TyG, hs-CRP, and Lp(a) provide complementary information for ASCVD risk stratification, and multi-biomarker profiling may help identify individuals with higher cardiometabolic risk than single-biomarker assessment alone.
The highest quintile of TyG index was independently associated with significantly higher ASCVD risk compared to the lowest quintile.
The highest quintile of hs-CRP was associated with higher ASCVD risk compared to the lowest quintile, with the largest effect size among the three individual biomarkers.
The highest quintile of Lp(a) was associated with higher ASCVD risk compared to the lowest quintile.
ASCVD risk increased progressively with the number of concurrently elevated biomarkers.
Concurrent elevation of all three biomarkers (TyG, hs-CRP, and Lp(a)) identified the highest-risk profile for ASCVD among all eight possible biomarker combinations.
In exploratory subtype analyses, associations of the three biomarkers with ASCVD appeared generally more pronounced for coronary heart disease (CHD) than for stroke.
This research suggests that three different biological markers — the triglyceride-glucose (TyG) index (a measure of metabolic dysfunction), high-sensitivity C-reactive protein (hs-CRP, a marker of inflammation), and lipoprotein(a) (Lp(a), a type of cholesterol particle) — each independently predict the risk of developing cardiovascular disease such as heart attacks and strokes. Using data from over 320,000 UK adults followed for nearly 14 years, the study found that people in the highest fifth of any single marker had roughly 23–36% higher risk of a cardiovascular event compared to those in the lowest fifth. Importantly, these three markers appear to capture different aspects of cardiovascular risk, since they come from different biological pathways (metabolism, inflammation, and lipid genetics). The study also found that the more of these markers that were elevated at the same time, the greater the risk: people with all three markers elevated had about 90% higher risk of cardiovascular disease compared to those without any elevated markers. When every possible combination of elevated markers was examined, having all three elevated simultaneously identified the single highest-risk group. The associations were generally stronger for coronary heart disease (blockages in heart arteries) than for stroke, though both subtypes were affected. This research suggests that measuring just one of these biomarkers may underestimate a person's true cardiovascular risk, and that combining information from metabolic, inflammatory, and lipoprotein markers together could better identify individuals who are at high risk and might benefit from preventive interventions. Multi-biomarker profiling, rather than relying on any single test, may offer a more complete picture of cardiometabolic health.
Chen G, Lan Y, Wu D, Liu P, Zheng H, Wang Y, et al.. (2026). Metabolic, inflammatory, and lipoprotein(a)-related risk profiling for incident ASCVD: a multi-biomarker study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1901020