The Expanding Knowledge Base for Lipoprotein(a): Insights from INTERASPIRE and Beyond

In recent years, lipoprotein(a), or Lp(a), has garnered significant attention in the medical community due to its strong association with cardiovascular risks. Elevated levels of Lp(a) have been linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD), which includes conditions such as heart attacks and strokes. This growing interest was prominently highlighted at the 2024 European Society of Cardiology (ESC) Congress, where Dr. Kausik Ray, MD, MPhil, presented groundbreaking data from the INTERASPIRE study. This comprehensive study aimed to assess Lp(a) levels in patients with recent coronary heart disease across 13 countries, providing invaluable insights into the prevalence and variability of elevated Lp(a) levels globally.

The INTERASPIRE study, spearheaded by Dr. Ray, was designed with several primary objectives. Firstly, it sought to determine the prevalence of elevated Lp(a) levels among patients who had recently experienced coronary heart disease. Secondly, the study aimed to identify key factors influencing Lp(a) levels in this population, including genetic predispositions, lifestyle choices, and other comorbid conditions. By collecting data through patient interviews, lab analyses, and various testing methods, the study provided a robust dataset that could be used to explore the complex interplay between Lp(a) levels and cardiovascular risk.

One of the key findings from the INTERASPIRE study was that the median Lp(a) levels in patients with recent coronary heart disease were generally below the threshold considered to pose an increased risk for ASCVD. However, the study also revealed significant variability in Lp(a) levels across different regions and countries. This variability underscores the importance of localized risk factor management and highlights the need for accurate measurement of Lp(a) levels in patients with coronary heart disease. The proportion of patients eligible for Lp(a)-lowering therapies varied significantly by country, indicating that a one-size-fits-all approach may not be effective in managing this risk factor.

Dr. Ray emphasized the importance of understanding Lp(a) levels and their impact on risk factor control during his presentation at the ESC Congress. He pointed out that while Lp(a) is a significant risk factor for cardiovascular disease, it is often under-recognized and under-treated. This lack of awareness can lead to suboptimal management of patients at high risk for ASCVD. Dr. Ray’s presentation highlighted the need for routine Lp(a) testing in clinical practice, especially for patients with a history of coronary heart disease, familial hypercholesterolemia, or other conditions that predispose them to elevated Lp(a) levels.

Complementing the findings from the INTERASPIRE study, new research from London, UK, has provided additional insights into the role of Lp(a) in cardiovascular health. This research focused on the relationship between low levels of Lp(a) and the risk of developing type 2 diabetes. Using a genetic method known as Mendelian randomization (MR), the study demonstrated that high levels of insulin, rather than low Lp(a) levels, are responsible for reducing Lp(a) concentrations. This finding alleviates concerns that drugs aimed at lowering Lp(a) might inadvertently increase the risk of diabetes.

Presented by Prof. Tadeusz Osadnik from the Medical University of Silesia in Poland, the study used data from the UK Biobank and conducted several statistical analyses to explore the causative relationship between insulin levels and Lp(a). The results confirmed that higher insulin levels lead to a decrease in Lp(a) concentration, with no evidence of reverse causality. This suggests that therapies targeting insulin resistance could potentially increase Lp(a) levels, but the overall benefits of improved blood sugar control and reduced cardiovascular risk outweigh the potential downsides.

Prof. Maciej Banach, a co-author of the study from the Medical University of Lodz in Poland and Johns Hopkins University School of Medicine in the USA, emphasized the need for a holistic approach to patient health. He highlighted that while elevated Lp(a) is an independent risk factor for coronary artery disease, managing other cardiovascular risk factors such as insulin resistance and blood sugar levels is equally important. The study’s findings underscore the complexity of the relationship between Lp(a) and cardiovascular health, necessitating further research to fully understand the clinical implications.

Routine measurement of Lp(a) levels in all adults has been recommended by heart experts, based on research showing that high levels of Lp(a) are common in the general population. Studies presented at the ESC Congress in London revealed that Lp(a) carries fats and proteins in the body, and high levels can lead to clogged arteries and blood clots. These conditions significantly increase the risk of heart attacks, strokes, and other cardiovascular diseases. Given that Lp(a) levels are influenced by genetic factors and certain medical conditions like kidney disease, routine testing could help identify individuals at higher risk and enable early intervention.

In Poland, research has shown a high prevalence of elevated Lp(a) levels among patients with cardiovascular diseases, familial hypercholesterolemia, and thyroid diseases. The PMMHRI-LP(a) registry, which analyzed data from 511 patients with high or very high cardiovascular disease risk, found that 20% of patients had Lp(a) levels of 30 mg/dl or higher, and 28% had levels of 50 mg/dl or higher. Significant differences in Lp(a) levels were observed in patients with familial hypercholesterolemia, previous heart attacks, and thyroid diseases, suggesting that Lp(a) should be measured more routinely in populations with a higher risk of cardiovascular diseases.

Another study, the STAR-LP(a) study, analyzed data from 553 patients without established cardiovascular disease and found a link between Lp(a) levels and the progression of atherosclerosis. Similarly, the Zabrze-LIP(a)R registry, which studied 2,001 patients with very high and extremely high cardiovascular disease risk, found that 27% had elevated Lp(a) levels. Elevated Lp(a) levels were also found in 25% of patients with acute coronary syndrome and 34% of patients who had previously experienced a heart attack. These findings highlight the significance of Lp(a) as an additional risk factor for cardiovascular diseases and the need for more research to better understand its role.

The growing body of research on Lp(a) underscores its importance in cardiovascular health and the need for routine testing and targeted therapies. The INTERASPIRE study, along with other research presented at the ESC Congress, provides valuable insights into the prevalence and impact of elevated Lp(a) levels globally. These studies highlight the need for personalized approaches to managing cardiovascular risk, taking into account regional differences and individual patient characteristics. As our understanding of Lp(a) continues to evolve, it is crucial to integrate this knowledge into clinical practice to improve patient outcomes.

In conclusion, the expanding knowledge base for Lp(a) offers new opportunities for improving cardiovascular health. The INTERASPIRE study and other research presented at the ESC Congress have shed light on the prevalence and variability of elevated Lp(a) levels, the relationship between Lp(a) and other cardiovascular risk factors, and the potential benefits of routine Lp(a) testing. By incorporating these insights into clinical practice, healthcare providers can better identify and manage patients at risk for cardiovascular diseases, ultimately leading to improved patient outcomes and reduced healthcare costs. Continued research and collaboration are essential to further our understanding of Lp(a) and its role in cardiovascular health.