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Reframing Primary Prevention for Young Adults

Perspective by Nolan Fox, Nicholas Fox, Wendy Ying, Miguel Cainzos-Achirica, Roger S. Blumenthal

Coronary artery disease and its consequences account for a significant number of premature deaths in the world. Although rates of heart attack (myocardial infarction) and heart disease deaths have been declining in older adults due to better preventive efforts and medications, these rates have actually increased in younger adults, particularly women between the ages of 35 to 54 years.

Current individual-level approaches for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) include lifestyle modifications, such as increased exercise and healthier dietary habits, as well as medications for high blood pressure, cholesterol, and diabetes. These medications are overwhelmingly prescribed to older individuals.

The absolute risk of ASCVD increases with age, so the majority of individuals do not meet the current risk criteria for initiating these preventive therapies until their 50s or 60s, as determined by the American College of Cardiology and American Heart Association’s 2018 Guideline on the Management of Blood Cholesterol. However, recent studies show that ASCVD risk of some younger individuals may be underestimated with the current available calculators. These individuals at risk may be delaying risk factor modification and potential medications that could markedly lower their long-term heart attack and stroke risk.

Are We Underestimating Cardiovascular Risk in Young Adults?

In a recent study, researchers from Duke University Medical Center analyzed over 6,000 patients who presented with a heart attack, and assessed whether the 2018 ACC/AHA Cholesterol Guideline would have identified young adult participants with a heart attack as being eligible for statins (cholesterol-lowering medications) prior to their heart attack. Specifically, the study divided subjects into the categories of young adults (<55 years of age), middle-aged adults (55 to 65 years of age), and older adults (66 to 75 years of age).

In this study, young adults who had a heart attack were more likely to have a history of smoking, obesity, and metabolic syndrome, and higher LDL-C (the harmful type of cholesterol) and lower HDL-C compared with middle-aged or older adults. However, they were far less likely to qualify for statin therapy at the time of their heart attack compared with middle-aged adults and older adults (46% vs 74% vs 88% respectively).

Additionally, most young adults did not meet criteria for intensive cholesterol management after their heart attack, even though many were at a high risk of adverse cardiovascular events in the future. These findings suggest that more needs to be done to improve the approach to primary prevention in younger populations.  

The development of atherosclerotic plaques (buildup of cholesterol, fat and other substances) in the coronary arteries that lead to a heart attack later in time begins in childhood, as circulating apoB particles (the main protein constituent of LDL) in the blood accumulate over time. Although these plaques do not obstruct arteries until much later in life, the process begins early on. As individuals age, new plaques form and existing plaques continue to grow. In less advanced disease states, there tends to be more room on the arterial lining for new plaques to form, making the early stages a critical time for intervention to prevent further plaque formations.  

Statins are a class of generally well-tolerated and safe drugs that can lower LDL-cholesterol levels and subsequently the risk of the development of atherosclerotic heart disease. Current ACC/AHA guidelines for primary prevention of ASCVD qualify patients for treatment with statins if they fall into any three of the following categories:

  • Those with very high LDL-C levels (≥190mg/dL)
  • Those with diabetes
  • Those with the greatest short-term ASCVD risk (10-year estimated risk of ≥7.5% using the ACC/AHA 10-year ASCVD Risk Estimator)

These characteristics identify a population of individuals who are at the greatest short-term risk (10-year horizon) of ASCVD events. However, the high short-term risk criterion may not be capturing a population of younger adults who may be at greater long-term­ ­risk of events, in whom early preventive interventions could have dramatic lifetime benefits.

Should Young Adults Be Prescribed Statins for Moderately Elevated LDL-C?

The current guidelines for statin initiation may be missing or underestimating the risk of cardiovascular events for younger individuals, as well as missing the potential lifetime benefit to ASCVD risk reduction that statin therapy can introduce. Studies have suggested that high-intensity statin therapy could prevent 51% to 71% of ASCVD events in patients 30 to 39 years of age, when treated for 30 years. 

Additionally, the majority of studies looking at the benefit derived from statin therapy are carried out in older patients, so the true benefit to longer-term usage in young adults may be underestimated.  It may thus be reasonable to consider 30-year risk estimation as opposed to the traditional 10-year risk estimation, to better incorporate the long-term benefit for young patients. The current U.S. and European guidelines on cholesterol use 30-year risk estimates to reinforce better lifestyle habits and not to support medication use.

Additionally, the coronary artery calcium (CAC) score may be considered to build a more in-depth depiction of long-term risk in the younger adult population. Among individuals who would not otherwise qualify for statin therapy, an elevated CAC score is associated with higher rates of cardiovascular events and death. Therefore, obtaining a CAC score can add additional information to the decision-making in whether a patient at least 40 years of age may benefit from statin therapy.

First Things First

Although statin therapy is the key pharmacological intervention to reduce ASCVD risk, the first, foundational step in primary prevention of ASCVD is lifestyle modification, which includes adhering to a healthy diet, being physically active, avoiding tobacco products, managing stress, and having a normal weight. In young adults with various cardiovascular risk factors, these healthy lifestyle changes make particular sense and should be energetically pursued, as their lifetime impact on a person’s health and wellbeing can be dramatic.

Indeed, healthy lifestyle changes not only reduce the risk of ASCVD, but also of multiple types of cancers, improve physical functioning and overall well-being, and result in healthier aging. Although many clinical practice guidelines focus on pharmacological strategies to reduce cholesterol as a means to reduce ASCVD risk, clinicians delivering preventive cardiology care should set lifestyle modification at the center of the intervention, particularly in young adults.

Given the recent data, when lifestyle modification is not effective, the initiation of statin therapy should be more strongly considered in persons younger than 50 years old, especially if they have multiple risk factors or risk enhancers, an elevated 30-year risk score, or a high CAC score for their age. Future guidelines on statin therapy eligibility should be adjusted to more accurately portray both short-term and lifetime risk to account for the lifetime benefit that lipid-lowering therapy could have in young adults. 

More broadly, future primary prevention guidelines should further emphasize the importance of early interventions (before age 40) as means to lower lifetime risk of a heart attack, stroke, and heart failure. A greater emphasis on healthy lifestyle modification since childhood and early adulthood can have dramatic health benefits for young adults and for our society as a whole.  

To learn more healthy habits to prevent heart disease, visit CardioSmart.org/Prevention.

Nicholas Fox and Nolan Fox are premedical students at Drexel University. Wendy Ying, MD, is a cardiovascular disease fellow at Johns Hopkins Hospital. Miguel Cainzos-Achirica, MD, is Associate Director for Preventive Cardiology Research at Houston Methodist. Roger S. Blumenthal, MD, FACC, is Director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease. 

"Performance of Guideline Recommendations for Prevention of Myocardial Infarction in Young Adults" ; Michel Zeitouni, MD, MS, et al. Journal of the American College of Cardiology, August 2020.

"The Expected 30-year Benefits of Early Versus Delayed Primary Prevention of Cardiovascular Disease by Lipid Lowering"; Allan D. Sniderman, MD, FRCP(C). Circulation, Sept. 1, 2020.

"Who Benefits From Taking a Statin, and When? On Fundamentally Restructuring Our Thinking Regarding Primary Prevention of Cardiovascular Disease"; Maarten J.G. Leening , MD, PhD. Circulation, Sept. 1, 2020.

"Cholesterol Guidelines: A Missed Opportunity for Young Adults?" Ron Blankstein, MD, FACC, and Avinainder Singh, MD, MMSC. Journal of the American College of Cardiology, August 2020.

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