There is no risk of thrombosis from higher Lp(a) levels

Milan – In contrast to indications from previous studies, there is no association between increased lipoprotein(a) concentrations and the risk of subsequent thrombotic events, suggests a new, large-scale analysis.

For the study, Lp(a) levels, as well as a genetic risk Lp(a) score, were evaluated in approximately 500,000 participants in a prospective cohort study who were followed for each of the major coronary venous thromboembolic events.

The results shown in European Society of Atherosclerosis 2022 Congress on May 24, showed that there is a strong correlation between the occurrence of major coronary events, including fatal or nonfatal myocardial infarction (MI) or coronary revascularization, increased Lp(a) levels and increased Lp(a) genetic risk scores.

However, no such correlation was found between determinants of Lp(a) concentrations and outcomes, such as venous. blood clots (VTE), deep vein thrombosis (DVT) and pulmonary embolism.

And although Lp(a) was significantly associated with major coronary events, the risk for Lp(a) did not appear to diminish among those with genetic scores that mimic the effects of antiplatelet or antithrombin therapies.

“The messages from this study are very simple but very important from a clinical point of view,” said study presenter Elena Olmastroni, PhD, Department of Pharmaceutical and Biomolecular Sciences, Università degli Studi di Milano, Milan.

Essentially, the results show that Lp(a) does not have a clinically significant venous or arterial thrombotic effect, and that the increased risk of major coronary events, “is unlikely to be reduced by antiplatelet or thrombin therapy,” Olmastroni said.

There is therefore an “urgent need for drugs specifically aimed at lowering apolipoprotein(a)”, she added, noting that drugs that target apolipoprotein(a) production are under clinical development.

I told | Medscape Heart The main implication of their findings is that, in either primary or secondary prevention, antiplatelet or anticoagulant therapy is ‘not effective in reducing the risk’ of major cardiac events in patients with elevated Lp(a) levels.

Florian Cronenberg, MD, who was not involved in the study, called the findings “very important” because previous small studies “gave the impression” that giving aspirin May reduce the risk of cardiac outcomes in patients with elevated Lp(a) levels.

However, he said the current analysis is “the best evidence we can have at the moment” | Medscape Heartbecause the genetic data that was used is “not confusing” and is not subject to reverse causation.

Cronenberg, of the Medical University of Innsbruck, said the results show “very clearly” that “if someone has a Lp(a) variant associated with lifelong increases in Lp(a) concentrations, there is absolutely no association” with thromboembolic events. , Austria.

In contrast, such people have a “significantly increased risk of cardiovascular disease”, which is a “very important point”.

‘mysterious’ lipoprotein

In her presentation, Olmastroni Lp(a) described a “mysterious” lipoprotein believed to contribute to Arteriosclerosis By binding LDL cholesterol, calcium and other components.

Furthermore, recent Mendelian randomized analyzes and genome-wide association studies “clearly demonstrated that Lp(a) is an independent contributor and cause of cardiovascular disease events,” she said.

Although Lp(a) is known to be proangiogenic, Olmastroni noted, researchers have suggested that it may also have a blood clotting effect after dimensional analysis indicated that increased lipoprotein levels were associated with an increased risk of venous thromboembolism.

In contrast, a genetic study Show the oppositewith rs3798220 and rs10455872 single-nucleotide polymorphisms (SNPs) associated with Lp(a) concentrations showing no increase in the odds ratio for VTE for each variant allele.

For further investigation, the researchers examined data from UK Biobankwhich contains genetic, physical and health data for nearly 500,000 individuals between the ages of 40 and 70.

This includes Lp(a) measurements at the time of enrollment in the data bank and determination of a Lp(a) genetic risk score based on previously studied SNPs.

The team calculated the association between Lp(a) concentrations and subsequent major coronary events and VTE, divided not only by the Lp(a) genetic score, but also by the GUCY1A3 score and the polygenic risk score for factor II and V for recurrence of antiplatelet effect and antithrombin treatments. .

They evaluated 445,774 participants from Biobank in the UK who had a mean age of 57.3 years, of whom 54.3% were women. During follow-up, there were 23,302 major coronary events (MCE), 15,974 VTEs, 11,097 DVTs, and 6,602 pulmonary embolisms.

The results showed that among individuals with Lp(a) levels of at least 100 nmol/L, the hazard ratio for MCE was 1.35 (95% CI, 1.32 – 1.38).

Looking at the genetic score Lp(a), they found that compared to individuals with a score of 0, those with a score of 1 had a risk ratio for major cardiovascular events of 1.47 (95% CI, 1.43–1.52), rising to 1.89 ( 95% CI, 1.70 – 2.10) in individuals with a score of 2.

In contrast, there was no association between Lp(a) concentrations of at least 100 nmol/L and the risk of venous thromboembolism, DVT, or pulmonary embolism, even when stratified by Lp(a) genetic score.

Although GUCY1A3, Factor II, and V scores were significantly associated with risk of both MCE and VTE, this effect disappeared when researchers focused on individuals with Lp(a) levels of at least 100 nmol/L.

No funding has been announced. Olmastroni declares no financial relations. Cronenberg announces relationships with Amgen, Novartis, and Kanika.

European Atherosclerosis Society (EAS) 2022. Filed May 24, 2022.

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