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Teachable Moment
January 19, 2021

Screening for Lipoprotein(a) Levels in Persons at Low Risk for Cardiovascular Disease: A Teachable Moment

Author Affiliations
  • 1IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 2Università degli Studi di Milano, Milan, Italy
  • 3Division of Cardiology, Department of Medicine, School of Medicine, University of California, San Diego
  • 4Division of Cardiology, Department of Medicine, School of Medicine, University of California, San Francisco
  • 5Editor, JAMA Internal Medicine
JAMA Intern Med. 2021;181(4):539. doi:10.1001/jamainternmed.2020.8367

A 64-year-old woman with a history of breast cancer and paroxysmal atrial fibrillation was referred by her primary care physician to our cardiology clinic for cardiac risk assessment. She had no cardiovascular risk factors or family history of cardiovascular disease (CVD) and reported having a healthy diet and regular exercise.

The patient’s primary care physician had ordered lipid profile testing, the results of which were total cholesterol, 224 mg/dL; high-density lipoprotein cholesterol, 107 mg/dL; low-density lipoprotein cholesterol, 97 mg/dL (to convert all cholesterol results to mmol/L, multiply by 0.0259); triglycerides, 96 mg/dL (to convert to mmol/L, multiply by 0.0113); and lipoprotein(a) (Lp[a]), 110 mg/dL (to convert to mg/L, multiply by 10). The physician advised starting treatment with a statin and referred her to a cardiologist.

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2 Comments for this article
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Tunnel vision with regard to Lp(a)
J David Spence, M.D. | Robarts Research Institute, Western University, London, ON, Canada
The focus of the Teachable Moment article by Furlan et al.[1] is on the low risk of cardiovascular events such as myocardial infarction, and the (for now) absence of specific treatments to lower levels of Lp(a). However, the patient was referred because of paroxysmal atrial fibrillation.

Lp(a) is a clotting factor,[2] so high levels in a patient with atrial fibrillation would be an indication for anticoagulation. Similarly, the patient should have had a serum B12 and plasma total homocysteine (tHcy) measured, to assess for the presence of hyperhomocysteinemia due to either biochemical B12 deficiency or metabolic B12 deficiency. Hyperhomocysteinemia
markedly increases the risk of stroke,[3] is extremely common (40% of stroke patients over age 80),[4] and is easily treated with vitamin therapy. Contrary to widespread belief, B vitamins to lower homocysteine do reduce the risk of stroke.[5]

In patients with atrial fibrillation, besides a CHADS/VASC score, measuring Lp(a), B12 and tHcy would inform decisions about anticoagulation.

1. Furlan L, Azcarate P, Redberg RF. Screening for Lipoprotein(a) Levels in Persons at Low Risk for Cardiovascular Disease: A Teachable Moment. JAMA Intern Med. Jan 19 2021;doi:10.1001/jamainternmed.2020.8367
2. Spence JD, Koschinsky M. Mechanisms of lipoprotein(a) pathogenicity: prothrombotic, proatherosclerotic, or both? Arterioscler Thromb Vasc Biol. Jul 2012;32(7):1550-1. doi:10.1161/ATVBAHA.112.251306
3. Poli D, Antonucci E, Cecchi E, et al. Culprit factors for the failure of well-conducted warfarin therapy to prevent ischemic events in patients with atrial fibrillation: the role of homocysteine. Stroke. 10/2005 2005;36(10):2159-2163. Not in File.
4. Spence D. Mechanisms of thrombogenesis in atrial fibrillation. Lancet. 3/21/2009 2009;373(9668):1006-1007. Not in File. doi:S0140-6736(09)60604-8 [pii];10.1016/S0140-6736(09)60604-8 [doi]
5. Spence JD, Yi Q, Hankey GJ. B vitamins in stroke prevention: time to reconsider. Lancet Neurol. Sep 2017;16(9):750-760. doi:10.1016/S1474-4422(17)30180-1
CONFLICT OF INTEREST: None Reported
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A bit more
H Silverstein, MD | Preventive Medicine Center
The purpose of Lp (a) was mentioned in this article to be "clotting": yes, it is a survival tool to stop bleeding from injury by competing with plasminogen, thereby resulting in a decrease in plasmin synthesis and then inhibiting fibrinolysis--reducing bleeding. It does not affect venous clotting. It is a sink for oxidized phospholipids, increases pro-inflammatory interleukin-8, promotes vascular calcification, and doubles the risk of acute myocardial infarction. The PCSK9 inhibitors reduce Lp (a) by about 30%. In development, is a oligonucleotide (Tsimikas) that targets the relevant messenger RNA (mRNA), vastly reducing its concentration. Some effect in decreasing its concentration has been reported with statins but also "natural"/over the counter products including NAC (N-acetyl cysteine), naringin, niacin, and carnitine. HRS, MD, FACC
CONFLICT OF INTEREST: None Reported
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