The heart is also a gland

Most people think of the heart as a pump and nothing more. It is also an endocrine organ. It makes and releases hormones.

The two that matter here are atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). They are short protein chains, peptides, released when the heart's chambers are stretched by too much volume.

When they are released, they do two main things. They relax blood vessels, which lowers pressure. And they tell the kidneys to get rid of more salt and water, which lowers volume. The word "natriuretic" literally means promoting sodium excretion.

In other words, the heart has its own built-in pressure release valve. When it is overfilled, it chemically asks the body to let some fluid go.

The tug of war

In heart failure there is a constant fight going on in the background.

On one side are the neurohormonal systems: the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. When the body senses the heart is not pumping well, these kick in. They tighten blood vessels, hold on to salt and water, and push the heart harder. In the short term that props up blood pressure. In the long term it overloads the heart and drives damage.

On the other side are the natriuretic peptides, working against those systems.

The paper describes it this way: excessive activity of the RAAS and sympathetic nervous system is a major driver of natriuretic peptide secretion. The more the body is fighting to hold on to fluid, the more the heart pumps out peptides to fight back. So a high natriuretic peptide level is effectively a readout of how hard that battle is being fought, and a sign of volume expansion with a higher risk of getting worse.

BNP and NT-proBNP

When you have your natriuretic peptides tested, you will usually get one of two numbers. BNP itself, or NT-proBNP.

When the heart makes BNP, it first makes a larger precursor molecule. That gets split into two pieces: the active BNP hormone and an inactive leftover fragment called the N-terminal fragment, NT-proBNP. Both circulate in the blood. NT-proBNP hangs around longer and is often the one measured.

They carry similar information but use different scales, which is why the numbers look so different.

The rule-out numbers worth knowing

This is one of the most practical facts in the paper.

Natriuretic peptide testing has a very high negative predictive value. That means a low result is very good at ruling heart failure out.

The thresholds given are:

  • BNP below 35 pg/mL
  • NT-proBNP below 125 pg/mL

Below those levels, prior or current heart failure is unlikely.

If you are being investigated for breathlessness or swollen ankles and wondering whether it is your heart, this is often one of the first tests. A result below those thresholds is genuinely reassuring. A result above them does not diagnose heart failure on its own, since many things push the numbers up, but it tells your doctor to look further.

Turning a hormone into a drug

The paper includes one more story worth knowing because it shows how understanding biology becomes treatment.

If BNP is beneficial, relaxing vessels and clearing salt and water, the obvious question is: can we get more of it? Researchers came at this sideways. BNP is broken down in the body by an enzyme called neprilysin. Block neprilysin and BNP survives longer.

That is the idea behind sacubitril/valsartan. Sacubitril blocks neprilysin, keeping natriuretic peptides active longer. Valsartan blocks the angiotensin receptor, damping down part of the RAAS. So one pill boosts the helpful side of the tug of war and restrains the harmful side at the same time.

Sacubitril/valsartan is now one of the four pillars of treatment for heart failure with reduced ejection fraction, alongside beta-blockers, mineralocorticoid antagonists and SGLT2 inhibitors. It comes up again in Part 6, because the paper's own data on it is revealing.

A confusing wrinkle

Here is something that trips people up. Because sacubitril blocks the enzyme that breaks down BNP, it can push BNP levels up in the blood while the patient is actually improving. NT-proBNP is not broken down the same way, so it is generally the more useful marker to follow in someone on this drug.

If you are on sacubitril/valsartan and your results are being tracked, it is fair to ask which test they are using and why.

The big idea for this series

The takeaway from this part is simple. Your heart is constantly telling your body how stretched it is, and a single blood test lets you listen in.

The next part goes one step further. What counts as a "good" level? The paper's answer is that it depends on you, and that the number that matters most is not the normal range but your own personal "dry" level.

This series discusses a peer-reviewed clinical review. Nothing here is medical advice. Heart failure treatment should always be guided by your own cardiology team.