Considering statin for high CRP amidst good cardio labs

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circular
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Considering statin for high CRP amidst good cardio labs

Post by circular »

Most of the posts that I've read here about statin use discourage it in ApoE4s to lower cholesterol, and maybe there is a case to be made for a blanket statement against statins in our population for any reason. I was hoping I'd never have to deal with the statin question, but now I do, and others here are way ahead of me in knowing the relevant papers.

My cardio labs are all good, including oxLDL and CAC=0. The problem is that I've had high hs-CRP for years. Nothing I do has brought it down. It is always between 2 and 4.5. Then I found this 2018 paper:

Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers (n=2656)
ApoE4 coupled with chronic low-grade inflammation, defined as a CRP level of 8 mg/L or higher, was associated with an increased risk of AD, especially in the absence of cardiovascular diseases (hazard ratio, 6.63; 95% CI, 1.80-24.50; P = .005), as well as an increased risk of earlier disease onset compared with ApoE4 carriers without chronic inflammation (hazard ratio, 3.52; 95% CI, 1.27-9.75; P = .009). This phenomenon was not observed among ApoE3 and ApoE2 carriers with chronic low-grade inflammation. Finally, a subset of 1761 individuals (66.3%) underwent brain magnetic resonance imaging, and the interaction between ApoE4 and chronic low-grade inflammation was associated with brain atrophy in the temporal lobe (β = -0.88, SE = 0.22; P < .001) and hippocampus (β = -0.04, SE = 0.01; P = .005), after adjusting for confounders.

Conclusions and relevance: In this study, peripheral chronic low-grade inflammation in participants with ApoE4 was associated with shortened latency for onset of AD. Rigorously treating chronic systemic inflammation based on genetic risk could be effective for the prevention and intervention of AD. [Emphasis added]
I'll be testing my CRP to see if it's 8 or above, since all I have are hs-CRP levels which weren't looked at in this study.

I was leaning toward considering metformin to lower CRP (if it does?) given my history of PCOS, but my doctor is suggesting possible statin use for its anti-inflammatory effect. Do I understand correctly that inflammation in the vessels in the absence of high LDL or athlerosclerosis can raise the risk of cardiovascular events and by extension cerebrovascular events independently of cholesterol levels and oxidation? Is it possible that a low-moderate dose of a hydrophilic statin that doesn't cross the BBB might help reduce the inflammatory risk that high CRP poses to the brain without risking the brain's own production of cholesterol that it needs?

Another 2018 paper discusses the paradoxical role of statins for brain health:

The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms

Leaving aside the potential for myopathy for the moment, this paper indicates that when statins worsen cognition it is reversible (at least generally?), and the adverse affect is more commonly associated with lipophilic statins (atorvastatin, simvastatin, and lovastatin). I'm considering, if my doctor recommends a statin, requesting a hydrophilic statin with a baseline cognitive test first and a plan to do a followup cognitive test, just in case there are changes that I'm not myself aware of. I would also get back on CoQ10.

I haven't checked the 'cited by' references for more current information in any detail, and this paper is somewhat old for this area of research, but I like that the authors' stance is to acknowledge the 'paradox' that there are (inadequate) data to suggest that statins can have both protective and harmful effects on cognition depending on context.

Are there others here with high CRP and ApoE4, but no errant CVD markers? If so, have you been able to lower your CRP? I eat quite a lot of high omega 3 fish and recently also supplement with omega 3, so if my CRP is still high, I don't think that will be the answer.

I would love to hear others' thoughts on this predicament.
Last edited by circular on Tue Oct 26, 2021 1:01 pm, edited 1 time in total.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
JD2020
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Re: Considering statin for high CRP amidst good cardio labs

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circular wrote:Most of the posts that I've read here about statin use discourage it in ApoE4s to lower cholesterol,
Hi Circular,

Your post (like most) is way beyond my understanding, so I apologize if this is not on point: I have a friend whose doctor has been telling her for a long time that she needs to go on statins. At the beginning of this year, he told her that she now MUST. She called home to Mexico, complaining to her mother that she had to take the drugs and did not want to. Her mother told her to eat a clove of garlic a day. Crush the garlic and spoon it in like its a pill. My friend has been doing this. She just went back to the doc a couple of weeks ago and he told her that her numbers were great. Then she told him that she was doing something else, not taking the pills. He said, whatever you are doing is working and you don't need the meds. (Strange to me that he did not ask what she was doing).

So...n=1. I can't ask her for the detail of her labs. It is a cultural thing. I think it would be crossing a line.
circular
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Re: Considering statin for high CRP amidst good cardio labs

Post by circular »

JD2020 wrote:
circular wrote:Most of the posts that I've read here about statin use discourage it in ApoE4s to lower cholesterol,
Hi Circular,

Your post (like most) is way beyond my understanding, so I apologize if this is not on point: I have a friend whose doctor has been telling her for a long time that she needs to go on statins. At the beginning of this year, he told her that she now MUST. She called home to Mexico, complaining to her mother that she had to take the drugs and did not want to. Her mother told her to eat a clove of garlic a day. Crush the garlic and spoon it in like its a pill. My friend has been doing this. She just went back to the doc a couple of weeks ago and he told her that her numbers were great. Then she told him that she was doing something else, not taking the pills. He said, whatever you are doing is working and you don't need the meds. (Strange to me that he did not ask what she was doing).

So...n=1. I can't ask her for the detail of her labs. It is a cultural thing. I think it would be crossing a line.
Thanks for your response JD2020! I suspect your friend had high cholesterol and the garlic helped lower that, since most doctors don't even check the inflammatory marker CRP, and to my knowledge, if that's high in the absence of lipids that are out of range, they don't do anything about it.

I've tried all kinds of things to get my hs-CRP down but nothing has worked. I haven't, however, tried garlic, other than I eat two garlic-stuffed, large green olives a day … my favorite way to incorporate it into my everyday diet. You sent me looking and I found a 2020 paper saying that it might help with CRP:

Effects of garlic supplementation on serum inflammatory markers: A systematic review and meta-analysis of randomized controlled trials
Results: 17 randomized controlled trials (RCTs) were included in the meta-analyses. Garlic supplementation significantly reduced the level of circulating CRP (P < 0.05), whereas it did not have any significant effect on IL-6 level (p > 0.05). Sub-group analysis showed that aged garlic extract (AGE) was able to reduce CRP and TNF-α significantly (P < 0.05).

Conclusions: This meta-analysis showed that supplementation with garlic could reduce the level of circulating CRP and AGE could reduce the level of TNF-α and CRP, whereas it had no significant effect on the IL-6 level.
I may try the aged garlic extract before a statin.

Back to your friend … I'm not an expert on this literature (or anything else), but a 'review' at VeryWell Health (which shouldn't be considered the last word), that was updated in 2019, says:
In the very few studies that looked at the long-term effects of cholesterol, it appears that the cholesterol-lowering effect of garlic may be only temporary.3
Your friend may want to be sure to do repeat labs to ensure it is still working.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Considering statin for high CRP amidst good cardio labs

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circular wrote:I'll be testing my CRP to see if it's 8 or above, since all I have are hs-CRP levels which weren't looked at in this study..
Defining hs-CRP
To illustrate the difference between CRP and hs-CRP, traditional testing measures CRP within the range of 10 to 1,000 mg/L, whereas hs-CRP values range from 0.5 to 10 mg/L. In simpler terms, hs-CRP measures trace amounts of CRP in the blood.
Source

Hence my interpretation is if your hsCRP is between 2 & 4.5, then your CRP is certainly < 8.

The late Dr. Duane Graveline was an astronaut and MD. He was prescribed statins which had a profound negative effect on him. He had a website (which still exists). I read some of what he'd found in the research years ago and my takeaway was that the positive effects of statins were due primarily from the inflammation lowering properties and that these effects could be had at rather small doses. With a much lower dose was a much lower probability of side effects. If you do take statins, research taking CO Q10 along with them. I think the info I saw is still on the website, but what I just wrote is from memory after reading the stuff many years ago.
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circular
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Re: Considering statin for high CRP amidst good cardio labs

Post by circular »

Tincup wrote:
circular wrote:I'll be testing my CRP to see if it's 8 or above, since all I have are hs-CRP levels which weren't looked at in this study..
Defining hs-CRP
To illustrate the difference between CRP and hs-CRP, traditional testing measures CRP within the range of 10 to 1,000 mg/L, whereas hs-CRP values range from 0.5 to 10 mg/L. In simpler terms, hs-CRP measures trace amounts of CRP in the blood.
Source

Hence my interpretation is if your hsCRP is between 2 & 4.5, then your CRP is certainly < 8.

The late Dr. Duane Graveline was an astronaut and MD. He was prescribed statins which had a profound negative effect on him. He had a website (which still exists). I read some of what he'd found in the research years ago and my takeaway was that the positive effects of statins were due primarily from the inflammation lowering properties and that these effects could be had at rather small doses. With a much lower dose was a much lower probability of side effects. If you do take statins, research taking CO Q10 along with them. I think the info I saw is still on the website, but what I just wrote is from memory after reading the stuff many years ago.
Thanks Tincup, I've been thinking the same thing about CRP likely being low given the relative low hs-CRP. I had my blood drawn today, so the proof will be in the pudding, but your logic makes sense.

I remembered that I'm taking ubiquinol rather than CoQ10. I'll have to learn more about the differences between those.

Regardless of my CRP outcome, I think the paper I first linked to should be a wake up call for anyone with high CRP and ApoE4. I'm not sure this specific data has been posted here yet, although we know that inflammation isn't our friend. I think CRP is cheap to test and probably fairly easy to get covered by insurance, at least in the US. That said, I'm not a statistics whiz or otherwise qualified to appropriately comment on how robust the reported research was.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
Tincup
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Re: Considering statin for high CRP amidst good cardio labs

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circular wrote:I remembered that I'm taking ubiquinol rather than CoQ10. I'll have to learn more about the differences between those.
I think ubiquinol is the better form.
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circular
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Re: Considering statin for high CRP amidst good cardio labs

Post by circular »

Tincup wrote:
circular wrote:I remembered that I'm taking ubiquinol rather than CoQ10. I'll have to learn more about the differences between those.
I think ubiquinol is the better form.
Thanks Tincup. I believe I'd concluded that too but I never have time for deep dives, so I'm glad to know your take was the same.

My CRP came back normal … yea! … although I'd still like to resolve the hs-CRP, and I haven't yet heard whether the doctor would advise using a statin for that. If she does, I'll certainly give it a lot of thought.
The late Dr. Duane Graveline was an astronaut and MD. He was prescribed statins which had a profound negative effect on him. He had a website (which still exists). I read some of what he'd found in the research years ago and my takeaway was that the positive effects of statins were due primarily from the inflammation lowering properties and that these effects could be had at rather small doses. With a much lower dose was a much lower probability of side effects.
Thanks. I think it's encouraging that with careful use of statins (choosing hydrophilic and taking as small a dose as possible), we could have a safe and powerful antiinflammatory in our arsenal when lifestyle isn't enough, although I realize the science is all over the map, and I'm not sure any research has settled the issues once and for all.

I also read statins have antiviral properties that include preventing replication. Since I've tested positive for antibodies against a plethora of different viruses, at least some of which are probably latent in my body, this possible benefit also appeals to me.

The abstract for this 2021 review is intriguing:

Implications on the Therapeutic Potential of Statins via Modulation of Autophagy
Abstract
Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders.
On the more concerning side, I heard that statins cause insulin resistance. I haven't yet looked into this. Do all forms do this? Is it inevitable based on their mechanism of action, or does it depend on the patient? I'll have to see if I can learn more. I definately don't want insulin resistance.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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