Firstly I want to thank everyone who has written in with their condolences following the tragic unexpected death of my wife’s father from a heart attack last week, it really is very much appreciated. It has been a difficult time for all of us, but like many families faced with an unexpected loss, it has sparked conversations about risk — where it comes from, how we assess it, and how much of it is really within our control.
Most of what we measure in cardiology relates to modifiable risk: blood pressure, cholesterol, blood sugar, weight, fitness. These remain incredibly important. But as I’ve said before, two people can live strikingly similar lifestyles and still have very different outcomes. And increasingly, we’re learning why.
A substantial component of cardiovascular risk is genetic. Not in the traditional sense of a single “faulty gene,” but through the cumulative effect of hundreds of thousands of small inherited variations that each nudge the probability of coronary artery disease in one direction or another.
Until recently, we had no practical way of quantifying this.
Now we do.
Where the science has come from
Over the last 15 years, enormous international datasets — involving hundreds of thousands, and in some cases millions, of individuals — have allowed researchers to identify genetic markers associated with coronary heart disease. These large “genome-wide association studies” (GWAS) revealed not one or ten, but many thousands of variants that influence risk.
While each variant on its own has a minuscule effect, when combined statistically, they form what’s known as a polygenic risk score (PRS).
A PRS essentially asks:
“Given the pattern of DNA you were born with, how similar are you to the people who went on to develop coronary disease, and how similar to those who didn’t?”
This is not genetic determinism. It doesn’t diagnose heart disease. But it provides a remarkably accurate readout of inherited susceptibility, something no routine blood test can capture.
For many patients, this is the missing piece of the puzzle.
How a polygenic risk score actually works
Although the underlying science is highly complex, the practical process for patients is very straightforward.
In my clinic, it begins with a simple home saliva kit. Once I have discussed the testing process with the patient for consent purposes, I post the kit directly to them, they provide a sample in their own time, and then send it straight to the laboratory using pre-paid packaging. No needles, no appointments, no inconvenience.
Once the laboratory receives the sample, it analyses a large panel of genetic markers associated with coronary disease and combines them using a statistical model to generate the person’s polygenic risk score — essentially an estimate of their inherited susceptibility.
But the crucial part is what happens after the result comes back.
A polygenic risk score should never be interpreted in isolation. It only becomes meaningful when combined with:
cholesterol levels
blood pressure
family history
lifestyle factors
existing medical conditions
any relevant imaging or previous cardiac assessments
So once results are available (usually around 5 weeks), I arrange a dedicated consultation — either virtually or in clinic, depending on preference — to go through the findings in detail. This includes discussing what the score means, how it fits with the person’s overall clinical picture, and whether it suggests we should adjust cholesterol targets, consider medication, change lifestyle priorities or arrange further investigations.
In other words, this is not a test that leaves people with numbers they don’t know how to interpret. It is a fully managed, clinician-supported service, designed to give patients clarity rather than confusion.
The key point is that this score reflects pure genetic predisposition, independent of lifestyle or current health status. It tells you about risk that has been present since birth, long before cholesterol begins to rise, plaque begins to form or symptoms begin to appear.
In cardiology, having this early warning can be transformative.
Why this could revolutionise prevention
What has become increasingly clear from the research is that people with a high genetic score can have a threefold or even fourfold increased lifetime risk of coronary disease — even if their traditional risk factors appear relatively unremarkable.
These are the people who “look fine on paper” in their forties and fifties but who may quietly accumulate plaque earlier than expected.
Conversely, some individuals with modestly abnormal cholesterol but a low genetic burden may be at far lower risk than we once assumed. This of course is the category that I’m hoping my wife falls into, but if not, at least we are in a position to look at ways of lowering her risk moving forwards.
This is where prevention becomes genuinely personalised.
A PRS can help answer questions such as:
Should cholesterol targets be more aggressive?
Should statin or other lipid-lowering therapy start earlier?
Should we be checking arteries with imaging sooner?
How intensively should lifestyle changes be pursued?
How worried should someone really be about a borderline cholesterol or a marginally raised blood pressure?
In other words, it helps us stop guessing.
Why this has become personal
My wife is 46. She is active, eats well, and has none of the classic features that would normally suggest high cardiovascular risk. And yet her father — with the same outward profile — died suddenly of a heart attack. This is exactly the type of situation where genetics may hold clues that routine screening cannot provide.
We discussed it at length, and she has decided to undergo a polygenic risk score. Not because she wants to pathologise herself, but because she wants clarity — a clearer picture of how seriously she needs to treat her cholesterol and how proactive she should be with prevention.
Whatever her result shows, it will help guide our decisions together.
And that, ultimately, is the point of these tests:
not to frighten, not to over-medicalise, but to inform.
Looking ahead — and what comes next
Polygenic risk scoring is still relatively new, which is why it isn’t yet routinely available in the NHS. But the evidence behind it is robust, the clinical utility is increasingly recognised internationally, and for some patients it has the potential to change the trajectory of their prevention entirely.
In my practice at Coastal Cardiology, I will now be offering this test — exactly the same one my wife is having — for patients who want a more complete, personalised understanding of their risk. This is always done with full explanation, shared decision-making, and without commercial pressure, in line with GMC guidance on transparency and patient autonomy.
Next week I will outline how readers who feel this might be relevant to them — for example, those with raised cholesterol, a family history, or unexplained early heart disease in relatives — can access this form of testing privately through my clinic. As with any investigation, this will always be done with full explanation, shared decision-making, and no obligation whatsoever.
The aim is not to label people, but to empower them.
Some will discover their inherited risk is lower than expected.
Some will learn it is higher — and can then act early, decisively and effectively.
Either way, knowledge is better than guesswork.
For us, this is now a very human story — one shared by many families — and I hope that by writing about our own experience, it helps others make more informed choices about their own prevention.