Opinion: What Is Cardiogenetics And How Genetic Screening Aids In Early Diagnosis Of Cardiovascular Diseases

Cardiogenetics plays a crucial role in understanding hereditary factors in cardiovascular diseases (CVDs). Genetic screening in India, where CVDs are prevalent, aids in early diagnosis and management.

By Dr Thenral S. Geetha

Cardiovascular diseases (CVDs) are a leading cause of death globally with significant genetic factors influencing their onset, progression, and severity. In India, where CVD prevalence is rising rapidly due to lifestyle changes, urbanisation, and risk factors like hypertension, diabetes, and obesity, concurrently genetic screening offers a crucial tool for early diagnosis and management of the disease. Several reports indicate that Indians face CVDs about a decade earlier than Western populations, and the country has the highest global rate of coronary artery disease (CAD), with a 20-50% higher mortality rate. 

What Is Cardiogenetics?

At the heart of cardiovascular diseases lies cardiogenetics, a field dedicated to understanding the hereditary factors involved in heart disorders. Cardiac conditions influenced by genetic factors can manifest at any age and often with life-threatening implications. 

Inherited heart conditions with a clear genetic cause can occur due to a variant that causes aberrant activity in any one of the critical genes that are required for the proper functioning of the heart. These disorders are often genetically heterogeneous, meaning that mutations in different genes can lead to similar cardiac phenotypes (genetic heterogeneity), while a single genetic mutation can cause different types of heart conditions (clinical heterogeneity). This makes genetic diagnosis particularly challenging and critical, as the genetic basis of these disorders varies widely. 

Examples include cardiomyopathies, where the heart muscle is affected such as hypertrophic cardiomyopathy dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), which can lead to cardiac failure. Other genetically predisposed disorders include congenital heart disease (CHD), vascular disorders, including Marfan syndrome and aortopathies; and metabolic disorders, such as Familial Hypercholesterolemia.

Genetic Inheritance In Cardiovascular Diseases

The inheritance patterns of cardiac diseases vary widely. Over 40 inherited cardiovascular disorders have a direct genetic basis, caused by single DNA mutations. Some conditions, such as hypertrophic cardiomyopathy (HCM) are inherited in an autosomal dominant manner requiring just one copy of the mutated gene from either parent.

At times the variants can also arise "de novo" from random mutation events during embryonic development. The likelihood of autosomal recessive disorders, which occur when both copies of a gene have an abnormal copy, is higher among children born into consanguineous marriages or founder populations. Others, like mitochondrial disorders are passed down maternally and can affect multiple family members across generations. Familial Hypercholesterolemia, which causes high cholesterol and premature coronary artery disease, is also inherited in an autosomal dominant manner affecting about 1 in 500 people worldwide. If undiagnosed, Familial Hypercholesterolemia can lead to early-onset heart disease. Similarly, long QT syndrome affecting the heart’s electrical activity can cause life-threatening arrhythmias and sudden cardiac death, particularly in young individuals. 

Cardiovascular diseases are in part due to a cumulative effect of several hundred predisposing variants contributing to the increased risk along with lifestyle factors including hypertension, diabetes mellitus abnormal lipid levels, smoking, obesity etc., referred to as complex or multifactorial inheritance. 

How Genetic Diagnosis Help In Cardiovascular Care

Genetic diagnosis has revolutionised precision medicine by identifying specific mutations linked to heart disorders enabling early interventions and personalised treatments that address the root cause. For those with a family history of heart disease, genetic screening can detect mutations before symptoms appear, allowing for preventive measures to be implemented in time. For example, individuals identified with mutations associated with Familial Hypercholesterolemia can begin early cholesterol-lowering therapies significantly reducing their risk of premature coronary artery disease. Similarly, families with a history of cardiomyopathies, such as dilated cardiomyopathy (DCM), can benefit from early diagnosis, enabling more effective monitoring and intervention strategies to prevent heart failure or sudden cardiac death.

Role Of Preventive Tests And Personalised Medicine

One of the most significant benefits of genetic diagnosis is its potential to transform the prevention and management of cardiovascular diseases. With the rise of personalised medicine, healthcare providers can tailor treatment plans to an individual’s genetic makeup, ensuring more effective interventions and better outcomes. Preventive tests such as genetic screening for at-risk individuals allow doctors to predict the likelihood of certain heart conditions and act before symptoms develop.

For instance, people identified with a genetic predisposition to long QT syndrome can be monitored more closely for signs of arrhythmia while those with a family history of hypertrophic cardiomyopathy can be advised on lifestyle changes to reduce their risk of developing heart failure. The role of genetic diagnosis extends beyond individual care as it also informs family members who may share the same genetic risk factors, enabling them to take preventive measures and undergo appropriate screening. 

In the absence of specific gene mutation, CAD risk prediction has been evolving for several years starting initially with relatively few Single nucleotide polymorphisms (SNPs). Recent studies have shown improvement of both CAD risk stratification and prediction by incorporating a large number of SNPs.

The Future Outlook

With awareness around genetic testing increasing, and technological advancements making these tests more accessible and affordable, genetic testing is expected to become an integral part of cardiovascular care. This shift will enable earlier detection of heart conditions, allowing for the implementation of preventive measures before symptoms arise. Personalized treatment strategies tailored to a patient’s unique genetic profile will become more common, significantly improving disease management and outcomes for individuals at risk of or suffering from cardiovascular diseases. Its integration into routine care promises to significantly improve patient outcomes and reduce the global burden of heart disease.

Dr Thenral S. Geetha is Principal Scientist at MedGenome.

[Disclaimer: The information provided in the article, including treatment suggestions shared by doctors, is intended for general informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition.]