Dr. Weeks’ Comment: For far too long, doctors have targeted cholesterol as the culprit in heart disease. High cholesterol was called “bad” and low cholesterol was the goal. Too simplistic? Yes! Now we see that low cholesterol is DANGEROUS.
“…This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information…”
Here is the 2007 paradigm shifting article Lipids in Aging and Chronic Illness: Impact on Survival
“Hypercholesterolemia has been implicated as a risk factor for atherosclerosis by numerous observational studies in the general population. Observational studies in patients suffering from various chronic illnesses and in individuals with advanced age have indicated an inverse association between cholesterol level and mortality, suggesting that the classical Framingham paradigm may not apply to these groups. It is yet unclear what the reasons for these paradoxically inverse associations are. We present a summary of the descriptive studies that have examined the association between cholesterol levels and outcomes in a variety of patient groups. The various possible mechanisms behind the observed “lipid paradox”and the potential implications of reverse epidemiology of hypercholesterolemia in clinical medicine and public health are discussed…..
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) affects approximately 16 million Americans and is the fourth leading cause of death worldwide . Cardiovascular mortality accounts for roughly 50% of deaths in COPD patients,  but the relationship between cholesterol and mortality is reversed in these patients too. While studies examining cholesterol and outcomes in COPD are sparse, one large study found a trend towards lower risks of hospitalizations and death in men with COPD who had higher cholesterol levels .
“It is possible that lower cholesterol is not the causebut merely a consequence of conditions that lead to poor outcomes in patients with chronic disease states who exhibit a paradoxical risk factor profile. Reverse causation is a known possible source of bias in epidemiologic studies that examine associations without a clear distinction for the direction of the causal pathway. While it is plausible to attribute the association between low cholesterol and higher mortality to reverse causation, this fails to explain why high cholesterol is associated with better outcomes in the populations discussed above.”
“Changing our current practice pattern could take 40 or more years, but we may one day prescribe cholesterol-raising medications to certain patients. After all, paradigm shifts can lead to scientific revolutions.”
Evid Based Med.2017 Mar;22(1):15-19. doi: 10.1136/ebmed-2016-110602. Epub 2016 Dec 20.
Cholesterol paradox: a correlate does not a surrogate make.
The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.