CRP, at concentrations
VLDL, very low density lipoprotein; IDL, intermediate- known to predict cardiovascular disease, inhibits EPC
density lipoprotein; TG, triglyceride; C, cholesterol. survival, differentiation and function, thereby inhibiting an

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 BSR Cardiac Biomarkers
important mechanism of angiogenesis and compensatory
response in chronic ischemia

D. Interleukin- 6
Involved in inflammation, bone metabolism, immunity,
reproduction, neural development, and hematopoiesis, and
is a major regulator of synthesis of acute phase reactants in
the liver
Source of IL-6 may be from macrophages activated by
infection or undergoing inflammatory activation in vessel
wall, with contributions from fibroblasts and endothelial cells;
also from adipose tissue
In CHD, IL-6 has more central role than CRP or fibrinogen
Cytokine genes are candidates for predisposing to CHD risk
Two polymorphisms in IL-6 promoter region: -174 G>C and Figure 7. Hazard ratios (95% CI) associated with IL-6
-572 G>C genotypes in non-smokers and smokers, after adjustment
o The number indicates the position of the guanine to for age, clinic, body mass index, systolic blood pressure,
cytosine mutation, for example 174 bases upstream of the cholesterol, triglyceride and fibrinogen levels at baseline.
transcription start site Genotypes are shown with numbers of individuals in each
Effect on blood pressure likely through inflammatory group.
mechanisms but genotype effect on CHD risk is largely GC in both a smoker and non-smoker has relatively the
unexplained by blood pressure highest risk
V. OTHER MARKERS
Table 2. Carrier frequencies and means (SD) of baseline A. Coagulation Marker: Plasma Fibrinogen
characteristics by coronary heart disease event status Association with increased CVD risk is stronger in men than
Risk Controls CHD event P-value women
Factors (n=2589) (n=762)
Age (years) 56.0 (3.4) 56.7 (3.6) 0.02 B. Cardiac Troponin - I
Body Mass 26.2 (3.4) 26.9 (3.4) 0.0024
Used for diagnosis of MI, assess the prognosis of individuals
Index
presenting with acute coronary syndrome, and select those
(kg/m2)
most likely to benefit from early invasive management
Systolic 136.7 143.9(20.3) <5x10-5
Blood Levels below the diagnostic threshold for MI may signal the
Pressure presence of CAD and increased future CVD risk even
Diastolic 83.6(11.3) 87.4 (1.3) <5x10-5 mild Troponin-I elevations may predict the presence of
Blood angiographic CAD and future CVD events including mortality
Pressure
Current 27.5% 40.1% 0.0025 C. Brain Natriuretic Peptide (BNP)
smokers Originates from the heart, representing cardiac hormone;
Cholesterol 5.71 (1.0) 6.14 (1.07) 0.00005 The major source of BNP synthesis and secretion is [from]
(mmol/L) the ventricular myocardium
Triglyceride 1.78(0.94) 2.04(1.07) 0.0005 BNP is synthesized as a prehormone (proBNP) and upon
(mmol/L) release into circulation it is cleaved in equal proportions into
Fibrinogen 2.70(0.51) 2.85 (0.50) 0.001 the biologically active BNP and the biologically inactive
(g/L) NT-proBNP fragment
IL-6 174G>C 827/1263/47 40/95/25 0.051 The main stimulus for the synthesis and secretion of both
genotype 0 molecules is myocardial wall stress, an indicator of heart
(GG/GC/CC) disease
IL-6 174C 0.43 0.45 0.329 BNP and N-terminal pro-BNP (NT-proBNP) as predictors for
freq. CVD risk (death or CVD)
IL-6 573>C 2224/225/9 135/19/0 0.656 Higher NT-proBNP levels are associated with increased
genotype long- and short-term mortality in stable CAD cases and
(GG/GC/CC) those with acute coronary syndrome, with increased risk for
IL-6 573 0.05 0.06 0.579 CVD death, MI, stroke or revascularization
freq. Synthesized by, and released from, ventricular myocardium
Based on the p-value, this indicates that it is a good in response to myocardial stretch but a variety of pro-
biomarker for CHD events. inflammatory cytokines and neurohormones may also
stimulate its release

Figure 6. Graph of the estimated survivor functions from

the Coxs proportional hazard model stratified by IL-6
genotype. Adjustment has been made for clinic, body
mass index, specific blood pressure, triglyceride and
fibrinogen levels at baseline Figure 8. Physiological effects of B-type natriuretic
GG-normal in survival curve peptide (BNP). Volume of or pressure overload leads to
GC- lower survival ventricular wall stress and BNP release. The systemic
CC- lower survival biological effects of BNP are peripheral vasodilation,
increase in natriuresis and diuresis, and inhibition of the
sympathetic nervous system (SNS) and the RAAS
It is very holistic and systemic effect on the different regions
of the body.

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 BSR Cardiac Biomarkers
Table 3. Cut-off values for BNP and NT-pro BNP for the o Increased abdominal aortic diameter in patients screened
diagnosis of heart failure of patients presenting with by ultrasonography correlated inversely with serum
dyspnea. cystatin C levels
Rule out CHF Rule in CHF o Imbalance between cysteine proteases and cystatin C in
(pg/ml) (pg/ml) arterial wall remodeling
BNP 100 500 o Cystatin C deficiency occurs in vascular disease
NT-pro BNP Study by Taglieri, Koenig and Kaski, 2009
(years) 300 450 o High cystatin C concentrations are directly relatedto
<50 inflammation, atherosclerosis, and hypermetabolic states
50-75 300 900 o Rather than circulating levels, the imbalance between
75 300 1800 proteases and inhibitors affects CV system
Lower values would let you rule out CHF while higher values o Human cathepsins (proteases) are expressed in ECs,
would likely rule in CHF SMCs, and macrophages, and are involved in the
The clinical information that can be obtained from BNP or progression, composition, and rupture of atherosclerotic
NT-pro BNP assessment is for heart failure and prognosis plaques may be genetically determined
for CAD, ACS and aortic stenosis. o High cystatin C concentration also associated with
hypermetabolic status
ROLE OF BNP AND NT-PROBNP IN CLINICAL ROUTINE:
KEY POINTS VI. CLINICAL IMPACT
Btype natriuretic peptide (BNP) and NTproBNP are reliable
biomarkers, reflecting myocardial stress caused by various A. Translation from Lab to Clinic
cardiovascular diseases For biomarkers of CV risk to make the transition from clinical
Both markers are stable in whole blood and can be research to clinical setting, the biomarkers must satisfy the
measured in clinical routine using fully automated following issues:
commercially available assays o Availability of population-based cut points for interpretation
and risk assessment in which you should have base line
The diagnostic performance of BNP and NTproBNP is
levels for particular populations
comparable and there is no meaningful difference between
the two o Existence of potential therapeutic and risk assessment
where you should have prognostication that may be done
The particular strength of BNP and NTproBNP is to rule out
with the biomarkers
heart failure in patients with shortness of breath in the
emergency department o Reliability of the analytical systems used for measurement
To be clinically useful, biomarkers must change
Both markers provide prognostic information in patients with
management. They must be able to evolve in the clinical
heart failure, coronary artery disease, and valvular heart
pathway.
disease
Assessment of CV risk vs. extending this to modifying
treatment as a result of biomarker data:
D. Cystatin C
o Rosiglitazone
o Statin: individuals without prevalent CVD who may not be
indicated for statin therapy but who are at increased CV
risk due to elevated hsCRP level may benefit from
Rosuvastatin treatment

Figure 9. Proposed mechanisms linking renal
dysfunction, inflammation, atherogenesis and
cardiovascular events
Obesity, aging, hypertension, dyslipidemia, metabolic
syndrome and heart failure increases Cystatin C, renal
dysfunction. Cathepsin production may increase cystatin C
which decreases cathepsin production and genetic factors
may decrease cystatin C.
RENAL DYSFUNCTION AND CVD
Patients with chronic kidney diseases are at high risk for
developing CVD and CV events
Cystatin C, a protease inhibitor, synthesized in all nucleated
cells, is more sensitive than serum creatinine in diagnosing
mild reductions in glomerular filtrations rate, and in
assessing renal function
Plasma cystatin C concentration is influenced by factors
such as age, BMI, sex, smoking, and high CRP
concentrations
CYSTATIN C IN CAD
Associated with increased CV risk high levels had
increased risk for all-cause mortality, CV events, and
incident heart failure
Better predictor of coronary artery calcium progression than
serum creatinine or GFR
Cystatin C has also been shown to be directly involved in the
atherosclerotic process
Study by Shi et al., 2004
o It is normally expressed in vascular smooth muscle cells
but it is severely reduced in atherosclerotic and
aneurysmal aortic lesions
B. Multi-biomarker Approach
Whether use of multiple biomarkers improves CV risk
stratification in the outpatient setting of CAD cases remains
unknown (Shlipak et al., 2009)
Ideal scheme might combine traditional risk factors known to
promote atherosclerosis (hyperglycemia, dyslipidemia, etc.)
with:
o Measures of inflammation (CRP, IL-6)
o Myocyte necrosis (troponins)
o Hemodynamic stress (BNP or NT-proBNP)
o Renal dysfunction/vascular damage (creatinine, cystatin
C, microalbuminuria)
C. Prognostic Significance
USEFUL IN:
Evaluating the risk/benefit tradeoff of possible intervention
strategies
For counselling patients about their prognosis
For making decisions about non-CV prevention strategies,
such as cancer screening
Presence of elevated NT-proBNP earlier initiation of
ACE inhibitors and beta blockers
Kidney damage by either increased albuminuria or cystatin
C trigger use of RAAS inhibitors or more aggressive
systolic blood pressure control
Inflammatory biomarkers like CRP and IL-6 have been
consistently predictive of CV outcomes, but may not be
modifiable in either primary or secondary prevention
settings
VII. BIOMARKER TECHNOLOGY FOR CARDIOVASCULAR
DISEASE
Cardiovascular disease is a leading cause of mortality and
morbidity in the Philippines and the rest of the world.
It is a life course disease that begins with the evolution of
risk factors that in turn contribute to the development of
subclinical atherosclerosis which culminates in overt
disease.
Although clinical assessment is the keystone of patient
management, such evaluation has its limitation. Clinicians
have used additional tools to aid clinical assessment and to
enhance their ability to identify the vulnerable patient at risk
for CVD.

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 BSR Cardiac Biomarkers
Biomarkers are one such tool to better identify high-risk
individuals, to diagnose disease conditions promptly and
accurately and to effectively prognosticate and treat patients
with disease.
BIOMARKER
A characteristic that is objectively measured and evaluated
as an indicator of normal biological processes, pathogenic
processes or pharmacologic responses to a therapeutic
intervention (NIH Working Group, 2001)
It may be measured on a biosample ( urine, blood, tissue
test), a recording obtained from a person (blood pressure,
ECG, Holter) or from an imaging test (echocardiogram, CT
scan)
GENETIC BIOMARKERS
Variants in the DNA code (alone or in combination with
other variants) are associated with disease susceptibility,
disease expression and disease outcome, including
therapeutic responses.
A. Genomics and Cardiovascular Medicine Initiative
The first comprehensive study of genetic variation
associated with coronary artery disease and its
complications in Filipinos
This involves integration of St. Lukes Cardiovascular
Disease Information System, GCMI Biobank and
Cardiovascular Genomics Databank
CORONARY ARTERY DISEASE (CAD) GENOMICS
1. Genes and SNPs
a. Adiponectin Gene (atheroprotective adipokine)
b. Lipoprotein Lipase Gene (catabolism of chylomicrons)
c. Plasminogen Activator Inhibitor-1 (inhibits fribrinolytic
factors)
2. Genes Affecting Response to Drugs
a. Response to Statins (cholesterol metabolism)
i. Apolipoprotein E
ii. Cholesteryl ester transfer protein
iii. Kinesin-like protein 6
b. Clopidogrel Response (inhibits blood clots in CAD)
3. Genes affecting Response to Anti-Hypertension Drugs
a. Beta blockers
b. Renin Angiotensin System
i. ACE Insertions/Deletion (ACE I/D)
ii. Angiotensin Receptor
iii. Angiotensinogen
c. Diuretic and Salt Sensitivity
i. Adducin alpha
ii. G-protein guanine binding b polypeptide 3
B. Genotyping ACE I/D Polymorphism
This was genotyped by PCR wherein primer binding sites
flanked the 287 ALU sequence deletion
A single 599-bp amplicon indicates the II (homozygous
insertion) genotype while a 312-bp amplicon indicates the
DD (homozygous deletion) genotype
o Bigger amplicon- insertion genotype
o Smaller- deletion genotype
Because the D allele in heterozygous samples is
preferentially amplified in PCR (due to shorter product
length), all DD genotyped samples were subjected to a
second, independent PCR amplification with a primer pair
that recognizes an insertion-specific sequence amplifying a
366 bp PCR product, indicating an ID genotype
The second reaction was done in multiplex with a 268 bp
beta-globin gene PCR product used as amplification control
o Housekeeping genes (Beta globin, GAPDH) are used to
verify that the PCR conditions are optimum
(Vinayagamoorthy et al., 2015)
C. Association of AGT M235T with Severe (70%) Stenosis
Univariate analysis with a larger sample size was also
performed for ACE and several other genes related to CAD
This showed no significant association to ACE I/D
polymorphism and several other genes
There was homozygosity to the angiotensinogen Thr235
allele in reference to having at least one Met 235 allele with
an Odds Ratio (OR) of 3.38
Multiple logistic regression analysis after adjustment with
several potential confounders showed that DD genotypes
poses a higher risk of developing severe stenosis when
compared with the II genotype with an OR of 4.37
This becomes more significant when compared collectively
with acquiring at least one I allele with an OR of 4.5
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D. Gene Polymorphisms and Hypertension
Only the presence of the C allele in ADR1-389
polymorphism has significant association to hypertension.
However, this association disappears when adjusted to
confounding factors
E. Summary
This was a report on the first genomics database generated
from Asian Filipinos with coronary artery disease
Genetic variations (SNPs, Indels) were analyzed using PCR-
RFLP and Taqman Real-time PCR methods.
o (Taqman is just a brand of PCR equipment, not a specific
procedure)
Allele and genotype frequencies were calculated and
presented
Chi square analysis was used to determine Hardy-Weinberg
equilibrium for all samples in a set
o The Hardy-Weinberg theorem characterizes the
distributions of genotype frequencies in populations that
are not evolving, and is thus the fundamental null model
for population genetics
o It also demonstrates that Mendelian loci segregating for
multiple alleles in diploid populations will retain
predictable levels of genetic variation in the absence of
forces that change allele frequencies.
Chi square analysis, multiple logistic regression and
univariate analysis were done to determine genetic
associations
OTHER FINDINGS:
Although LPL 447Ser>X variant was not associated with
CAD, when traditional risk factors like Type 2 diabetes
mellitus, smoking history and BMI are taken into account,
this variant appeared to be protective for CAD among non
diabetics, former smokers and overweight individuals
The adiponectin 45G- allele which is associated with low
levels of the atheroprotective adipokine was observed
more with those with Left Main Coronary Disease but did
not reach statistical significance
Association with higher risk for severe stenosis was
detected only for the homozygous deletion genotype of
ACE gene and the homozygous 235Thr genotype of the
angiotensinogen gene
Association of C-allele of beta -1-adrenergic receptor
(ADR-1) gene with higher risk for hypertension was also
detected.
ONGOING AND FUTURE WORK:
Further analysis of these polymorphisms with other clinical
traits
Multivariate analysis of the combined genetic profiles will
be performed
For next year, high throughput next generation sequencing
platform will be used for more extensive and cost effective
genetic characterization of cardiovascular and relates
diseases in Asian Filipinos
Establishment of CVDIS and Biobank for Heart Institute,
SLMC-Global City
VIII. REFERENCES
Hardy Weinberg-
https://www.nature.com/scitable/knowledge/library/the-
hardy-weinberg-principle-13235724
Vinayagamoorthy, T., Maryanski, D., Vinayagamoorthy, D.,
Hay, K.S.L, Yo, J., Carter, M and Wiegel, J. 2015. Improved
internal control for molecular diagnosis assays. MethodsX.
2:159-164
IX. QUIZ
1. T/F. BNPs are examples of coagulation markers.
2. T/F. Pro-inflammatory cytokines may trigger the release of
BNPs.
Ans: F, T
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