Nearly one in five Chinese adults has elevated lipoprotein(a) levels, significantly increasing their risk of subclinical atherosclerosis at multiple vascular sites, a major epidemiological study has shown.
Researchers found those with the highest Lp(a) levels had up to 67% greater odds of multisite atherosclerosis, according to the study of 2.9 million adults published in JACC [link here].
The research, led by Dr Sailimai Man from Peking University, is the largest epidemiological study to date examining Lp(a) prevalence and its association with subclinical atherosclerosis in a non-Western population.
“A significant burden of elevated Lp(a) was found in China, highlighting the necessity of prioritized Lp(a) screening in high-risk groups,” the authors wrote.
The study analysed adults who underwent Lp(a) testing between 2017 and 2023 at health check-up centres across 30 Chinese provinces. Subclinical atherosclerosis was assessed using imaging examinations at the carotid artery, brain, and coronary artery.
The prevalence of Lp(a) >30 mg/dL was 18.67% and >50 mg/dL was 8.41%. Women showed significantly higher prevalence than men (21.45% vs 16.29% for >30 mg/dL), and prevalence increased with age.
A key finding was that elevated Lp(a) was independently associated with subclinical atherosclerosis across all measured sites. Compared with those with Lp(a) ≤30 mg/dL, individuals with Lp(a) >30 to ~50 mg/dL exhibited 11%, 15%, 9%, and 11% greater odds of increased carotid intima-media thickness, carotid plaque, subclinical brain infarcts, and coronary artery calcification, respectively.
For those with Lp(a) >50 mg/dL, these odds were even higher at 15%, 32%, 10%, and 19%, respectively. The association was particularly strong for multisite atherosclerosis, with 67% greater odds of having atherosclerosis at three vascular sites for those with moderately elevated Lp(a).
“Elevated Lp(a) was identified as a significant risk factor for site-specific subclinical atherosclerosis, with stronger associations observed in severe extent and multisite involvement,” the researchers noted.
The study found varied prevalence across different populations, with significantly higher rates among women, elderly individuals, and those with hypertension, elevated total cholesterol, elevated LDL-C, and impaired kidney function. Conversely, lower prevalence was observed in those with obesity, elevated triglycerides, diabetes, and fatty liver disease.
The findings suggested that individuals with elevated Lp(a) should undergo comprehensive assessment of subclinical atherosclerosis at multiple sites to help prevent atherosclerotic cardiovascular disease, according to the authors.
They stressed that despite its impressive scale, the study had limitations. The authors acknowledged their sample may have under-represented rural participants and could have underestimated elevated Lp(a) prevalence due to selection of a potentially healthier sample compared with past survey studies in China, raising concerns about generalisability.
‘Pivotal step in understanding Lp(a) risk: editorial
In an accompanying editorial, three American cardiologists, including Dr Nathan Wong from the University of California, described the research as “arguably the largest single study in the world examining the prevalence of elevated Lp(a)” and “a pivotal step in bridging this knowledge gap.”
“Most striking, the study showed a clear dose-response relationship between Lp(a) levels and subclinical atherosclerosis across multiple vascular territories,” they wrote.
The editorialists observed that despite the impressive scale of the study, an important question remained: “Do these large-scale observational data sets truly reflect the broader population?”
They suggested the findings had implications for novel therapies targeting Lp(a) currently in development, noting that “a double-enrichment strategy of incorporating both Lp(a) levels and measures of subclinical atherosclerosis into trial eligibility criteria may improve trial efficiency, ensuring interventions target those at highest risk.”
“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,” the editorial concluded.