Introduction

Have you ever noticed how certain disorders run in families through several generations? Have you ever wondered why it happens? The answer to this question lies in understanding the concept of genetics. Genetics refers to the study of genes and genes are the ones that carry the information that gets passed on from one generation to another. There are certain diseases that can be passed on from generations. One such group of disorders include vascular diseases.

What are vascular diseases?

As the name suggests, vascular disease refers to any condition or disorder that affects the components of the circulatory system that are the blood vessels, heart and the blood. Vascular diseases are among the many disorders that cause death globally. In the year 2000, approximately 14 million people died due to cardiovascular diseases and this number has only increased since to a whopping 18 million as recorded in 2019.¹

There are many factors that are responsible for causing these disorders. One of the major factors is the lifestyle one adopts and in their daily routine. Certain habits like smoking, stress, and a diet rich in trans fat, and saturated fat makes a person more susceptible to vascular diseases. Lack of regular exercise or physical activity can lead to excessive weight gain, which is also associated with developing vascular diseases.

However, maintaining a healthy lifestyle and getting regular check-ups can help in early diagnosis of any such hereditary conditions. This will help in better management of the condition. There are many ways in which genetic factors contribute to your susceptibility to these disorders. In this article, we will discuss in detail how genetics can contribute to vascular diseases.

Types of vascular diseases

Arteriosclerosis

Arteriosclerosis is a condition in which the artery walls become stiff and hardened. Pathological changes (caused by disease) in the blood vessels is the main reason behind this condition. The inner wall of the artery gets calcified and the smooth muscle cells of the artery become modified, thereby reducing elasticity.² This leads to narrowing of the passage for blood and can give rise to conditions like hypertension (high blood pressure), stroke and heart attacks. 

Arteriosclerosis can be managed by maintaining a healthy lifestyle and certain medications. Sometimes, surgical interventions might also be required depending on the severity of the condition.³ 

Atherosclerosis

Atherosclerosis is considered a type of arteriosclerosis. It is a chronic inflammatory disorder with involvement of different immune cells like T lymphocytes and macrophages.² Any injury or dysfunction of the endothelial cells of the artery wall can increase the permeability of lipids, cholesterol and calcium into the vessel. The deposition of these substances on the inner wall is called “plaque”. This causes narrowing of the artery and thus restricts blood flow.⁴ 

Peripheral artery disease (PAD)

Peripheral artery disease (PAD) is a circulatory condition and mainly affects the legs. Hence, it is also called lower limb disorder. The main cause of this disease is atherosclerosis. Atherosclerosis, as discussed before, is the narrowing of the arteries due to plaque formation and deposition, reducing blood flow to the legs. The symptoms of PAD include:

• Pain in the leg while walking and relief by rest 
• Frequent cramps 
• Numbness 
• Overall fatigue in the legs 

In severe conditions, PAD can also lead to sores, infections and gangrene. Lifestyle changes and medications can help manage this disorder.⁵ 

Stroke

Stroke is experienced when there is reduced blood flow to the brain. It is a heterogeneous and complex disorder that can be of two types: ischaemic (80% of cases) and haemorrhagic (20% of cases). 

Ischemic stroke is usually caused by a blockage in the artery that supplies blood to the brain, whereas a haemorrhagic stroke is caused by internal bleeding in the brain due to a rupture of a blood vessel.⁶ Symptoms of stroke include: 

• Numbness 
• Confusion 
• Trouble speaking 
• Severe headache 
• Difficulty in walking 

Immediate medical attention should be given in cases of stroke so as to minimise brain damage and improve outcomes. Treatment strategies can involve medication, rehabilitation or surgery, depending on the severity of the stroke.⁷

Coronary artery disease (CAD)

Coronary artery disease (CAD) is a chronic inflammatory disease, due to the narrowing of the arteries that supply oxygen to the heart muscles, called the coronary arteries. This shortage in blood supply to the heart occurs due to plaque buildup in the arteries that restricts the blood flow. 

Prolonged CAD can lead to chest pain (angina) and potentially cause a heart attack. A heart attack can cause permanent damage to the muscle cells of the heart, thereby affecting its pumping efficiency. Lifestyle changes, medications and sometimes surgical procedures like bypass surgery or angioplasty can help manage CAD and prevent further complications.⁸ 

Genetic risk factors

Familial hypercholesterolemia (FH)

Familial hypercholesterolemia (FH) is a genetic disorder which is inherited by several generations of a family. It is characterised by increased low-density lipoprotein (LDL) cholesterol levels from birth. LDL cholesterol is known as ‘bad cholesterol’ and it makes a person more susceptible to vascular diseases at an early age. It is caused by mutations in certain genes involved in cholesterol metabolism that are inherited.⁹ About 60-80% of people have mutations in the LDLR, APOB and PCSK9 genes which are responsible for removal of cholesterol from the body.¹⁰ 

Hypertension-related genes

Hypertension-related genes contribute to increased risk of getting vascular diseases. Mutations in genes such as ACE, AGT and NOS3 are usually associated with hypertension susceptibility. These genes are responsible for regulation of blood pressure mechanisms. 

High blood pressure can cause damage to the walls of the arteries, promote inflammation and plaque formation, thereby causing atherosclerosis. However, early diagnosis can help better manage hypertension through medications and hence prevent further complications.¹¹ 

Inflammation-associated genetic markers 

Inflammation plays a significant role in development of atherosclerosis and there are several genetic biomarkers that have been discovered. Inflammatory biomarkers are associated with increased risk of vascular diseases. These biomarkers are usually inherited by several generations, thereby making them more susceptible to cardiovascular diseases. Some genetic biomarkers associated with inflammation are:¹²

• C-reactive protein 
• Soluble intercellular adhesion molecule-1 
• Interleukin-6 
• P-selectin

Genetic predisposition to blood clotting disorders

Mutations in several genes that are inheritable can make a person more prone to blood clotting disorders. One such mutation involves the factor V Leiden mutation that increases the tendency of forming abnormal clots. These abnormal clots can cause blockage of blood vessels thereby giving rise to vascular diseases. It can also cause conditions like deep vein thrombosis, arterial thrombosis or pulmonary embolism. Understanding and managing these genetic factors is essential in treatment of vascular diseases.¹³

Genetic testing and screening

Importance of genetic testing for early detection

Genetic testing refers to examining a person’s blood or other tissues to determine if they have any changes or mutations in their genetic material that can cause any severe condition in the future.¹⁴ It enables early detection of any inheritable risk factors for future development of vascular diseases. This helps in better management of other factors that might contribute to the disease like lifestyle modifications, medications and close monitoring of the patients.¹⁵ 

Current limitations and challenges

Genetic testing is the way forward in early diagnosis and treatment of many severe disorders and better management of genetic risk factors. However, it does have certain limitations and challenges that need to be overcome for better reliability in the future. Some of these limitations include:¹⁶

• Sometimes, there are chances of negative results indicating that you will not get the disease in future. However, there is still a chance that you might possess the genetic variant. This can make the person confident that they will never get the disease
• A positive test might also reveal other family members and close relatives that have the genetic variant, causing stress and arguments in the family
• There is also a possibility that the variant detected is of unknown significance. In these cases, it makes it difficult to predict if a person has susceptibility to a certain disease or not 

Ethical considerations in genetic screening

There are a lot of ethical guidelines to be followed by the clinicians who conduct genetic testing as there are many opportunities where misuse of information can occur. Ensuring the consent and privacy of the patient is of utmost importance. 

When a patient obtaining a genetic test has a close relative also having the variant, they must be given proper psychological help with follow-up visits. Offering proper professional genetic counselling to the patients will reduce the mental trauma and stress that might be caused by a positive genetic test.¹⁷ 

Future directions

Further developments in the field of genetic research on vascular disorders involve: 

• Enhancement of risk prediction models 
• Creation of personalised medicines based on genetic profiles 
• Investigation of gene editing methods to target underlying genetic abnormalities 

These methods will help in the prevention and treatment of vascular disorders thereby improving the quality of life of the patients.¹⁸

FAQs

What percentage of heart disease is genetic?

Approximately, one-third to one-half of every person’s chance of developing vascular diseases lies in their genes. However, maintaining a healthy lifestyle can help prevent these diseases.

At what age is heart disease genetic?

Inherited heart conditions run in the family and are passed down several generations. They can affect people of any age.

How to test for a genetic heart disease?

Genetic screening is a test that is conducted to detect if you have any genes that might cause the condition in the future. It is usually examined using blood, hair, skin cells or any other tissue.

Summary

• Genetic factors are those factors that are inherited by birth and can increase the susceptibility of getting a vascular disease in the future
• Genetic factors contributing to vascular disease include familial hypercholesterolemia, hypertension-related genes, genetic markers associated with inflammation, and genetic predisposition to blood clotting disorders
• There is no way of eliminating genetic factors, but early detection can help better manage the condition
• A genetic test should be carried out if you have any close relatives with a vascular disease as it will better prepare you for the future
• Maintaining a healthy lifestyle and medications will help better manage the vascular disease