Cardiovascular disease including stroke is the leading cause of death both in developed countries like US and developing countries like Sri Lanka. In the year 2000 approximately 941000 deaths in US (i.e. 39 per cent of all deaths) were due to cardiovascular diseases.

Although coronary artery disease is largely a preventable disease, there is evidence to show that there is a heritable component to cardiovascular disease and in a significant number of patients the heart disease is due to genetic causes. Some of these cardiovascular diseases which have a genetic basis, will be discussed in this article.

Low density lipoprotein (LDL) is the major cholesterol carrying lipoprotein in the plasma and elevation of LDL (bad cholesterol) is the causal agent in many forms of coronary artery disease.

It is noteworthy that in majority of people with hypercholesterolaemia, the cause of elevation of cholesterol is due to consumption of high fat diet and poorly understood susceptibility to high cholesterol diet. It is common knowledge that the, plasma cholesterol goes up in some people even with the consumption of one or two eggs a day whereas in others there is no such increase in cholesterol level even if they consume 2-3 eggs a day.

There are 4 monogenic (i.e. where only one gene is affected) types of heart disease where elevation of plasma LDL is due to impairment of LDL receptors in the liver. Normally LDL receptors in liver clear LDL from plasma.

This is the most common monogenic disorder of cholesterol metabolism. The primary defect in this disease is a deficit in the number of LDL receptors in the liver and more than 600 mutations in the LDL R gene have been identified in patients with this disorder and familial hypercholesterolaemia is the commonest genetic disorder of cholesterol metabolism in our experience according to research carried out in the Institute of Cardiology during early 1970s.

A majority of patients (heterozygous type) have only half the normal number of LDL receptors in the liver leading to a two fold or three fold rise in plasma LDL (bad) cholesterol. In a very small group of this disorder called homozygous type, the plasma LDL level is six to ten times the normal level. These unfortunate homozygous patients have severe coronary atherosclerosis (thickening and plague formation involving the intimal layer of coronary arteries) and usually these patients die in childhood from myocardial infarction (heart attack).

In another genetic type of cholesterol disorder, there is a deficit in cholesterol transport resulting in elevated LDL cholesterol. This disorder in LDL synthesis is called familial ligand-defective apolipoproteinaemia.

Hypertension is the most common cardiovascular disease in the developed countries like US and people with hypertension are prone to stroke, myocardial infarction, heart failure and kidney failure. It is common knowledge that hypertension goes in certain families and there is a genetic basis for hypertension in these families. That is why physicians advise patients suffering from hypertension to get their close relatives especially those over the age of 40 years their blood pressure checked regularly by their family physician or by a medical officer attached to the O.P.D. of a hospital (if the person does not have a family doctor). The Majority of hypertension patients don’t have any symptoms and by the time they develop complications like transient ischaemic attacks (TIA) or stroke or heart attacks it is too late. The best way to diagnose hypertension is by getting the blood pressure (B.P) checked by a doctor or a nurse or a medical student and if the B.P. is raised, the person must see his family physician or a specialist and get a full check-up.

This is the most common cause of sudden death in children and adolescents and patients with this heart muscle disease get angina or difficulty in breathing or palpitations. Some of them don’t have cardiac symptoms and are referred to cardiologists by their family physicians because of the detection of a cardiac murmur.

ECG is helpful in the diagnosis of HOCM and shows evidence of led ventricular hypertrophy (thickening of cardiac muscle of the main pumping chamber). The most useful instrument helpful to diagnose HOCM is the 2D - Echo machine. This condition sometimes affects a number of people in the same family. The left venticular cavity is small.

Some of these patients get syncopal attacks and a patient can die during a bout of sudden exertion such as running to a bus. In the series of HOCM cases studied at the Institute of Cardiology by N. J. Walloopillai, D. P. Atukorale et al, familial incidence was 37.5 per cent and in the familial cases the males appear to suffer from HOCM more than females (British Heart Journal; 1973, 35, 181 - 188). In one of the HOCM families studied in the Institute, all nine children were affected and by 1976 8 out of 9 children were dead, and all the children were between the ages of 10 and 25 at the time of diagnosis. The coronary arteries in HOCM patients are normal or dilated and the myocytes (heart muscle cells) are enlarged.

Cardiac arrhythmias (abnormal heart rhythm) can be due to congenital causes. In the year 2001, about 450000 people in U.S. had died of cardiac arrhythmias and majority of cases of abnormal cardiac rhythm have been due to acquired causes such as coronary artery disease, hypertension and rheumatic heart disease. Only some of these cases such as long QT syndrme and idiopathic ventricular fibrillation are due to genetic causes and majority of these arrhythmias can be diagnosed by doing an ECG. In some cases, Holter-monitoring (24 hours recording of the patients ECG) has to be done to confirm the diagnosis of cardiac arrhymia.

Reference: E. G. Nabel N. Engl. J. Med. 349, July 3, 2003.