Caption: Misinformation on how to protect our health are circulating all over internet. Only equipped with knowledge, we will not be misguided. Unlike some perpetuated false claims, statins have been effectively protecting people from heart attack, stroke.
Statins are a class of medicines for lowering LDL cholesterol. High levels of cholesterol are the cause of cardiovascular events such as heart attacks, or strokes and death. The broad term of heart attack actually includes myocardial infarction, unstable angina, revascularization. The beneficial effect of statins in the prevention of cardidiovascular events is substantial. In statin therapy, a 22% reduction of the risk of cardiovascular events is correlated with each reduction in the LDL cholesterol level of 39 mg per deciliter (1 mmol / L ). In statin class, rosuvatatin, atorvastatin, simvastatin, lovastatin and pravastatin are commonly prescribed. The most complained side effect of statin is muscle ache. The concern of the increased risk of diabetes associated statins was raised based on some clinical trials, subsequently FDA added a warning label of this risk to statin therapy in 2012. I had dispensed many prescriptions of statins, but never encountered any question concerning this risk in my patient consultations. Recently, I came across a video clip on this topic from WeChat Channel. The irresponsible contents of the video presentation have prompted me to this writing.
Everybody, even a clown, can give advises for health in a internet platform
In the video presentation, the speaker warned his viewers about the dangers of taking statin drugs, he emphasized a number: 71% increased risk of diabetes if you take a statin drug, meanwhile a graphic illustration with English caption in background was displayed to enforce the authenticity of what came out from his tongue. He further declared that dietary cholesterol had nothing to do with heart attacks by citing some changes of FDA policies. He asserted that the marketing of statin medications, namely for the treatment of cholesterol, was simply a plot of collecting wealth from Chinese people by foreign countries. I have heard about the distorted argument of dietary cholesterol having no impact on heart attacks before. Conspiracy theory is also everywhere these days. I was not surprised by either. However, the 71% increased risk of diabetes associated with statins is surprisingly high, did he fabricate this number? My journey of searching the source of 71% increased risk began.
Misunderstandings a statistic measure can lead to a perception of high risk
In 2012, a clinical trial on the risk of diabetes associated with statins among postmenopausal women reported the result of 71% increased risk ( Hazard ratio = 1.71 ) . This reported risk is much higher than either previous or later results from larger trials. Direct comparison of results is difficult because protocol designs of each trial were different. A result of 27% increased risk of diabetes associated with a statin-rosuvastatin from a larger, high quality trial (JUPITER Trial 2009) has been frequently referred by researchers. Other studies have reported results of increase risk variously lower. If we do not understand the nature of relative risk ratio, even the 27 % increased risk still does not sound like a low risk at all. It is very easy mistakenly to perceive the 27% increased as such “For every 100 persons took the statin, 27 of them had developed diabetes”. This perception is wrong because of the confusion between relative risk ratio and absolute r risk ratio. Both the 71% and the 27% increased risk are relative risk ratio. The 27% increased relative risk rate, derives from a statistic measurement of Hazard Ratio, it compares the rates of people with statin group and without statin group (placebo) in developing diabetes with exaggeration. The formula of calculating Hazard ratio is complicated. A simplistic way can help us understand the exaggeration component in relative risk ratio by using the same data from JUPITER Trial. It reported “The new onset diabetes during the 1.9 year trial duration as 3.0% in the rosuvastatin (a statin) group and, 2.4% in the placebo group). The relative increased risk ratio can be calculated: the 0.6 difference of 3% and2.4% gives a relative increased risk ratio of 25% , close enough to the 27% (not the same because 27% was calculated from Hazard ratio). The absolute risk rate of diabetes is 0.6 %. In a plain language, 6 more persons had diabetes in 1000 participants taking the statin, compared to 1000 participants without taking the statin during 1.9 year trial duration.
From the same data, the same trial, the perceptions for 27 % relative increased risk rate, 0.6% absolute risk rate or, 6 more in every 1000 compared placebo, are dramatically different.
A clown can utilize biased data in the disguise of science to misguide people
The video presentation ignored the data of low risk provided by many other larger trials, and it selected the result of highest relative risk from one single trial purposefully to exaggerate the risk level. However, the trial reported the 71% risk has many limitations due to its design of investigation protocol:
A. The participants of trial were all postmenopausal women.
B. The diagnosis of new onset diabetes was relied on results of patients’ self-reporting.
C. It used non-standardized criteria of diagnosis of diabetes.
D. It is a hypothesis-generating study.
On the contrary, other high quality trials were participants of all genders, physician-diagnosis, and randomized. Therefore, data from this trial were not accepted for later mega-analysis by other researchers.
Several results in its report conflicted with results from trials conducted later. For example, it reported no difference of risk levels between each individual statin ( it stated, for example, atorvastatin has the same level of risk as pravastatin), it also reported that women of overweight were not prone to the risk of diabetes associated with statin compared to women of low or normal body weight. At present, the conclusions from other researcher are just opposite. The particular trial reporting the 71% increased risk seems open to questions. Regardless its report of 71% increased risk, the investigators of this trial (The Women’s Health Initiative) concluded that benefit of statins much outweighed its risk of diabetes, and the results of the trial should not interfere with the current guideline on statin therapy. Why did the video presentation cited the result of trial, but told people a contrary interpretation?
Expression of relative ratio has an exaggeration component
The relative benefit ratio could cause misinterpretation just as easy as the relative risk ratio. One review article commented the benefit of the statin (rosuvastatin) based on the JUPITER Trial:” After almost 2 years of treatment, heart attack, stroke, arterial revascularization, hospitalization for unstable angina or cardiovascular death was reduced by almost half”. This expression should not be understood as “By taking the medicine, 50 out 100 patients had prevented heart attack, stroke—etc.”. The original report expressed the beneficial result in absolute reduction rate. The occurrence rates of cardiovascular events were 0.77 per 100 persons in the statin group and 1.36 per 100 persons in placebo group per year of follow-up. To do the math, the difference of 0.77 and 1.36 in the percentage of 1.36 in placebo group leads to the description of “risk was reduced by almost half”. This is also said “almost 50% reduction”.
(Same result can be calculated from the Hazard Ratio)
By understanding the relative ratio, we can teach ourselves not be fooled by the phony health-adviser from internet video clip. To me, studying statistics has always been difficult, boring and tasteless. Whoever being able to read this writing to this far, is definitely a superhero of patience. However, if someone abuses a statistic result of a report and misleads people into harm’s ways, our actions will be called upon. How many patients may increase their risks of suffering heart attacks, stroke or death due to discontinue or reject statin therapy, because they had believed the video presentation?.
When we need to start statin therapy to protect ourselves from heart attack or stroke, we know that the risk of diabetes associated statins is low. On the other hand, we will have a reasonable expectation from statin therapy. we will continue watching our diet and exercising, rather than doing nothing but relying on taking the statin because you may have thought the drug so powerfully effective.
Manipulating the expression of statistical relative risks to catch attention of viewers is not a new trick. In 2020, a published article in a journal of Diabetes Metabolism Research and Review reported “ it found that statins doubled the risk of developing diabetes, with the risk greatest among those taking statins for two years or longer.” The statement of “a doubled risk” from this article has been doomed to be criticized by other scientists. Because of its intention using the “doubled risk” to receive the media coverage, and it could lead patients to be leerier of starting a statin therapy. ( Eric Seaborg, Feb 2020, Endocrine News).
Does high dietary cholesterol raise your blood LDL cholesterol?
Regarding the preaching in the video presentation that eating high cholesterol food does not increase the risk of heart attacks and other cardiovascular events, CDC has clearly stated the strong correlation between dietary cholesterol and cardiovascular events, in addition to other risk factors compounded(LinK). Did the speaker from internet video presentation know that CDC is the best friend of FDA? How dare he play the tone of FDA to mess with CDC? No need to sift through a plethora of documentation, a simple example can explain well the contribution of dietary cholesterol to the elevation of blood cholesterol. Ezetimibe is a non-statin cholesterol medicine. Its mechanism of action to reduce plasma LDL cholesterol is its ability of blocking the intestinal uptake of dietary cholesterol. Ezetimibe reduces LDL cholesterol in 18 percent when used alone. When taken with statin, further reduces LDL in 25 percent (Product information for Zetia. Merck/Schering-Plaough Pharmaceuticals. North Wales,PA 19454 Aug. 2013). Statins are more efficacious, able to reduce up to 50% LDL cholesterol by inhibition of endogenous production of LDL cholesterol.
More questions
The existence of increased risk of diabetes associated statin has raised some questions out of cautions. For example, before starting statin therapy, a patient may ask questions: A. which statin has lowest risk of diabetes? I want that one! B. If I take a statin at low dose, will the risk be lower? C. I am afraid of heart attacks and stroke more than diabetes, so I want starting statin therapy now. I can stop taking the statin if I notice any sign of diabetes, can’t I? —- More others. It is my intention to organize the available information to answer those questions. On another hand, the side effect of muscle ache caused by statins is more problematic than the risk of diabetes, and needs more attention for solutions.
The conclusion of benefit of statins vs the risk of diabetes
All in all, the statement of therapeutic benefit of statins outweighing its associated risk of diabetes is undisputable. A quote can help us to shake off the hesitance of starting statin therapy:
“Statin therapy substantially reduces cardiovascular events in those with and without diabetes mellitus and in the latter case, several cardiovascular events are prevented for every new diagnosis of diabetes mellitus. Furthermore, when considering the increase in newly diagnosed diabetes mellitus, it is important to note that this represents a far less dramatic and threatening event than the occurrence of myocardial infarction, stroke, or cardiovascular death.” — Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association, December 2018
Are you still listening to advices for your health from those amateur actors?
Key ref:
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207).
Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative. Arch Intern Med 2012; 172(2):144–152).
John Keaney; Bemoedoic Acid and the Prevention of Cardiovascular Disease, New England Journal of Medicine March 4, 2023
Statins and Diabetes: How Big Is the Risk? Eric Seaborg, Feb 2020, Endocrine News
Byron J. Hoogwerf MD, Statins may increase diabetes, but benefit still outweighs risk, MD, Cleveland Clinic Journal of Medicine January 2023, 90 (1)
Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association, December 2018
PharmcistsLetters, August 2014
PurenHealthInfo.com 