Progress in the sciences is as much a matter of finding novel questions to ask as it is a matter of answering existing questions. The novel question here is this: given that high blood cholesterol is harmful over the long term, accelerating the progression towards atherosclerosis, so why haven't we evolved to feel pain and discomfort from being in that state, leading to avoidance? The answer is mostly likely that issues that arise in later life, after reproduction is carried out, are not subject to selection pressure to anywhere near the degree needed to improve the situation for the individual. Evolution optimizes for early life success and reproduction.
To avoid any kind of potential harm to the body, to restore physiological functions when out of balance, and to satisfy the biochemical needs of the organism by giving itself signals that favour respective behaviour. Acknowledging this, one may ask why causal drivers of cardiovascular disease do not prompt the individual to behave in a way that diminishes these risk factors. Why does the insult to the vascular endothelium by smoking, high blood pressure, or high blood sugar not cause discomfort? Why does the vasculature of a person with familial hypercholesterolemia not hurt? Why does a person with high cholesterol not feel antipathy for fatty and high-caloric meals?
From an evolutionary perspective, the mentioned physiological functions preserve the integrity of the body with the ultimate goal to enable the organism to reproduce. Physical harms and unsatisfied physiological needs directly affect the probability of reproductive success and therefore, individuals displaying favourable behaviour in this regard are more likely to pass their genes on to the next generation. Any genetic trait with effects that become relevant only after reproduction does not exert pressure to be sustained. Such traits may even have been beneficial under the circumstances of feast-famine cycles under which they evolved. This explanation why detrimental genetic traits leading to hypercholesterolemia, diabetes mellitus, and obesity, occur with such high prevalence has been called "thrifty gene hypothesis".
Hypercholesterolemia affects one in two individuals in Western societies and is, relying on different lines of evidence, causal for the development of atherosclerotic cardiovascular disease. Genetic traits that favour high blood levels of cholesterol have likely been beneficial long ago to foster energy security and in consequence, lead to early reproduction. It is indisputable that cholesterol is an essential element of the human body, but with 93% of all cholesterol being intracellular and famine episodes being virtually absent today, do we than still need any cholesterol in our bloodstream? Very low levels of LDL cholesterol, due to mutations or aggressive medical treatment, do not appear to have any detrimental effects.
While the question why hypercholesterolemia does not hurt may primarily be of academic interest, the answer provided may be useful for patient care as well. It can explain why cholesterol levels referred to as "normal" by patients and physicians is still associated with subclinical atherosclerosis as precursor of established cardiovascular disease and should be a target of treatment. Since high cholesterol does not hurt, lipid lowering will not confer symptomatic benefit. Therefore, patient discussion - including the principles discussed here - is the key to medication adherence.