The gift that keeps on giving: Post-menopausal elevation in lipoprotein(a)

Abstract

Background/Synopsis

Lipoprotein(a) [Lp(a)] is an established causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is 70-90% genetically determined, traditionally thought to reach steady state adult levels by age 5 in most individuals. However, certain biological states have been shown to alter Lp(a) plasma levels. Driven by adverse cardiometabolic changes in the absence of estrogen, menopause has been shown to accelerate cardiovascular risk. Population-based studies have identified an association between the menopause transition and an increase in Lp(a) levels, with a blunted response conferred by hormone replacement therapy. Here we describe a patient who developed a marked increase in Lp(a) levels after both menopause and initiation of anastrozole therapy for breast cancer (BC).

Objective/Purpose

To understand the effect of meno-pause on serum Lp(a).

Methods

Manual chart review of clinic visits.

Results

A 68-year-old female with estrogen receptor positive localized BC status post lumpectomy and radiation, on anastrozole maintenance therapy, 32-pack-year smoking history in remission, class I obesity, and hypercholesteremia presented to the preventive cardiology clinic for evaluation of elevated Lp(a). At age 48, her Lp(a) was 12 mg/dL. At age 53, she attained menopause after a bilateral salpingo-oophorectomy. At age 63, she was diagnosed with BC, underwent resection and 52 fractions of radiation followed by maintenance anastrozole therapy. Evaluation was notable for Lp(a) 151 mg/dL (> 4x ULN) (Figure 1) and Coronary Artery Calcium (CAC) score 64 (74th percentile for age). The patient's cardiovascular risk was addressed with the addition of aspirin to her existing regimen of high-intensity statin and ezetimibe therapy.

Conclusions

In this case, our patient was found to have > 12-fold increase in Lp(a) 15 years post-menopause and 5 years post initiation of anastrozole. The patient's elevated CAC is likely multifactorial, driven by her smoking history, recent radiation therapy, elevated Lp(a), and hypercholesterolemia. Limited data exists on the effect of anastrozole on Lp(a) expression. In one study of post-menopausal BC patients, anastrozole led to an increase in Lp(a) levels only in patients previously treated with tamoxifen. This effect was thought to be driven by tamoxifen withdrawal rather than directly from anastrozole itself. Further investigation is needed to elucidate the mechanism of Lp(a) expression and its association with menopause and aromatase inhibitors. This will help inform whether repeat Lp(a) testing is warranted in post-menopausal women to guide CV risk-management in this elevated risk population.