Clinicians have identified a gene variant that causes a common type of high blood pressure, and a way to cure it.
A tiny benign nodule, present in one in 20 people with hypertension, produces a hormone, aldosterone, that controls how much salt is in the body. The new discovery is a gene variant in some of these nodules which leads to a vast, but intermittent, over-production of the hormone.
The gene variant, discovered by researchers at Queen Mary University of London and Barts Hospital, causes several problems which makes it hard for doctors to diagnose some patients with hypertension. Firstly, the variant affects a protein called CADM1 and stops cells in the body from “talking” to each other and saying that it is time to stop making aldosterone.
The fluctuating release of aldosterone throughout the day is also an issue for doctors, which at its peak causes salt overload and hypertension. This fluctuation explains why patients with the gene variant can elude diagnosis unless they happen to have blood tests at different times of day.
The researchers also discovered that this form of hypertension could be cured by removing one of the two adrenal glands. Following removal, previously severe hypertension despite treatment with multiple drugs disappeared, with no treatment required through many years of observation.
Fewer than 1 per cent of people with hypertension caused by aldosterone are identified because aldosterone is not routinely measured as a possible cause. The researchers are recommending that aldosterone is measured through a 24-hour urine test rather than one-off blood measurements, which will discover more people living with hypertension but going undiagnosed.
The initial patient in this study was detected when doctors noticed fluctuation in his hormone levels during his participation in a clinical trial of treatments for difficult hypertension.
In most people with hypertension, the cause is unknown, and the condition requires life-long treatment by drugs. Previous research by the group at Queen Mary discovered that in 5 to 10 per cent of people with hypertension, the cause is a gene mutation in the adrenal glands, which results in excessive amounts of aldosterone being produced. Aldosterone causes salt to be retained in the body, driving up the blood pressure.
Patients with excessive aldosterone levels in the blood are resistant to treatment with the commonly used drugs for hypertension, and at increased risk of heart attacks and strokes.
Professor Morris Brown, co-senior author of the study, and professor of endocrine hypertension at Queen Mary University of London, said: “In the 900th anniversary of Barts Hospital, this story illustrates benefits from the virtuous circle of science and medicine.
“Most patients consent to our undertaking non-routine molecular analyses of their surgical samples, from which we discover how their hypertension was caused, and how to cure it in future patients. Because the aldosterone nodules in this study were so small, we are now investigating whether momentary cauterisation of the nodule is an alternative to surgical removal of the whole adrenal gland.”
The study is published today in Nature Genetics.
