A significant burden of elevated lipoprotein(a) [Lp(a)] was observed in a large health check-up population in China and elevated Lp(a) was associated with site-specific subclinical atherosclerosis and a stronger association with severe extent and multisite involvement, according to a study published April 23 in JACC. Additionally, a study from Europe published in the same issue advises that more common laboratory measures of risk are not alternatives to Lp(a) in assessing the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS).

In the cross-sectional, nationwide study from China, Sailimai Man, PhD, et al., examined data from nearly 3 million Chinese adults who had Lp(a) testing as part of a preventive health check-up between 2017 and 2023 and were included in the Meinian database. Separate analyses were conducted for test results reported as a mass unit (n=2,788,206) vs. molar unit (n=167,114).

Results showed that in the mass unit group, the prevalence of Lp(a) >30 mg/dL was 18.67% while Lp(a) >50 mg/dL was 8.41%. Women, older participants and those with cardio-renal-metabolic risk factors all had significantly higher rates of elevated Lp(a) (all p<0.05).

Looking at the association between elevated Lp(a) and subclinical atherosclerosis, researchers found a greater likelihood in individuals with an Lp(a) level >30 mg/dL up to approximately 50 mg/dL, compared with <30 mg/dL, specifically with higher odds of 11% for increased carotid intima-media thickness, 15% for carotid plaque, 9% for subclinical brain infarcts and 11% for coronary artery calcification. Risk was even higher in those with Lp(a) >50 mg/dL.

A dose response was seen between higher levels of elevated Lp(a) and the extent of coronary artery calcification and the number of sites involved (one, two or three sites), suggesting that "elevated Lp(a) may be extensively involved in the early asymptomatic stage of [ASCVD] across multiple sites."

The authors note that findings were similar in the molar unit group.

"In light of the significant prevalence of elevated Lp(a) in China, coupled with China's large population base, our findings provide support for the consideration of universal screening of Lp(a) in the Chinese population," write the authors.

In an accompanying editorial comment, Nathan D. Wong, MD, PhD, FACC, Harpreet D. Bhatia, MD, FACC, and Khurram Nasir, MBBS, FACC, add, "This study raises the question of whether further follow-up of those with elevated Lp(a) should include evaluation of subclinical atherosclerosis to enhance risk stratification, optimize preventive therapies and guide appropriate patient selection in future clinical trials."

In the research from Europe, Peter E. Thomas, MD, et al., examined the proportion of risk of ASCVD and AVS from elevated Lp(a) explained by LDL-C, non–HDL-C, apoB and hsCRP using four-way effect decomposition.

Among 70,189 participants from the Copenhagen General Population Study (CGPS), over the 11-year follow-up, 7,155 developed ASCVD and 1,521 developed AVS. Of the 458,601 UK Biobank participants, over the 14-year follow-up, 32,292 developed ASCVD and 6,864 developed AVS. Both populations were similar, with a median age about 60 years old, 53% women and all White.

Furthermore, little of the cardiovascular risk associated with Lp(a) was explained by LDL-C, non–HDL-C, apoB or high-sensitivity C-reactive protein (hsCRP). In the CGPS and UK Biobank groups, respectively, among participants who were not taking a statin, LDL-C explained only 19% and 13% of the risk, non–HDL-C only 22% and 15%, apoB 14% and 16% and hsCRP only 0.2% and 1.1%. For statin users, the proportions were 6.3% and 6.2% for LDL-C, 14% and 7.1% for non–HDL-C, 9.8% and 7.5% for apoB, and 1.1% and 0.4% for hsCRP. Similar results were seen for AVS.

The authors write that, "This analysis helps to drive home the point that we cannot rely on other laboratory measures to tell us meaningfully about [Lp(a)]-related risk." They note that multiple guidelines and consensus statements worldwide endorse measuring LP(a) once in a person's lifetime.