New strategies for the promotion of guideline-recommended cholesterol management in young adults are needed. A study investigating the management of severe and moderate hypercholesterolemia in young adults in a large health care system revealed that fewer than 1 out of 3 young adults with severe hypercholesterolemia reached guideline-directed LDL-cholesterol reductions (≥50%) [1]. In addition, less than 50% of the investigated young adults were on lipid lowering therapies (LLT). In females and younger patients, the rates of achieved guideline-directed LDL-cholesterol reductions and LLT prescriptions were particularly low. Physician’s Weekly spoke with Dr. Shauna Newton of the Massachusetts General Hospital, Boston, MA, to address the key takeaways of the study, which was presented as a poster presentation during the virtual meeting of the American Heart Association Scientific Sessions, held from 13 to 15 November 2021.

In adults between 20 and 39 years of age, hypercholesterolemia guidelines recommend statin therapy in patients with moderate hypercholesterolemia (LDL-cholesterol levels between 160-190ml/dL) if other high-risk factors are present, or patients with severe hypercholesterolemia (LDL-cholesterol levels ≥ 190 ml/dL) [2]. To counter an increased cardiovascular risk in the future it is important that patients with severe or moderate hypercholesterolemia achieve their guideline-recommended targets of ≥50% and ≥30% LDL-cholesterol reductions, respectively. Dr. Newton and colleagues conducted an observational cohort study to describe the contemporary management of LDL-cholesterol in adults with hypercholesterolemia between 20 and 39 years. More than 5,400 patients with severe hypercholesterolemia and 12,500 patients with moderate hypercholesterolemia, registered in the Mass General Brigham clinical data registry between 2005 and 2018, were included in the analysis.

In patients with severe hypercholesterolemia, only 30% achieved their primary LDL-cholesterol goal (≥50% reduction) over a median follow-up period of 7.8 years. Males were more likely to attain their goal (31.9%) than females (27.2%; P<0.001). In addition, younger patients were less likely to achieve their goal (20-24 years 24.9%; 25-29 years 25.4%) than older patients (30-34 years 31.0%; 35-39 years 33.0%). Correspondingly, fewer females than males received LLT (43.7% versus 51.5%), and younger patients had lower LLT prescription rates than older patients (20-24 years 37.3% versus 35-39 years 55.6%).

The primary LDL-cholesterol reduction goal in patients with moderate hypercholesterolemia (≥30% reduction) was achieved in 36% of the cases over a median follow-up period of 7.5 years. Again, younger patients had lower goal attainment rates than older patients. However, in contrast to the population with severe hypercholesterolemia, females achieved the guideline-recommended LDL-cholesterol reduction goal numerically more frequently than men (37.1% versus 35.4%). The prescription rates of LTT were similar in the moderate hypercholesterolemia cohort, with younger patients and females displaying lower prescription rates.

Physician’s Weekly discussed the implications of the study with lead author Dr. Shauna Newton.

Physician’s Weekly: Could you explain the rational for conducting this study?

“If we look back at the 2018 AHA/ACC guidelines on the management of hypercholesterolemia in young adults, there is a class 1 indication for prescribing high-intensity statins in patients between 20 and 75 years of age with LDL-cholesterol levels of 190 mg/dL or higher. However, in young patients with moderate hypercholesterolemia, meaning patients between 20 and 39 years of age with LDL-cholesterol levels between 160 and 190 ml/dL, the guidelines are not clear. The guidelines recommend aggressive lifestyle modification and the consideration of prescribing a statin. This consideration is based on risk calculators. The problem is that the atherosclerotic cardiovascular disease (ASCVD) 10-year risk calculator is not designed for patients below 40 years of age. So, the management of young patients with hypercholesterolemia in clinical practice lacks clear guidance. Therefore, we aimed to describe the real-world management of young patients with hypercholesterolemia, dividing patients with moderate and severe hypercholesterolemia into two cohorts for analysis. The 8 participating Mass General Brigham facilities ensured that the LDL-cholesterol levels of patients were measured at least two times during the course of the study. In addition, we collected prescription data on LLTs, including statins, ezetimibe, and PCSK9 inhibitors.”

Physician’s Weekly: How should our physician readers interpret the results?

“In the severe hypercholesterolemia cohort, fewer than one in three young adults achieved guideline-directed LDL-cholesterol reductions (≥50%) across an average follow-up of 8 years. Additionally, nearly one in four patients had LDL-cholesterol levels that were persistently above 190 mg/dL, and fewer than half of the patients with LDL-cholesterol levels of 190 mg/dL or greater were prescribed LLTs. This is unfortunately consistent with prior studies. Notably, the youngest patients and female patients showed lower prescription rates of LLTs. One explanation is that physicians are hesitant to prescribe LLTs to young women, due to possible teratogenic effects of these agents.

“In my view, the results emphasize the need for education in the primary care sector about the risks of moderate, mild, and severe hypercholesterolemia. Since the arrival of the 2018 guidelines, there have been different studies that have shown that cumulative exposure to LDL-cholesterol increases cardiovascular risk over time. Education could help to optimize the management of these patients and reduce their cardiovascular risk in the long term. In patients with moderate hypercholesterolemia, we observed even reduced LLT prescriptions. This may be attributed to the guidelines being less clear in this population. Therefore, stronger guideline recommendations for young adults with moderate and severe hypercholesterolemia are needed. Moreover, an overall new population health management approach should be considered.”

Physician’s Weekly: What are the next steps to improve the management of young adults with hypercholesterolemia?

“One step could be to conduct a survey for physicians who are treating young patients with hypercholesterolemia and evaluate the barriers to prescribing lipid-lowering therapy for these patients. Similarly, we could investigate why patients with LLT prescriptions would not be adherent to this therapy. Finally, it would be interesting to study the long-term cardiovascular risk reduction of LLTs in this population. Currently, data on this topic is scarce. Such data could lead to the development of a lifetime risk estimator that we could implement in the next guidelines.”


  1. Newton SL, et al. Management of Severe and Moderate Hypercholesterolemia in Young Adults. P2370. AHA 2021, Scientific Sessions, 13-15 November
  2. Grundy SM, et al. 2018. J Am Coll Cardiol. 2019;73(24):3168-3209