NT-proBNP, as well as being a very helpful diagnostic, particularly rule-out diagnostic, has important prognostic information. And this has been shown to be true at almost every level of cardiovascular disease.
So even people that are not unwell, but are simply starting to carry a degree of risk, they may be a little bit hypertensive, they may have a degree of dyslipidaemia, they may have some diabetes or early diabetes, or some combination of those, these are the people that carry the risk of later developing heart failure.
But even at that stage, which we would call Stage A heart failure, an NT-proBNP level has a predictive power. It would add to other information about that person to point out whether they are at a greater or lesser risk of later on developing heart failure.
And then when we move up the scale to Stage B patients, which are people who have had some change in the function and structure of their heart, for example, they may have developed some left ventricular hypertrophy, or if there’s a degree of coronary disease that’s relatively subtle, they may have developed a small wall motion abnormality, or a degree of insufficient blood supply, to at least part of their heart muscle.
These people remain free of symptoms. They don’t feel unwell in themselves, but you can detect abnormality if you make the appropriate imaging and test. Even there, if you add in an NT-proBNP, you get a much sharper idea of whether they’re high risk or relatively low risk of remaining stable or deteriorating.
And when we move into the frankly symptomatic stages of heart failure, which is Stage C, when people have reduced exercise tolerance and crisp breathlessness on exertion, and other symptoms, or Stage D, when they’re very unwell and can almost do nothing without feeling breathless and exhausted, then even at those stages, an NT pro-BNP will tell you whether there’s greater or higher risk, whether it’s extreme or moderate or relatively low risk.
And given that, it means that following the peptide levels in a serial way can help give an idea as to whether that person’s outlook is improving or deteriorating over time. This has been nicely illustrated in some large-scale studies, associated with clinical trials.
The Val-HeFT trial is probably the best in terms of having a neuro-hormonal database. And what that trial showed is that if you recruit a patient under study, and they have a high NT-proBNP level when they enter the trial, and you measure it again at 4 months later, then whether or not it’s gone up or down or stayed the same in that 4-month interval will give you a good – sort of crystal ball as to whether they are high risk of being okay, or even having suffered mortality by the time 2 years has passed by.
So we know that if it stays high between time day 1 and 4 months, these people have about a 1 in 4 risk of dying in 2 years. If it stays low at both baseline and 4 months, it’s more like 7 or 8% risk. But interestingly, if they move from one to the other, if you start high and drop low, then actually your outlook improves, along with that drop in your peptide. If it starts low and goes high, then your outlook deteriorates along with that rise in the peptide level.
And all of that underpins the rationale for using repeated measurements of NT-proBNP to help you firstly monitor how well things are going, but secondly actually guides your treatment as well.
