Optimal cholesterol levels: the Lipid Limbo


The lipid hypothesis was promulgated in the 1960s, basically stated that hardening of the arteries, the leading cause of death in Western society, was a result of abnormal blood fat levels.   This concept was derived from extensive pathological analyses of plaques removed from the arteries of afflicted patients, and correlating it with blood levels of serum fats drawn during their lives.   This assessment was thus based on the science of epidemiology, or the study of the distribution of risks and their relationships to diseases.   The famous Framingham Heart Study was the prototype for this type of investigation.


An appreciation for the genetics and impact of modifiable risk factors derived from these types of epidemiologic studies, and the impact of lifestyle modifications began to clarify how one may alter the otherwise inexorable course of atherosclerosis, now more properly referred to as atherothrombosis.   Medications were developed over the ensuing decades.   Some worked, some didn't, and all had adverse effects that gave doctors and patients pause before prescribing and taking them.


In 1987, two key events occurred essentially simultaneously that changed the management of atherothrombosis forever.   The first was the release of the first member of the statin class of drugs.   These drugs provided the average doctor with a pharmacologic tool that allowed him to achieve the same levels of lipid lowering that we achieved at the National Institutes of Health on aggressive dietary and high dose combination drug therapy that made patients wonder if the treatment was worse than the disease.


The second event was the release of the first Adult Treatment Panel recommendations of the National Cholesterol Education Program that made specific recommendations to practicing doctors on what levels of which lipids were to be targeted.   These recommendations were the consensus of the best lipid experts and based on the rather meager, but fairly solid evidence base available at that time.


Thus armed with a map and a potent tool, doctors began to guide and lead patients towards much better blood fat levels that their genes were otherwise dictating.   New, more potent statin drugs were developed.   Randomized clinical trials, a topic I have covered multiple times in past columns, began to document the huge health and beneficial economic impact of these therapies on at-risk patients.


The Second Adult Treatment Panel recommendations came out in the early 1990's based on the then expanding evidence, and further clarified target lipid values and special populations of patients.   The Third ATP recommendations were released in mid-2001, again refining the goal levels for the bad LDL-cholesterol (lower), the good HDL-cholesterol (higher), as well as triglycerides (lower).


The overwhelming trend in all of these recommendations has been pushing the target levels of LDL-cholesterol lower and lower.   These goals have been achievable largely because of the development of more potent statins.   Statins have now been shown to have additional beneficial effects on blood vessel health and reduction of inflammatory triggers of sudden rupture of atherothrombotic plaques beyond just lipid lowering.


At the just completed annual Scientific Sessions of the American College of Cardiology, late-breaking clinical trial data has suggested that even our currently recommended and accepted goals of LDL-C lowering in our highest risk patients may be too high.   The current standard in high-risk patients is to achieve an LDL-cholesterol level of below 100 mg/dL.   A well-designed and well-done clinical trial demonstrated reduced cardiac events in patients that achieved LDL-cholesterol levels of 62 mg/dL compared to group well treated to the current LDL-cholesterol standard of 95 mg/dL.   And, as has been shown before, women did even better than men.   And having a high good cholesterol, HDL-cholesterol, is wonderful, but does not convey absolute protection.   It is being increasingly appreciated that the quality of HDL-cholesterol, not just the quantity, may be important.   And a high LDL-cholesterol trumps a high HDL-cholesterol as far as cardiac risk is concerned.


It's not the specific drug per se .   It's the lipid levels achieved.   And newer statins and combinations of older and newer agents are able to achieve these numbers quite regularly.   The Ventura Heart Institute has been and remains active in the development of these new agents, and I can assure you that even more dramatic approaches are on the horizon.   We are starting a trial with a combination agent that both lowers LDL-cholesterol and markedly raises HDL-cholesterol.


But under treatment remains a serious issue because of the cost and politics.   At least 36 million Americans should be on statins, and only a third are.   Health care plans (an oxymoron in many cases) are hesitant to embrace these guidelines because of the higher cost of the new approaches.   Good enough is just not anymore.   It will be up to you to “encourage” your doctors and health plans based on the evolving evidence of benefit of these lower lipid level targets.   You need to talk to your doctor to determine if you fall into a category of risk that would benefit.