Note from Dave: This long-awaited installment from Siobhan is a must-read for every female interested in cholesterol and risk. Enjoy!
The First Hint
As the #LDLBounty continues, and the question of whether high LDL in isolation raises the risk of cardiovascular mortality (or all-cause mortality) in and of itself remains unanswered, there may be a group which may give one even more pause when contemplating the answer. My first hint that things weren’t exactly equal in regards to cholesterol between men and women was way back in 2015. Far before I had even thought about picking up a textbook on lipidology, I noticed there seemed to be something a little odd going on in regards to women and high cholesterol levels. For one, I had heard talk of some research that women with low cholesterol were more at risk for symptoms of depression1, 2, and while I found this interesting it was merely an association. So what if you’re less likely to become depressed if you have higher cholesterol as a woman? You’ll still be more likely to die of things like heart disease, and die more over all, anyway.
More Cholesterol, Less Death
In fact, there appears to be a bit of a difference when it comes to women and men in regards to mortality risk when it
comes to cholesterol. Because, while in men it appears as though there’s a U shaped risk when it comes to
cholesterol levels – meaning that rates of death are higher with lower and higher total cholesterol – with women it appears to be quite a bit more simple. As stated in the paper3, in women it appears as though when cholesterol levels are higher, death from all causes is lower.
That study didn’t appear to be a random fluke, either. As time went on I found more4, and more5 and more6 studies all showing that, specifically in women, either there was no difference in death from all causes with varying cholesterol levels, or those in the lowest cholesterol group had the highest rates of mortality. But, admittedly, this is looking at total cholesterol, so I thought that at the very least higher LDL (often considered the true bad guy in regards to cholesterol) would correlate to higher mortality rates.
More of the Same
Even after looking for studies which looked at LDL levels in regards to the rate of mortality and cardiovascular disease, the result ended up being the same with studies I encountered generally coming to similar conclusions. Some said that LDL levels in women were “not significantly related” to all-cause mortality7, while other said that LDL was not associated with Peripheral Artery Disease in women8, and yet more indicating variations of the same result.9, 10
But, clearly women aren’t bulletproof when it comes to cardiovascular disease, as they get it at about the same rates as men do, and it’s not like we’re especially good at avoiding death in general (as much as we might like to think of ourselves as invincible), either. So, it doesn’t appear as though this is a case of women being immune to cardiovascular disease, or being particularly resistant to death, so much as total cholesterol and LDL seemingly being poor predictive markers for women.
If neither LDL nor total cholesterol is especially predictive in women, then what can we look for to determine our risk? Some studies indicate other, potentially more relevant markers for women, and luckily no additional tests need be ordered, as the information can be found on a standard lipid panel.
For example several studies found that the ratio of triglycerides to HDL were predictive of carotid plaque11, insulin resistance12, 13 (which is related to increased cardiovascular disease risk), cardiovascular mortality14 and all-cause mortality in women.15 Atherogenic Index of Plasma (AIP) also has some promise to better predict all-cause mortality among women.16 Although AIP is unlikely to show up on your lab report, you can easily calculate it via our report tool so long as you have your triglyceride and HDL levels.
While these markers do appear to predict cardiovascular and all-cause mortality risk better than Total Cholesterol or LDL this doesn’t mean that these markers are perfect. For one, both of these measures can be impacted by how long you fasted before the test, as well as issues which may raise triglycerides in isolation. Use of medication which influences HDL and triglycerides may also potentially interfere with their value as health markers, as well, so looking at multiple risk markers together may help avoid some of the pitfalls of relying on one marker alone.
Final Note From Siobhan
As always, the evaluation of personal health is a topic that, first and foremost, should be had with your doctor. Likewise, we always recommend researching all reputable sides of this debate as we do ourselves.
1 Horsten, Myriam, et al. “Depressive Symptoms, Social Support, and Lipid Profile in Healthy Middle-Aged Women:” Psychosomatic Medicine, vol. 59, no. 5, 1997, pp. 521–28. Crossref, doi:10.1097/00006842-199709000-00009.