Understanding heart diseases for individuals under 45

As World Heart Day approaches, it is crucial to highlight and talk about the silent epidemic in India, inherited heart diseases, particularly alarming when it occurs in the young, defined as onset before age 45 years. Traditionally associated with older adults, these conditions are now increasingly seen in individuals in their thirties or early forties, a shift that is particularly concerning.

The most common form of heart disease is cardiovascular disease (CVD), particularly coronary artery disease (CAD), where latest data highlights that India faces a higher age-standardized CVD death rate of 272 per 100,000 people, compared to the global average of 235. Further reports indicate that Indian youth are experiencing cardiovascular events a decade earlier than their counterparts in Western countries. This health crisis emphasizes the urgent need to address hereditary cardiovascular conditions in younger individuals, focusing on early detection and intervention to mitigate the risks associated with these potentially life-threatening diseases.

Though not commonly seen as CVDs, the Inherited Heart Condition (IHC) often manifest early in life with few warning signs and are lethal. It can further pose serious health risks, including sudden cardiac death in young. Few common IHCs include:

• Hypertrophic Cardiomyopathy (HCM): Characterized by abnormal thickening of the heart muscle, which can obstruct blood flow and cause arrhythmias.
• Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Involves the replacement of heart muscle with fat and scar tissue, increasing the risk of life-threatening arrhythmias.
• Dilated Cardiomyopathy (DCM): Characterized by enlargement and dilation of one or both ventricles along with impaired contractility defined as left ventricular ejection fraction (LVEF) less than 40%.
• Long QT Syndrome: Affects the heart’s electrical system, causing rapid and irregular heartbeats, which can lead to fainting, seizures, or sudden death.
• Familial Hypercholesterolemia: A genetic disorder that leads to high LDL cholesterol levels, elevating the risk of coronary artery disease at an early age.

Genetic basis of heart diseases

The genetic basis of Inherited Heart Conditions (IHCs) is defined by rare genetic mutations either passed down from one generation to another or novel genetic variation (called as denovo variant) seen in an individual that can have a significant impact on the structure, function, and/or rhythm of the heart.

As mentioned earlier the most common form of heart disease is CAD, where a plaque build-up happens in the wall of the arteries that supply blood to the heart, which can cause a myocardial infarction or a heart attack. Even though CAD can arise from monogenic conditions such as Familial hypercholesterolemia, the genetic basis of CAD is polygenic. Several thousands of millions of genetic variants cumulatively contribute to the development of the disease.

Role of Genetic Screening Tests

Genetic screening is pivotal in identifying individuals at risk for heart diseases, with a diagnostic yield of up to 40%. There are genetic diagnostic tests available to check the presence of the rare genetic variation which can screen the risk of developing IHCs. The genetic screening for risk of developing CAD is done using polygenic models. These preventive tests are crucial for detecting genetic predispositions and screening at-risk relatives, particularly those with a family history of cardiovascular disease.

In India, where CVDs account for a significant portion of deaths, early detection through genetic screening can reveal specific genetic risk factors for condition like CAD. Genetic screening tests using polygenic risk score provides a comprehensive assessment of an individual’s genetic risk for CAD, offering valuable insights before symptoms develop. This proactive approach enables timely interventions, lifestyle changes, and continuous monitoring, and help in planning preventive measures for at-risk family members.

Recent advancements in genetic screening technologies using Next Generation Sequencing (NGS), have further enhanced diagnostic accuracy and management of cardiovascular diseases. NGS-based tests provide detailed genetic profiles, allowing healthcare providers to create personalized treatment plans tailored to individual genetic makeups. Such proactive approach empowers patients to make informed decisions about their health, ultimately helping clinicians to make early intervention and improve overall outcomes.

Written by Dr Ramesh Menon, Associate Director – Personal Genomics & Genomic Medicine, MedGenome