Anti-inflammatory 20mg/day Rosuvastatin reduced C-reactive protein, heart attacks, strokes in people with normal LDL but elevated C-reactive protein

[sammmy]

A randomized placebo-controlled trial of the anti-inflammatory effect (reduction of C-reactive protein) of 20mg/day Rosuvastatin in the so called JUPITER trial in people with normal LDL, but elevated C-reactive protein:

https://www.nejm.org/doi/full/10.1056/NEJMoa0807646

The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.

It is interesting to see if the reduction in heart attacks and strokes is dose dependent or it can be achieved at the lowest dose 5mg/day with less side effects (new physician reported diabetes was more frequent in the Rosuvastatin group).

Rosuvastatin is a water-soluble statin and is not associated with increased risk for dementia, unlike the fat-soluble statins.

 

[sammmy]

Summary for the less scientifically inclined:

Statin Therapy for Elevated hsCRP: What Are the Public Health Implications?

Randomized trial data indicate that heart disease risk associated with elevated hsCRP can be cut by almost half with a safe, proven pharmacologic therapy.

www.ajmc.com

In brief, the 18,000-participant JUPITER trial overwhelmingly confirmed (1) that those with elevated hsCRP are at substantially elevated vascular risk despite low LDL-C levels and low Framingham Risk Scores and (2) that in this setting rosuvastatin 20 mg compared with placebo reduced the risk of myocardial infarction by 55%, stroke by 48%, bypass surgery and revascularization by 46%, deep vein thrombosis by 43%, and total mortality by 20%.7-9 These hard clinical benefits were statistically significant in all subgroups evaluated, including women, minorities, and the elderly, groups that in the past had been understudied in major trials. Overall, the 5-year number needed to treat (NNT) was 25, a value smaller than that already considered to be effective in primary prevention for those with hyperlipidemia and substantially more efficient that the comparable NNT value for the treatment of hypertension.


The trial was funded by AstraZeneca, but this company played no role in the analysis of the trial data and had no access to unblinded trial data until after the fully independent JUPITER Steering Committee had submitted its results for publication.

 

[Guided_by_Voices]

Lots of safer things are anti-inflammatory such as aspirin and reducing the causes of inflammation.

 

[sammmy]

Aspirin has not been shown to consistently lower CRP in healthy people with elevated CRP, which this thread is about. In those people, often the reason for CRP elevation is not known, so it is not clear how to "reduce inflammation".

Aspirin also causes gastrointestinal lesions even at the lowest doses and increases the risk of bleeding everywhere.

If you have actual studies of anti-inflammatory things that lower CRP in people considered healthy otherwise, I would like to see them.

 

[Guided_by_Voices]

First, there is no reason to think that even if aspirin increases risk of bleeding (not necessarily actual bleeding) or lesions that it is clinically significant given the millions of people who take it on a regular basis (including me).

Second, Rosuvastatin is far from risk-free. I had occasion to look into it recently and the user reviews showed a lot of negative outcomes even at low doses. This obviously does not apply to everyone, but before anyone tries a statin, they should do (at a minimum) the things in the link below, and any study in which the control group was not doing these things (which is all of them) can go straight in the trash. A control group which was consuming seed oils for example would likely have excess inflammation due to that alone.

20 Heart-Healthy Actions With Better Risk/Reward Than Statins

Here at Excelmale there are frequent posts discussing the pros and cons of statins, and one in particular several weeks ago where a position paper was cited where the assumption was that statins are not only a viable option but should be the first line of defense against heart disease. As I have...

www.excelmale.com

Third, coincidentally enough, I was just listening to a podcast yesterday that made the point that CRP is often falsely elevated (e.g. due to exercise), so as with many other things, the marker is not necessarily the same as he actual underlying condition. Further, if statins really had a net beneficial affect, it should have shown up in other studies such as those that looked at 5 year mortality and found essentially no benefit. (BTW, one of the statin studies was found to have likely fraudulent data (beyond just an invalid control group) and I can't remember which one, but I think it may have been the JUPITER study.)

Fourth, if you want some aspirin studies, some are in the Sources and References section at the bottom of this link:

https://articles.mercola.com/sites/articles/archive/2024/08/29/aspirin-health-benefits.aspx

Last, as a side note, a lot of people seem to think that if you lower the statin dose to where you can't feel side effects that damage is not occurring, however it could still be occurring at a slower pace that you don't feel. It is unlikely that the drugs suddenly became completely safe.

 

[sammmy]

The Rosuvastatin reviews are really bad but I don't see studies of actual alternatives that can safely lower CRP inflammation of unclear origin.

Colchicine is approved for decreasing CRP and it does decrease risk of cardiovascular events, as expected, but it is an immune suppressing drug (presented as "anti-inflammatory") with the corresponding risks in the elderly.

Aspirin leading to bleeding is a well known risk no matter what Mercola says:

Advice about daily aspirin - Harvard Health

The heart-protecting benefits of a daily low-dose aspirin have to be weighed against the risk of bleeding, a common side effect that is usually minor but sometimes serious. The decision depends on ...

www.health.harvard.edu

I would not believe medical "authorities" of any kind, neither pro pharma, nor the ones against it.

Let's focus on good quality studies, not what some self-proclaimed "authority" said on internet.

 

[Guided_by_Voices]

If you want to dig deeper into CRP I would start by listening to minutes 25-30 of Ben Greenfield's recent podcast with Dr. Matt Dawson. He says the CRP as typically measured does not correlate well as a predictor of diseases mediated by inflammation but a version called methylated CRP does. Regular CRP can apparently be influenced by benign or helpful things like exercise and apparently doesn't distinguish between good inflammation and bad inflammation. So, it sounds like one would need to get the better tests in order to get a valid reading.

Personally, my CRP has been stubbornly high so I've been trying to minimize my inflammation for years. I applaud the intent, I'm just saying that statins are such a toxic brew of issues that it is hard to ever see them getting into a positive risk/reward area compared to other things like eliminating visceral fat, which almost no one does.

As an aside, this topic reminded me that taking COQ10 orally to offset its loss via statins is no guarantee that it will actually get into the cell at the right time as it would if the body is making it naturally. Yet another issue that should take statins off the table for most people.