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Comment by DocSavage | Hacker News Reader

I'm suggesting that the reliance on a very fallible test (LDL Cholesterol) for asymptomatic individuals is bad. People could be started on statin treatment and yet have no underlying pathology. I understand CAC imaging is expensive, but so is decades of statin treatments and potential side effect issues.

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My understanding of "the statin issue" is that in the 1970's drug companies found new chemicals to poison the liver's ability to manufacture cholesterol. They reasoned, "as cholseterol is a major part of the arteriosclerosis that hardens blood vessels, people whose bodies are depositing cholesterol where it shouldn't will benefit from poisoning their liver," and promoted the new patent medicines to medical professionals as anti-heart-disease medications.

The medical profession is rather vulnerable the promise of miracle cures to offer their patients, and prescribed the new anti-cholesterol drugs with gusto. Later studies have found the benefit of statin therapy to be minuscule: the "number needed to treat" to prevent one fatal cardiac event is rather high, on the order of 217 for low-risk patients [1]. That is, ~216 patients get to experience the side effects of artificially-reduced cholesterol levels while only 1 person avoids the problem the pill was prescribed to prevent.

In the holistic way of looking at the role of cholesterol, it is more important to think about why the body is manufacturing excess cholesterol and depositing it where it does. As you indicated above, inflammation is an important consideration. Another line of thinking is that there is a roadblock in the steroidogenesis pathway, and that supporting the body's effort to make steroids takes care of the elevated cholesterol levels too.

But our medical professionals tend to develop tunnel vision as they specialize, and assume their specialty's understandings of their domain is basically correct. The drug companies find it much more profitable to peddle anti-cholesterol drugs than to address patients' actual problems.

At least patients who are harmed by statins have the freedom to discontinue their anti-treatment.

[1] http://www.thennt.com/nnt/statins-persons-low-risk-cardiovas...

CAC imaging is expensive and exposes people to (a very small amount of) radiation. Statins are safe and well tolerated. Side effects are treated by temporarily stopping the medication. In people with an appropriately elevated risk, they are cost effective for risk reduction. I.e., they keep people alive longer. So, I don't agree that CAC screening is necessary or helpful prior to initiating therapy in most cases. CAC imaging is a good choice when there is equipoise or disagreement.

> In people with an appropriately elevated risk, they are cost effective for risk reduction.

And this is where this is disagreement. What is appropriately elevated risk? In the case of asymptomatic high cholesterol individuals, especially those without additional risk factors beyond cholesterol, (1) there are flawed studies that include people with underlying pathology together with people who have none to assess statin "benefit", and (2) there are flawed studies that show statins might actually be detrimental with regard to overall mortality. Mainstream medicine currently is fine with #1 (your "they keep people alive longer") and disregard #2 ("they are inversely associated with mortality").

I completely disagree with your dismissal of statin side effects and definite overplaying of the radiation dose of CAC scanning. Nobody has complete understanding of the full side-effect profile of long-term statin treatment let alone all the different types of statins. You have a point with expense, but lets not kid ourselves about the relative side effect profile of long-term statins vs a CAC scan. There's also the management advantages knowing CAC score vs just using LDL.

http://imaging.onlinejacc.org/content/10/3/304 "The presence of CAC is both a sensitive and specific indicator of atherosclerosis, while the total CAC score is a strong predictor of both short- and long-term clinical outcomes. A zero CAC score has become the most definitive predictor of low risk, mild CAC score elevations are indicators for initiating optimal prevention strategies, and high CAC scores may indicate the need for more aggressive management and follow-up. Furthermore, the test has become inexpensive and, with current imaging technologies, is associated with radiation exposure that has decreased to 1.0 to 1.5 mSv per study and to even lower radiation exposure with the newer low-dose imaging protocols (34)."

Average person receives about 3 mSv per year from natural sources. The annual dose for flight attendants is 1.5-1.7 mSv. Mammograms and CAC imaging is similar and less than what flight attendants get in a year.

As I have been doing throughout this thread, I'll continue to agree that a zero CAC score is a really valuable piece of prognostic data, and that the radiation dose is very small. But I'll continue to disagree that we need to scan every adult who qualifies for a statin. And I don't agree that the statin literature is a set of flawed studies. The statin literature is robust - this topic is one of the best-studied topics in medicine. Within medicine, this topic isn't controversial. Even the conservative USPSTF recommends statins for primary prevention above some cutoff: https://www.uspreventiveservicestaskforce.org/Page/Document/...

Re: there's robust literature on statins and it's settled. We're not talking about statin studies on CVD patients. We're talking about asymptomatic treatment. I'm not aware of any study that partitioned asymptomatic high-cholesterol individuals on underlying pathology, e.g., by CAC score, and then seeing if statins were of any benefit to the zero score group. That's because we wouldn't treat those individuals. Instead, all studies (used to argue for treatment of asymptomatic high-LDL) I'm aware of lump "high-risk" individuals together, give them all statins, and then say the outcome is improved for the whole group.

So on one hand, you argue the OP article is fatally flawed because the low-cholesterol group contains high-risk people given statins. On the other hand, you don't concede that the studies lumping all asymptomatic "high risk" individuals together suffer from the same issue. The EISNER study started with "an older population with baseline risk factors" and found 52% had CAC abnormality. I would be interested to see what percentage of asymptomatic high cholesterol people have CAC zero scores and would be treated with statins anyway under current guidelines.

There is a categorical difference between the OP, in which failure to account for statins creates the observation, and a clinical trial that successfully reduces mortality even though the event rate in the control arm wasn’t 100%. That difference is so great that there is almost no relationship between those scenarios.

You don’t know how many people in the low-cholesterol group were on statins in OP article, correct? And despite you completely downplaying it with “the event rate in the control arm wasn’t 100%”, you don’t know how many people in the high-cholesterol group in asymptomatic studies had zero CAC scores (e.g., 50% from EISNER). In both cases you are drawing a conclusion based on incomplete partitioning.

There’s also no consideration of non-CVD mortality and especially morbidity in most of these studies. Despite your unequivocal statement that (all) statins are safe, there’s still a lot we don’t know about long-term use including effects on cognition (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830056/).

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