Giordano Botta: A Single Measurement in Midlife Can Reveal Future Heart Attack Risk
Giordano Botta, CEO and Co-Founder of Allelica, shared a post on LinkedIn about a recent article by Raysha Farah et al, adding:
“A single measurement in midlife can tell us much more about future heart attack risk than many still assume.
In this JACC paper, a model based on just four biomarkers:
- CAD polygenic risk score
- hsCRP
- LDL-C
- and Lp(a)
Strongly predicted future coronary artery disease incidence across men and women and across ages 40 to 69.
Importantly, this biomarker-based approach performed better than traditional clinical risk calculators, while also identifying people who may be missed by conventional risk assessment.
What makes this especially important is that two of these markers, PRS and Lp(a), are fundamentally different from the others.
Both are stable across life and can provide a long-term baseline of inherited cardiovascular risk.
Lp(a) is genetically determined and, unlike many conventional biomarkers, does not meaningfully fluctuate in the way LDL-C or inflammatory markers can.
PRS is even more distinct: it is a lifelong measure of inherited susceptibility that can be assessed with a simple non-invasive saliva test and only needs to be measured once in a lifetime.
That single result provides a baseline layer of risk information that is present long before disease becomes clinically visible.
So we can act in time.
This is also highly relevant clinically because both Lp(a) and PRS are now reflected in the new ACC/AHA dyslipidemia guideline framework, underscoring the shift toward earlier and personalized risk assessment.
The guideline recommends at least one lifetime measurement of Lp(a), and the 2026 guideline includes PRS in cardiovascular risk assessment for the first time.
This matters because LDL-C does not mean the same thing in everyone.
We and others have shown that PRS modifies the impact of LDL-C on heart attack risk.
In practice, this means that someone with apparently ‘normal’ LDL-C may still be on a trajectory toward building dangerous atherosclerotic plaque if their inherited risk is high.
Looking at LDL-C alone can therefore be misleading.
Looking at LDL-C through the lens of PRS is much more informative.
This is exactly where prevention needs to go: earlier, more personalized, and biologically grounded risk assessment.”
Title: Combining Genomics With Lipid and Inflammatory Biomarkers to Predict Coronary Artery Disease Risk: UK Biobank Study
Authors: Raysha Farah, Min Seo Kim, Buu Truong, Yang Sui, So Mi Jemma Cho, Sarah Margaret Urbut, Aniruddh Patel, Paul M Ridker, Pradeep Natarajan, Akl C Fahed
Read the Full Article on JACC
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