PULS For Cardiovascular Disease

Using Biomarker of Endotelial Damage to Identity
Residual Risk and Predict Acute Coronary

Syndorme (ACS)
Prodia PULS Cardiac Marker and

Expanded Lipid Profile
Prodia.co.id
Cardiovascular Disease
CVDs are the number 1 cause of death globally: more people die annually from CVDs than
from any other cause.
http://www.who.int/mediacentre/factsheets/fs317/en/ Reviewed September 2016

http://www.world-heart-federation.org/fileadmin/user_upload/images/CVD_Health/Global_CVD_Atlas.pdf
CHD is a Leading Cause of Death
This presentation has been prepared specifically by Prodia. The content of this presentation may not be used,
duplicated or transmitted in any form without the written consent from Prodia. All rights reserved.
Transition Epidemiology In Indonesia
Top 10 causes of death in 2017 and percent change, 2007-2017, all ages, number
.
http://www.healthdata.org/indonesia
• Cardiac Disease remains #1 cause of death worldwide1
• 41.5% prevalence in 2015 which was not predicted to
occur until 20302
• $1 Billion a day in medical costs & lost productivity in US 3
The Clinical • Current clinical evaluation fails to identify the majority of
patients who subsequently have heart attacks
Challenge: • More than 50% of heart attack patients have normal
Cardiac cholesterol
Disease • 80% of premature deaths are potentially preventable

with early diagnosis, management of risk factors, and
lifestyle modification
• 90% of patients who have an acute
coronary syndrome will survive4
• Over half of the survivors will be
1. American Heart Association 1/17DS11775, 2017
2. Medpage Today/AHA February 15, 2017 permanently disabled within 2 years
3. CDC Foundation, April 29, 2015
4. https://www.health.harvard.edu/heart-
health/surviving-a-heart-attack-a-success-story
COVID-2019 Comorbidities
Karyono and Wicaksana, 2020, J Co Emph

What are Unusual Consequences of COVID-19?
• Severe pneumonia followed by a

cytokine storm
• Unexpected causes of death
(especially younger patients under the
age of 50)
• Blood clots
• Heart attacks
• Strokes
• Severe endothelial damage
Unexpected Cause of Death in Younger COVID-19 Patients is

Related to Blood Clotting | BioSpace
Fakta terkait Serangan Jantung
Penyakit jantung merupakan penyebab kematian dan
1 kecacatan tertinggi di dunia.1
70% pasien yang mengalami serangan jantung dan
membutuhkan perawatan di rumah sakit, memiliki 2
kadar kolesterol dalam rentang target terapi-nya.2
Faktor risiko tradisional, kurang akurat dalam
3 memprediksi risiko serangan jantung dikemudian hari.3
Lebih dari 50% serangan jantung terjadi pada orang dengan

kadar kolesterol normal atau hanya memiliki 1 faktor risiko 4
tradisional.3
75% serangan jantung karena terkoyaknya plak yang tidak

5 stabil (Unstable cardiac lession).4
1.) Murphy, et al . National Vital Statistics Reports, 2013; 61; Issue 4
2.) Fleisher, et al. 2014 . J Am Coll Cardiol. 2014; 64; Issue 22
3.) Sachdeva, et al. Li . AHJ. 2009; 157; Issue 1
4.) Hill S, et al. BMC Public Health. 2010:10:108.
terkoyaknya plak
yang tidak stabil
merupakan
penyebab terjadinya
serangan jantung
yang utama
Plak yang tidak
stabil dan terkoyak
kemudian pecah
sehingga membentuk
bekuan darah →
Serangan Jantung
lapisan lemak pada dinding Semakin banyak akan
pembuluh darah mengakibatkan peradangan Akumulasi lemak yang semakin
kemudia menyebabkan banyak dan peradangan
kerusakan jaringan meningkatkan pembentukan plak
yang tidak stabil (plak yang
mudah terkoyak)
Risk Factor
Am I at Risk?
Assessment of
Cardiovascular Risk
Assessment of ASCVD risk remains the foundation

of primary prevention
All individuals should be encouraged to follow

a heart-healthy lifestyle,
estimating an individual’s 10-year absolute ASCVD
risk enables matching the intensity of preventive
interventions to the patient’s absolute risk,
to maximize anticipated benefit and minimize
potential harm from overtreatment
Arnett et al, 2019 ACC/AHA Guideline onhasthe

This presentation beenPrimary Prevention
prepared specifically by Prodia.of
TheCardiovascular Disease
content of this presentation may not be used,
• Age
• LDL/Cholesterol
Current • BP
Cardiac Risk • Weight/BMI
Assessment • Smoking
Priorities • Sex
• Single Biomarkers (hsCRP, LP-PLA2, Myoglobin, etc.)
• Framingham, ASCVD Calculator, Reynolds etc.
Stratifikasi risiko PJK
Mengidentifikasi individu dengan kondisi subklinis secara akurat (infark
miokard atau angina tidak stabil) yang mendapat manfaat dari intervensi sedini
mungkin adalah kunci pencegahan PJK
• Beberapa model risk faktor saat dianggap kurang akurat, terutama pada
kelompok risiko intermediate.
• Hanya sekitar 20% pasien yang menggunakan kalkulator risiko untuk
mengidentifikasi risiko pasiennya
• 2 per 3 pasien misklasifikasi, underestimasi terhadap risiko serangan jantung.
What Next?
Prodia.co.id
Need a Better Way
to Evaluate Patients
1. Sachdeva, et al. Lipid levels in patients hospitalized with coronary artery disease: An
analysis of 136,905 hospitalizations in Get With The Guidelines. DOI:
http://dx.doi.org/10.1016/j.ahj.2008.08.010
2. PUBLIC RELEASE: 16-MAY-2016 American Heart Association rapid access journal report
3. Kones et al., Drug Design, Development and Therapy 2011, 5:325-380
4. Greenland et al., Circulation 2001, 104:1863-1867
• Keterbatasan -Score, Framingham 2008, ACA/AHA
Coronary Artery Disease
Also known as ischemic heart disease, Coronary Heart Disease, Coronary
Microvascular Disease
Coronary syndromes are a spectrum of conditions

CAD is caused by atherosclerosis of the
coronary arteries that leads to a
restriction of blood flow to the heart.
Depending on the degree of stenosis
(narrowing) and plaque characteristics,
patients may experience stable angina
(angina pectoris) or remain asymptomatic
until a plaque ruptures and thrombosis
occurs, causing ACS.
Patients with CAD often have ischaemic

vascular disease affecting two or more
vascular beds (known as polyvascular
disease)
Patophysiology
Artery wall with Unstable

Healthy artery wall Cardiac Lesion in danger
of rupturing
Progression of Cardiovascular Disease
Unstable cardiac lesions form progressively involving multiple biological pathways
Protein biomarkers (signals) are released into the blood stream
Fatty streaks caused by Inflammation caused by Lipid accumulation and Plaque rupture and
lipid oxidation from free oxidized lipids in the arterial inflammation increase forming
blood clot formation
radicals form in arterial wall results in tissue damage Unstable Cardiac Lesions
wall and fibrosis (Vulnerable Plaque) → Heart Attack
No single biomarker is sufficient to detect this process;

multiple biomarkers are needed
Atherosclerosis Pathophysiology
Atherosclerosis is a process of The presence of such The recruited leukocytes The expression of adhesion molecules
chronic endothelial injury or compounds stimulates the are transformed into lipid- and chemokines participate in platelet
inflammation that increases vessel cells to produce laden foam cells and are aggregation, lymphocyte and
permeability of the arterial molecules and recruit responsible for the growth monocyte adhesion, further activating
wall allowing oxidized lipid leukocytes (monocytes, of the lesion. Growth the lesion injury. A physical change in
particles to bind and granulocytes, and T-cells) factors then are released the smooth muscle cells, and cell
aggregate on the arterial to the arterial walls, and and stimulate the turnover (apoptosis), produce
surface, contributing to the stimulates the proliferation generation of new excessive amounts of collagen, elastin
formation of cardiac lesions of smooth muscle cells. capillaries through the and proteoglycans transforming the
(atheroma) process of angiogenesis lesion into a fibrous plaque comprised
providing the growing of a lipid Core and Thin
lesion with an adequate
blood supply. Vibrous Cap creating an unstable
This presentation has been prepared specifically by Prodia. The content of this presentation may not be used, lesion that is prone to rupture
CELL ADHESION, PLATELET AGGREGATION & APOPTOSIS
1. Cross et al; Current Medical Research & Opinion Volume 28, Number 11 November 2012 UK Ltd: 1829
Over 70% of Heart Attacks are Caused by Unstable
Cardiac Lesion Rupture
• Individuals frequently have no symptoms
• Risk of rupture is difficult to predict with conventional evaluations
• Detecting unstable cardiac lesion biomarkers increases the chances of identifying truly at-risk patients
NO SYMPTOMS HEART ATTACK
Blocked
Blood Flow
Endothelium Vulnerable Normal Blood Flow Vulnerable Rupture Blood Clot

Plaque Plaque
Source: New insights into atherosclerotic plaque rupture | Postgraduate Medical Journal https://pmj.bmj.com/content/77/904/94
Rupture of Unstable Lesion
PULS
(Protein Unstable Lession
Signature)
Prodia.co.id
Advance Intrepretation laboratory result
Prodia PULS Cardiac Marker
(Protein Unstable Lesion Signature)
ü Prodia PULS Cardiac Marker adalah tes darah yang dirancang untuk
membantu mengidentifikasi orang yang tampak sehat tetapi mungkin
memiliki penyakit jantung aktif yang dapat menyebabkan serangan jantung.
ü Tes ini mendeteksi tahap awal penyakit jantung dengan mengenali
cedera pembuluh darah dan pembentukan plak yang tidak stabil,
bahkan pada pasien yang tidak memiliki tanda atau gejala.
ü Prodia PULS Cardiac Test mengukur penanda protein dalam darah
yang terkait dengan plak yang tidak stabil untuk melihat apakah
serangan jantung mungkin terjadi dalam lima tahun

ke depan.
Development and Validation of a 9 Protein Unstable
Lession Signature
2. Younus M, Fan W, Harrington D, Wong N: Usefulness of a Coronary Artery Disease Predictive Algorithm to Predict Global Risk for Cardiovascular Disease and Acute Coronary Syndrome Younus M, Fan W, Harrington D, Wong
N: The Am J Card. Volume 123, Issue 5, Pages 769–775
PULS Cardiac Test Cardiac Test Development & Validation
Gene expression in mice and
1 humans Identified over 250 2 Narrowed 250 proteins to 45
detectable by immunoassay,
proteins expressed in
vulnerable coronary plaque and biomarkers like MPO,
hsCRP, and LP-PLA2 along
with all global risk factors
4 5
3 1. Method of Akaike
Multi-Ethnic NHLBI Population
2. Bayesian Method
Midwest Population
3. Drop-in Deviance
Validation: NHLBI applied the 9
Three statistical software systems All three systems confirmed 9 The 9 biomarker biomarker assessment to a
tested biomarker permutations and biomarkers and the 4 global Algorithm predicts second population MESA and
global risk factors to predict ACS risk factors who is at risk for confirmed the findings
ACS in a 5 year
period
2. Younus M, Fan W, Harrington D, Wong N: Usefulness of a Coronary Artery Disease Predictive Algorithm to Predict
Global Risk for Cardiovascular Disease and Acute Coronary Syndrome Younus M, Fan W, Harrington D, Wong N: The Am
J Card. Volume 123, Issue 5, Pages 769–775
PULS Cardiac Test1,2
A serum blood test, 40 y/o and older; <40 y/o if Native American, South
Asian, and Middle Eastern, Familial Hypercholesterolemia
Identifies the “Vulnerable Patient” at risk Measures the body’s immune response to
of a heart attack but who does not know endothelial injury (lining of the arteries)
Developed in 5 cohorts representing 41,000 patients and validated at the

NIH in MESA (Multi-Ethnic Study of Atherosclerosis)
Quantifies Endothelial Predicts Acute Coronary

Identifies Residual Risk
Damage Syndromes (ACS)
2. Younus M, Fan W, Harrington D, Wong N: Usefulness of a Coronary Artery Disease Predictive Algorithm to Predict
Global Risk for Cardiovascular Disease and Acute Coronary Syndrome Younus M, Fan W, Harrington D, Wong N: The Am
J Card. Volume 123, Issue 5, Pages 769–775
PULS Cardiac Test Cardiac Test Performance
Normal Values have a 97% Negative Predictive Value

• Serum frozen 5-8 years earlier tested to predict who would have an ACS
• All patients were disease free at admission by MESA standards
• 61% of patients who experienced an ACS detected

9 Protein Unstable Lession Signature
Membantu menurukan LDL
Menginisiasi kematian dan siklus sel.
Mencegah Kematian sel,

mengindikasikan proses Healing
Menstimulasi regenerasi, dan
perbaikan pada jaringan
sebagai marker inflamasi pada jaringan

pembuluh darah. Sinyaling molekul yang
memicu proses perbaikan
Merekrut Eosinofil
Memandu arah dan aktivitas sel imun

merekrut monosit dan macrophage
Marker Diabetes
Merekrut sel T yang mengatur

respon inflamasi pada tempat
terjadinya lesi
Result Interpretation
http://pulstest.com/
Echocardiography and
Treadmill Stress Test
CT Scan
Cardiac CT
CARDIAC CATHETERIZATION
FOR TRAINING PURPOSES ONLY. DO NOT DISTRIBUTE!
Biomarkers are read from right to left

There’s a zero line-anything that’s below is protecting
you and anything above is increasing your risk for
Zero line
having a heart attack.
• In this graph, IL16 is the primary contributor to the
PULS Cardiac Test score
• Mostly associated with: Visceral Fat, Sleep Apnea,
Physical and/or Mental Stress
IL16 is still suggestive in the 2nd or 3rd contributor to PULS Cardiac Test score
6
Progression (Stage of Disease)
• When FAS is higher than FasLigand, this is considered a a repair phase (turning off cell death)
• When Fasligand is higher than Fas, this is considered a more acute injury phase (turning on cell
death)
7
The inflammation is more significant when the biomarker is on the right side of the clinical risk factor (Age,
Family Hx and/or Diabetes).
Here, age is the biggest contributor to the PULS Cardiac Test score. The inflammation is not as critical
because the biomarker is on the LEFT side of the clinical risk factor.
8
In the above example, a cascade of activated biomarkers is evident. In these cases, more in-depth evaluation is required including potentially a cardiology
referral if the clinical situation warrants such as fatigue, shortness of breath etc. A good indicator for a more aggressive work up is if the relative risk (score
gap) is ≥ 5x expected.
10
If patient has an elevated PULS Score and is not on cholesterol medication,

In this example, patient’s HGF = 1118 pg/ml.
implementing a statin should be considered even if lipids are normal specifically for
its pleiotropic effect. HIGH HGF Pattern: >1011 pg/ml is 3 times more likely to have stroke event. Consider
carotid artery ultrasound or CIMT.
**Automatic test comment in PULS Cardiac Test Cardiac test report if elevated.
11
PULS Cardiac Test

score is normal
Female Patient: 38 years old smoker: PULS Cardiac Test score is normal but HGF is 1100 pg/ml.
Even though PULS is normal, she is at increased risk of a stroke. Lifestyle and medications (BCP) should
be reviewed and prophylactic anti-platelet therapy considered
In this example, the patient had Stem Cell transplant for Achilles rupture. This is considered a
false cardiac positive and should be repeated after 4 to 6 months.
PULS Cardiac Test Non-Compliant Patient
PULS Cardiac Test Compliant Patient
PULS Cardiac Test Post Stent
When PULS
Cardiac Test is
ELEVATED: Keep
Calm
• This is not a death sentence-the “check
engine light” is on
• Review potential contributing lifestyle

risks
• Respond to the risks and ENTIRE
CLINICAL PICTURE as necessary
• Focus on prevention
Source:
PREVENTION
80% of Heart Disease
is due to Lifestyle
80% of Heart Disease is Preventable with

6 Healthy Lifestyle Modifications
When individuals know important information about their heart health, they are empowered to make critical lifestyle
changes that can save their life
+
Nutrition/ Physical Smoking/ Stress Compliance Sleep
Diet Activity Substance Management with prescribed
Cessation medication
1. Yusuf S, Hawken S, Ounpuu S, et al, for the INTERHEART Study Investigators. Effect of potentially
modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study):
case-control study. Lancet. 2004 Sep 11-17. 364 (9438):937-52.
Apakah yang dapat menurunkan skor PULS?
9 Protein Unstable Lession Signature
biomarker-biomarker sebagai penanda pembentukan plak yang tidak
stabil yang merupakan pma serangan jantung.
Fokus pada pengurangan faktor risiko. Anda dapat melakukannya dengan:

• Makan banyak makanan berbeda yang rendah lemak, gula, dan garam.
Makanlah buah-buahan dan sayuran setiap kali makan dan minum lebih
banyak air daripada minuman manis. Ini dapat membantu Smoking/
Nutrition/ Physical
Substance
meningkatkan tekanan darah, gula darah, kadar kolesterol dan Diet Activity
Cessation
menyebabkan penurunan berat badan.
• Tetap aktif secara fisik dengan olahraga teratur akan membantu
mengendalikan berat badan, menurunkan tekanan darah, dan kadar
kolesterol LDL. Hindari duduk lebih dari satu jam setiap kali.
• Minum obat yang diresepkan oleh dokter Anda untuk menurunkan
tekanan darah, kolesterol darah, dan kadar gula darah. Penting bahwa
Anda berbicara dengan penyedia medis Anda untuk mengembangkan
+
Stress Compliance Sleep
rencana yang bekerja untuk Anda. with prescribed
Management
medication
Select Contributing Risk Factors That Can Induce
Endothelial Injury and Inflammation
Examples of contributing Risk Factors
Metabolic Syndrome  Cholesterol  Visceral Fat
 Insulin Resistance  High Triglycerides
 Weight gain BMI >30  Diabetes
 Blood Pressure  Low HDL
Oxidative Stress  Diet (Process Food, Sugar, Trans Fats, Refined  Physical stress
(Systemic Inflammation) Carbs, Deep Fried Food, Etc.)  Sleep Apnea
Imbalance between free  Gut health (Microbiome)  Smoking / COPD
radicals &  Vitamin deficiency / malnutrition  Lack of Exercise
antioxidant
 Lack antioxidant  Too Much Exercise
 Pollution / UV Rays  Mental stress
 Viral Infection  Depression
 Bacterial Infection  Anxiety
 Periodontal Disease  Lack of sleep
Medications  Long term drug therapy  Proton Pump Inhibitors
 Poly Pharmacy  Psychoactive Drugs
 Substance abuse (Opioids and alcohol) (Anti-Depressant, Bipolar Meds)
 NSAIDs
Auto Immune Disease  Psoriasis  MS
 Lupus  IBD
 RA
Hormones  Thyroid
 Hormone imbalance
 Menopause
Cancer  Cancer Dx
 Cancer drugs
 Chemotherapy
Prodia PULS Cardiac Marker Empowering Prevention
Economic Health Benefits
Conclussion
Don't wait for symtomp !!!
• Assessment of ASCVD risk remains the foundation of primary prevention

• Expanded Lipid Profile Suitable for measure traditional risk factors After age 20 years
with easier interpretation regarding ACC/AHA guideline.
• Prodia PULS Cardiac Marker A Simple Blood Test that Detects the Leading Cause of
Heart Attacks: Unstable Cardiac Lesion Rupture.
• Prodia PULS Cardiac Marker provide:
• PULS Profile : A patient’s personalized 5-Year diagnosis and prognosis of Unstable Cardiac Lesion
Rupture
• Heart Age: A calculated “Heart Age” which shows the patient’s Cardiac Risk Score relative to their
Age and Gender group.
• Lifestyle Changes :Specific recommendations for reducing risk according to clinical guidelines.
Thank You
1500-830 e-prodia @prodia_lab Laboratorium Klinik Prodia
Prodia.co.id

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Using Biomarker of Endotelial Damage to Identity

Residual Risk and Predict Acute Coronary

Prodia PULS Cardiac Marker and

http://www.who.int/mediacentre/factsheets/fs317/en/ Reviewed September 2016

Disease • 80% of premature deaths are potentially preventable

Karyono and Wicaksana, 2020, J Co Emph

• Severe pneumonia followed by a

Unexpected Cause of Death in Younger COVID-19 Patients is

Lebih dari 50% serangan jantung terjadi pada orang dengan

75% serangan jantung karena terkoyaknya plak yang tidak

Assessment of ASCVD risk remains the foundation

All individuals should be encouraged to follow

Arnett et al, 2019 ACC/AHA Guideline onhasthe

Coronary syndromes are a spectrum of conditions

Patients with CAD often have ischaemic

Artery wall with Unstable

Protein biomarkers (signals) are released into the blood stream

No single biomarker is sufficient to detect this process;

NO SYMPTOMS HEART ATTACK

Endothelium Vulnerable Normal Blood Flow Vulnerable Rupture Blood Clot

serangan jantung mungkin terjadi dalam lima tahun

Developed in 5 cohorts representing 41,000 patients and validated at the

Quantifies Endothelial Predicts Acute Coronary

Normal Values have a 97% Negative Predictive Value

• All patients were disease free at admission by MESA standards

• 61% of patients who experienced an ACS detected

Menginisiasi kematian dan siklus sel.

Mencegah Kematian sel,

sebagai marker inflamasi pada jaringan

Memandu arah dan aktivitas sel imun

Merekrut sel T yang mengatur

Biomarkers are read from right to left

Progression (Stage of Disease)

If patient has an elevated PULS Score and is not on cholesterol medication,

PULS Cardiac Test

• Review potential contributing lifestyle

80% of Heart Disease is Preventable with

Fokus pada pengurangan faktor risiko. Anda dapat melakukannya dengan:

• Assessment of ASCVD risk remains the foundation of primary prevention

1500-830 e-prodia @prodia_lab Laboratorium Klinik Prodia

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