Dr Simon Smail, GP, Evergreen Medical & Wellness Clinic
A patient recently asked me a question that many GPs will recognise: ‘Why did this happen to me?’
He had survived an out-of-hospital cardiac arrest. He was in his mid-fifties, physically active, a lifelong non-smoker, and had no history of diabetes. He had undergone successful coronary stenting to his LAD and completed cardiac rehabilitation. His cholesterol was now excellent. His blood pressure was controlled. Yet he remained troubled by a simple question: Why?
His father had died from a myocardial infarction before the age of 50 so he had spent much of his life trying to ensure the same did not happen to him. So why had it?
“… occasionally we encounter patients whose illness appears disproportionate to the risk factors we can see. The standard explanations feel incomplete.”
As clinicians, we are often asked to explain disease after the event. Sometimes we can point to obvious risk factors: smoking, hypertension, diabetes, familial hypercholesterolaemia. But occasionally we encounter patients whose illness appears disproportionate to the risk factors we can see. The standard explanations feel incomplete.
In this case, one piece of the puzzle had not been measured: lipoprotein(a), or Lp(a) as it is known for shorthand. The result was markedly elevated. That finding did not change the cardiac arrest. It did not remove the need for secondary prevention. It did not prove causation. Yet it changed the conversation completely.
The consultation left me reflecting on a broader question. Why are so many patients with premature or apparently unexplained cardiovascular disease still passing through the healthcare system without ever having their Lp(a) measured?
“Why are so many patients with premature or apparently unexplained cardiovascular disease still passing through the healthcare system without ever having their Lp(a) measured?”
The invisible risk factor
Lp(a) was first described more than 60 years ago by Kåre Berg.1 Unlike conventional cholesterol measurements, Lp(a) is largely genetically determined and remains relatively stable throughout life.2 It is estimated that approximately one in five people globally have elevated levels.3
The evidence linking elevated Lp(a) with atherosclerotic cardiovascular disease and calcific aortic valve stenosis is now substantial. The 2022 European Atherosclerosis Society (EAS) consensus statement describes Lp(a) as a causal risk factor for cardiovascular disease and aortic valve stenosis and recommends that Lp(a) should be measured at least once in an adult’s lifetime.2
Yet despite growing scientific interest, Lp(a) remains curiously absent from routine clinical practice.
Most lipid profiles requested in primary care do not include it. Many clinicians have never ordered the test. Access varies significantly across the NHS. Patients often assume that a ‘cholesterol test’ has assessed all relevant lipid-related risk when, in reality, an important inherited contributor may never have been measured.
The consequence is that we may provide false reassurance. A patient can have apparently excellent cholesterol results and still carry substantial inherited cardiovascular risk.
“Patients often assume that a ‘cholesterol test’ has assessed all relevant lipid-related risk when, in reality, an important inherited contributor may never have been measured.”
A once-in-a-lifetime test
One of the striking features of Lp(a) is how little testing is actually required. Unlike LDL cholesterol, Lp(a) testing is not used to monitor response to treatment. Because levels are largely genetically determined and stable throughout adulthood, measurement is usually required only once in a lifetime.2 This raises an obvious question. If a single blood test can identify a common inherited cardiovascular risk factor that cannot be detected through a standard lipid profile, why is it not discussed more often in general practice?
The direction of travel in international guidance is increasingly clear. The EAS recommends at least one lifetime measurement in adults.2 The National Lipid Association now recommends measuring Lp(a) at least once in every adult for cardiovascular risk assessment.4 The recent ESC/EAS dyslipidaemia guideline update further recognises elevated Lp(a) as a cardiovascular risk-enhancing factor.5 The reality on the ground, however, is rather different.
Many GPs cannot directly request Lp(a). Many patients have never heard of it. Many clinicians encounter it only when reviewing specialist correspondence or private laboratory reports. There is therefore a growing gap between what guidelines increasingly recommend and what many patients experience in routine practice.
Why measure it after the event?
A reasonable challenge is that discovering elevated Lp(a) after a myocardial infarction or cardiac arrest is simply too late. The event has already happened. The horse has bolted. Yet that argument underestimates the value of explanation.
Patients frequently want to understand why they became ill. This is not merely curiosity. It is part of how people make sense of serious disease. An inherited risk factor may not provide a complete explanation, but it can provide a medically coherent one.
There is also real practical value. Recognition of elevated Lp(a) may support more intensive management of other modifiable cardiovascular risk factors. Current guidance recommends early and intensive control of modifiable cardiovascular risk in individuals with elevated Lp(a), particularly in the absence of approved Lp(a)-specific therapies.2 It may also influence decisions regarding specialist referral and future screening or treatment options. Most importantly, however, it changes the conversation from an individual patient to a family.
The real beneficiary may be someone else
The strongest argument for measuring Lp(a) may not concern the patient sitting in front of us. It may concern their children. In the case that prompted this reflection, the patient’s father died from a myocardial infarction before the age of 50. A generation later, bystander CPR, defibrillation, emergency angiography and PCI meant that his son survived a cardiac arrest and was able to ask the question, ‘Why?’ The discovery of markedly elevated Lp(a) offers a plausible inherited explanation linking the two events.
Yet the most important beneficiaries of that result may be neither father nor son. They may be the next generation. Elevated Lp(a) is inherited. First-degree relatives of individuals with markedly elevated levels are substantially more likely to have elevated levels themselves. Current guidance supports cascade testing in appropriate families because identifying inherited risk in one individual can reveal risk in many others.2,4 This means that one patient’s result can have implications across an entire family.
A son or daughter who learns about elevated Lp(a) in early adulthood has decades in which to address other modifiable cardiovascular risk factors. They may never experience the event that first brought their parent to medical attention.
Seen through this lens, measuring Lp(a) after a cardiovascular event is not merely an exercise in retrospective explanation. It is an opportunity for prospective prevention. One generation died without knowing the risk existed. The next survived long enough to discover it. With awareness, testing, and appropriate risk-factor management, perhaps the generation that follows can avoid the event altogether.
What should GPs do?
Most GPs do not need to be experts in inherited lipid disorders. We do, however, need to recognise the patients in whom the standard lipid profile may not tell the whole story. The patient with premature cardiovascular disease. The patient whose cardiovascular event appears disproportionate to their conventional risk factors. The patient with a strong family history of early myocardial infarction or stroke. The patient who asks, “Why did this happen to me?”
Not every one of these patients will have elevated Lp(a). Equally, elevated Lp(a) does not guarantee disease. Cardiovascular risk is rarely explained by a single factor. But increasingly, it feels difficult to justify never asking the question. This may become even more important as a pipeline of therapies specifically targeting Lp(a) is progressing through clinical development. For example, the phase 2 studies of olpasiran demonstrating substantial reductions in circulating Lp(a) concentrations, although cardiovascular outcome data are still awaited.6
Conclusion
The consultation that prompted this reflection was memorable because the patient was seeking an explanation rather than a treatment. The answer turned out not to be hidden in his LDL cholesterol, his blood pressure, or his lifestyle. It emerged from a well-established but infrequently performed test that had not been requested in primary or secondary care despite his history and guidelines suggesting it should have been.
As evidence accumulates and guideline recommendations evolve, Lp(a) increasingly looks less like an obscure specialist investigation and more like a neglected part of routine cardiovascular risk assessment. International guidance already points towards measuring it at least once in every adult.
Reaching that point in everyday practice will take time, and the argument here is not that every patient must be tested tomorrow. It is that we can begin with patients already raising the question: those with premature or unexplained cardiovascular disease, and those with a strong family history of early events.
For them, the lesson is straightforward. When someone asks why a major cardiovascular event occurred, we should be careful not to assume a normal lipid profile has already provided the answer and at least think of Lp(a) testing.
References
1. Berg K. A new serum type system in man – the Lp system. Acta Pathol Microbiol Scand; 1963; 59: 369-382.
2. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J; 2022; 43(39): 3925-3946.
3. Doherty S, Hernandez S, Rikhi R, et al. Lipoprotein(a) as a causal risk factor for cardiovascular disease. Curr Cardiovasc Risk Rep; 2025; 19(1): 8.
4. Koschinsky ML, Bajaj A, Boffa MB, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol; 2024; 18(3): e308-319.
5. Mach F, Koskinas KC, Roeters van Lennep JE, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J; 2025; 46(42): 4359-4378.
6. O’Donoghue ML, Rosenson RS, Gencer B, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med; 2022; 387(20): 1855-1864.
Featured Photo by Hush Naidoo Jade Photography on Unsplash
