The challenges of lipoprotein(a)

Background/Synopsis

We present a case of a patient with elevated Lipoprotein(a) [Lp(a)] who was diagnosed 10 years after coronary bypass. He trialed multiple pharmaceutical agents in an attempt to achieve his LDL goal, but had progressive atherosclerosis and recurrent procedures.

Objective/Purpose

To highlight the challenges of treating patients with elevated Lp(a) and acknowledge the value of early testing for Lp(a) in patients with a family history of coronary artery disease.

Methods

A case report reviewing a patient's clinic visits from 2013 to 2024 via electronic medical records.

Results

A 54-year-old male with a history of coronary artery disease with a coronary artery bypass, obstructive sleep apnea, prior smoker, and hypertension presented to clinic for lipid management. His family history showed significant coronary artery disease, including a mother and father who passed from myocardial infarction in their 50s and 60s, two brothers with a coronary artery disease, one with bypass in his 40s, and a sister with a coronary artery bypass in her 60s. His brother discovered that his Lp(a) was elevated. Thus, ten years after his coronary artery bypass, his Lp(a) was tested and found to be elevated at 404 mg/dL (reference range 0-40 mg/dL). Throughout the years he was trialed on multiple statin therapies but had intolerance to these drugs. The use of Ezetimibe and Niacin were added but despite these interventions, he was unable to achieve an LDL threshold of 70 mg/dL consistently. Ten years after the initial bypass, he developed dyspnea. He had a repeat coronary angiogram requiring stenting of the distal left main, proximal LAD, and RCA. He was then started on Evolocumab. His LDL level decreased from 80 mg/dL to 17 mg/dL two months after beginning Evolocumab. His Lp(a) level decreased to 295 mg/dL. Despite these changes, he required laser atherectomy and balloon angioplasty for in-stent restenosis of the RCA. There are currently ongoing trials investigating novel therapies targeting Lp(a) which include an antisense oligonucleotide and small interfering RNAs (siRNA). The patient and his brothers are now enrolled in a clinical outcome trial of a novel Lp(a) lowering therapy to determine if lowering Lp(a) aggressively will decrease cardiovascular events.

Conclusions

Early detection of Lp(a) allows for early aggressive cardiovascular risk factor modification and for cascade screening of family members given the autosomal dominant inheritance of elevated Lp(a). New therapies that lower Lp(a) up to 90% hold promise for reducing events in these patients.