Why a Zero Calcium Score Isn’t Enough: A New Study on LDL, Young Adults, and Hidden Plaque
If you’ve been following our Atherosclerosis series (Part 1 and Part 2), you know that heart disease begins long before symptoms appear—and often long before plaque becomes visible on a standard test. We have explored how early arterial injury takes shape, how ApoB particles slip beneath the surface, and how plaques evolve from "soft" and active to hardened and stable.
This week, a major new study from the Western Denmark Heart Registry, published in the European Heart Journal, gives us a critical real-world look at how this biology plays out.
The short version: LDL cholesterol still matters—even when your Coronary Calcium Score (CAC) is zero. And for adults under 45, it may matter even more.
This study reinforces an essential principle of preventive cardiology: A zero calcium score is excellent news for short-term risk, but it does not tell the whole story of your arteries.
The Study: Comparing Calcium Scores vs. CCTA
To understand hidden risk, investigators looked at 23,777 adults experiencing mild symptoms (like chest discomfort).
The Baseline: All participants had a Coronary Calcium Score of Zero (CAC = 0). This means a standard CT scan found no calcified, hardened plaque.
The Deep Dive: They also underwent a Coronary CT Angiography (CCTA). Unlike a calcium score, CCTA uses contrast dye to see inside the vessel wall, allowing it to detect the earlier, "soft" plaques that have not yet calcified.
They followed these individuals for over 7 years to answer two critical questions:
Was high LDL associated with hidden, non-calcified plaque, even when the calcium score was zero?
Did LDL levels predict future heart attacks despite the "perfect" score?
A Note on LDL vs. ApoB: The researchers measured LDL-C because that is the standard metric in large registries. However, LDL is just one of the particles that carries cholesterol. ApoB (Apolipoprotein B) is the protein tag on all atherogenic particles. While this study tracked LDL, we know that ApoB provides an even more precise count of the particles driving this risk.
Key Findings: High LDL Predicts Hidden Plaque
Even though every patient had a "perfect" calcium score of zero, the CCTA scans revealed a different reality.
1. Higher LDL meant more hidden plaque. The advanced imaging found non-calcified (soft) plaque in 11% of people with a zero calcium score. The risk was directly tied to cholesterol levels:
For every 1 mmol/L (~39 mg/dL) increase in LDL-C, the odds of having hidden plaque increased significantly.
2. The risk is highest in young adults (Under 45). This association was strongest in the youngest group. In adults 45 and under, every 1 mmol/L rise in LDL was associated with:
39% higher odds of having non-calcified plaque.
37% higher risk of future coronary events (like heart attack).
Getty Images
Why does LDL matter more when you’re younger? Because early atherosclerosis is almost always soft plaque. It is biologically active and inflamed, but it hasn't been there long enough to calcify. A calcium score cannot see this stage—but CCTA can.
Soft Plaque vs. Calcified Plaque: The Prevention Gap
At Ikigai, we celebrate a zero calcium score. It confirms that you have no advanced, hardened disease. However, it does not rule out the early stages of atherosclerosis—the stages where prevention is most effective.
The disconnect works like this:
Short-term risk is low with a zero score (soft plaque takes time to rupture).
Lifetime risk may still be high if you have elevated ApoB, Lp(a), or inflammation driving soft plaque accumulation.
Case Study: When a Zero Score Isn't Zero Risk
Dr. David Saintsing, co-founder and physician at Ikigai Health Institute, experienced this firsthand.
Age 50: He had a Coronary Calcium Score of 0.
Age 57: His score had risen to 21.
While 21 is still considered low, he underwent a CCTA with Cleerly analysis for a deeper look. The imaging revealed mild, non-calcified plaque in multiple coronary vessels. Further testing showed he carries elevated Lipoprotein(a), a genetic risk factor that drives plaque independent of lifestyle.
If Dr. Saintsing had relied solely on his calcium score at age 50, the early soft plaque would have been missed.
Connecting the Biology: Why CCTA Sees What CAC Misses
This study validates exactly what we covered in Part 2 of this series:
The Glycocalyx fails: ApoB particles slip into the artery wall.
Soft Plaque forms: The body creates a lipid-rich core (invisible to calcium scoring).
Calcification happens late: Only after years of inflammation does the plaque harden (visible on calcium scoring).
The Danish study proves that LDL and ApoB correlate with that early, invisible phase.
Practical Takeaways for Your Heart Health
If you have recently had a heart scan or are evaluating your risk, here is the bottom line:
CAC = 0 is not a lifetime guarantee. It is a snapshot of calcified disease only.
Young arteries hide early disease. If you are under 45, a calcium score is less likely to catch early atherosclerosis.
Know your ApoB. Since we can't CCTA everyone, measuring ApoB gives us the best proxy for the particle burden driving hidden plaque.
Check Lp(a). This genetic risk factor is a potent driver of early, soft plaque.
You deserve a prevention strategy built around your biology—not just a single test score.
