Cardiovascular disease is the number one cause of death worldwide.  Globally, more people die annually from cardiovascular disease than from any other cause.  Nearly one out of three deaths in Singapore are due to heart attack or stroke.  Coronary artery disease is by far the most common type of heart disease.  It is due to the deposition of cholesterol plaques in the arteries supplying the heart which gradually builds up and narrows the arteries, eventually leading to a restriction of blood flow to the muscles of the heart.  People with coronary heart disease may suffer one or more episodes of heart attack.

There are many factors that can contribute to the risk of developing coronary artery disease. This can be broadly classified as :

• Modifiable (lifestyle associated) risk factors and
• Non-modifiable risk factors

The modifiable risk factors include lifestyle risk factors such as high cholesterol, high blood pressure, high blood glucose, smoking, unhealthy diet and stress. The non-modifiable risk factors are age, gender, family history which are not controllable.  However, your genes may also play a significant part in your risk of developing a heart attack.  It is found that your genes can contribute up to 60% of your risk for coronary heart disease.

Your genes are inherited from both your parents.  They form the blueprint which codes for how the various organs and body function.  There are many genes that can predispose a person to coronary artery disease and heart attack.

How do you know if you have genes that are related to coronary artery disease and heart attack?

There are some clues that may predispose you to inheritance of genes for coronary heart disease and heart attack.  The easiest is to review your family history and to see whether there is a history of premature heart attack in the family defined as a first degree relative having suffered a heart attack at the age of below 55 years old (in males) and below 65 (in females).  However there are still many people who do not have family history of premature coronary artery disease and who appears to be physically fit but yet may suffer a heart attack.   Here is where genetic testing may be useful.

Why is it important to know your risk of coronary heart disease?

It has been shown through years of research and epidemiological studies that cholesterol deposition in your coronary arteries developed at a very early stage of life (as early as childhood and adolescence).  There are conditions that predispose your arteries to develop cholesterol deposition at an early age and genetic testing can define if you do possess this risk.  Knowing your heart risk and your risk of heart attack early will allow you to prevent this by applying and modifying your risk factors including improving your lifestyle to prevent coronary heart disease.

Genetic testing is one way to further personalise your risk assessment for coronary heart disease.  However not everybody requires this test to be done and therefore a consult with your physician will be useful.

Genesis Heart Attack Panel – Your Personalised Risk Assessment for Coronary Heart Disease

The genetic test that we have selected for the Genesis Heart Attack Panel is the CardioCAD Genetic Screening Program developed by researchers in the Yong Loo Lin School of Medicine, National University of Singapore, through more than 20 years of research on thousands of human subjects.  It estimates your risk of coronary heart disease by using the common panel of genes and combining them with the usual traditional risk factors to offer a more accurate assessment of your risk of heart attack.  We have selected CardioCAD as it was developed based on the Asian population and hence performs much more accurately compared to some of the genetic screening programs offered in other countries especially from the USA and Europe. Through genotyping, one is able to check whether you have risk genes for heart attack.  The estimated risk of developing a heart attack is highly personalised.

CardioCAD will generate a risk chart and provide a full personalised report and interpretation based on your risk factors after combining your genetic and lifestyle risk factors.  With this chart your doctor will be able to better advise you on how you can manage your risk, your lifestyle changes and medical treatment to prevent you from getting a heart attack.

What is required for genetic testing of risk for heart attack?

• You will be seen by a cardiologist who will go through a cardiovascular screening history and examination.
• A small volume of blood will be taken from you. DNA will be extracted from the specimen for testing and the result will be available to you within seven working days. At the same time, the blood drawn will also be used to analyse your lipid profile.

The cost of the Genesis Heart Attack Panel will include 2 visits to a cardiologist, the CardioCAD genetic test and a lipid profile.

Inherited cardiovascular conditions, sometimes called genetic heart conditions, are disorders that can be passed down from one generation to the next in the family. These conditions can affect individuals at any point in their lives and can be life threatening. Unfortunately, for most families, the first sign of the presence of an inherited cardiovascular condition is when a family member dies suddenly with no obvious cause or explanation.

What are Some Types of Inherited Cardiovascular (Heart) Conditions?

There are two main types of inherited heart conditions, inherited cardiac arrhythmias and inherited cardiomyopathies. Examples of each include:

Inherited Cardiac Arrhythmias (Heart Rhythm Disturbances)

• Long QT Syndrome (LQTS)
• Brugada Syndrome
• Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Inherited Cardiomyopathies (Disease of the Heart Muscle)

• Hypertrophic Cardiomyopathy
• Dilated Cardiomyopathy
• Arrhythmogenic Right Ventricular Dysplasia (ARVD)

Who Should be Screened for Inherited Cardiovascular Conditions?

Situations where screening for Inherited cardiovascular conditions should be considered Include:

1. Individuals with an unclear cardiomyopathy or arrhythmia diagnosis that appears to be inherited.
2. Individuals with an inherited cardiomyopathy or arrhythmia diagnosis and a family history of a different cardiomyopathy, arrhythmia, congenital heart defect and/or sudden unexplained death who want a genetic diagnosis confirmation.
3. Deceased family members with sudden unexplained cardiac death.

Why is it Important to Know Your Risk of Inherited Cardiovascular Conditions?

Knowing your risk of inherited cardiovascular conditions can assist both you and your doctor in tailoring your healthcare with regard to the cardiovascular conditions you might be susceptible to.

Examples include:

1. Clarifying a diagnosis and risk for sudden cardiac arrest.
2. Clinical management options specific to the gene mutation and syndrome identified
   1. Increased cardiovascular screening for carriers of mutations in cardiovascular disease susceptibility genes:
      1. More frequent screening (ECG, echocardiogram, Holter Monitoring)
      2. Initiate cardiac screening at a younger age
   2. Intervention options such as:
      1. Potential need for an Implantable Cardioverter Defibrillator (ICD) or pacemaker
      2. Medications specific to a patient’s phenotype
      3. Restrictions or limitations of physical activities as necessitated by specific gene mutation
   3. Options for risk-reducing procedures can be discussed
   4. At-risk family members identified through targeted genetic testing can develop an individualised cardiovascular disease screening and prevention program.
   5. Reproductive planning for couples may be offered

Genetic testing is one way to further personalise your risk assessment for cardiovascular conditions. However not everybody requires this test to be done and therefore a consultation with your physician will be useful.

ATLAS Genesis Hereditary Cardiovascular Panel

The ATLAS Genesis Hereditary Cardiovascular Panel screens for 84 genes associated with an increased risk of inherited cardiomyopathies and arrhythmias, and other inherited cardiovascular conditions.

What is required for genetic testing for inherited cardiovascular conditions?

• You will be seen by a physician who will go through your personal and family history of cardiovascular disease and an examination.
• A small volume of blood or saliva will be taken from you. DNA will be extracted from the specimen for testing.

The cost will include 2 visits to a physician.

If you have any queries with regards to the genetic testing, please feel free to contact us.

Disclaimer

Due to the inherently sensitive nature of genetic testing, all genetic testing need to be performed in conjunction with physician consultations to determine your suitability for and to discuss the potential medical, psychological, sociological and other consequences of doing genetic testing.

What is Pharmacogenomics (Pharmacogenetics)?

Pharmacogenomics is the study and the understanding of how genes can affect an individual response to medications. It combines the field of pharmacology (the science of drugs) and genomics (the study of genes and their function) to develop effective, safe medications that will be tailored to an individual’s genetic make-up and thereby help doctors select the right drugs and dosages that best suits each person.

Genes contain the blue prints (instructions) written in DNA for building protein molecules. Different people will have different blue prints (i.e. slightly different DNA sequence of the same gene) that will affect health in one way or the other (e.g. genes that are associated with a tendency to develop certain diseases).

Therefore pharmacogenomics researched into genetic variations in genes for proteins that influence the individual genetic response to different drugs. It involved how genes can produce the proteins that are required to carry drugs from the gut into the blood stream and their disposition in the liver, the number of liver enzymes that will convert medications in their active or inactive forms and the breakdown and excretion of drugs by the liver and kidneys.

Knowing whether an individual carries any of these genetic variations can help doctors individualise drug therapy, decrease the chance of adverse drugs events and increase the effectiveness of drugs.

What are the Expected Benefits of Pharmacogenomics?

Pharmacogenomics has the potential to provide tailor-made drug therapy based on genetically determined variations in effectiveness and side effects. This will mean :

• More powerful medicines – medications more targeted to specific disease, maximizing therapeutic effects and decreasing damage to nearby healthy cells
• Better, safer drugs – improved recovery and safety with reduction in adverse reactions
• More accurate methods of determining appropriate drug dosages with refinement and replacement of current dosing based on age and weight to a person’s genetic make-up (i.e. how well the body process the medicine and the time it takes to metabolise them)

How will Pharmacogenomics Affect the Prescribing of Drugs in the Future?

Currently pharmacogenomic information is already available for more than 150 medications.

The information will cover the effectiveness of such drugs to the individual with certain genomic variations, cover dosage guidance and possible side effects and therefore help doctors tailor their drug prescription for individual patients (personalised medicine). The ability to identify the genetic basis for certain serious side effects allows doctors to prescribe such drugs only to people who are not at risk for them.

Imagine a Scenario

You have a heart attack and had a stent deployed in one of your major coronary arteries. You will be required to take anti-platelet drugs (i.e. a kind of mild blood thinner – asprin and/or clopidogrel) to prevent aggregation of blood cells that will form a blood clot (thrombus) that will eventually block the stent (stent thrombosis) leading to another heart attack. Currently the common anti-platelet drugs available are “one size fits all”. But they may not work the same way for everyone. The drug(s) may have little effect on preventing the clot from forming on your stent. It is difficult to predict who will benefit from the medication and who will not respond at all and who will experience negative side effects. Luckily your doctor sequences your genome to decide if the anti-platelet drug will be effective for you. It happens that you have a genetic variant indicating that this commonly used drug will have little effect on you. Armed with this knowledge, your doctor will not be giving you this common anti-platelet drug. Instead another drug will be provided to you that will prevent the dreaded stent thrombosis.

Simply put, this means using pharmacogenomic testing to “get the right doses of the right drug to the right patient at the right time”.

How is Pharmacogenomic Testing Done?

• Two buccal swabs collection are required.
• Your doctor will see you and fill up a request form (with all the necessary information).
• The sample are collected by rubbing the buccal swabs firmly on the inside of one cheek for at least 45 seconds and then on the other cheek.
• The swabs are then placed in the sample collection envelop and deliver to the genetic lab for analysis.
• A personalised pharmacogenetics report will be given in 4 weeks with instructions for use, impact on medications, compilation of genetic review and individual gene review. A physician will also discuss this report with you and advise you accordingly.

Once again not all (or everyone) needs to do a Pharmacogenomics Test as you may currently not require to take any forms of medications.  Moreover, every day new genetic information is added to the growing list of drugs tested.

Speak to us at WL&H to understand more on Pharmacogenomic Testing.