Editor's Note: Commentary based on Daniels SR. Prevention of atherosclerotic cardiovascular disease: what is the best approach and how early should we start? J Am Coll Cardiol 2014;63:2786-88, an editorial response to Robinson JG, Gidding SS. Curing atherosclerosis should be the next major cardiovascular prevention goal. J Am Coll Cardiol 2014;63:2779-85.

An intriguing editorial by Dr. Stephen R. Daniels titled "Prevention of Atherosclerotic Cardiovascular Disease: What Is the Best Approach and How Early Should We Start?"¹ has been published in the Journal of the American College of Cardiology in response to a perspective piece, titled "Curing Atherosclerosis Should be the Next Major Cardiovascular Prevention Goal" by Dr. Jennifer Robinson and Dr. Samuel S. Gidding, MD.^1,2

The piece by Robinson and Gidding is in response to the increasing burden of cardiovascular risk in children, adolescents, and young adults due to the rising rate of obesity over the past 30 years. They propose "a new paradigm for resetting the vascular aging clock, consisting of a short term, aggressive [low-density lipoprotein cholesterol] LDL-C lowering intervention early in the course of atherosclerosis to induce atherosclerotic regression and normalize vascular function, in essence 'curing' atherosclerosis."²

Daniels acknowledges that atherosclerosis begins early in life and is progressive, ultimately leading to coronary heart disease and cerebrovascular disease in adulthood. He further reviews data on the importance of risk factors (elevated LDL-C, low high-density lipoprotein cholesterol [HDL-C], hypertension, diabetes mellitus, cigarette smoking and obesity) on lifelong development or prevention of atherosclerosis. However, Daniels ultimately contends that Robinson and Gidding raise many more questions than legitimate clinical strategies at this time.

First, it is not clear how individuals would be selected for "short term, aggressive LDL-C lowering." Daniels points out that "lifetime" risk scores are still limited to 30 years and of questionable utility in children and notes that carotid intimal media thickness (CIMT), the suggested measure by Robinson and Giddings, is a surrogate measure for heart disease and stroke with limitations that have kept it out of the latest American College of Cardiology/American Heart Association practice guidelines for routine assessment of atherosclerotic risk.³

The suggestion that "those in the in the top quartile of CIMT for their decade of age" should be selected for treatment would allow for selection and administration of preventive measures independent of age. We agree that "allowing" risk factors to go untreated with pharmacotherapy until they have done enough vascular damage to increase your 10-year absolute risk to that which "justifies" pharmacotherapy via current prevention guidelines seems more reactive than preventive. Targeting individuals at elevated risk for development of atherosclerosis as compared to their age equivalent peers is a strategy worthy of testing. Unfortunately, data is lacking for this approach, including data on the financial implications on an already burdened health care system.

Robinson and Gidding further contend that statin treatment in younger individuals need not be lifelong to be effective; however, data supporting a "legacy effect of statin therapy" is incomplete and derived from non-randomized post study follow-up data. Furthermore, we believe that post-trial data has been incompletely examined. Post-trial follow-up data is valuable observational data in which subjects not taking a statin during follow-up can be assessed for the impact of statin use in the preceding trial years, a comparison that would allow for the assessment of whether statins are associated with ongoing risk reduction after cessation of therapy.

A similar comparison among subjects taking a statin after the trial would provide insight regarding the potential benefits of early versus delayed statin therapy in primary prevention.⁴ If delaying statin usage is not associated with a substantial increase in subsequent events, as compared to long-term users, this would argue against Robinson and Gidding's early usage approach.

Finally, one must consider the long-term effects of prolonged statin therapy as there remains insufficient data to assess the effect of statin use for decades. Robinson and Gidding suggest early intensive treatment with "periodic retreatment once every decade or so"; however, no trial data exists to guide the optimal clinical model for early periodic treatment.

Daniels concludes that while the proposal by Robinson and Gidding is logical, until the data is better developed to support this approach, the Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents continue to provide the best evidence-based approach to evaluation and management of risk for atherosclerosis in young individuals.⁵ These guidelines focus on understanding the constellation of CVD risk factors, primordial prevention of risk factors through adoption of lifelong healthy behaviors and more aggressive pharmacologic intervention only for a very small proportion of children who are deemed to be at very high risk, usually because of genetic abnormalities, leading to quite high levels of risk factors.

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References

1. Daniels SR. Prevention of atherosclerotic cardiovascular disease: what is the best approach and how early should we start? J Am Coll Cardiol 2014;63:2786-88.
2. Robinson JG, Gidding SS. Curing atherosclerosis should be the next major cardiovascular prevention goal. J Am Coll Cardiol 2014;63:2779-85.
3. Goff DC, Jr., Lloyd-Jones DM, Bennett G et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-59.
4. DeFilippis AP, Bansal S, Blumenthal RS. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2008;358:194-5.
5. Daniels SR, Benuck I, Christakis DA, et al. on behalf of the Expert Panel on Integrated Guidelines for Cardiovascular Health Risk Reduction in Children and Adolescents. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128(Suppl 5):S213-56.

Keywords: Atherosclerosis, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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