April 20, 2026
3 min read
Key takeaways:
- High Lp(a) was linked to risk for venous thromboembolism among premenopausal women and postmenopausal women on hormone therapy.
- Estrogen levels may modify the clotting risk associated with elevated Lp(a).
Elevated lipoprotein(a) was associated with increased risk for dangerous blood clotting among premenopausal women and postmenopausal women taking menopausal hormone therapy, according to a UK Biobank study.
Circulating estrogen levels may contribute to the prothrombotic effects of Lp(a), increasing risk for venous thromboembolism among women with already elevated Lp(a), according to data presented at the American College of Cardiology Scientific Session and simultaneously published in the European Heart Journal.
High Lp(a) was linked to risk for venous thromboembolism among premenopausal women and postmenopausal women on hormone therapy. Image: Adobe Stock
“The hematology community hasn’t widely adopted Lp(a) as a clotting risk factor because the data are so mixed,” Michael C. Honigberg, MD, MPP, cardiologist and researcher at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Healio. “There’s biological plausibility based on the structure of Lp(a) that makes one think it could be proclotting. It shares some structural homology with plasminogen. That said, maybe Lp(a) isn’t one static risk factor that operates the same in everybody. We know that there are other factors that modify risk for blood clots, like obesity, use of oral contraceptive pills, menopausal hormone therapy or smoking. Maybe the risk is actually a little bit heterogeneous depending on these other factors. That’s what prompted this analysis, where we disaggregated the population by sex and by hormonal status.”
Honigberg and colleagues evaluated UK Biobank data from 55,302 premenopausal women (mean age, 46 years), 129,045 postmenopausal women (mean age, 60 years) and 189,013 men (mean age, 56 years) with baseline Lp(a) data. Participants with a history of VTE, cancer or anticoagulant use were excluded.
In line with the 2026 update of the American Heart Association/ACC cholesterol guidelines, elevated Lp(a) was defined as 125 nmol/L (50 mg/dL) or higher.
Fourteen percent of premenopausal women, 19% of postmenopausal women and 15% of men in the present study had elevated Lp(a) levels.
During a median follow-up of 13.6 years, VTE events occurred at a cumulative incidence rate of 2.2%, according to the study.
Researchers reported that elevated Lp(a) was associated with incident VTE among premenopausal women (adjusted HR = 1.32; 95% CI, 1.04-1.66; P = .02) but not among postmenopausal women (aHR = 1.03; 95% CI, 0.94-1.13; P = .47) or men (aHR = 1; 95% CI, 0.92-1.08; P = .94).
The difference in Lp(a)-associated incident VTE was significant between pre- and postmenopausal women (P for interaction = .03), Honigberg and colleagues found.
Oral contraceptive use did not impact Lp(a)-associated incident VTE risk among premenopausal women (P for interaction = .61). However, among postmenopausal women taking menopausal hormone therapy, elevated Lp(a) was associated with increased risk for VTE (aHR = 1.48; 95% CI, 1.03-2.12; P = .03), but the same was not true for postmenopausal women not taking hormone therapy (P for interaction = .04).
“We observed an association with VTE in premenopausal women, but not in men and not in postmenopausal women. When we stratified the postmenopausal female group, however, those who were taking menopausal hormone therapy showed the same Lp(a)-associated risk as the premenopausal women, and biologically, that’s an interesting signal. It almost serves as an internal validation that Lp(a) can be promoting VTE risk in a higher estrogen state, but not in a lower estrogen state,” Honigberg told Healio. “We performed some more exploratory analyses, stratified by measured circulating estradiol levels in the premenopausal and postmenopausal women, which further supported those findings with a sort of dose-responsive relationship with higher Lp(a)-associated risks for VTE the higher the measured circulating estradiol was. All of this seems like a consistent signal that Lp(a) associates with VTE risk, but uniquely in higher estrogen states, not in lower estrogen states.
“One might theorize a kind of ‘two hit’ hypothesis: That the procoagulant effects of Lp(a) and the procoagulant effects of a higher estrogen state may work together to promote clots,” Honigberg said.
For more information:
Michael C. Honigberg, MD, MPP, can be reached at mhonigberg@mgh.harvard.edu or X @mchonig.
Sources/Disclosures
Source:
Honigberg MC, et al. Targeting Lp(a) to reduce risk. Presented at: American College of Cardiology Scientific Session; March 28-30, 2026; New Orleans (hybrid meeting).
Reference:
Disclosures:
Honigberg reports receiving consultant fees from Comanche Biopharma, receiving research support from Genentech and serving as site principal investigator for Novartis.
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