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Managing Dyslipidemia for PCPs

CE / CME

Optimizing Cardiovascular Health: Attaining LDL-C Targets Through Comprehensive Therapeutic Approaches—A Primary Care Update

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Released: August 21, 2024

Expiration: August 20, 2027

Rachel M. Bond
Rachel M. Bond, MD, FACC
CME/CE Information

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Additional Risk Factors That Inform ASCVD Risk

Among the lipoproteins associated with LDL-C are apoB, a major component of LDL and very-low-density lipoprotein, and Lp(a), a modified form of LDL that possess atherogenic potential.20

Lp(a) is one of many risk-enhancing factors. The 2018 cholesterol guidelines help us to determine the potential for initiating therapy when there is evidence of risk enhancers when more common risk factors are not obvious. These include family history of ASCVD, persistently elevated LDL-C, chronic kidney disease, or metabolic syndrome. Certain sex-specific factors, such as preeclampsia or premature menopause are things we may not traditionally consider. We know CVD is an inflammatory process and the presence of other inflammatory conditions is going to increase the risk. Race and ethnicity play a role as well. Other considerations include persistently elevated triglycerides, high-sensitivity CRP that indicates an inflammatory role, apoB, and an ankle brachial index <0.9, which would be deemed abnormal. But we will now focus attention on Lp(a) ≥50 mg/dL (125 nmol/L).20

Lp(a) and Residual ASCVD Risk

LP(a) is genetically predetermined.36 Normal levels are <30 mg/dL but approximately 20% to 25% of the population have levels ≥50 mg/dL, where cardiovascular risk is elevated.37 Lp(a) levels have not been proven scientifically to be reduced by diet or exercise. Yet, a retrospective analysis showed us that Lp(a) levels independently influence long-term MACE, even without traditional risk factors. One possible hypothesis is that Lp(a) may play a role in aortic calcification.38

Lp(a) Testing: Guidance and Challenges

Despite a current lack of FDA-approved pharmacotherapy directed at Lp(a), guidelines suggest testing in people that have a personal history of premature ASCVD, a family history of premature ASCVD, or who have primary severe hypercholesterolemia, particularly FH. An elevated Lp(a) could indicate the need to add statins earlier in the treatment course to help ensure efforts at reducing ASCVD risk.20,39 The National Lipid Association recommends that Lp(a) be measured in everyone least once.39 This is also standard practice in Europe with the most recent European Society of Cardiology guidelines.40

Dallas Heart Study: Lp(a) Levels by Race/Ethnicity

Available data support that Black individuals have higher Lp(a) than other racial or ethnic groups.41,42 There is also an elevated ASCVD risk in the South Asian population when Lp(a) is elevated.43

Lipoprotein(a) Levels and Risk of Aortic Valve Stenosis

LP(a) levels increase the risk of aortic valve stenosis, as shown in this plot.44 This highlights the need to consider valvular structure in estimating ASCVD risks related to lipids.

Effects of Approved Lipid-Lowering Therapies on Lp(a)

It is important to highlight that statins, which are first-line for hyperlipidemia, may actually increase Lp(a).37 Despite this elevation, when put into the context of greatest risk association with CVD, the ApoB component of LDL-C remains a significant concern aside from Lp(a).45 Various nonstatin lipid-lowering therapies like the PCSK9 monoclonal antibodies and inclisiran can actually lower the number by approximately 20% to 25%.37

Lp(a) Antisense Oligonucleotide Therapy

There are many phase III trials underway, and new information on antisense oligonucleotide therapy is now available. As shown here, oligonucleotide therapy functions by degrading the RNA such that Lp(a) production pathways are reduced. Current study data indicate Lp(a) reduction of by nearly 78% in a dose-dependent manner.46 This is a significant effect in comparison to current monoclonal antibodies, that can reduce Lp(a) by approximately 25%. Pending cardiovascular outcomes data may contribute to FDA approval in the coming months or years.

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