High levels of Lp(a), coronary artery calcium confer ASCVD risk
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Elevated levels of lipoprotein(a) and coronary artery calcium were associated with risk for atherosclerotic CVD, researchers reported in the Journal of the American College of Cardiology.
“The cross-sectional associations of Lp(a) and CAC have been previously studied, but simultaneous evaluation of the associations of these risk markers with ASCVD risk has not been performed to date,” Anurag Mehta, MD, cardiology fellow at Emory University, and colleagues wrote. “To address this important knowledge gap, we sought to evaluate the independent and joint association of Lp(a) and CAC score with ASCVD risk among asymptomatic participants of two contemporary, multiethnic American epidemiologic cohorts.”
The researchers analyzed 4,512 participants from the MESA cohort (mean age, 62 years; 53% women; 37% white) and 2,078 participants from the Dallas Heart Study (mean age, 45 years; 56% women; 34% white) who had plasma Lp(a) and CAC measured at enrollment.
Participants were stratified into tertiles by CAC (0, 1 to 99 or at least 100 Agatston units) and into quintiles by Lp(a), with the highest race-specific quintile defined as having elevated Lp(a).
During 13.2 years of follow-up, there were 476 incident CVD events in the MESA cohort and 98 incident CVD events in the Dallas Heart Study cohort.
Lp(a), CAC and CVD
In the MESA cohort, elevated Lp(a) (HR = 1.29; 95% CI, 1.04-1.61) was associated with increased risk for CVD compared with the other four Lp(a) quintiles, whereas a CAC score of 1 to 99 (HR = 1.68; 95% CI, 1.3-2.16) and a CAC score of at least 100 (HR = 2.66; 95% CI, 2.07-3.43) were linked to elevated CVD risk compared with a CAC score of 0, according to the researchers.
In the Dallas Heart Study cohort, there was a trend toward elevated Lp(a) being associated with increased CVD risk (HR = 1.54; 95% CI, 0.96-2.46), whereas compared with a CAC score of 0, a CAC score of 1 to 99 (HR = 3.32; 95% CI, 1.74-6.33) and a score of 100 or more (HR = 5.21; 95% CI, 2.46-10.98) were linked to elevated CVD risk, the researchers wrote.
In the MESA cohort, compared with those without elevated Lp(a) and a CAC score of 0, those with elevated Lp(a) and a CAC score of at least 100 had more than fourfold higher risk for CVD (HR = 4.71; 95% CI, 3.01-4.7), but those with elevated Lp(a) and a CAC score of 0 did not have higher CVD risk (HR = 1.31; 95% CI, 0.73-2.35), and findings were similar in the Dallas Heart Study cohort, according to the researchers.
There was no multiplicative interaction between Lp(a) and CAC in either cohort (P for interaction in MESA = .99; P for interaction in Dallas Heart Study = .61), the researchers found.
“In our report, we were able to redemonstrate that the associations of elevated Lp(a) level and CAC score with ASCVD risk are independent of traditional cardiovascular risk factors, including family history of MI,” Mehta and colleagues wrote. “A novel finding of our report is that the association of these two risk markers with cardiovascular risk is independent of each other. Importantly, we validated this finding in two distinct multiethnic U.S. cohorts. Furthermore, when examining ASCVD subcomponents, CHD and stroke, separately, we observed that elevated Lp(a) and CAC have a stronger association with CHD than with stroke risk.”
Next steps in risk evaluation
In a related editorial, Sotirios Tsimikas, MD, professor of medicine and director of vascular medicine at the University of California, San Diego, explained why elevated Lp(a) might not be associated with elevated CAC.
“CAC can be thought of as analogous to C-reactive protein, in that it summates inflammatory components but is not actually the causal mediator,” he wrote. “On the other hand, most of the data on Lp(a) shows its strongest association to be with acute myocardial infarction rather than plaque burden per se, and therefore it may reflect the propensity for atherothrombosis of lipid-rich plaques not detected by CAC.”
What this means, he said, is that “the next step in the risk evaluation should be to measure either Lp(a) or CAC, respectively, if not already performed, to identify the patients at highest risk. Such patients can be considered at secondary prevention risk, and, pending approval of specific Lp(a)-lowering agents, treatment and targets of therapy for all risk factors should be according to this higher risk. In addition, such patients may be considered for PCSK9 inhibitor therapy to reduce ASCVD risk.”
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