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Cardiac Imaging

Primary Prevention Management of Elevated Lipoprotein(a)

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.

1 Credit CME

JAMA Cardiology

Published Online: November 16, 2022

JAMA Cardiology Clinical Challenge

Article Information and Disclosures

Anandita Agarwala, MD¹;

Christie Ballantyne, MD²;

Neil J. Stone, MD^3,4

Author Affiliations

¹Center for Cardiovascular Disease Prevention, Cardiovascular Division, Baylor Scott & White The Heart Hospital–Plano, Plano, Texas
²Sections of Cardiology and Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
³Feinberg School of Medicine, Department of Medicine (Cardiology), Northwestern University, Chicago, Illinois
⁴Feinberg School of Medicine, Department of Preventive Medicine, Northwestern University, Chicago, Illinois

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A South Asian male individual in his early 40s with a strong family history (FHx) of atherosclerotic cardiovascular disease (ASCVD) including premature cardiovascular events in multiple family members presented to establish care for cardiovascular risk stratification. He had no traditional risk factors for ASCVD and no cardiac symptoms or limitations. He had never smoked, was physically active, and did not take any medications. His 10-year ASCVD risk was estimated at 1.6% (low risk) based on the pooled cohort equations (PCEs); however, he had 2 risk-enhancing factors: South Asian ancestry and a FHx of premature ASCVD. His father had a myocardial infarction at age 39 years, and, importantly, his older brother had angioplasty with multiple stents at age 43 years. Additionally, multiple male cousins on his father’s side had coronary artery disease, the details of which were unspecified.

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Elevated Lp(a) in the setting of strongly positive FHx and high coronary artery calcium score for the patient’s age

C. Address all modifiable cardiovascular risk factors, initiate cascade screening, and start high-intensity statin therapy and aspirin, 81 mg, daily

Lp(a) is proatherogenic, prothrombotic, and proinflammatory¹^,2 and has an estimated global prevalence of around 20%.¹ While the upper Lp(a) threshold that indicates an elevated ASCVD risk does vary, values above the 80th (100 nmol/L) or 85th (125 nmol/L) are clinically accepted.¹^,3 Although Lp(a)-lowering therapies are currently under investigation, elevated Lp(a) is actionable. This patient’s elevated Lp(a) level is concerning due to his FHx of premature ASCVD and South Asian ancestry. Despite being at low 10-year ASCVD risk by the PCEs, he was noted to have 3 risk-enhancing factors (REFs). The presence of 3 or more REFs may incrementally increase ASCVD risk beyond the PCE estimates.⁴ In individuals with a FHx of premature ASCVD, risk stratification using the PCEs may not be high enough to merit consideration and points to a unique use of the REFs. This patient’s clinical management can be improved by (1) counseling, (2) coronary artery calcium (CAC) scoring to guide medical therapy, and (3) cascade screening of family members. Counseling patients about the association between elevated Lp(a) and ASCVD should underscore the need for comprehensively treating all modifiable ASCVD risk factors. While treating risk factors does not lower Lp(a) levels, it can reduce overall ASCVD risk. Lifestyle modifications outlined in the American Heart Association’s Life’s Essential 8 can significantly reduce ASCVD risk.¹^,2 CAC scoring is recommended when a risk decision for statin therapy is uncertain. Indeed, with this patient’s FHx and elevated Lp(a) level, risk information to support statin therapy is already available. However, a significantly elevated CAC score could support more intensive lipid-lowering and aspirin therapy. A CAC score and Lp(a) level add independently to risk stratification in these individuals.¹^,2 While PCSK9 inhibitors can lower Lp(a) by 15% to 25%, therapy should focus on lowering low-density lipoprotein cholesterol (LDL-C), which has greater ASCVD risk reduction per mmol/L.¹^,2 Given that approximately 80% to 90% of an individual’s Lp(a) level is genetically determined in an autosomal codominant inheritance pattern,¹ cascade screening, a high-yield method of screening first-degree relatives who have a much higher likelihood of having the abnormal trait, may be warranted (Figure 2).

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Article Information

Corresponding Author: Anandita Agarwala, MD, Baylor Scott & White The Heart Hospital–Plano, 1100 Allied Dr, Plano, TX 75093 (anandita.kulkarni@bswhealth.org).

Published Online: November 16, 2022. doi:10.1001/jamacardio.2022.4063

Conflict of Interest Disclosures: Dr Ballantyne reported grants from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, Novo Nordisk, and Regeneron to their institution and personal fees from 89Bio, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi-Synthelabo outside the submitted work. Dr Stone reported personal fees from Knowledge to Practice outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References

Wilson DP , Jacobson TA , Jones PH , et al. Use of Lipoprotein(a) in clinical practice. J Clin Lipidol. 2019;13(3):374-392. doi:10.1016/j.jacl.2019.04.010 PubMed Google Scholar Crossref

Virani SS , Koschinsky ML , Maher L , et al. Global think tank on the clinical considerations and management of lipoprotein(a). Prog Cardiovasc Dis. 2022;73:32-40. doi:10.1016/j.pcad.2022.01.002 PubMed Google Scholar Crossref

Grundy SM , Stone NJ , Bailey AL , et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2018;2018:CIR0000000000000625.Google Scholar

Akintoye E , Afonso L , Bengaluru Jayanna M , Bao W , Briasoulis A , Robinson J . Prognostic utility of risk enhancers and coronary artery calcium score recommended in the 2018 ACC/AHA multisociety cholesterol treatment guidelines over the pooled cohort equation. J Am Heart Assoc. 2021;10(12):e019589. doi:10.1161/JAHA.120.019589 PubMed Google Scholar Crossref

Miedema MD , Duprez DA , Misialek JR , et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention. Circ Cardiovasc Qual Outcomes. 2014;7(3):453-460. doi:10.1161/CIRCOUTCOMES.113.000690 PubMed Google Scholar Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.