Mounting data suggests that early-life exposure to elevated cholesterol levels—chiefly apolipoprotein B-containing cholesterol particles (eg, LDL cholesterol)—are strongly linked to the development of coronary heart disease later in life, explains Michael Honigberg, MD, MPP. “We know these cholesterol particles cause heart and vascular disease,” he says. “Accordingly, our cardiovascular guidelines are very clear that adults with severe hypercholesterolemia (defined as LDL cholesterol ≥190 mg/dL) should be treated with statins (or, in some cases, other lipid-lowering medications) to reduce this disease risk. However, in our clinical practice, we continue to observe that patients often are undertreated or go untreated for many years until they have their first heart attack or stroke. Prior data suggest treatment gaps are particularly pronounced for younger adults, who may be falsely perceived as low risk due to their young age.”

For a research letter published in JAMA Cardiology, Dr. Honigberg and colleagues sought to better understand how the current healthcare system is dealing with hypercholesterolemia, in terms of appropriately managing high-risk young adults in contemporary practice. “We used data from the Mass General Brigham’s clinical data registry to assess how many young adults (aged 20-39) with severe hypercholesterolemia achieve the guideline-recommended 50% or greater reduction in LDL cholesterol and received prescriptions for lipid-lowering therapies throughout 8 years of follow-up,” Dr. Honigberg says. “We identified a cohort of patients with severe hypercholesterolemia diagnosed between 2005-2018 and followed their LDL cholesterol levels and prescriptions through the end of 2019. We also examined a second group of young adult patients, those with slightly less severe, or moderate, hypercholesterolemia, with LDL 160 to less than 190 mg/dL. This group is also at high risk for cardiovascular disease, but guidelines are substantially less prescriptive regarding management.” The researchers assessed how many patients in this group with moderate hypercholesterolemia achieved 30% or more reduction in LDL cholesterol and how many received prescriptions for lipid-lowering therapies.

Women Less Likely to Receive Prescriptions

Dr. Honigberg and colleagues reported these key findings:

  • Fewer than half of young adults with severe hypercholesterolemia received prescriptions for lipid-lowering medications and only 30% achieved the guideline-recommended 50% or greater reduction in LDL cholesterol throughout 8 years of follow-up.
  • At the end of follow-up, nearly one in four young adults with severe hypercholesterolemia still had an LDL cholesterol level ≥190 mg/dL.
  • Women were less likely to receive prescriptions for lipid-lowering therapy or to achieve guideline-recommended cholesterol reduction.
  • Rates of prescriptions for young adults with moderate hypercholesterolemia were even lower (20% overall). In this group, only 36% achieved a reduction in LDL cholesterol of 30% or more.

“Among young adults aged 20-39 with severe hypercholesterolemia, LDL levels, on average, remained well above the guideline-recommended treatment target of reducing LDL cholesterol by at least 50%, and women had consistently higher LDL cholesterol levels than men during the follow-up period, which is consistent with the observed lower rates of cholesterol-lowering treatment among women (Figure).”

 Evidence for Treating Hypercholesterolemia Is Robust

These findings suggest the healthcare system continues to do a poor job of providing guideline-recommended preventive care for high-risk young adults, Dr. Honigberg notes. “There is likely no single ‘magic bullet’ answer to effectively address the problem we have identified. Our findings are likely most relevant to primary care clinicians, who are often the first to screen cholesterol levels and determine whether or not to recommend further evaluation and treatment.”

The scientific evidence for treating severely elevated cholesterol is robust, and therapies to lower cholesterol and reduce cholesterol-associated heart risk are inexpensive, effective, and well-tolerated, he points out. “We urgently need research on implementation strategies to better identify high-risk individuals and implement effective therapies in a timely fashion. How can primary care clinicians be supported to follow practice guidelines while simultaneously managing a multitude of other issues? How can healthcare systems and non-physician health professionals help fill these gaps? How can we most effectively combat widespread misinformation about cholesterol-associated heart risks and the risks and benefits of statin therapy? These represent critical areas of future research.”

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