Thread by @bschermd

1/ A new RCT in @JAMACardio found that vitamin K2, specifically MK7, slowed coronary artery calcification progression compared to placebo in 180 adults over two years.

Promising finding. But it raises a fascinating question about how we measure cardiovascular disease. 🧵

2/ And the finding makes sense. Vitamin K2 activates proteins that direct calcium away from arteries and toward bone where it belongs. Sounds like a good thing. But does it help heart and vascular health?

3/ The study randomized 180 adults to either 360 micrograms of MK7 daily or placebo for two years, with CAC and CTAs repeated at baseline, 12 months, and 24 months. Serial measurements, same scanner, two years. That is reasonably rigorous for a supplement trial.

4/ But here is where it gets interesting. A baseline CAC score is genuinely valuable for cardiovascular risk stratification. It helps identify who is at higher or lower risk. That clinical utility is well established.

Serial CAC scoring is a different story.

5/ When CAC increases it could mean two very different things. New plaque forming, which is concerning. Or existing non-calcified plaque turning into calcified plaque, which may actually reflect disease stabilization rather than progression.

CAC alone cannot tell you which one it is. That is a fundamental limitation of serial CAC as a monitoring tool.

6/ And this study's own CTA data sheds light on this. Increases in CAC correlated with the partial calcification of non-calcified plaques, but apparently not with new plaque formation. So one possible conclusion is that rising calcium in this study reflected stabilization of existing soft plaque, not necessarily new disease.

7/ But the CTA data also showed something fascinating. There was no significant difference between K2 & placebo in total plaque progression or stenosis severity on CTA. All 3 plaque categories increased in both groups.

K2 slowed calcification but did not appear to reduce overall plaque burden on CTA.

8/ This is precisely why CTA with quantitative plaque analysis is more informative than serial CAC alone. It tracks total disease burden, not just the calcified fraction. As radiation doses continue to fall and AI-guided plaque quantification becomes more standardized, CTA-based analysis should become the new gold standard for tracking CAD progression.

9/ Of course there are plenty of caveats. What about a higher dose of K2? Or longer duration? All good questions. But from what the trial shows, CAC decreased, but we are left wondering if that is a good thing or not.

So be careful reacting to a headline about decreased coronary calcium over time. It may not mean what you think.

Here's a link to the study jamanetwork.com/journals/jamac…