1. What is atherothrombosis ?

Atherothrombosis is derived from 2 Greek words – athero which comes from atherosclerosis and is defined as a systemic inflammatory disease characterized by the accumulation of inflammatory cells in the walls of the large arteries leading to cholesterol deposition in the walls and the formation of cholesterol plaques also known as atheroma.  Thrombosis is the formation of blood clot (thrombus) within the cholesterol plaque in the blood vessel as a result of a rupture of the plaque and obstruction of blood flow.  Atherothrombosis therefore is characterized by sudden (often unpredictable) atheroma plaque disruption leading to activation of a series of clotting factors and blood cells adhesion and accumulation resulting in a thrombus (blood clot formation).

2. Why is atherothrombosis so important?

Atherothrombosis is the underlying condition that leads to a heart attack, stroke, obstruction of large vessels in the legs known as peripheral arterial disease and consequently death.  Atherothrombosis is the leading cause of cardiovascular morbidity and mortality worldwide accounting for 52% of all deaths ahead of all cancer (24%).  Putting it in another way, people are twice as likely to die from atherothrombosis as from cancer.  In 2005 the prevalence of atherothrombosis in the world is 222 million (in people above 50 years), 10.7 million people had heart attack and 8.4 million people had stroke.

Atherothrombosis significantly reduces life expectancy by at least 11 to 12 years for an individual aged above 50 years old.

3. Where is atherothrombosis found?

Atherothrombosis is commonly found in 1 or more arterial bed in an individual –

• heart – (coronary arteries) leading to heart attack
• brain – (cerebral vascular disease) leading to stroke
• peripheral arterial bed – (peripheral arterial disease) leading to pain of the legs when walking, rest pain, gangrene leading to amputation

The manifestation of atherothrombosis is commonly found in more than 1 arterial bed in an individual.  More than 60% of patients aged > 40 years old develop the above disease in the arterial bed.

• Atherothrombosis occurring in the brain leads to ischemic stroke

Ischemic stroke is a major health burden worldwide.  Stroke is the 3^rd/4^th commonest cause of death in Singapore and is a leading cause of disability in adults.  Stroke is a 2^nd most common cause of dementia.  In USA every 33 seconds, someone suffers from a stroke and in UK more than 57 000 working lives are lost each year.

• Atherothrombosis occurring in the heart leads to heart attack

Thrombosis leading to heart attack is the leading cause of death in developed countries.  In Singapore it is the number 2 killer with more than 4000 people die each year from heart attacks.  In USA every 29 seconds, someone will suffer a heart attack.

• Atherothrombosis occurring in the lower limbs leads to peripheral artery disease and gangrene with subsequent infection and amputation and may also result in death.

Patients with peripheral artery disease are 6 times more likely to die within 10 years than those without peripheral artery disease.  Patients with peripheral artery disease have a 5-year mortality of 28% compared to 15% of people who have breast cancer.

4. What causes atherothrombosis?

The same risk factors that cause a heart attack or stroke are in operation in atherothrombosis, i.e. :

1. High blood pressure
2. High cholesterol
3. Obesity
4. Diabetes mellitus
5. Smoking

5. How can we diagnose atherothrombosis ?

When atherothrombosis occurs in 1 of the vascular bed, usually it occurs acutely and suddenly and if the burden of atherothrombosis is big enough, it will manifest as heart attack, stroke or gangrene of the foot.  Diagnosis is made through the following investigations : ECG,  2-Dimensional Echocardiography/Doppler study, coronary CT angiogram, invasive coronary angiogram, CT/MRI of the brain and carotid ultrasound.  Peripheral vascular disease can also be diagnosed through an ankle-brachial index, Doppler ultrasound of the lower legs and MRI of the arterial bed of the lower limbs.

6. How do we prevent and treat atherothrombosis?

Prevention begins by avoiding atherosclerosis from developing in all the vascular beds and will include the usual lifestyle modifications of a healthy diet, cessation of smoking, weight loss and exercise.  Definitive treatment for atherothrombosis is the use of antiplatelet drugs such as Aspirin or Clopidogrel (Plavix).  These 2 medications are the main stay of treatment for atherothrombosis.  In severe acute atherothrombosis, the combination of[1] Aspirin and Plavix is indicated especially in patients who presents with unstable angina – acute coronary syndrome with an impending heart attack.  The benefits of using Aspirin and Plavix are being confirmed in numerous large clinical trials.  These 2 drugs are also used in treatments of heart attack patients, in the deployment of coronary stents and ischemic stroke.

Up to recently Aspirin and Plavix have to be taken separately.  However recently there is the availability of a combination pill of Clopidogrel and Aspirin called Co-Plavix.  Singapore is fortunate to be the first country in Asia to have access to this combination pill and therefore will significantly reduce the pill burden of the patients.

In addition it is very important to reduce the bad cholesterol and to stabilise the atheromatous plaque with the use of statins and to ensure the LDL-C levels drop below 80 mg/dl.  In conclusion, not many people are aware of this disease called atherothrombosis.  It is a silent disease which is linked to the common cardiovascular risk factors of high cholesterol, smoking, high blood pressure, diabetes and obesity.  If left unchecked, the acute stage of the disease will be manifested as heart attack, stroke and peripheral vascular disease leading to gangrene of the lower limbs, hence resulting in potential death.  The definitive treatment of atherothrombosis is the use of Aspirin, Clopidogrel and statins.  However as in most modern lifestyle diseases, prevention of atherothrombosis would be more important than its treatment.