Filippo Cademartiri: 3 Biomarkers Are Better Than 1: Refining ASCVD Risk in MESA
Filippo Cademartiri, Consultant Advanced Cardiovascular Imaging at UPMC Salvator Mundi International Hospital, shared on LinkedIn:
”Three biomarkers are better than one: refining ASCVD risk in MESA
Traditional risk assessment often treats biomarkers in isolation.
This large analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) shows why that approach may miss the people at highest cardiovascular risk.
What was studied?
Researchers evaluated the individual and combined effects of:
Lipoprotein(a) [Lp(a)]
High-sensitivity CRP (hs-CRP)
Total homocysteine (tHcy)
on coronary heart disease (CHD) and stroke over ~16 years of follow-up in >6,600 asymptomatic adults.
Key findings
Alone, biomarkers showed modest or inconsistent associations.
Risk rose sharply only when biomarkers were elevated together.
Individuals with all three elevated had:
~2× higher risk of CHD
~3× higher risk of stroke
In contrast, having just one elevated marker often did not meaningfully increase risk after adjustment.
Why this matters
This study highlights a core limitation of single-marker thinking:
ASCVD risk is multidimensional
Inflammation, thrombosis, and atherogenesis interact
“Average” risk estimates can obscure high-risk biological phenotypes
Notably, homocysteine—not currently a guideline risk enhancer—emerged as a powerful amplifier of risk when combined with inflammation and Lp(a).
Important nuance
Adding these biomarkers only modestly improved population-level prediction metrics (C-statistics). But for individual risk stratification, the signal is clinically meaningful.
Take-home message
ASCVD risk is not additive—it’s synergistic.
Looking at biomarker combinations, rather than single values, may better identify who truly carries residual cardiovascular risk.
Precision prevention beats one-number medicine.”
Read the full article here.
Article: Lipoprotein(a), high-sensitivity c-reactive protein, homocysteine and cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis
Authors: Sarah O. Nomura, Harpreet S. Bhatia, Parveen K. Garg, Amy B. Karger, Weihua Guan, Jing Cao, Michael D. Shapiro, Michael Y. Tsai
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