THIS ARTICLE, which assessed the efficacy of the Vitamin K homolog menaquinone-7 (MK-7) in mitigating coronary plaque progression as assessed by serial CAC measurements, is almost assuredly destined for “Most Likely to Result in Supplement Companies Leveraging the Headlines Because People Won’t Actually Read the Study” status. And it’s pretty interesting, but I think it ultimately just leads to some provocative speculations…but that’s why we’re here!
So first off, there are different subtypes of Vitamin K. Vitamin K1 is Klassically found in Kale, while Vitamin K2 includes primarily MK-4 or MK-7. A study shoveling kale down people’s throats would have NEVER been approved by the IRB, so this trial used MK-7 or placebo in these 180 patients with CAC scores between 50 and 400. The CAC scores increased from a median baseline of 135 to 180 at 2 years in the MK-7 group compared to an increase from 145 to 214 in the control group. The reduction in CAC progression was statistically significant in the MK-7 arm, although the percentage of “rapid progressors” did not differ between groups. And the subanalysis of noncalcified, partially calcified, and calcified plaque between groups didn’t seem to show any radical differences, although it was speculated that MK-7 may mitigate calcification in developing plaques while “leaving the already-calcified plaques essentially unaffected.”
So why would we even think to use Vitamin K in Koronary Disease? Well, the reason this is relevant to coronary calcification is because the synthesis of something called matrix Gla protein depends on Vitamin K2. And since you almost assuredly enjoy both lizards and Keanu Reeves movies, you can remember matrix Gla protein as a Gila Monster with Matrix-style fighting moves that dissolves calcification in your vasculature. (This is thought to be the primary reason that Warfarin, a Vitamin K antagonist, can turn your arteries into cement. Warfarin’s inhibition of all Vitamin K subtypes prevents matrix Gla protein from being appropriately deployed). Interestingly, several studies demonstrate an inhibitory effect of statins on MK-4, which may contribute to the increased coronary calcification seen after initiating statin therapy.
However, statins have been shown to reduce cardiovascular events in numerous trials, and the pro-calcific effect of statins is thought to confer stability to existing plaque. So is it actually a good thing that we observe a little less CAC progression with MK-7? Or is the attenuation in calcified plaque content leading to increased plaque vulnerability? Or is this Linkin Park Circa 2000 all over again? (In the End, It Doesn’t Even Matter?)
The short answer is that we don’t know. But since you’re here, I’ll highlight a few interesting studies that are somewhat related to this topic:
-Rapid progressors on CAC had greater risk of all-cause mortality in THIS STUDY, and these rapid progressors were still at significantly elevated risk of major adverse cardiovascular events (MACE) even if on statins HERE.
-The absolute CAC score of 300 confers similar risk of MACE as those who have had prior cardiovascular events, and although statins attenuate this risk, there was still a greater than twofold risk of CV events in these folks even if statin-treated HERE.
-In this small study of PCSK9 inhibition in addition to statin therapy, the progression of CAC in those treated with only statins was about double the combination group. We at least know PCSK9i mAbs reduce cardiovascular events and reduce other high-risk plaque features in other studies, so maybe the decreased CAC progression is encouraging in this case.
But ultimately, would I be Konfident that Vitamin K homologs are Kapable of reducing Kardiovascular events? I’m not quite ready to give it the A-OK, especially if there is further opportunity to bolster one’s Home Security System and move to a safer Lipid Neighborhood with proven methodologies. But I’d love for it to be studied further!
EXTRA CREDIT: For a fantastic editorial on this study from Dr. Michael Blaha, who is one of the true luminaries in the realm of preventive cardiology (and I don’t say that lightly), check out this link HERE.
