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)
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.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 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.