Future therapeutics to reduce elevated Lp(a) might help prevent recurrent disease

Elevated Lipoprotein(a) levels, a form of 'unhealthy cholesterol,' in the blood pose a risk for recurring coronary heart disease (CHD) in individuals aged 60 or older, based on findings from a recent 16-year-long study.

The findings, released today in Current Medical Research & Opinion, indicate that prevailing cholesterol-lowering drugs might not effectively diminish the likelihood of recurring CHD, such as a heart attack, caused by increased Lp(a) levels.

"The discovery further contributes to mounting evidence linking elevated Lp(a) levels with the susceptibility to recurring CHD," states Associate Professor Leon Simons, the lead author from the School of Clinical Medicine at the University of New South Wales Sydney. "It is widely acknowledged that individuals with a history of CHD face a considerably heightened risk of experiencing another episode. Our latest findings suggest that emerging therapeutic approaches targeting the reduction of elevated Lp(a) could potentially aid in preventing recurrent diseases. However, the actual clinical advantages of employing therapies to lower elevated Lp(a) levels still require confirmation."

Coronary heart disease (CHD) is the prevalent form of cardiovascular disease. It arises when the arteries responsible for delivering oxygenated blood to the heart gradually narrow due to the accumulation of fatty substances in their walls. CHD stands as the primary cause of heart attacks and was the leading cause of mortality globally for both men and women in 2019.

Elevated cholesterol levels in the bloodstream can heighten the susceptibility to CHD. Cholesterol is transported in the blood by lipoproteins, which consist of proteins and fats. There are different types of lipoproteins, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and Lp(a). LDL cholesterol, often referred to as 'bad cholesterol,' tends to accumulate in the walls of blood vessels, thereby raising the risk of cardiovascular ailments. Adopting lifestyle modifications and/or utilizing medications like statins can assist in achieving healthy cholesterol levels.

Although previous studies have established the significance of elevated Lp(a) levels as a risk factor in the onset of CHD, most of these investigations have focused on the association between Lp(a) levels and the risk of experiencing an initial CHD event. The present study aimed to determine whether increased Lp(a) levels can predict the occurrence of a subsequent or recurrent CHD event. The research encompassed 607 participants aged 60 years and above from Australia, all of whom had preexisting CHD, and were monitored over a span of 16 years as part of the Dubbo study. Among the participants, there were 399 cases of incident CHD.

The researchers found that:

• The median Lp(a) in people who had a recurrent CHD event was 130 mg/L, compared to 105 mg/L in those who did not.
• 26% of people who had a recurrent CHD event – and 19% of those who did not – had Lp(a) levels of >300 mg/L.
• 18% of people who had a recurrent CHD event – and 8% of those who did not – had Lp(a) levels of >500 mg/L.

Associate Professor Simons emphasizes that elevated Lp(a) levels play a significant role in predicting recurrent CHD in older individuals. He suggests that both 500 mg/L and 300 mg/L can serve as suitable upper reference levels for identifying individuals at higher risk who may benefit from more intensive interventions to reduce their risk. While current medications like statins are commonly prescribed to lower "bad cholesterol" in high-risk cardiovascular disease patients, they do not have a substantial or proven impact on reducing elevated Lp(a) levels. However, there is hope on the horizon, as novel therapeutics specifically designed to lower Lp(a) levels are currently in advanced stages of clinical development.

An important limitation of this longitudinal study is that the baseline data were collected in 1988-89. It is worth noting that there might have been additional factors influencing CHD risk over the course of the follow-up period, particularly with the introduction and increased usage of statin therapy. However, it is reasonable to assume that individuals with elevated Lp(a) levels at the beginning of the study would likely maintain that status throughout the entire duration of the study