No 'cheap cure' for high blood pressure

“Cheap cure for thousands with high blood pressure," reports the Mail Online, as it suggests that a “simple test could save thousands from life-threatening problems each year”.

This headline is based on research looking for genetic mutations that give rise to a form of benign (non-cancerous) tumour called an aldosterone-producing adenoma. These growths produces extra amounts of a hormone called aldosterone, which causes the kidneys to hold on to water and salt, increasing blood pressure.

The researchers managed to identify mutations in three genes that seemed to be causing a proportion of these tumours.

Removing the tumour can usually reduce blood pressure, avoiding the need to take high blood pressure medication.

Mail Online says that “the tumours can be detected by an ‘exquisitely accurate’ and inexpensive blood test”. However, this is not what the current study suggests.

The mutations identified are found just in the tumour tissue and not in all of a person’s cells, so they would not be detected by testing their DNA using a standard blood test. Currently diagnosis of these tumours is a multistage process, which involves blood tests for aldosterone and related hormones, and may also include scans to look for tumours and an invasive procedure to collect blood from the veins around the adrenal glands.

The current findings improve researchers' understanding of the potential causes of these tumours, but they don’t have immediate implications for those with this uncommon cause of high blood pressure.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and other research centres in the UK, and other countries in Europe. It was funded by the British Heart Foundation, the Wellcome Trust, the National Institute of Health Research (NIHR), NIHR Cambridge Biomedical Research Centre (Cardiovascular), and a research award from the pharmaceutical company Servier. The individual researchers also had various other sources of support.

The study was published in the peer-reviewed journal Nature Genetics.

The reporting of this study is mixed. BBC News implies that the study has found a new type of tumour, but this is not the case. These types of tumours were already known, and the current study has identified their genetic causes.

Puzzlingly, Mail Online focused on the possibility of a “cheap, simple blood test could save thousands from life-threatening blood pressure problems each year”.

In fact, due to the nature of the type of genetic mutations that causes these tumours (the mutations arise in the tumour tissue and are not carried in all the cells of the body), testing for these mutations would not be as simple as a testing the DNA collected in a standard blood test.

It is a multistage process that would involve a blood test to measure the levels of the hormone aldosterone and related hormone renin, followed up by imaging in those whose results indicate that they may have an adrenal tumour. It may also include an invasive test to collect blood from near to the adrenal glands.

A 2011 Behind the Headlines story covered a study on a new imaging test to detect this condition, also called Conn’s syndrome.

The current study did not assess the performance of this or other methods of identifying the tumours. It is not clear to what extent the specific genetic findings of the current study will change clinical practice.

What kind of research was this?

This was a genetic study that looked for the mutation causing a particular condition that leads to high blood pressure. In this condition, called aldosterone-producing adenoma (APA), individuals have benign (non-cancerous) tumours that produce excess amounts of aldosterone. This hormone causes the kidneys to retain more water and sodium (salt) in the body, which leads to increased blood pressure. The researchers say that APAs are found in 5% of people with high blood pressure. It is generally curable by removing the tumour, and it is reported to be the most common curable cause of high blood pressure.

These tumours are often caused by genetic mutations occurring in a cell that leads it to divide in an uncontrolled way. Previous studies have found mutations in three genes in about 47% of these tumours. These three genes produce proteins that are involved in transporting potassium, sodium and calcium between cells. The current study aimed to identify any other mutations that could cause APA.

What did the research involve?

In their study, the researchers looked at the DNA sequence in cells taken from a specific subtype of APA tumours. They compared this DNA sequence with sequences from non-tumour cells from the same people, and from people not known to have these tumours. This comparison was done to see if they could identify any changes (mutations) that could have caused the tumours.

The researchers had DNA samples from 10 APA tumours of the subtype they were interested in (called zona glomerulosa-like APAs). They looked at the entire sequence of all the pieces of DNA that contain instructions for making proteins and compared these with the DNA sequences from 100 healthy individuals without high blood pressure, and from 8,000 other control individuals. Once they identified mutations they then looked for mutations in the affected genes in samples from 152 individuals with other adrenal tumours or growths: 53 other APAs, 39 adrenal tumours (adenomas), and 91 adrenal nodules.

They also assessed the impact of the mutations identified by producing the mutated proteins in cells in the laboratory and seeing how they differed in their functions from the normal proteins.

What were the basic results?

The researchers identified mutations in a gene called ATP1A1 in four tumours, mutations in a gene called CACNA1D in five tumours, and a mutation in a gene called CTNNB1 in one tumour. The researchers concentrated on the two more commonly affected genes in the current study.

The ATP1A1 gene produces a protein that is involved in sodium and potassium transport (how cells move sodium and potassium). Mutations in this gene have already been associated with APA tumours. While the CACNA1D gene produces a protein that is involved in calcium transport.

All of the mutations identified would lead to a change in which building blocks (amino acids) were used to make the proteins. None of the mutations identified in the tumours were identified in the DNA from the 8,100 control individuals.

They identified mutations in ATP1A1 in three of 53 additional APAs, four of 39 adenomas and one of the 91 nodular lesions they tested. They also identified mutations in the CACNA1D gene in seven individuals in these additional samples. The APAs carrying the ATP1A1 and CACNA1D mutations tended to be smaller than those that did not (less than a centimetre in diameter).

The mutated forms of the ATP1A1 and CACNA1D proteins performed differently from the normal versions when produced in cells in the laboratory.

How did the researchers interpret the results?

The researchers concluded that a substantial proportion of zona glomerulosa-like APAs have mutations in genes important for regulating sodium and calcium, ATP1A1 and CACNA1D. They suggest the fact that the APAs carrying mutations in these genes tend to be smaller indicates that a diagnosis of APA should not rely on finding a definite nodule (a small clump or “bump” of tissue) on scans of the adrenal gland.

Conclusion

This study has identified mutations that appear to give rise to a particular type of aldosterone-producing adenoma (APA). These benign tumours produce excess amounts of the hormone aldosterone, and lead to an increase in blood pressure. These tumours are reported to be the cause of 5% of cases of high blood pressure, and to be the most common curable form of the condition.

These findings are of interest, and should help researchers to better understand the biology of APAs. They may also be used to determine the cause of the APAs once they are found. What is less clear is whether these findings will lead to changes in how easy it is to identify APAs as the cause of a person’s high blood pressure. This is because the genetic mutations that cause these tumours arise in the cell that gives rise to the tumour, rather than being inherited and carried in all the cells of the body.

Therefore, a blood test would be unlikely to identify these mutations and subsequently point doctors to APA as a cause of a person’s high blood pressure. It is not clear to what extent these genetic findings will change clinical practice in the investigation and treatment of APAs.

The website of the British Heart Foundation, one of the organisations that funded the study, reports that one of the study authors has developed a screening process for these tumours “using an ultra-sensitive ‘PET-CT’ scanner combined with advanced genetic testing”. This process was not assessed in the current study, and it is unlikely that this process is one that would be practical to carry out on all people with high blood pressure.

Due to this information, it is hard to fathom on what the Mail Online is basing its claims that a "simple test could save thousands from life-threatening problems each year".

For the majority of people with high blood pressure, whose condition is not caused by these tumours, these findings will not have an impact on their care.

While “curing” high blood pressure may be possible for some with this specific condition, for most people with high blood pressure (who won’t have this condition) there are non-medical ways to reduce high blood pressure. Instead, they make use of commonsense lifestyle advice, such as:

aim to eat less than less than 6g (0.2oz) of salt a day
moderate your consumption of alcohol
quit smoking if you smoke
take regular exercise
maintain a healthy weight