What is Personalised Cardiovascular Medicine?

In January 2015 during the US State of the Union address, President Obama launched the Precision Medicine Initiative. Since then there has been renewed interest in the field of personalised medicine.

Personalised medicine is not new and genetic predisposition to diseases have long been recognised, reported and appreciated.  However it is only recently through the development of more efficient and robust methods of molecular genotyping and specific gene testings (e.g. next-generation sequencing [NGS] based genetic diagnostics especially whole-exome sequencing) as well as significant cost reduction that allows detailed genomic evaluation to influence clinical medicine and provide new approaches and directions to improving the human health and disease.  There are currently an ever-growing number of studies, editorials and literatures published in well-established journals from various disciplines that have been written on the subject of precision medicine.

Personalised medicine (through genome sequencing) may be thought of as tailoring medical treatment to the individual’s specific set of genes and preferences of each patient.  In other words, the ability to provide the right drug at the right dose to the right patient at the right time.

Spear-heading the development of personalised medicine are numerous disciplines including cancer (oncogenomics), inherited cardiac disease (cardiovascular genomics /cardiogenomics) and diabetes mellitus (diabetic genomics).

In the field of cardiology, personalised cardiovascular medicine is slowly gaining renewed interest and will probably be the next big wave of advancement in the management and  treatment of cardiovascular diseases.

Personalised Cardiovascular Medicine                                           

• Genetic screening for risk of heart attack (with Genetic Risk Score – GRS)
• Genetic screening for sudden cardiac death
• Pharmacogenomics

In January 2015 during the US State of the Union address, President Obama launched the Precision Medicine Initiative. Since then there has been renewed interest in the field of personalised medicine.

Personalised medicine is not new and genetic predisposition to diseases have long been recognised, reported and appreciated.  However it is only recently through the development of more efficient and robust methods of molecular genotyping and specific gene testings (e.g. next-generation sequencing [NGS] based genetic diagnostics especially whole-exome sequencing) as well as significant cost reduction that allows detailed genomic evaluation to influence clinical medicine and provide new approaches and directions to improving the human health and disease.  There are currently an ever-growing number of studies, editorials and literatures published in well-established journals from various disciplines that have been written on the subject of precision medicine.

Personalised medicine (through genome sequencing) may be thought of as tailoring medical treatment to the individual’s specific set of genes and preferences of each patient.  In other words, the ability to provide the right drug at the right dose to the right patient at the right time.

Spear-heading the development of personalised medicine are numerous disciplines including cancer (oncogenomics), inherited cardiac disease (cardiovascular genomics /cardiogenomics) and diabetes mellitus (diabetic genomics).

In the field of cardiology, personalised cardiovascular medicine is slowly gaining renewed interest and will probably be the next big wave of advancement in the management and  treatment of cardiovascular diseases.

How will precision medicine fit into cardiology?

This lecture will feature the clinical utility of 4 aspects of personalised precision cardiovascular medicine :

1. Gene risk profiling of cardiovascular diseases (inclusive of familial predisposition to myocardial infarction, congestive heart failure, sudden cardiac death – dilated and hypertrophic cardiomyopathies and ion-channelopathies and atrial fibrillation). Role of genetic risk scores (GRS).
2. Cardiovascular pharmacogenomics (assessing inter-individual variability response to cardiovascular drugs with special focus on statins, Clopidogrel and Warfarin)
3. Nutrigenomics (relationship between diet and genes resulting in “personalised diet” through a person’s genome)
4. Role of Mendelian randomisation in accelerating development of new cardiovascular drugs from bench to clinical application (PCSK9 monoclonal antibodies, NCP1L1 inhibitor [ezetimibe], anti-sense, oligonucleotide for ApoC).

What are the barriers of personalised medicine?

The practice of personalised cardiovascular medicine also comes with significant potential challenges, consequences and uncertainties.  Importantly the following has been argued as to why it is still not the right time to embark on genomic medicine.

1. Interpretation of genetic test results can be difficult, challenging and often time-consuming for clinicians and patients
2. Scepticism about the clinical utility of genetic risk prediction (with only modest hazard ratio for individual SNPs or even panels of SNPs and the minor change in receiver operating characteristics curve areas)\
3. The rapid pace of identification of additional SNPs associated with common CVDs making established genotyping panels obsolete rapidly and thus creating the scenario of “a wait and see” approach for “better” genetic screening panels in the near future rather than use the “now-generation” series of genotyping
4. No clinical trials have been performed that demonstrate the benefit of genotyping in influencing the clinical outcomes and therefore difficulties in applying the correct intervention
5. Barriers in bringing the new drugs to the clinical practice
6. The cost of doing genetic testings are still rather prohibiting as it usually exceed above SGD$1,000 to as high as SGD$4,000 to SGD$5,000 depending on the number of genes being assessed
7. A wide range of emotional reactions that ranges from a sense of relief from removing uncertainties as to whether patient or their family members inherit the mutation to a feeling of disappointment and worry on learning that they or their children may have inherited the mutation and may subsequently progress to the risk of development of the specific heart disease and especially when currently there may be no treatment to alter the fate. Emotional reactions would therefore range from anger, guilt, grief, sadness, fear and anxiety.
8. Insurance coverage for genetic testing is also variable and uncertain.
9. Under the personal data protection, there are concerns about how genetic test results may potentially be used against the patient by insurance company and the use and misuse of the genetic information for research as there are potential breaches of anonymity, privacy and confidentiality.

In view of all the above, there will need for a proper genetic counselling for both pre-test as well as post-test as to how to manage the numerous new and very challenging issues of the practice of genomic medicine.

Conclusion

There is no doubt that personalised medicine through whole genome and exome sequencing is the way forward and its impact on medicine is highly significant.  Cardiovascular medicine is no exception.  However the key questions still remain as to current relevance of the clinical utility of genome sequencing for CVD risk prediction and treatment.  Importantly can genotyping offer better prediction than standard risk assessment and is this enhanced prediction clinically meaningful?  Will the results of genotyping change the patient’s management?

In the future, we will be able to obtain a “pan-omics” data on individuals (i.e. genomics, pharmacogenomics, epigenomics, transcriptomics, proteomics and metabolomics) which will allow for a truly integrated personalised management of the patient’s medical and health issues.

Cardiologists should start embracing this new paradigm shift taking place in cardiovascular care.  The integration of clinical information obtained from history and physical examination, functional and imaging studies, biochemical biomarkers, genetic/epigenomic data and the pathophysiological insights into disease-driving processes will allow for personalised cardiovascular disease management that will have potential and major health benefits for the individual and the population affected by cardiovascular diseases.