Is Statin Therapy Ever Indicated in Young Adults?

Abstract & Commentary

By Harold L. Karpman, MD, FACC, FACP

Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.

Synopsis: Initiating treatment for hypercholesterolemia at age 30 years instead of age 60 years might very well prevent not just 30% of the CAD events as occurred in the 5-year statin trials, but perhaps as many as 60% of the CAD events lifetime.

Source: Steinberg D. Earlier intervention in the management of hypercholesterolemia: What are we waiting for? J Am Coll Cardiol 2010;56:627-629.

Historically, adults younger than 35 years of age who do not have an extremely rare genetic disorder, such as familial hypercholesterolemia, have been considered to be at very low short-term risk of developing coronary artery disease (CAD), and it has been presumed that lipid-lowering therapy at this stage in life is unlikely to provide any short-term or medium-term benefit. In fact, current guidelines for the treatment of high cholesterol in young adults have been conservative, based upon the calculated Framingham 10-year risk score, and recommend drug therapy with statins only if cholesterol levels remain very high after a trial of lifestyle modification.1 However, recent publications make a persuasive case for changing our guidelines from evaluating only the 10-year Framingham risk score to considering lifetime risk,2 since the reality exists that most persons will die of coronary artery disease sooner or later. For example, while the 10-year risk for a 40-year-old male with a plasma cholesterol level between 200 and 239 mg/dL is only 5%, the lifetime risk is 43%, confirming the fact that CAD pathology in these hypercholesterolemic young men will progress to the point where 50% or more of them will eventually die of CAD.

Steinberg carefully points out that, for example, initiating statin treatment at age 30 instead of age 60 might very well prevent not just the 30% of events seen in the 5-year statin trials, but as many as 60% of events. It is well known that CAD starts early,3 and there is good reason to believe that lowering abnormal lipid levels and treatment of other reversible risk factors, such as cigarette smoking, hypertension, and diabetes mellitus, will significantly reduce the progression and final incidence of the abnormal structural characteristics and plaque composition in the coronary arteries that will result over time in symptomatic CAD.

Up until recently, adequate imaging techniques to easily measure quantitatively the burden of early coronary artery lesions have not been available; however, recent significant improvements in low-dose radiation coronary computed tomographic angiography (CCTA) have given us the ability to detect the presence and quantity of calcified coronary artery plaque (CAC) and, perhaps more importantly, non-calcified coronary artery plaque, which is among the earliest signs of evolving CAD. Preliminary results of a recent and yet unreported study in 40 young type 1 and type 2 diabetic patients have revealed that CCTA provided more complete and earlier identification of disease than did CAC, since noncalcified plaque is frequently the only coronary artery abnormality present in many of these patients, especially early on. Obviously, a larger, carefully controlled trial in diabetic and nondiabetic patients is necessary; however, this trial might have to be 30 years or more in duration and would be extremely difficult to mount both from technical and ethical points of view. Having a non-invasive tool such as low-radiation CCTA available at this time for the evaluation of early, asymptomatic CAD may prove to be extraordinarily valuable from objective and practical points of view to determine which patients should start statin drug and lifestyle therapies in their youth and conceivably even in late childhood since obesity and hyperlipidemia are now also becoming epidemic in children.

The Adult Treatment Panel of the National Cholesterol Education Program's fourth report, due in early 2011, will cover whether and how to expand statin-prescribing strategies. Reducing life-long cumulative exposure to LDL-cholesterol via statin therapy initiated early in life may provide more complete protection against future CAD than can be achieved with initiation later in life;4 however, we must be cognizant of the possible negative effects of statin therapy in general and in young adults, especially since much of this information is still lacking in the literature. Also, we have to be concerned about the special circumstances of young women who may become pregnant and/or who are breastfeeding and the possible negative psychological effects of "labeling" a young person as being unhealthy or disabled because he/she is taking a pharmaceutical preparation, even though these effects almost certainly will be diminished if adequate education about the benefits of drug treatment is provided.

At the present time, vigorous preventive CAD measures, including statin therapy, appear to be indicated for hyperlipidemic persons of any age if they have an elevated CAC score or abnormal CCTA findings such as noncalcified plaque. While we shouldn't sit back and wait to see what happens to these individuals given our current level of knowledge, we should recognize that these conclusions may be changed after the results of carefully controlled long-term studies, which are currently being performed become available.

References

1. National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at www.nhlbi.nih.gov/guidelines/cholesterol. Accessed Oct. 11, 2010.

2. Lloyd-Jones DM, et al. Lifetime risk of coronary heart disease by cholesterol levels at selected ages. Arch Intern Med 2003;163:1966-1972.

3. Enos WF, et al. Coronary disease among United States soldiers killed in action in Korea; preliminary report. JAMA 1953;152:1090-1093.

4. Forrester JS. Redefining normal low density lipoprotein cholesterol: A strategy to unseat coronary disease as the nation's leading killer. J Am Coll Cardiol 2010;56: 630-636.