Seeing LDL Cholesterol in a New Light

Maintaining optimal levels of low-density lipoprotein (LDL) cholesterol from early adulthood through middle age may reduce the risk of developing coronary heart disease later in life, results of a recent study show.

LDL cholesterol levels usually can be kept low through exercise, a heart-healthy diet and other lifestyle modifications, according to the study’s authors. But for young adults with high LDL levels that don’t respond to lifestyle changes, cholesterol-lowering statin drugs may be necessary.

“For these individuals, pharmacological therapy to lower LDL cholesterol levels earlier in the life course when atherosclerosis is less advanced may be a more successful way to reverse the disease course and prevent future CVD (cardiovascular) events,” Yiyi Zhang, Ph.D., M.S., of Columbia University Medical Center and her co-authors wrote in the September 2021 issue of JAMA Cardiology. If clinicians were to follow their suggestions, many more Americans could be taking statins starting at much younger age.

Lowering LDL cholesterol, often by taking a statin, has been a tenet of cardiovascular disease prevention in the United States for decades, but most of the prescriptions are written for older people with a history of heart attack, stroke or another major cardiovascular event.

The editor’s note accompanying the study noted that current hypertension guidelines recommend treating all adults with high blood pressure despite a dearth of evidence that lowering blood pressure in young adults translates into a health benefit. “If the clinical community can support treating hypertension early in life to prevent the long-term risks of elevated blood pressure, the findings in the study by Zhang et al. suggest that a similar paradigm (for cholesterol lowering) should be considered,” wrote Ann Marie Navar, M.D., Ph.D., and Gregg C. Fonarow, M.D., associate editors at JAMA Cardiology.

But the emphasis that has been put on LDL cholesterol levels also has been questioned. Rita F. Redberg, M.D., a cardiologist at the University of California, San Francisco, and editor of JAMA Internal Medicine, has said that an LDL cholesterol level should be seen as marker of potential cardiovascular disease rather than a target for treatment. Speaking on the Healthy Skeptic MD podcast earlier this year, Redberg said focusing on LDL cholesterol is “misguided.” Instead, she said, doctors should instruct patients to eat a healthy diet and get regular physical activity. “If you have a healthy diet and your cholesterol is high, that’s OK,” she said. “If you have an unhealthy diet and your cholesterol is low, that’s not so good. You really have to focus on lifestyle and stop focusing on lab values.” Redberg also said that the side effects of statins — muscle aches, fatigue — may actually contribute to heart health issues.

By pooling four prospective cohort studies, the study researchers had data from more than 18,000 study participants to evaluate. Using accepted statistical techniques, they calculated the participants’ cumulative exposure to cholesterol levels. The study results suggest that exposure to high levels was associated with a greater likelihood of experiencing coronary heart disease but not stroke or heart failure.

Zhang and her colleagues discussed possible explanations for cumulative high LDL cholesterol levels increasing the likelihood of coronary heart disease. Small particles of LDL cholesterol may lodge inside arterial walls starting in young adulthood. Some research suggests that those retained particles go through various modifications, including oxidation, which can lead to an inflammatory response and vascular injury and atheroma formation. The accumulated particles, teaming up with circulating LDL cholesterol, may develop atherosclerotic plaque. Thus, keeping LDL cholesterol levels low may prevent that process from starting.

Introduced in 1987, statins are among the most prescribed medications in the world. They are routinely prescribed for patients 55 and older who have had a heart attack or stroke or who have elevated LDL cholesterol levels. Prescribing statins for younger adults was mentioned by the American College of Cardiology and the American Heart Association in their 2019 guidelines on the primary prevention of cardiovascular disease. The guidelines say for young and middle-aged adults, the 30-year and lifetime risk of cardiovascular disease are reasons for reinforcing a lifestyle recommendation and, for some, medication. Still, the vast majority of statin prescriptions are written for older patients. Zhang’s study is far from the final word on prescribing statins for younger people, but it may seed more research and discussion of looking at LDL
cholesterol through the lens of lifetime exposure.

Robert Calandra is an independent journalist in the Philadelphia area who writes about healthcare and other topics.