The idea that statin drugs reduce operative mortality is ridiculous. This is so wrong one wonders how it was approved for peer-review publication.

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Link to original article.

I was intrigued by Dr London's report in December 2016 JAMA of decreased peri-operative mortality in statin users.(1) This result does not seem immediately intuitive. Statin drugs inhibit an enzyme in the liver called HMG-CoA reductase involved in cholesterol production, thereby reducing cholesterol levels. Left Image: Surgeons by Reginald Brill 1934 courtesy of Wikimedia Commons.

Higher Cholesterol is Protective of Post-Operative Sepsis

Higher cholesterol in the surgical patient is protective of endotoxemia, a dreaded complication of non-cardiac surgery that carries a high mortality rate. According to Dr Wilson writing in Critical Care 2003, "lipoproteins can bind and neutralize lipopolysaccharide, hypocholesterolemia can negatively impact outcome." (2)

Severely ILL Patients Have Low Cholesterol

Another observation made by Dr Wilson is that severely ill patients tend to have low cholesterol. If so, then these severely ill patients would not be good candidates for statin drugs in the days prior to their surgical procedure as their cholesterol levels are already low. No need to give a drug to make it lower. On the other hand non-critically ill patients tend to have higher cholesterol values, which does make them good candidates for a statin drug.

The Cholesterol-Endotoxin Hypothesis

This explains the spurious findings of the JAMA article. The patients not taking statins were sicker and had lower cholesterol values, a marker for increased mortality from sepsis.

Conclusion:

Low cholesterol is an excellent marker for increased mortality from sepsis. (3-7) Therefore, driving down serum cholesterol with a statin drug is not a way to reduce surgical complications, most of which are related to post-op sepsis. This study in JAMA by Dr London is therefore a medical hoax, a result of patient-selection bias, not due to any imaginary benefits of statin drugs, which are non-existent. The damage that this JAMA article could produce is frightening, since some surgeons may actually believe it and give their patients statin drugs. This would be a catastrophe of monumental proportions.

Link to original article.

Articles with Related Interest:
Low Level Endotoxemia and Cholesterol

Jeffrey Dach, MD

Links and References:

1) Association of Perioperative Statin Use With Mortality and Morbidity After Major Noncardiac Surgery. Martin J London, JAMA Dec 19 2016.

2) Wilson, Robert F., Jeffrey F. Barletta, and James G. Tyburski. "Hypocholesterolemia in sepsis and critically ill or injured patients." Critical Care 7.6 (2003): 1.

3) Leardi, S., et al. "[Blood levels of cholesterol and postoperative septic complications]." Annali italiani di chirurgia 71.2 (1999): 233-237.
Hypocholesterolemia seems to represent a significant predictive factor of morbidity and mortality in critically ill patients.

4) Marik, Paul E. "Dyslipidemia in the critically ill." Critical care clinics 22.1 (2006): 151-159. Total and HDL cholesterol levels fall at the onset of acute illness and the cholesterol levels normalize as the patient recovers. Hypocholesterolemia may predispose the critically ill patient to sepsis and adrenal failure.

5) Chiarla, Carlo, et al. "Severe hypocholesterolemia in surgical patients, sepsis, and critical illness." Journal of critical care 25.2 (2010): 361-e7.

6) Biller, Katharina, et al. "Cholesterol rather than procalcitonin or C-reactive protein predicts mortality in patients with infection." Shock 42.2 (2014): 129-132.

7) free pdf Thomas Whitney Serum cholesterol Superior Prognostic Marker Sepsis Mortality in ICU 2015Thomas, Whitney. "Serum cholesterol: A Superior Prognostic Marker of Sepsis Mortality in the ICU Compared to Procalcitonin or C-reactive Protein." (2015).
Total cholesterol may be a useful and superior prognostic marker of mortality for patients admitted to the ICU with sepsis secondary to infection.

8) Sandek A., Utchill S, Rauchhaus M. The endotoxin-lipoprotein hypothesis-an update. Arch Med Sci. 2007;3(4A):S81. The endotoxin lipoprotein hypothesis Anja Sandek 2007.

9) Pajkrt D, Doran JE, Koster F, et al. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med. 1996;184(5):1601-8.

10) Vreugdenhil AC, Rousseau CH, Hartung T, et al. Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons. J Immunol. 2003;170(3):1399-405.

11) Statin Drugs Tied to Better Surgery Outcomes By NICHOLAS BAKALARDEC. 21, 2016.

12) Shock. 2016 Jan;45(1):10-5. Incidence of Sepsis and Mortality With Prior Exposure of HMG-COA-Reductase Inhibitors in a Surgical Intensive Care Population.
Schurr JW1, Wu W, Smith-Hannah A, Smith CJ, Barrera R.

13) McAuley, Danny, Pierre-Emmanuel Charles, and Laurent Papazian. Intensive Care Med "Statins in patients with sepsis and ARDS: is it over? We are not sure." (2016): 1-3.Intensive Care Med

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Authors Bio:

Jeffrey Dach MD is a physician and author of three books, Natural Medicine 101, and Bioidentical Hormones 101, and Heart Book all available on Amazon, or as a free e-book on his web sites.

Dr. Dach is founder and chief medical officer of TrueMedMD, a clinic in Davie, Florida specializing in Bioidentical Hormones, natural thyroid, functional medicine and low level laser therapy.

Dr. Dach was originally trained and board certified as an Interventional and Diagnostic Radiologist, and worked in the hospital setting for 30 years in Broward County at the Memorial Hospital System. Because of declining visual acuity, Dr Dach retired from radiology and returned to clinical medicine about 8 years ago when he founded the TruMedMD Clinic offering bioidentical hormones and natural thyroid to the South Florida region. For more information about Dr Dach, you can find his entire CV posted on-line on his web site.