The document provides a cardiovascular disease risk report for a 60-year-old male client. It includes information on risk factors such as total cholesterol, blood pressure, family history of CVD, and diabetes. It finds the client has a high 34% 10-year risk of CVD based on risk factors. It also finds moderately elevated troponin levels, indicating possible heart injury, and a moderate genetic predisposition to CVD based on analysis of 17 genetic markers. It recommends the client increase physical activity, consult a cardiologist due to the elevated risks, and inform the cardiologist of any planned medications due to results of a CVD pharmacogenetics test.

1. Cardiovascular Disease Risk Report
Personal Information
Name of the Client XYZ
Age 60 Years
Gender M
Weight 68 Kg
Height 5’ 5”
Total Cholesterol 240mg/dl
HDL cholesterol 40mg/dl
Blood Pressure (Systolic) 125mmHg
Blood pressure (Diastolic) 90mmHg
Diabetes Yes
Family History of CVD Yes
Your Summary Results
Physical Activity MET-min/week 540 MET-mins Moderate exercise
Troponin I Test 0.02 ng/ul Elevated level
CVD Clinical Risk Score 34% High CVD risk
Genetic Predisposition Score 2.76 Moderate Risk
CVD Pharmacogenetics See Results below
Your Summary of Actions to be taken:
Sr.No. Actions to be taken
1 Physical Activity MET – Follow plan as advised by Trainer to increase MET-min/week
2 Troponin levels elevated – Investigate occurrence of heart muscle injury
3 CVD Clinical Risk Score High – advice immediate Cardiology Consultation
4 CVD Genetic Predisposition Score – Moderate – but in view of 2&3 above advice
immediate Cardiology Consultation
5 CVD Pharmacogenetics – inform Cardiologist before starting medicines

2. Detailed Report
1.0 Physical activity Report
Regular physical activity reduces the risk of obesity, blood lipid abnormalities, hypertension,
and non-insulin dependent diabetes mellitus and has been shown to reduce substantially the
risk of coronary heart disease (PMID:15044412).
Leisure-time exercise, including as much as 35-40 minutes per day of brisk walking, was
protective for CHD risk. Reduced sedentary behaviour and TV time also makes positive
impact on lowering the risk.
Physical activity can be measured in terms of MET-min. One MET minute equals one minute
spent at a MET score of 1 (inactivity). To reach 1,000 MET minutes, a person could combine
brisk walking and low-impact aerobics, both with a MET score of 5, for 200 minutes a week (5
x 200 = 1,000). Generally, an improvement in health requires 500-1000 MET minutes a week.
We have developed a calculator to measure number of calories burnt through the physical
activity. You Met-min per week is 540 which is moderate. You need to increase the physical
activity till it achieves MET-min in the range of 6000 to 1000. This achievement will improve
your lipid profile and blood sugar levels and thereby decrease the clinical risk of CVD.
2.0 Troponin I Test Report
This test measures the levels of cardiac biomarkers in your blood. These markers include
enzymes, hormones, and proteins.
Cardiac biomarkers show up in your blood after your heart has been under severe stress and
becomes injured because it isn't getting enough oxygen. These markers start appearing in
individuals who are apparently healthy. This might be because of silent cardiac events or these
levels can be elevated for other reasons. The levels of biomarkers are often used to provide
an indication of cardiac events in your body.
The following cardiac biomarkers can be used to diagnose cardiac events:
Cardiac Troponin. This protein is by far the most commonly used biomarker. It has the highest
known sensitivity. It enters into your bloodstream soon after a heart attack. It also stays in your
bloodstream days after all other biomarkers go back to normal levels. Two forms of troponin
may be measured: Troponin T and Troponin I. Troponin I is highly specific to the heart and
stays higher longer than Creatinine Kinase-Myocardial Band (CK-MB). Current guidelines
from the American Heart Association (AHA) say this is the best biomarker for characterizing
a cardiac event.
Troponin I Test Report
Name: XXYZ Age: 65 years Sex: Male Referred by: Dr. Cardio, MD
Sample Receipt Date: 27-08-2022 Reporting Date: 27-08-2022

3. Test Name Results Biological Range Units
Troponin I 0.01 0.0 to 0.01 ng/ul
Signed by
Dr. ABC, MD (Cardio)

4. 3.0 CVD Clinical Risk Score Report
We have developed a Cardiac Clinical Risk Calculator for the Indian population aged between
25 to 74. This risk score is applicable to those who had not yet had any known previous heart
disease or event. The score predicts 10-year risk for heart attack, stroke and Cardio Vascular
Disease (CVD).
CVD Clinical Risk score is based on Age, raised Cholesterol and Lipid profile, raised blood
pressure, Body Mass Index (BMI), Type 2 Diabetes, smoking & tobacco use, physical activity
and family history of cardiac events.
Your CVD Clinical Risk Score is 34%
CVD Clinical Risk Score:
1) Risk score < 10 - Low risk
2) Risk score > 10 and < 20 - Moderate risk
3) Risk score > 20 - High risk
3.2 Risk Factors for CVD clinical Risk
Smoking: Number of cigarettes smoked per day
Cholesterol: Lipid profile including total cholesterol, HDL, LDL and triglyceride levels and
HDL to total cholesterol ratio
Diabetes: Type 2 Diabetes is also a risk factor included in the clinical risk score
Blood Pressure: Blood pressure is one of the significant factor and Blood pressure
medication is also considered for the risk calculation.
Obesity: BMI is one of the risk factor included in the CVD risk calculation.
Family History: indicates genetic disposition

5. 4.0 CVD Genetic Predisposition Risk Report
Cardiac Genetic Predisposition Risk Panel is designed to highlight confounding factors barring
appropriate cardiovascular risk reduction in patients. The panel focuses on 17 genetic markers
affecting Coronary artery disease, Myocardial infarction, Myocardial Ischemia, Stroke,
hypertension, total cholesterol, LDL (low-density lipoproteins) and HDL (high-density
lipoproteins) cholesterol, triglycerides, thrombotic risk, homocysteinemia, insulin resistance,
and statin-induced myopathy risk.
Your CVD GPRS is calculated based on the number of risk alleles associated with CVD
predisposition in 17 SNP markers associated with the CVD risk.
CVD What is GPRS?
Genetic predisposition Risk Score (GPRS) give cumulative risk score based on the number of
SNP risk alleles associated with a trait. GPRS is not significant as Genetic Predisposition can
be overcome with suitable lifestyle and nutritional modifications.
GPRS= Genetic Predisposition Risk Score
GPRS Scale
0.1 to 1.5: Typical normal risk
1.51 to 3.00: Moderate risk
3.10 o 5.0: Increased risk
CVD Genetic Predisposition Risk Results
Cumulative CVD Genetic predisposition risk score 2.76
CVD Type GPRS Score
Atherosclerosis 1.50
Coronary artery disease 3.75
Myocardial infarction 4.00
Myocardial Ischemia 3.75
Thrombosis risk 2.60
Stroke 1.45
Hypertension 2.80
HDL 1.25
LDL 3.80
Triglycerides 2.75
Homocysteinemia 1.70
Statin risk 2.60
Genetic Markers Included Genetic Predisposition Risk Calculation
9p21 – The genetic marker 9p21 is strongly associated with coronary artery disease.
Researchers believe that mutations in this region may affect uncontrolled cell proliferation
leading to atherosclerosis, and eventually coronary artery disease. Carrying one variant allele

6. increases the risk of coronary artery disease by 25 percent, with the risk doubling in a person
with two of these variant alleles.
9p21 – The genetic marker 9p21 is strongly associated with coronary artery disease.
Researchers believe that mutations in this region may affect uncontrolled cell proliferation
leading to atherosclerosis, and eventually coronary artery disease. Carrying one variant allele
increases the risk of coronary artery disease by 25 percent, with the risk doubling in a person
with two of these variant alleles.
AGT – Angiotensinogen (AGT) is a protein produced by the liver, which plays a role in the
renin-angiotensin-aldosterone system (RAAS). This system is crucial for maintaining blood
pressure and cardiovascular homeostasis, and is a target of many antihypertensive drugs. A
hyperactive RAAS resulting from genetic variants, in addition to environmental factors, can
lead to coronary artery disease.
APOE - Apolipoprotein E (APOE) is a lipid/protein complex associated with chylomicron
formation and the transport of dietary lipids via binding of the LDL (low-density lipoprotein)
receptor. APOE is synthesized mainly in the liver, with a small amount of synthesis occurring
in other organs such as the brain. There are three alleles of the APOE gene: E2, E3, and E4.7
E2 is a protective allele, and individuals with this variant have a reduced risk of coronary
disease. E3 is considered the normal variant of APOE and not associated with any altered risk
of cholesterol management. E4 is the risk allele and is associated with increased cholesterol
levels, as well as coronary disease, myocardial infarction, stroke, and Alzheimer disease.
CDKN2B‐AS1 - Cyclin‐dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B‐AS1) is a
significant susceptibility locus for cardiovascular disease by regulating inflammation
response and cell cycle.
eNOS/NOS3 – Nitric oxide synthase (NOS) exists in three forms: neuronal, inducible, and
endothelial. The form predominantly associated with cardiovascular health is the endothelial
form, known as eNOS or NOS3. The eNOS/NOS3 - gene regulates vascular nitric oxide
production, which helps to regulate vasodilation, vascular repair, platelet aggregation and
adhesion, reduction of vascular smooth muscle proliferation, and oxidation of low-density
lipoprotein (LDL) particles leading to atherosclerotic plaques. The homozygous variant of
eNOS/NOS3 is associated with decreased nitric oxide production and a higher rate of
endothelial dysfunction, leading to an increased risk of hypertension, myocardial infarction,
and stroke.
Factor II (Prothrombin) – Single nucleotide polymorphisms (SNPs) affecting the coagulation
cascade have been implicated in many cardiovascular ailments, such as venous thrombosis,
ischemic stroke, pulmonary embolisms, coronary artery disease, and myocardial infarction.
Prothrombin is an inherited mutation that increases the likelihood of blood clot formation. The
variant allele of the prothrombin gene significantly elevates thrombin generation, and

7. increases risk for coronary disease, as well as embolisms.
Factor V Leiden – Factor V is part of the coagulation cascade, a multi-tiered interaction of
proteins and co-factors responsible for proper blood clotting. Factor V is degraded by activated
protein C in the absence of hemostasis. A mutation in this gene increases the protein’s
resistance to degradation, thereby increasing the risk of venous thrombosis and
thromboembolisms.
MTHFR – Methylene tetrahydrofolate reductase (MTHFR) is an enzyme that helps convert
folate into the specific form of 5-methyl-tetrahydrofolate. The key metabolic role of this form of
folate is to aid homocysteine conversion to methionine. Two common mutations in the MTHFR
gene (C677T and A1298C) can result in reduced enzyme functionality,20 and may contribute
to increased levels of homocysteine, a known risk factor for heart disease,21 atherosclerosis
and venous thrombosis.
SLCO1B1 – The SLCO1B1 gene encodes a transporter that brings statin medications to the
main tissues of the liver.23 Individuals who carry one or two copies of the variant allele have
a reduced response to treatment for low-density lipoprotein (LDL) cholesterol (a risk factor for
cardiac health), and with too much statin medication in the liver, an increased risk of statin-
induced myopathy.
5.0 Pharmacogenetic Screening Report CVD Drug Dosing and Prescription
Investigating the genomic basis for variable responses to cardiovascular therapies has been
a model for pharmacogenomics in general and has established critical pathways and specific
loci modulating therapeutic responses to commonly used drugs such as clopidogrel, warfarin,
and statins (PMID: 23689943). Pharmacogenomics aims to discover new therapeutic targets
and understand genetic polymorphisms that determine the safety and efficacy of medications.
The goal of pharmaco-genomics is customization of drug therapy with administration of a
medication in an optimum dose that will be safe and effective with reduction in morbidity and
mortality (PMID: 34232575).
This report helps in development of initial clinical guidelines that consider how to
facilitate incorporating genetic information to the bedside in order to provide better
treatment and care to the patients.
Clopidogrel
Drug class: Antiplatelet
Description: Variation in antiplatelet response leading to resistance in a subset of patients
Genes and Variants: CYP2C19*2 and CYP2C19*3
Problem: Carriers of above variants have insufficient active metabolite formation
leading to resistance

8. Metabolizer Type: Ultra-Rapid metabolizer
Clinical Implications: Dose increase or consider newer antiplatelet agents for loss-of-
function variant carriers Clopidogrel is an antiplatelet drug used in the treatment of patients
with ACS, managed medically or with PCI. Clopidogrel is also used in the treatment of patients
with atherosclerotic vascular disease, as indicated by a recent MI, a recent ischemic stroke,
or symptomatic peripheral arterial disease. Clopidogrel has been shown to reduce the rate of
subsequent MI and stroke in these patients. Clopidogrel is given to treat or to prevent further
occurrences of arterial thrombosis, which occurs when a blood clot (thrombus) forms inside
an artery.
Diplotype results
Drug Diplotype Metabolizer Type Implications for clopidogrel FDA therapeutic recommendations
Clopidogrel CYP2C19*17/*1 Ultra rapid Increased platelet inhibition Dose recommended by drugs label
Dose Recommendation
Standard dosing of clopidogrel, as recommended in the product insert, is
warranted among ACS/PCI patients with a predicted CYP2C19 extensive
metabolizer or ultrarapid metabolizer phenotype (i.e., *1/*1, *1/*17, and *17/*17).
Recommendation
CYP2C19 Ultra Rapid Metabolizer: Clopidogrel
NO action is required for this gene-drug interaction.
The genetic variation results in increased conversion of clopidogrel to the active metabolite.
However, this can result in both positive effects (reduction in the risk of serious cardiovascular
events) and negative effects (increase in the risk of bleeding).
Carvedilol
Drug class: non-selective beta blocker
Description: Considered to be the standard of care for patients with heart failure, particularly
for patients who also have hypertension.
Genes and Variants: CYP2D6*4/*4
Problem: Higher rate of dizziness during up-titration in poor metabolizers of Carvedilol
Metabolizer Type: Poor metabolizer
Clinical Implications: The plasma concentration of carvedilol can be elevated in case of the
poor metabolizers
Carvedilol is widely considered to be the standard of care for patients with heart failure,
particularly for patients who also have hypertension. Carvedilol is used to treat mild to severe
congestive heart failure, as well as hypertension, and left ventricular dysfunction in patients
who recently had an MI, but are otherwise stable.
Carvedilol is a non-selective beta blocker (blocks beta 1 and beta 2 receptors) and an alpha
1 blocker. By blocking beta receptors found in the heart, carvedilol reduces the heart rate and
decreases the force of heart contractions. By blocking the alpha 1 receptors found on blood
vessels, carvedilol relaxes and dilates the blood vessels, which lowers blood pressure.
Diplotype results

9. Recommendations
CYP2D6*4/*4 Carvedilol: Poor metabolizer
NO action is required for this gene-drug interaction.
Retrospective analysis of side effects in clinical trials showed that poor CYP2D6 metabolizers
had a higher rate of dizziness during up-titration, presumably resulting from vasodilating
effects. The plasma concentration of carvedilol can be elevated. This however, has no side
effects in the patients.
Metoprolol
Drug class: Beta blocker
Description: Variation in blood pressure lowering response and reduction in cardiovascular
events
Genes and Variants: CYP2D6*3/*4
Problem: CYP2D6*3/*4 carriers have increased sensitivity to metoprolol
Metabolizer Type: Poor metabolizer
Clinical Implications: Dose reduction for loss-of-function variant carriers
Metoprolol is a beta blocker used in the treatment of hypertension, angina, and heart failure.
Metoprolol selectively blocks beta1 adrenoreceptors mainly expressed in cardiac tissue.
Blockade of these receptors reduces the heart rate and decreases the force of heart
contractions.
Metoprolol is primarily metabolized by the CYP2D6 enzyme. Approximately 8% of Caucasians
and 2% of most other populations have absent CYP2D6 activity and are known as “CYP2D6
poor metabolizers.” In addition, a number of drugs inhibit CYP2D6 activity, such as quinidine,
fluoxetine, paroxetine, and propafenone.
Diplotype results
Recommendations
CYP2D6*3/*4 Metoprolol: Poor Metabolizer
Poor metabolizers and extensive metabolizers who concomitantly use CYP2D6 inhibiting
drugs will have increased (several-fold) metoprolol blood levels, decreasing metoprolol's
cardioselectivity.
The gene variation reduces the conversion of metoprolol to inactive metabolites. However, the
clinical consequences are limited mainly to the occurrence of asymptomatic bradycardia.
If a gradual reduction in heart rate is desired, or in the event of symptomatic bradycardia then
Increase the dose in smaller steps and/or prescribe no more than 25% of the standard dose.
Drug Diplotype Metabolizer Type Implications for Carvedilol FDA therapeutic recommendations
Caevedilol CYP2D6*4/*4 Poor Meatbolizer Increased plama levels Drug Interactions, Clinical Pharmacology
Drug Diplotype Metabolizer Type Implications for Metoprolol FDA Drug Labels
Metoprolol CYP2D6*3/*4 Poor Meatbolizer Increased metoprolol blood levels Drug Interactions, Clinical Pharmacology

10. In other cases, no action is required.
Warfarin
Drug class: Anticoagulant
Description: Variation in dose requirement for achieving and maintaining INR in therapeutic
range
Genes and Variants: CYP2C9*2, CYP2C9*3, VKORC1 1639G
Problem: Carriers of above variants have increased sensitivity to warfarin
Metabolizer Type: Poor metabolizer
Clinical Implications: Dose reduction to maintain therapeutic range
Warfarin is an anticoagulant (blood thinner). Warfarin acts by inhibiting the synthesis of vitamin
K-dependent clotting factors and is used in the prevention and treatment of various thrombotic
disorders.
Warfarin is a drug with narrow therapeutic index; thus, a small change in its plasma levels may
result in concentration dependent adverse drug reactions or therapeutic failure. Therefore, the
dose of warfarin must be tailored for each patient according to the patient’s response,
measured as INR (International Normalized Ratio), and the condition being treated.
Diplotype results
Recommendations
Calculate warfarin dosing using a published pharmacogenetic algorithm, including genotype
information for VKORC1-1639G>A and CYP2C9*2 and *3. In individuals with genotypes
associated with CYP2C9 poor metabolism (e.g., CYP2C9 *2/*3, *3/*3) or both increased
sensitivity (VKORC1-1639 A/A) and CYP2C9 poor metabolism, an alternative oral
anticoagulant might be considered.
Statins
Drug class: Statins includes atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin,
rosuvastatin, and simvastatin
Description: Variation in lipid lowering efficacy and increased risk of myopathy
Genes and Variants: SLCO1B1*5
Problem: OATP1B1*5 carriers have increased systemic exposure and risk of myotoxicity
Metabolizer Type: Poor drug transport to liver
Clinical Implications: Avoid using high-dose or consider using alternatives
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering
medications that reduce illness and mortality in those who are at high risk of cardiovascular
disease. They are the most common cholesterol-lowering drugs .
Drug Diplotype Metabolizer Type Implications for Warfarin FDA Drug Labels
Warfarin CYP2C9*3/*3 Poor Meatbolizer Increased sensitivity Dosage, Drug Interactions, Clinical Pharmacology
Warfarin VKORC1 AA Poor Meatbolizer Increased sensitivity Dosage, Drug Interactions, Clinical Pharmacology

11. The SLCO1B1*5 allele (defined as consisting of rs4149056) is assigned as a no function allele
by CPIC. Patients with the *5 allele in combination with a normal, no, or increased function
allele may have increased exposure to rosuvastatin as compared to patients with two normal
function alleles. Other genetic and clinical factors may also influence rosuvastatin
pharmacokinetics.
Diplotype results
Recommendations
Start with a low dose of statins that can be increased not more than once every 2 to 4 weeks.
Monitor the patient for muscle weakness leading to muscle myopathy. Perform liver function
tests periodically to monitor side effects of liver damage. Statins may cause increase in the
blood sugar or may induce Type 2 diabetes.
Drug Drug Class Diplotype Metabolizer Type Implications for Statins FDA Drug Labels
Statins Statins SLCO1B1*5 Poor Meatbolizer Increased systemic exposure Dosage, Drug Interactions, Clinical Pharmacology