Rising Lp(a) Levels Increase Risk of Subsequent CVD Events in Adults with ASCVD, According to Large Real-World Study
Any increase in lipoprotein(a) levels was linked to increased risk of myocardial infarction and stroke; women and Black adults are most likely to be affected.
The largest real-world study of its kind involving 273,770 individuals with atherosclerotic cardiovascular disease (ASCVD) found that every increase in levels of serum lipoprotein(a) [Lp(a)] is associated with increased risk of recurrent cardiovascular events. Individuals with the highest Lp(a) levels of 300 nmol/L or greater were 40% more likely to have a cardiovascular event compared to people at levels of less than 15 nmol/L.1
The research, simultaneously presented at the European Atherosclerosis Society Congress in Glasgow and published in the European Heart Journal,1 also found that treatment with "high-impact" LDL-C-lowering therapies may reduce the risk of subsequent CVD events. Investigators reported further that more women than men and more Black individuals than Hispanic and White individuals face elevated risk of recurrent ASCVD events due to high Lp(a).1
"While previous smaller studies have shown that the risk of cardiovascular events can increase within certain ranges of Lp(a), this is the first study to show that the risks of cardiovascular events including heart attack, stroke and cardiac surgeries continue to increase across all ascending levels of Lp(a) and that there is no indication that the risk plateaus," Katherine Wilemon, founder and chief executive officer of the Family Heart Foundation, said in a statement from the Family Heart Foundation.2
During a median follow-up of 5.4 years, 41,687 study participants, 15% of the original 273,770 drawn from the US Family Heart Database, experienced recurrent ASCVD event, including , including 15 078 women, 26 609 men, and 4064 Black, 3784 Hispanic, and 24 139 White individuals, according to the study. Higher Lp(a) levels were associated with "continuously increasing risk of a recurrent ASCVD event overall, and in stratified analyses of women, men, and Black, Hispanic, and White individuals."1
Compared to individuals with Lp(a) lower than 15 nmol/L, the adjusted hazard ratios for recurrent ASCVD events were1:
- 15–79 nmol/L: 1.04 (95% CI, 1.01–1.07)
- 80–179 nmol/L: 1.15 (1.12–1.19)
- 180–299 nmol/L: 1.29 (1.25–1.33)
- 300 nmol/L or more: 1.45 (1.39–1.51)
First author Diane MacDougall, MS, vice president, science and research at the Family Heart Foundation, and colleagues reported that at Lp(A) levels of 300 or more nmol/L, the magnitude of risk of a recurrent ASCVD event was slightly higher in Hispanic and Black than in White individuals. They found further that Lp(a)-associated CV event risk was similar or individual ASCVD components and across sex, race/ethnicity, baseline type of ASCVD, and diabetes subgroups.1
The Family Heart Database contains US medical claims from 340 million individuals between 2012 and 2022. Investigators, identified 273,770 with diagnosed ASCVD with measurements for Lp(a). The final cohort comprised 43% women, 8% self-identified as Black, 9% as Hispanic, and 59% as White.1
Within the study population, approximately one-third had low levels Lp(a) (less than 15 nmol/L), one-third had moderate levels (15-79 nmol/L), 15% had moderate-to-high levels (80-179 nmol/L), 10% had levels considered high (180-299 nmol/L), and 5% had levels considered very high (300 nmol/L or greater).1
"Among the many important findings in this study, we now know that in people living with cardiovascular disease every nmol/L of Lp(a) confers increased risk of a subsequent cardiovascular event. This is a meaningful advancement in our understanding of the impact of Lp(a) on one's health," first author MacDougall said in the statement.2
The findings also showed that high-impact LDL cholesterol-lowering therapy, particularly PCSK9 inhibitors, may mitigate the harmful effects of Lp(a) levels 180 nmol/L or higher, considered elevated, with participants receiving such treatment exhibiting reduced recurrent ASCVD compared with those taking low-intensity medications or none at all.1
While no FDA-approved medications currently target Lp(a) reduction specifically, promising investigational therapies demonstrating 80-98% reductions are being evaluated in ASCVD patients with Lp(a) levels above 175-200 nmol/L.1
"The US has lagged behind many other countries in recommending that adults complete a simple blood test to measure Lp(a)," Wilemon noted in the statement. "This study strongly confirms the importance of considering Lp(a) levels among other risk factors when determining an individual's risk of future heart attacks and strokes."2
This landmark study "is both the largest by 8-fold and the most diverse in race/ethnicity to examine the relationship of higher lipoprotein(a) on recurrent ASCVD events in a contemporary secondary prevention setting," the authors wrote.1
The findings underscore an unmet medical need for a Lp(a) lowering treatment across the diverse ASCVD population and reinforce the value of ongoing measurement of the biomarker, they added. Should the ongoing trials of lipoprotein(a)-lowering agents prove safe and effective, these agents should be added to the armamentarium of effective lipid-altering medications," MacDougall et al concluded.1
