Feature | Managing Cholesterol, Reducing Risk: Time To Double Down

Blood Cholesterol; Conceptual Image

National Cholesterol Education Month is a reminder to redouble efforts to address one of the biggest risk factors for cardiovascular disease: high cholesterol. More than 30% of Americans have high LDL levels and the Centers for Disease Control and Prevention estimate that only about half (55%) of the 86 million adults in the U.S. who could benefit from taking lipid-lowering medication are being treated. Here are two steps to start moving the needle.

Refresh Your Knowledge.

Review the recommendations in the 2018 ACC/AHA Guideline on the Management of Blood Cholesterol, including the more detailed risk assessments and new cholesterol-lowering drug options for people at the highest risk for cardiovascular disease. Recognizing the cumulative effect of high cholesterol over the full lifespan, identifying and treating it early can help reduce the lifetime risk for cardiovascular disease. Click here for the Guideline Hub for the full guideline, slide set, and point-of-care decision-making tools and apps, including the ASCVD Risk Estimator Plus, LDL-C Manager and Guideline Clinical app.

Start the Conversation With Patients.

The ACC/AHA Blood Cholesterol guideline establishes the importance of personalized care for patients with high cholesterol. CardioSmart provides a range of tools and information to support patient-physician conversations, including shared decision-making.

Click here for CardioSmart's High Cholesterol Condition Center to download tools, action plans and infographics.

In addition, don't miss the new CardioSmart Patient Voices video series for real-life tips and best practices from people living with high cholesterol. Access the series at: CardioSmart.org/PatientVoicesLDL.

A Vaccine-Like Strategy to Lower LDL?

A once-yearly dose of an siRNA to inhibit PCSK9 has the potential to dramatically reduce lifetime risk of cardiovascular events by as much as two-thirds – depending on baseline LDL and the age at which therapy is started, according to Brian A. Ference, MD, MPhil, MSc, FACC, who presented results from the NATURE-PCSK9 study at ESC Congress 2021.

Using a method to estimate the causal effect of each mmol-year of cumulative exposure to lower LDL due to genetic variants in PCSK9 and other genes, NATURE-PCSK9 investigators evaluated the effect of lowering LDL using a once-yearly dose of a PCSK9 siRNA compared with usual care beginning at age 30, 40, 50 or 60 years based on the lifetime risk of cardiovascular events up to 80 years. The primary outcome was age at first occurrence of a major coronary event, defined as the first occurrence of a fatal or nonfatal MI or coronary revascularization. The secondary outcome was age at first occurrence of a major cardiovascular event, defined as the first occurrence of major coronary event or ischemic stroke. Safety outcomes focused on lifetime risk of developing type 2 diabetes or any cancer.

All told, 445,765 patients, none of whom had a diagnosis of atherosclerotic cardiovascular disease, diabetes or cancer before the age of 30 years, participated in the study. The average age was 68 years and 54% were women. The mean baseline LDL level was 3.5 mmol/L (136 mg/dl).

Overall results, compared with usual care, found the vaccine-like strategy produced a sustained 34% time-averaged reduction in plasma LDL. A step-wise increase in the proportional reduction in lifetime risk of cardiovascular events was also observed with each earlier decade of life that LDL lowering was started. For example, treating men starting at age 60 was associated with a 27% reduction in lifetime risk, but starting treatment at age 30 was associated with a 52% reduction in risk. Similar results were observed among women.

In other findings, a significantly greater expected reduction in lifetime risk at all ages was observed with starting a once-yearly dose of a PCSK9 siRNA at age 40, compared with more aggressive twice-yearly doses of an siRNA starting at age 55 years. "This finding suggests that the residual risk of cardiovascular events observed among persons being treated with an LDL lowering therapy started later in life may be due to the cumulative exposure to LDL and the corresponding plaque burden that develops prior to the initiation of LDL lowering treatment," the researchers said.

Additionally, men and women with higher baseline LDL levels had a greater expected proportional reduction in lifetime risk of cardiovascular events in response to once- or twice-yearly doses of a PCSK9 siRNA at all ages, as compared with those who had lower baseline LDL levels. However, Ference and colleagues said all participants, regardless of LDL levels, had large, expected reductions in lifetime risk including participants and had step-wise greater expected reductions in lifetime risk with each decade earlier that LDL lowering was started.

"These findings motivate a greater focus on lowering LDL earlier in life," Ference said.

Clinical Topics: Dyslipidemia, Geriatric Cardiology, Vascular Medicine, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents

Keywords: ACC Publications, Cardiology Magazine, Aged, Middle Aged, Cholesterol, LDL, PCSK9 protein, human, Proprotein Convertase 9, RNA, Small Interfering, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Longevity, Point-of-Care Systems, Decision Making, Shared, Brain Ischemia, Goals, Stroke, Motivation, Anticholesteremic Agents, Hypercholesterolemia, Neoplasms, Risk Assessment, Plasma, Pharmaceutical Preparations, Centers for Disease Control and Prevention, U.S., Vaccines, Heart Disease Risk Factors, Ischemic Stroke, Decision Making, Physicians

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