A Long-Standing Love Affair…. with Cholesterol

cholesterol, Health & Wellness, Heart Health, nobel prize, Nutrition

The year was 1979.  As a first-year medical student at Rutgers, I still vividly recall the enthusiasm of our famed biochemistry professors (Drs. Bjorn Olsen and Darwin Prockop) as they lectured us about a recent discovery that they predicted would someday change the practice of medicine.  With their accompanying 20+ page handout, they detailed the elegant experiments conducted several years earlier by Drs. Michael Brown and Joseph Goldstein on understanding the genetic flaw (defective/deficient LDL receptors) that resulted in very high cholesterol levels and premature heart disease.

Brown and Goldstein were in fact inspired by the seminal work of another pioneering Rutgers professor, Dr. Avedis Khachadurian who studied genetically high cholesterol in a Lebanese population; he classified familial hypercholesterolemia (FH) into 2 distinct forms: homozygous and heterozygous.   In fact, skin cells (fibroblasts) from one of Dr. Khachadurian’s FH patients were used by Brown and Goldstein to uncover a novel cellular process (receptor mediated endocytosis) that culminated in the 1985 Nobel Prize in Medicine or Physiology

Cholesterol disorders were further discussed in our small groups (see picture above…I’m the bearded one in the center) where we drew blood on each other to measure our total cholesterol and HDL levels. Despite all the excitement generated by our professors about cholesterol and heart disease, our favorite lunch offerings continued to be bacon cheeseburgers and fries (yes, guilty as charged)!

Several years later, during my medical residency at the University of Cincinnati, 1st year residents were assigned to a month at the General Clinical Research Center (GCRC) where studies focused on plasmapheresis treatment for very high cholesterol and triglyceride levels.  The University of Cincinnati was also a national site for the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) trial that found that the cholesterol lowering medication, cholestyramine, reduced the risk of heart related events in men with high LDL levels.

Following this study, skeptics came out of the woodwork to voice their concern that lowering cholesterol did not translate into improved overall survival even though the LRC-CPPT trial was not designed to evaluate total mortality.  In fact, following my Senior Resident presentation on ”Cholesterol and Heart Disease”in 1986,  all agreed that while high cholesterol promoted heart disease, there was insufficient evidence that lowering cholesterol improved overall survival.  As a result, cholesterol lowering treatments were primarily used by lipid specialists and endocrinologists rather than specialists treating cardiovascular disease.

Even after statins came on the market in 1987, there was reluctance to use these meds in cardiac patients. In fact as a cardiology fellow in 1990, I added statin treatment to my post-MI patients recovering in the CCU only to have our Attending rescind these orders!  As might be said tongue in cheek,  he was correct in doing so because at that time there was no evidence to support statin treatment for post-MI patients.

In fact, cardiologists did not embrace lipid lowering therapy for heart disease until such evidence came to fruition. In the statin trial known as “4 S” (Scandinavian Simvastatin Survival Study) there was a 30% reduction in total mortality (in addition to reducing risk of heart attack and stroke), among men and women with very high levels of LDL cholesterol who received simvastatin treatment.   The floodgates then opened as study after study demonstrated the benefit of statins for reducing cardiovascular events.  Other add-on treatments including, cholesterol absorption inhibitors (ezetimibe), PCSK9 inhibitors and bempedoic acid have further contributed to LDL lowering and when tested, have demonstrated additional benefit (beyond statins) in reducing heart-related events.

The Bottom Line: In the 1960s, treatment for high cholesterol was not very effective and the medications used (bile acid resins, niacin) were often not well tolerated.  Today, we have therapies that can safely drive LDL levels down to those attained at birth (~30 mg/dL).   Yet, many still fear taking these medications, especially statins, because they have heard/read about myths popularized in lay books and social media.  As past Chair of the American Heart Association Counsel on Clinical Lipidology we recently wrote a Scientific Statement on the safety of statins, led by my colleague Dr. Connie Newman  that dispel falsehoods such as “statins will kill you”, “statins will destroy your liver”, “statins will paralyze you”, etc.

Suffice it to say that my longstanding love affair with cholesterol remains strong as we continue to battle cardiovascular disease, the nation’s top killer. Listed below are some takeaways with regard to cholesterol and heart disease.

  1. At birth, the average LDL (bad cholesterol) level is 30 mg/dL. As LDL levels rise above 50-60 mg/dL, “hardening of the arteries” (cholesterol plaques) develop.
  2. Heart disease is rare in countries whose average LDL cholesterol and triglycerides levels are less than 100 mg/dL.
  3. For every 10 mg/dL decrease in LDL, the risk of heart disease is reduced ~5%.
  4. Replacing saturated fat with an equal amount of polyunsaturated fat lowers LDL levels by 2.1 mg/dL.
  5. Higher LDL levels in childhood predict cardiovascular disease later in life.
  6. If you have heart disease, aim to lower your LDL cholesterol levels to less than 70 mg/dL.
  7. On average, statins raise blood glucose 2-5 mg/dL. However, statins do not cause the diabetes disease process. Rather, statins effectively reduce cardiovascular risk in diabetics.

Michael Miller, MD is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland and author of  Heal Your Heart….”: published by Penguin Random House.