New Cholesterol Guidelines: Lower LDL Targets & Early Intervention for Heart Health

Updated guidelines for treating dyslipidemia – abnormal levels of one or more types of lipids, including cholesterol and triglycerides – have been jointly released by the American College of Cardiology, the American Heart Association, and nine other U.S. Medical societies. High cholesterol levels increase the risk of heart attack and stroke, making this guidance a critical update for preventative care.

The consolidated guidance provides evidence-based recommendations for managing dyslipidemia, aiming to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). ASCVD, caused by the buildup of fatty deposits in the arteries, is the leading cause of death globally.

Published simultaneously in JACC, the journal of the American College of Cardiology, and Circulation, the American Heart Association’s journal, the guidelines establish different risk categories and corresponding cholesterol targets for patients, all under a physician’s supervision.

A key focus of the updated recommendations is early intervention through healthy lifestyle changes, including maintaining a healthy weight, regular physical activity, avoiding tobacco, getting adequate sleep, and taking cholesterol-lowering medications when recommended by a healthcare professional.

“We know that 80 percent or more of cardiovascular disease is preventable, and elevated LDL cholesterol, sometimes called ‘terrible’ cholesterol, is a significant part of that risk,” said Roger Blumenthal, chair of the guideline writing committee and director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.

The guidelines suggest considering medication sooner than previously thought if lifestyle changes don’t achieve desired lipid levels. “While we want to endeavor to optimize healthy lifestyle habits as a first step to lower cholesterol, we recognize that if lipid levels are not within the desired range after a period of lifestyle optimization, we should consider adding lipid-lowering medications sooner than we did 10 years ago,” Blumenthal explained. “And lower LDL for longer, just like lower blood pressure for longer, offers much greater protection against future heart attacks, and strokes.”

A key update to the dyslipidemia guidelines is the use of a more modern and accurate cardiovascular disease risk calculator – Predicting Risk of Cardiovascular Disease EVENTs (PREVENT). The updated PREVENT-ASCVD equations categorize 10-year ASCVD risk as low (less than 3 percent), borderline (3 to 4 percent), intermediate (5 to 9 percent), and high (10 percent or more), guiding treatment decisions, including whether to initiate statin therapy and the recommended intensity.

“With this new assessment tool, we can better calculate cardiovascular risk using health information already obtained during an annual physical exam – cholesterol, blood pressure readings, and other personal information like age and health habits – and then further personalize the risk score for each person by looking at ‘risk enhancers’ that can help guide the necessitate for lipid-lowering therapy,” Blumenthal added.

These risk factors include a family history of heart disease, chronic inflammatory conditions (such as lupus or rheumatoid arthritis), cardiometabolic conditions like overweight/obesity, diabetes, or chronic kidney disease, ancestry with a higher risk (such as South Asian or Filipino ancestry), and reproductive risk markers including early menopause, preeclampsia, and gestational diabetes. Additional markers, such as lipoprotein(a) [Lp(a)], apolipoprotein B (apoB), high-sensitivity C-reactive protein (hsCRP), and elevated triglycerides, can also be used to refine an individual’s ASCVD risk.

“Having healthy levels of LDL cholesterol or high-density lipoprotein (HDL-C) cholesterol, traditionally considered ‘fine’ cholesterol, is not necessarily a ‘acquire out of jail free’ card,” Blumenthal said. “Measuring other biomarkers can provide a more complete picture of a person’s cardiovascular risk and help inform decisions about whether lipid-lowering treatment is needed sooner rather than later, or if more intensive treatment is warranted.”

The new guidelines reinstate LDL-C and non-HDL-C cholesterol targets. To prevent a first heart attack or stroke, the LDL cholesterol target should be less than 100 mg/dL for individuals with borderline or intermediate risk, and less than 70 mg/dL for those with high risk. For individuals with ASCVD at particularly high risk of cardiovascular events, the LDL-C target should be less than 55 mg/dL for secondary prevention.

“lower LDL is better, especially for people at higher risk of having a heart attack or stroke,” said Pamela Morris, vice chair of the guideline writing committee and director of the Seinsheimer Cardiovascular Health Program at The Medical University of South Carolina. “Clinical trials have clearly demonstrated significant benefits in reducing cardiovascular events when LDL-C levels are even lower than those recommended in previous guidelines.”

If LDL-C levels are not adequately reduced through lifestyle changes and statin therapy – which remains the cornerstone of lipid lowering and risk reduction – the guidance recommends adding non-statin therapies. Depending on risk level and patient characteristics, evidence-based options include ezetimibe or bempedoic acid (a newer oral agent), or a PCSK9 monoclonal antibody, an injectable therapy. Inclisiran, another injectable option requiring less frequent injections, is still being studied in clinical trials to determine if the associated cholesterol reduction translates to better outcomes and fewer cardiac events.

The new guidance recommends considering additional testing, when appropriate, to improve cardiovascular risk assessment and evaluate the need for intensified LDL cholesterol lowering and management of other risk factors. These include:

• Selective use of a non-contrast coronary artery calcium scan: this can be used to detect early or subclinical calcium and plaque buildup in the walls of the heart arteries when uncertainty remains about a person’s true risk. It is recommended for men age 40 or older and women age 45 or older with borderline or intermediate risk of heart attack or stroke within 10 years if knowing this test will help inform the decision to prescribe a statin or not.

• Lipoprotein(a): Lp(a) should be measured at least once in adulthood. Lp(a) levels are largely genetically determined and remain relatively stable throughout life. A high Lp(a) level (≥125 nmol/L or ≥50 mg/dL) is associated with approximately a 1.4-fold higher long-term risk of heart attack or stroke. An Lp(a) level of ≥250 nmol/L is associated with at least a two-fold higher long-term risk of heart attack or stroke. Lifestyle changes have minimal impact on Lp(a) levels, so repeat testing is generally not necessary.

• Apolipoprotein B. Measurement can be used to assess residual ASCVD risk and guide treatment among people with cardio-renal-metabolic syndrome, type 2 diabetes, high triglycerides, or known cardiovascular disease who have reached their LDL-C and non-HDL-C goals. ApoB may be a more accurate risk marker than LDL-C in these groups of people.