Hi docs, I really enjoy listening to you guys talk about lipids but I have a few questions.
What do you guys make of the lack of association (and sometimes inverse association) between LDL and CVD in the elderly ? I often see paper like the one below cited by “skeptics”
Am I correct in my understanding that this can partially be explained by survivorship bias (those who had high LDL in their 40s and 50s were more likely to die of CVD and those who have high LDL in old age are just more resilient to the effects of higher LDL. Also, things like cancer and infection rates go up dramatically in this age group which I believe can lower LDL. We also don’t know whether those with high LDL in their 70s had high LDL throughout their life.
I often see papers being cited by “cholesterol skeptics” as proof that LDL can’t be a cause of CVD if lower LDL is not associated with less CVD even in younger people. My response is that the vast majority of studies do find a positive association between LDL and CVD, and that it’s ultimately the weight of the evidence that matters, not single studies finding paradoxical results. I usually point them to the paper ‘Low density lipoproteins cause Atherosclerosis’
What do you think of CAC as a marker for Atherosclerosis ? I see a lot of low carb guys say that LDL doesn’t matter bad instead you should get CAC measured. I’ve looked into this a bit and it seems that generally, CAC correlates pretty strongly with non-HDL anyway. So for most people measuring non HDL is sufficient. I’ve also read that there is a subset of the population that can have high LDL and CAC scores of 0. When would you choose to measure CAC ?
Are there any papers you would suggest explaining the lack of association between LDL and CVD mortality in the elderly ?
Any of evidence of a protective effect of higher LDL to things like cancer and infection ?
Yes, this is in part an issue due to survivorship bias. Additionally, these sorts of studies are snapshots in time that fail to recognize the mechanism of atherosclerosis as a process that depends on the cumulative lifelong exposure to ApoB-containing lipoprotein particles. In other words, looking at someone in late life and measuring their LDL-C doesn’t tell you what their blood lipid levels have been throughout their whole life leading up to that point, and you aren’t measuring those individuals who have had very high lipid levels (and thus ASCVD risk) earlier in life who succumbed to CVD.
Correct. The above statement I linked illustrates this quite clearly. A great example are those with PCSK9 knockouts, who have genetically very low blood lipids and upwards of 90% reduction in lifetime CVD risk.
I view CAC as specific, but not sufficiently sensitive, since it is possible to have clinically significant non-calcified “soft plaque” that can rupture and case cardiovascular events. The main situation where I’ll use CAC scoring is in an individual who is at intermediate cardiovascular risk, and who is reluctant to initiate lipid-lowering therapy. In this situation a CAC of 0 “re-classifies” them as low-risk, and we can likely defer initiating lipid-lowering therapy for now, whereas an elevated CAC suggests that they are more likely to benefit from lipid-lowering therapy.
I would start with the above linked statement (and subsequent series), which is heavily cited.