LDL cholesterol, which is popularly known as "bad" - despite experts insisting on stopping calling it that -, has a
"mysterious sister"
, Lp(a), which does occur at high values, such as
In one in five people
, the risk of suffering a heart attack and stroke increases, among other events and cardiovascular diseases. As a result, specialists advise measuring it at least once in your life.
Lp(a) has been known since the '60s, but in recent years research has accelerated. In fact, 10% of scientific publications on this lipoprotein correspond to the last two years.
Austrian researcher Florian Kronenberg described it as "mysterious" because although its study is booming (also driven by the development of therapies to lower its levels), there are still
many unresolved questions
about Lp(a).
"Its physiological role is not known, the structure is very complex, which makes it difficult to measure. We know that it has a
strong association with
atherosclerotic cardiovascular disease and aortic stenosis. And although it is genetically determined, variability is already being seen by various factors (such as postmenopause and kidney disease) and there is no specific approved drug," said Laura Schreier, head of the Lipids and Atherosclerosis Laboratory at the Hospital de Clínicas, University of Buenos Aires.
"This combination of factors gives rise to
uncertainty
," said Schreier during the first Virtual Seminar held jointly between the Argentine Lipid Society (SAL), the Lipid Clinic Network and the European Atherosclerosis Society (EAS).
But not all are doubts, the progress of the investigation has already yielded some certainties.
What is Lp(a)?
Cholesterol in the blood does not "travel" alone, but is transported by lipoproteins, which are measured in laboratory tests. We are used to reading in the results the values of total cholesterol, LDL (the target to treat when it is elevated) and HDL (popularly known as "good"). But it is not common for the Lp(a) to be requested.
Lp(a) is similar to apolipoprotein B100 (apoB100), a form of LDL, but it also has a small bond with another lipoprotein called Apo (a), which gives it its particularity,
the cardiologist explained to
Clarín.
Ezequiel Forte, former director and scientific advisor of the Cardiometabolism Council of the Argentine Society of Cardiology (SAC) and member of the SAL.
Its damage capacity is associated with three properties. "It is
atherogenic
(it produces cholesterol plaques),
pro-inflammatory
(it produces inflammation in the walls of the arteries) and
prothrombotic
(there is a part of the lipoprotein that has a structure very similar to plasminogen, a proenzyme that is involved in coagulation)", Forte indicated.
We all have Lp(a), but in very different concentrations that can vary up to hundreds of times from person to person. "Lp(a) particles are 6 times more atherogenic. In the vast majority of the population it is at normal values.
But when it is elevated, problems appear
," said Schreier.
And how common is that? Quite. “It is known that between 20% and 25% of the population has elevated Lp(a),
its value is determined genetically
in 95% of cases, and the only way to know if it is high is to perform a simple analysis of blood,” said Pablo Corral, former president of the SAL and principal investigator of the Argentine Group Estudio Lp(a) -GAELp(a).
What is the purpose of measuring Lp(a)?
"The increase in Lp(a) is recognized as a
potentiator of cardiovascular risk
and its measurement is very useful to optimize risk classification," say specialists from the SAL and some countries in the region in a position document, the first Spanish-speaking, published in 2022.
In this work, aligned with other medical societies worldwide (such as the EAS and the National Lipid Association), the authors recommend measuring Lp(a) in all people, which "in addition to improving risk assessment, will allow
detection of other family members with
elevated Lp(a) to take preventive measures".
"In recent years there have been a lot of studies that strongly relate the level of lipoprotein a to cardiovascular risk. In fact, at the same level of bad cholesterol, if there is high or low Lp(a), the risk
of patients
drastically changes.
"Forte warned.
And he added: "This allows us to have one more tool to make medicine that is a little finer,
a little more personalized
, since by measuring lipoprotein we can know if a patient is at greater risk."
High Lp(a): what to do
"About 20% of the population has levels above 50 ml/dl, which would be equivalent to
100-125 nmol/L
(N. de E.: specialists suggest using nanomoles as a unit of measurement and not performing conversions)
, From this value the risk of cardiovascular disease begins to increase," said Augusto Lavalle Cobo, head of the Cardiology Service at the Otamendi Sanatorium, in the webinar.
"The risk of having high Lp(a) increases more as the
patient's
baseline risk increases," he said.
But the Lp(a) value is determined by genetics and is not sensitive to changes in habits: that is, it is not modified by exercising more, losing weight or eating better. There are also no specific drugs approved (yes under study) to lower its concentration.
So there is nothing that can be done?
What is the point of knowing if Lp(a) is elevated?
According to specialists, a lot. Fernando Botto, head of Clinical Research at ICBA, explains to his patients that it is like
discovering that there is one leg of the table that is loose
, so you have to make sure that the others are very solid. If the rest are also weak, the basal risk that Lavalle Cobo spoke of is higher.
What you have to focus on, then, is
controlling everything that can be modified
through habits and/or drugs.
"If you have high Lp(a) and are also overweight or obese, have plaque in your arteries, hypertension, smoke,
all that risk accumulates
and there are many things that can be done to strengthen all the other 'weak legs': exercise, eat healthy, lose weight and control other risk factors such as hypertension, hypercholesterolemia and diabetes," Botto lists.
Forte defines high Lp(a) as a
"yellow caution light"
, which leads them to be "much more intensive" in their approach.
When to intervene? "The cardiovascular risk in patients with Lp(a) must be interpreted in the context of their overall cardiovascular risk," responded Lavalle Cobo.
"At the same level of cholesterol, blood pressure and age, a person with high Lp(a) is more at risk than another who has low Lp(a). What do we have to do?
Adjust everything related to lifestyle
, and reduce risk factors to lower cardiovascular risk. Knowing that you are genetically more at risk, we are much stricter with controls. For LDL cholesterol, for example, we take it to a lower target than the rest," Forte exemplified.
"It makes us open our eyes a little more
," said Lavalle Cobo along the same lines. To better stratify the risk, studies may also be indicated to see if there is accumulated plaque in the arteries of the neck or legs (echo-doppler of neck and femoral vessels).
"Many patients arrive with fear, but the idea is not to scare, because
it is not something uncommon
(it affects at least 20% of the population) and the risk is not imminent," Forte reassured.
The objective, in summary, is to know the level of Lp(a) and if it is high, to reduce the cardiovascular risk accumulated by other factors that can be intervened on.
Who should have Lp(a) measured?
Specialists agree that everyone over 18 years of age should have their lipoprotein measured at least once in their life. It is done through a simple blood test and
is not repeated at each routine check-up
, like other parameters that are evaluated periodically (cholesterol, blood glucose, red and white blood cells, etc.)
"
It is not massive, but it should be
. The recommendation of the medical societies has been made. It is a measurement that today any social work covers. It is not a rare or expensive study. There may be hospitals that do not do it and social works that they don't cover it, but it is something that is within the reach of the clinical cardiologist," Forte said.
"If we had to select the groups in which this would be most useful, we should include people with a family or personal history of vascular disease,
patients with LDL cholesterol greater than 190
and/or who are on treatment with statins and cannot reduce it, because It may be a false bad response," said the head of Cardiology at Otamendi.
And it added people with a history of familial hypercholesterolemia, which allows
cascade diagnoses
to be made (if the father or mother has elevated Lp(a), it is likely that the children do too) and patients aged 40 to 75 years with intermediate cardiovascular risk, since which serves to stratify them better.
"The values
usually remain stable
, so the indication would be at least once in a lifetime for most people," he said. However, there are already some studies that are beginning to show variations, "so possibly in the coming years one will not be enough."
Currently, it is suggested to repeat the analysis especially in people with chronic kidney disease, viral hepatitis, uncontrolled hypothyroidism and postmenopausal women.
Specific treatments under study
The most important treatment today is to ensure that the rest of the risk factors are controlled, especially LDL cholesterol, said Matías Arrupe, member of the GAEL group, during the virtual seminar. And aspirin could play a role, although it's still under discussion.
However, there are emerging drugs (pelacarsen, olpasiran, zerlasiran, among others) that are being studied, in different testing phases. In general, these are antisense oligonucleotides or silencing messenger RNA (siRNA).
The most advanced in the study phases (pelacarsen) has already shown
to lower Lp(a) levels by 80%
. "But it still needs to be demonstrated whether lowering it reduces the risk of cardiovascular events, which is what cardiologists are looking for: that patients have fewer heart attacks and fewer strokes," Forte said.
The thing is, as Arrupe mentioned, it is not yet known whether every decrease is accompanied by a cardiovascular benefit. In fact, very low levels could be associated with the development of type 2 diabetes, which is known as
"the Lp(a) paradox
. "
Lp(a) in Argentina
In the country, a registry is underway that aims to know and understand the behavior of Lp(a) in our territory,
estimate the prevalence of elevation at the local level
(currently it is extrapolated from statistics of other populations ) and characterize and describe the pattern of clinical and laboratory association between different values of this lipoprotein, explained Pablo Corral, principal investigator of GAELp(a).
"The group has generated a tool for researchers that
evaluates 50 variables
(filial, clinical, laboratory, imaging and therapeutic data)," said Corral, who has been researching the topic for more than a decade and today is a reference at a local and international level. There are professionals in centers throughout the country collecting data.
Some results of research in the country have already been published. A study carried out on 40 patients who had suffered a premature ischemic event (heart attack, stroke or peripheral) showed that almost one in three men under 55 and women under 65 had elevated Lp(a).
A significant fact:
none of them knew their Lp(a) value
, despite the fact that almost half had suffered recurrent cardiovascular events.
Another study led by Corral in Mar del Plata on 482 people without diagnosed cardiovascular disease (57% women, with a mean age of 53 years), showed that
30% had elevated Lp(a)
. What differentiated them from participants with lower levels was the presence of
subclinical atheromatosis
, that is, plaque in the arteries, measured through carotid and femoral ultrasound.
"It is necessary to know the values of our patients at least once in their lives and raise awareness about this cardiovascular risk factor that has
a high prevalence
," concluded Corral.
***
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