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Case Study: High Lipoprotein(a) Levels in Younger Patients Are Not So Clear Cut

— Clinicians ponder how to advise man in his early 40s with a strong family history of premature CV events

Ƶ MedicalToday
Illustration of a written case study over a blood droplet with an upward arrow over cholesterol

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

What preventive measures could be recommended to a man in his early 40s looking to reduce his cardiovascular risk, given his strong family history of premature cardiovascular events?

That's what Anandita Agarwala, MD, of Baylor Scott & White The Heart Hospital–Plano in Texas, and colleagues had to decide when the man presented for advice based on his level of cardiovascular risk.

As the team detailed in a clinical challenge in , the patient, who was of South Asian ancestry, had no symptoms or traditional risk factors for atherosclerotic cardiovascular disease (ASCVD), was physically active, had never smoked, and did not take any medications.

He did, however, have a concerning family history of premature cardiovascular events: Specifically, his older brother at age 43 had undergone angioplasty with placement of several stents, his father had a heart attack at age 39, and several male paternal cousins had coronary artery disease.

Clinicians estimated that the patient's personal 10-year ASCVD risk was low (1.6%), based on the pooled cohort equations (PCEs). He was, however, at increased CV risk related to his South Asian ancestry and his family history of premature ASCVD.

The medical team, therefore, ordered screening for elevated lipoprotein(a) -- Lp(a) -- and assessed his coronary calcium score. "His Lp(a) level was elevated at 136 nmol/L and his coronary calcium score of 137 Agatston units was notable and placed him in the 94th percentile for his age," Agarwala and co-authors reported.

The patient returned to the medical office later in the day and received counseling on how best to address the findings.

The optimum approach and next steps include, the case authors said:

  • Address all modifiable cardiovascular risk factors
  • Perform cascade screening of the patient's first- and second-degree family members
  • Initiate high-intensity statin therapy and aspirin, 81 mg, daily

Discussion

-- Lp(a) -- is proatherogenic, prothrombotic, and proinflammatory, and has a prevalence of about 20% worldwide, Agarwala and colleagues noted, adding that Lp(a) values that define an elevated ASCVD risk vary, but anything above the 80th (100 nmol/L) or 85th (125 nmol/L) percentile are clinically accepted as falling into the category.

"Elevated Lp(a) is actionable," the team said, noting that various lipid-lowering therapies are currently being . This patient's elevated Lp(a) level raised particular concern because of the preexisting risk factors of family history of premature atherosclerotic heart disease and his South Asian ancestry. Thus, although his 10-year risk as calculated in pooled cohort equations was low, the presence of three or more may incrementally increase ASCVD risk beyond the PCE estimates.

In the setting of a family history of premature ASCVD, results of PCE-based risk assessment may be too low to warrant consideration, which "points to a unique use of the REFs," the case authors said.

They advised that improving clinical management for this patient should include:

  • Lifestyle counseling -- for example, with the American Heart Association's ""
  • Assessment of coronary artery calcium (CAC) to guide medical treatment
  • Familial cascade screening -- i.e., first-degree family members, and second-degree family members with relevant family history

When helping patients understand how high levels of Lp(a) can affect ASCVD disease, comprehensive treatment of all modifiable ASCVD risk factors is key, Agarwala and co-authors said.

They added that even though Lp(a) levels cannot be lowered by treating risk factors, managing those that are modifiable can reduce an individual's overall ASCVD risk. In fact, this risk can be reduced significantly by making the lifestyle changes in Life's Essential 8.

Scoring of CAC is important to guide treatment options, when a risk decision for statin therapy is not clear, the case authors noted. In their patient, they said, his family history and elevated Lp(a) level provide sufficient support for the use of statin therapy, and a significantly elevated CAC score may justify a more aggressive treatment approach with lipid-lowering medications and aspirin.

While elevated levels of CAC and Lp(a) each play an independent role in the CV risks faced by these patients, PCSK9 inhibitors can lower Lp(a) by 15-25%, the authors said. Comparatively, the most efficient approach to addressing individual risk of ASCVD is to reduce levels of low-density lipoprotein cholesterol (LDL-C), as this offers a greater ASCVD risk reduction per mmol/L.

The case authors said that given that approximately 80-90% of an individual's Lp(a) level is genetically determined in an autosomal codominant inheritance pattern, the team recommends cascade screening – which was offered to relatives of this particular patient – as a high-yield way to identify first-degree relatives who carry the abnormal trait.

The authors said this case highlights the complexities of managing elevated Lp(a) in younger patients, since their young age may artificially reduce the 10-year ASCVD risk calculated using PCE. An LDL-C level of 160-189 mg/dL and a family history of premature ASCVD can help identify people likely to have familial hypercholesterolemia, as in this patient whose ethnicity further contributes to an increased ASCVD risk.

"Although this should be addressed by future guidelines, we believe that together these high-risk, long-term personal traits merit an intensive LDL-C and apolipoprotein B–lowering regimen," Agarwala and co-authors concluded.

Read previous installments in this series:

Part 1: Hypercholesterolemia: A Complex System

Part 2: Consequences of Hypercholesterolemia

Part 3: Genetics of Hypercholesterolemia

  • author['full_name']

    Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

Agarwala reported no conflicts of interests; co-authors reported various relationships with industry.

Primary Source

JAMA Cardiology

Agarwala A, et al "Primary prevention management of elevated lipoprotein(a)" JAMA Cardiology 2023; 8: 96-97.