New perspectives on lipids: What should doctors advise now?

By Naveed Saleh, MD, MS | Medically reviewed by James Beckerman, MD, FACC
Published March 27, 2023

Key Takeaways

  • According to the 2018 AHA/ACC/Multisociety cholesterol guidelines, patients at intermediate 10-year risk for an atherosclerotic cardiovascular disease (ASCVD) event can be considered for statin therapy as primary prevention.

  • In ASCVD patients, the guidelines call for an LDL-C treatment threshold of ≥70 mg/dL (1.8 mmol/L) when using non-statin therapy.

  • The value of HDL in the prediction of coronary heart disease has been questioned based on recent research.

Hypercholesterolemia is every physician’s concern. With one of three American adults exhibiting high levels of cholesterol, physicians caring for adult patients encounter statin use on a daily basis.[]

Guidelines on lipid management issued by the American College of Cardiology (ACC) and the American Heart Association (AHA) address cholesterol management (2018) and primary prevention of cardiovascular disease (2019). These have been reviewed in the Cleveland Clinic Journal of Medicine.[] It may be worthwhile to reflect on some of the key points of this guidance, as well as some more recent research on lipids. 

Primary prevention

With regard to primary prevention, the guidelines focus on decision-making for patients at intermediate risk of atherosclerotic cardiovascular disease (ASCVD).

The term “intermediate” refers to a 7.5%–20% 10-year risk of an ASCVD event, as determined by the Pooled Cohort Equations (PCE) tool. 

Risk factors include sex, age, race, smoking status, high-density lipoprotein cholesterol (LDL-C), systolic blood pressure, use of antihypertensives, diabetes status, and smoking status. The outcomes are categorized as follows: low risk, <5%; borderline risk, 5%–7.5%; intermediate risk, 7.5%–20%; high risk, >20%.

For individuals with borderline or intermediate scores per the PCE, an updated Expert Consensus Decision Pathway from the ACC offers some guidance.[] The HCP is advised to discuss factors that could increase the patient’s risk, and intensify statin therapy accordingly. Risk-enhancing factors include the following:

  • Family history of premature ASCVD (men aged <55 years; women aged <65 years)

  • Primary hypercholesterolemia

  • Metabolic syndrome

  • Chronic inflammatory conditions (eg, rheumatoid arthritis, psoriasis, lupus)

  • High-risk ethnicity (eg, Southeast Asian)

  • Increase in other biomarkers (eg, lipoprotein (a), high-sensitivity CRP)

  • History of premature menopause, preeclampsia, or other pregnancy conditions predicting later ASCVD

In intermediate-risk adults without diabetes whose LDL-C levels are ≥70 to 189 mg/dL, the decision for statin therapy depends on many factors, including the presence of risk enhancers, patient preference, costs, and adverse effects of statins. In case it is unclear whether to start the patient on statins, a coronary artery calcium score can help support decision-making.

Secondary prevention

The ACC categorizes ASCVD patients into two groups: not at very high risk and very high risk. 

Very-high-risk patients are those who have exhibited a history of multiple major ASCVD events, or one major ASCVD event plus multiple high-risk conditions. 

Based on data from clinical trials, the very-high-risk group can benefit from ezetimibe, evolocumab, and alirocumab.

What’s notable about the guidance is the low level of LDL-C set as an indication for treatment. An LDL-C threshold of ≥70 mg/dL (1.8 mmol/L) was established when determining the use of non-statin therapy in addition to maximally tolerated statin therapy in patients with ASCVD. Before PCSK9 inhibitors are considered, the patient should be on maximally tolerated doses of statins along with ezetimibe.

Updated guidance

In October 2022, the ACC updated the 2018 AHA/ACC/Multisociety cholesterol guidelines to include evidence-based information on various newer, non-statin agents that had received FDA approval for their lipid-lowering effects.

Here are some of the optional recommendations from the 2022 ACC Expert Consensus Decision Pathway that apply to certain patient groups:

  • Referral to a lipid specialist

  • Inclisiran

  • Bempedoic acid

  • PCSK9 monoclonal antibodies

  • Bile acid sequestrants

  • Lipid apheresis by a lipid specialist, in the case of familial hypercholesterolemia

  • Evinacumab (in patients with homozygous familial hypercholesterolemia)

  • Lomitapide (in patients with homozygous familial hypercholesterolemia)

Over-hyped HDL

HDL is commonly viewed as protective against heart disease, but is it? 

In a recent prospective study published in the Journal of the American College of Cardiology, US researchers prospectively followed a cohort of 23,901 White and Black participants without coronary heart disease (CHD) for a median of 10 years.[] 

They found that although LDL-C and triglyceride levels were modestly correlated with CHD risk, low HDL-C predicted increased CHD risk in White participants only, and not Black participants. Furthermore, high HDL-C levels did not predict against CHD in either White or Black participants.

"Our data suggest that the use of low HDL-C is informative in White adults but not in Black adults and the use of high HDL-C might not be helpful in either race."

Zakai NA, et al. J Am Coll Cardiol 

“Although we need to gather further population-based evidence,” the authors wrote, “our data support the notion that the value of high HDL-C in risk prediction algorithms should be demoted.“

What this means for you

The 2018 AHA/ACC/multisociety cholesterol guidelines call for more aggressive lipid-lowering therapies, which reflect an increased focus on achieving lower LDL-C levels. The lower threshold for non-statin therapy in ASCVD patients is ≥70 mg/dL. There is also more guidance in patients at intermediate 10-year risk of an ASCVD event, with the use of statins considered. High HDL levels may not predict against coronary heart disease.

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