Blood pressure, dietary salt, and genes: What happens when the dots don’t connect?

Michael Joyner, MD, is a medical researcher at the Mayo Clinic. He tweets as @DrMJoyner.

Blood pressure, dietary salt, and how genes influence human biology are among the most frequently reported health-related topics in the media. In the last couple of weeks the new and lower blood pressure guidelines have been widely publicized and critically analyzed; salt is always in the news; and there is no shortage of stories about genes that may influence health. Usually these stories are pretty straightforward or highlight an ongoing controversy.

However, sometimes there are observations and discoveries that aren’t straightforward and in this post I want to tell you about one.

Lots of genes with tiny effects

We are all probably familiar with the idea that high levels of dietary salt can contribute to high blood pressure in at least some people and in some populations (e.g. African Americans). High blood pressure also has a genetic component and it tends to run in families. For a number of years scientists thought that a few gene variants might explain a lot of the risk for high blood pressure. Instead over the last 10 or 15 years they have found literally hundreds of gene variants that can have tiny effects on blood pressure.

When these tiny effects are evaluated as whole, it is possible to create a genetic risk score (GRS) and categorize individuals as high, intermediate or low risk for higher blood pressure. When this is done in large populations, individuals with higher GRS typically have higher blood pressures than those with lower GRS. However, the differences are not huge, just a few points (or millimeters of mercury) for the individuals in the highest GRS category compared to those in the lowest category.

It has also been widely assumed that something related to gene scores would explain the effects of dietary salt on blood pressure. In other words, there should be a pretty simple connect-the-dots relationship between gene variants for higher blood pressure and salt, a well-established lifestyle-related risk factor for higher blood pressure.

But the dots don’t connect

In a terrific recent study published in the journal Hypertension, investigators from China and the US attempted to confirm the link between blood pressure gene scores and salt sensitivity in the so-called GenSalt study (which included a little over 1900 participants). Blood was sampled, genes variants were determined, and participants were also exposed to a couple of dietary interventions. For a week they ate a low sodium diet, for week a high-sodium diet, and the amount of potassium in their diet was also manipulated. Careful measurements of blood pressure were also made.

Guess what happened when the relationships between gene scores and the effects of changing dietary sodium on blood pressure were evaluated?

One the one hand, as expected, the researchers reported that blood pressure increased with increasing GRS. However, the researchers also reported a surprise: “Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP.”  

In other words, blood pressure changed less in response to changes in dietary sodium in the participants with the high gene scores than in the those with the low gene scores. This is the exact opposite of the relationship the researchers expected to find.

The other interesting thing is that depending on whether the higher or lower blood pressure number was analyzed, the group with the highest genetic risk had blood pressure values just 2-4 points higher than those with the lowest.  Incredibly, a week of either high or low salt in the diet caused blood pressure to vary about twice as much as the differences seen between the groups when they were on a normal diet.

A few weeks of dietary extremes beats a lifetime of genes!

Why wasn’t this news?

Nobody can say for certain why some news stories blow up and others fail to gain traction. But here’s my guess as to why this particular study garnered very little news coverage.

First, the study is in a medium profile journal but not in one of the “big six” journals: Science, Nature, Cell, the New England Journal, Lancet, or JAMA. Hypertension is a terrific journal, but it does not have the same kind of following among journalists as these other publications. I also couldn’t find any news release about the study, which means that it was all but invisible to anyone in the media who doesn’t read this journal.

Second, the gene score salt story outlined above is complicated and also counterintuitive.

Third, maybe the media has a case of collective confirmation bias and when the gene-to-disease dots don’t connect the way they are “supposed to,” journalists and the general public are simply less interested. Fourth, there have been lots of cuts in newsrooms and maybe there are just not enough experienced journalists around to take deeper dives into more complicated stories.

I should also add that my own personal bias is that we are going to be seeing more counterintuitive and “not quite so simple” stories about genes and disease in the coming years, but then that opinion might also reflect my own set of confirmation biases.

Michael Joyner, is a medical researcher at the Mayo Clinic. These views are his own. He has done preclinical technical consulting for GSK, Amgen, Boston Scientific, Edwards, and Nonin on issues related to physiological monitoring, cardiovascular disease and diabetes. He is on the board of Xcede a startup focused on tissue sealants. As a clinical anesthesiologist he prescribes no drugs or products related to his consulting. 

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Comments (5)

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Joel Anaple

November 22, 2017 at 7:24 am

So is there a definite link between salt and high blood pressure? It seems the science has more work to do.

Jackie Sanders

November 22, 2017 at 8:00 am

I did not follow the second part of this article. Can you explain it to me in plainer English? The results showed that those with a genetic link we’re not as affected by salt as previously thought and…I didn’t get the other finding.

Dr. Michael Joyner

November 22, 2017 at 1:48 pm

Joel … On a population basis dietary salt is linked to blood pressure (BP). However, there is a lot of individual variability in salt sensitivity. This paper showed that the effects of genes that are related to higher BP and salt were not as straight forward as anticipated. It also suggests there are many non-salt-related contributions to blood pressure.

Jackie … So those with the highest genetic risk for higher BP actually experienced smaller changes in BP when the amount of sodium in their diets was altered.That’s an inverse relationship. But the expectation underpinning the study was that the relationship would be positive.

John Galbraith Simmons

November 27, 2017 at 7:30 am

Thanks very much for this excellent post, which comes at an interesting time in light of new ACC/AHA BP guidelines that to many minds may be unrealistic and have unexpected consequences.

Megan Stephan

November 27, 2017 at 12:50 pm

Regardless of complexity and counterintuitive results, my thought would be that a week may not be long enough to detect an interaction between genes and diet, particularly in a relatively small number of subjects (as cardiology studies go).