Higher Lp(a) Linked to Increased Risk of Incident CHD in Postmenopausal Patients

Pradeep Natarajan, MD, MMSc

New findings suggest higher values of lipoprotein(a) (Lp[a]) were associated with increased risk of incident coronary heart disease in a cohort of postmenopausal patients.

Data show the use of menopausal hormone therapy was associated with modest reduction in Lp(a) levels, but investigators found no evidence of lower Lp(a)-associated risks in users compared to non-users.

“Clinicians should not be dissuaded from measuring Lp(a) in postmenopausal individuals if clinically indicated irrespective of [hormone therapy] use,” wrote study author Pradeep Natarajan, MD, MMSc, Massachusetts General Hospital.

A previous study from nearly 30 years ago suggested Lp(a)-associated risk was lessened among women using hormone therapy. As a result, investigators in the current study reexamined if its use modified the association of Lp(a) with CHD in a large cohort.

Patients from the UK Biobank who were postmenopausal at enrollment from 2006 - 2010 were included in the study. They were required to have had complete reproductive history and covariate data, no pre existing atherosclerotic cardiovascular disease (ASCVD), heart failure, aortic stenosis, or venous thromboembolism, and underwent phlebotomy with measurement of Lp(a) at enrollment.

Then, cox proportional hazards regression models tested the association of Lp(a) with CHD in the overall sample and stratified by current, previous, or never use of hormone therapy. Investigators made adjustments for age, race, socioeconomic status, type 2 diabetes, body mass index, as well as systolic blood pressure, antihypertensive and cholesterol-lowering medication use, total and high-density lipoprotein cholesterol, and C-reactive protein

They generated individual LPA genetic risk scores through 43 single-nucleotide variations significantly associated with Lp(a) in data sets external to the UK Biobank.

In sensitivity analysis, investigators assessed a subcohort propensity score-matched for use of hormone therapy using all covariates plus LPA genetic risk and LPA genetic scores in place of measured Lp(a).

A total of 114,029 postmenopausal patients with measured Lp(a) were identified, while 88,266 met inclusion criteria (mean age, 60.0 years). At enrollment, 4550 (5.2) patients were using hormone therapy and 34,396 (39.0%) reported previous use.

Investigators noted “the median Lp(a) was lower in [hormone therapy] users than nonusers, but the median LPA genetic score was higher in HT users.”

Following adjustment for age, medication use, and LPA genetic risk, data show current hormone therapy users had observed lower Lp(a) than previous users by 7.5 nmol/L (95% CI, -8.5 to -6.4 nmol/L; P <.001) and never users by 7.9 nmol/L (95% CI, -8.9 to -6.8 nmol/L; P <.001).

A median follow-up of 11.1 years was performed, in which 3537 incident CHD events were found to have occurred. Those in the highest versus lowest Lp(a) quartiles had the higher risk of CHD (adjusted hazard ratio, 1.15; 95% CI, 1.05 - 1.26; P = .003).

Additionally, hazards linked to greater Lp(a) may have been larger in those who previously used hormone therapy (P for interaction = .046) and those currently taking hormone therapy (P for interaction = .04), compared to those who never used therapy.

These findings may suggest that Lp(a) levels remain prognostic in individuals taking menopausal hormone therapy.

The research letter, “Lipoprotein(a), Menopausal Hormone Therapy, and Risk of Coronary Heart Disease in Postmenopausal Individuals,” was published in JAMA Cardiology.