The JUPITER Study: Statins for All?
A study called JUPITER (which stands for Justification for the Use of Statin in Prevention: An Intervention Trial Evaluating Rosuvastatin) involved 17,802 patients and physicians in 26 countries, evaluating whether statins were an effective preventative measure among patients who 1) had never had a cardiovascular event before, such as heart attacks or strokes, and who 2) had normal lipid levels, but elevation in hsCRP (an inflammatory marker more specific for the cardiovascular system.) Investigators report significant reduction of nonfatal cardiovascular events in these populations, leading to strong recommendations of statin therapy in patients with elevated hsCRP levels but normal cholesterol levels. This has broad implications: no longer are doctors only to treat high cholesterol with statins, but even patients with normal cholesterol levels but high hsCRP should be treated as well.
The reanalysis of the data, however, point out a discrepancy between this study and past studies involving rosuvastatin (Crestor), which showed no protection in high risk patients at all. They also point out that of the fourteen authors of the JUPITER study, nine of them have financial ties to AstraZeneca, the drug company that makes Crestor and which sponsored the trial, that AstraZeneca collected the trial data and monitored the study sites. According to MedPage Today, the first author on the study is also a co-inventor of the hsCRP assay test, and holds the patent on it.
Furthermore, the reanalysis authors cited this article, which looked at data from eleven large trials showing no benefit of statin therapy in preventing all-cause mortality in high risk patients. In their own calculations using the reported data from the JUPITER study, reanalysis authors found no difference between the placebo and the rosuvastatin group for cardiovascular mortality.
Bottom line: the JUPITER study stands alone in its recommendation of statins to prevent cardiovascular events, and there seems to be reason to suspect bias in its results.
In fact, in 2013, the American Heart Association evaluated all published evidence and found that there was no support for the target ranges for LDL previously considered “standard of care.” The focus should now be on treating the patient and his or her risk factors, rather than the labs—although the AHA does still recommend treatment for LDL levels above 190.
Increased Cancer Risk Involved with Taking Statins
Consider this data alongside some of the major risk factors involved with statins:
- The lower your LDL, the higher your overall cancer risk; statins suppressing LDL below 160 had THREE TIMES the cancer risk compared to those with normal to high cholesterol levels.
- Increased risk of breast cancer (83% increased for invasive ductal carcinoma and 97% increased risk of invasive lobular carcinoma)
- 51% increase in prostate cancer risk over a 15 year period
Total speculation on my part, but I wonder if this might be in part due to the fact that statins lower cholesterol production as well as everything downstream, including Vitamin D. There’s some solid data that getting your Vitamin D levels at least above 40 ng/mL is protective against cancer.
What to Measure Instead
Physiology 101: LDL and Oxidative Damage
The walls of your blood vessels can get damaged just like your skin can. When damage occurs (from too much sugar or uncontrolled diabetes, from too many trans fats, from cigarette smoke, etc), you get a scab to protect the wound while your body repairs the damage. The scab is made up primarily of LDL.
So LDL is sort of like a band-aid. The more extensive the damage, the more cholesterol you need to form an adequate band-aid. It’s trying to help you, and this is one reason why it makes sense that the new(ish) guidelines do not support suppressing LDL to particular ranges.
However, when you have a whole lot of LDL hanging around, combined with a lot of inflammation (which is your body’s physiologic response in the face of an injury, in an attempt to heal your tissues and protect you from invasion), what you get are oxidized LDL particles.
(Quick chemistry interlude here: the three components of an atom are electrons, neutrons, and protons. Electrons are the negatively charged particles, and they are only stable when they’re in pairs. If you get one by itself, it becomes promiscuous and tries to steal everybody else’s electrons so it can stabilize. Problem is, then the electron it stole from now has the same problem… and this sets off a chain reaction. Stripping a substance of one of its electrons is called oxidation, while adding an electron is called reduction. One of the ways your immune system protects you, and part of the inflammatory response, involves oxidizing foreign invaders… so this means when you are inflamed, there’s lots of indiscriminate oxidation going on in the surrounding tissues.)
Back to your LDL: there are little proteins sticking out of cholesterol called apolipoproteins, and these are the parts of LDL that can oxidize in the presence of inflammation. When this happens, the chain reaction goes on, except now it’s the oxidized LDL itself that’s wreaking havoc, increasing endothelial damage and recruiting more and more cholesterol to the area to patch it up. This is what can ultimately lead to plaques which can dislodge and cause cardiovascular events, and this is one good reason why a much better marker of cardiovascular risk factors than lipids alone is oxidized LDL.
Take-Home Message on Cholesterol and Heart Disease Prevention
- If you’re taking statins… talk to your cardiologist or your PCP (Primary Care Physician) about what the data says regarding risk reduction, and new guidelines which no longer recommend statin therapy to get into a particular LDL range. I’ve linked to a lot of the articles mentioned above; you might want to bring those in to inform the discussion.
- Test for oxLDL. Most standard labs do not test for oxidized LDL; however, they do test for ApoB and Apo A1, and the ratio between the two. These are the portions of the LDL that oxidize, so this is also a good measurement. There are specialty labs that will test for oxidized LDL directly, as well as some of the inflammatory cytokines involved in its formation… you just usually have to pay for these out of pocket. I like Neuroscience for this (and, considering some of the studies mentioned above, I feel obliged to say that I have no financial interests in the company!)
- Decrease Your Inflammation. You already know how to do this, but here’s a quick rundown: