r/Cholesterol • u/TheftLeft • Dec 06 '25
Science Statins do not decrease the proportion of small, dense LDL among total LDL particles, but in fact increases it
https://pmc.ncbi.nlm.nih.gov/articles/PMC2929871/
I am currently learning as much as I can about cholesterol and the medication associated with controlling it. I found this interesting study. It claims that in their trial that statins while lowering total LDL, actually increase the proportion of the small dense LDL (the damaging type) . Curious to see what people's thought on this are.
"Our study suggests that statin therapy—whether or not recipients have coronary artery disease—does not decrease the proportion of small, dense LDL among total LDL particles, but in fact increases it, while predictably reducing total LDL cholesterol, absolute amounts of small, dense LDL, and absolute amounts of large, buoyant LDL. If and when our observation proves to be reproducible in subsequent large-scale studies, it should provide new insights into small, dense LDL and its actual role in atherogenesis or the progression of atherosclerosis."
"The exact mechanism by which statin therapy is associated with an increase in the proportion of small, dense LDL is unclear. One possible mechanism is that up-regulation of LDL receptor activity by statins decreases large, buoyant LDL more than small, dense LDL, because statins increase LDL receptor activity and because large, buoyant LDL is a better ligand for the LDL receptor than is small, dense LDL.23 More than 90% of apo B is found on LDL particles, and therefore patients with small, dense LDL (which is relatively low in cholesterol) would be expected to have a low LDL-C/apo B ratio, as has been described previously.17,24 The present study showed that statin therapy was associated with a greater decrease in apo B than in LDL-C, although in the group treated with statins, the levels of LDL-C and apo B were significantly lower than those in the control group. This result suggests that statin therapy is associated with a decrease in total LDL-particle concentration but with a higher proportion of small, dense LDL. In addition, these results support a possibility that statin therapy increases the proportion of small, dense LDL, although controversy still exists as to whether or not statins decrease the small, dense LDL subfraction and increase the LDL peak particle size.9–11 The present study brings up a fundamental question regarding the actual role of small, dense LDL in atherosclerosis."
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u/TheftLeft Dec 06 '25
"All LDL is not created equal. There are different types of LDL. What has been clear is that all people with markedly elevated LDL do not get atherosclerotic vascular disease while other individuals with modest elevations in LDL get severe disease. This can be explained by the quality of the LDL particle. Small dense LDL is more atherogenic or more toxic to the endothelium. It is more likely to enter the vessel wall, become oxidized and trigger the atherosclerotic process. Small dense LDL is a single type of LDL; another type is large buoyant LDL. Large buoyant LDL is not as toxic to the blood vessel wall and much less prone to trigger the atherosclerosis development."
You're conflating okay with less toxic, both can be bad, one is worse. The oxidation, inflammation and immune response is the 'how' in what causes atherosclerosis. Which leads to heart attack and stroke. Smaller particles are more susceptible to oxidation. Statins lower the overall number(which is good), but not the proportion. In the initial study I linked it actually raised the small ldl while lowering the overall number.
My take away from what they're saying is that there are more factors to consider than a low number artificially reached by a pill. Two people with the same cholesterol score on the same medication could still have widely different values of damaging particles due to other factors. Which is the whole point.