High lipoprotein(a) linked to long-term risk for heart events, regardless of prior CVD
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Key takeaways:
- High levels of lipoprotein(a) are associated with elevated risk for an adverse heart event.
- The relationship was consistent regardless of whether patients had atherosclerotic heart disease at baseline.
In a real-world cohort, people with the highest levels of lipoprotein(a) had the greatest risk for long-term major adverse CV events, regardless of whether they had atherosclerotic CVD at baseline, researchers reported.
The researchers retrospectively analyzed the association of Lp(a) levels and MACE, defined as nonfatal MI, nonfatal stroke, coronary revascularization or CV death, in a cohort of 16,419 patients from two institutions in Boston who had Lp(a) levels measured from 2000 to 2019. The median follow-up was 11.9 years.
Among the cohort (mean age, 60 years; 41% women), 62% had ASCVD at baseline.
Patients were stratified into quartiles by Lp(a) level: first to 50th percentile (0-41 nmol/L), 51st to 70th percentile (42-111 nmol/L), 71st to 90th percentile (112-215 nmol/L) and 91st to 100th percentile (216 nmol/L or more).
In patients with ASCVD at baseline, compared with the lowest quartile, those in the 71st to 90th percentile (adjusted HR = 1.21; 95% CI, 1.11-1.32; P < .001) had elevated risk for MACE, as did those in the 91st to 100th percentile (aHR = 1.26; 95% CI, 1.12-1.41; P < .001), Adam N. Berman, MD, cardiology fellow at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote in the Journal of the American College of Cardiology.
In patients without ASCVD at baseline, compared with the lowest quartile, MACE risk also rose with increasing Lp(a) level, and those in the 91st to 100th percentile had significantly elevated risk for MACE (aHR = 1.93; 95% CI, 1.54-2.42; P < .001), though the risk in the other quartiles was not statistically significant, Berman and colleagues wrote.
“Our findings support the important role of Lp(a) in determining ASCVD risk in both primary and secondary prevention cohorts as demonstrated within a large, well-phenotyped U.S.-based registry,” the researchers wrote. “Additionally, this work provides novel insights that have the potential to inform both risk assessment as well as identifying populations for future therapeutic outcomes trials.”
In a related editorial, Nathan D. Wong, PhD, MPH, professor of medicine, epidemiology and biostatistics and population health and disease prevention and director of the UCI Heart Disease Prevention Program at the University of California, Irvine, wrote: “It may not be long before guidelines in the United States endorse universal screening, which many experts already support. Although some may question this approach until there are proven therapies for Lp(a) that reduce ASCVD, elevated Lp(a) levels, which are present in 20% of patients, identify increased ASCVD risk, warranting comprehensive risk reduction with existing preventive treatments. We should embrace this strategy as we wait for proven pharmacologic therapies.”
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Perspective
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This is an incremental study. It does not represent a big change in thinking. We have known for quite some time that a high level of Lp(a) is a risk factor for both primary and secondary prevention of heart disease. These authors suggest that perhaps the thresholds for risk are different for primary and secondary prevention. I don’t find that evidence compelling. This is one of many studies that have been performed on Lp(a) and risk. Perhaps they are right that if you are in the primary prevention subgroup, you need to have higher levels before risk goes up. But what I see here is risk across the spectrum extending from the lowest levels to the highest levels. The strongest data available come from the UK Biobank, which involved half a million people. Those data look like a straight line in level of risk, starting at 0 and going out to the very high levels of Lp(a). So, I think the risk is linearly related to Lp(a) levels, and what the authors of the current study observed may reflect some of the biases related to the population that they encountered, and other factors that are difficult to measure.
The important reason why we need to pay attention to these issues is that there will be trials with not just patients with ASCVD and high Lp(a), but also enrolling primary prevention patients at high risk. Those studies will need to decide on the threshold for increased risk for qualification in the trial. There may be some consideration of whether these risk levels should be different in the two populations. Whether people actually use the information from the current study in designing trials remains to be seen, but it is certainly relevant to the research currently underway. There are multiple drugs in development for treatment of high Lp(a), and the sponsors are doing studies with different designs.
We have said, as have others, that everyone should have Lp(a) measured at least once in their lifetime. We typically would expect measurement in their early 20s so a patient’s risk can be identified and they can manage their lifestyle in a way to try to mitigate risk. We do not have drugs for anybody yet, but people need to know their risk level. We need to change the thinking about Lp(a) such that it becomes an almost universally measured risk factor. The good thing about measuring it early in life is that it does not change, so if you have a high level, you will have it at all ages. Therefore, you only need to have it measured once. It is not a particularly expensive test, and it is being underutilized.
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