Mutations of the Angiotensinogen Gene and the Risk for Heart Disease and Stroke

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The summary below is from the full report titled "Angiotensinogen Mutations and Risk for Ischemic Heart Disease, Myocardial Infarction, and Ischemic Cerebrovascular Disease. Six Case–Control Studies from the Copenhagen City Heart Study." It is in the 15 May 2001 issue of Annals of Internal Medicine (volume 134, pages 941-954). The authors are AA Sethi, A Tybjærg-Hansen, MLM Grønholdt, R Steffensen, P Schnohr, and BG Nordestgaard.

What is the problem and what is known about it so far?

Blockages in the blood vessels to the heart (coronary arteries) can limit blood flow, causing what is known as ischemic heart disease. Temporary limitation of blood flow can cause chest pain (angina). If low blood flow lasts long enough, a section of heart tissue dies (a condition known as myocardial infarction, or "heart attack"). Ischemic cerebrovascular disease occurs when blockages develop in the blood vessels to the brain. Temporary blockage of blood flow to the brain is called a transient ischemic attack. If lack of blood lasts long enough, a section of brain tissue dies, a condition known as a stroke. Angiotensinogen is a protein in the body that influences blood vessels, blood pressure levels, and the way the body handles salt. Abnormalities ("mutations") in the genes for angiotensinogen are associated with high blood pressure. Since high blood pressure puts people at risk for ischemic heart and cerebrovascular disease, it is thought that changes in this gene may also be associated with these ischemic conditions. Some small previous studies of this issue have suggested that mutations in this gene are associated with heart disease and stroke, while others have not.

Why did the researchers do this particular study?

To find out whether people who have mutations in the angiotensinogen gene are more likely than people without mutations to have ischemic heart or cerebrovascular disease.

Who was studied?

People in a large study of risk factors for heart disease called the Copenhagen City Heart Study and people who had been cared for at the hospital where this study took place.

How was the study done?

From the heart study and the hospital records, the researchers identified groups of people who had ischemic heart or cerebrovascular disease and people who did not have these conditions. All patients had tests for two angiotensinogen gene mutations (M235T and T174M). The researchers then compared the frequency of the mutations in people with and without each of the conditions. The analysis also considered other factors related to ischemic conditions, including smoking, body size, and diabetes.

What did the researchers find?

The gene mutations, either one or both together, were not consistently associated with ischemic heart disease (with and without heart attack) or ischemic cerebrovascular disease in men or in women.

What were the limitations of the study?

The study took place in Denmark, and the results may not apply to persons in other geographic areas. Also, the researchers studied only two mutations; other unidentified mutations in the angiotensinogen gene could be related to disease.

What are the implications of the study?

Two known mutations in the angiotensinogen gene do not appear to be associated with ischemic heart or cerebrovascular disease.