Elevated Lp(a) associated with subsequent MACE in incident ASCVD

06/02/2024

In a retrospective UK Biobank cohort study, elevated Lp(a) was associated with increased risk of subsequent MACE (in particular nonfatal MI and coronary revascularization) in patients with incident ASCVD, compared with normal Lp(a).

This summary is based on the publication of Welsh P, Al Zabiby A, Byrne H, et al. - Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank. Atherosclerosis. 2023 Dec 27:389:117437 [Online ahead of print]. doi: 10.1016/j.atherosclerosis.2023.117437

Introduction and methods

Background

The association of elevated Lp(a) levels and risk of subsequent CV events in newly diagnosed ASCVD patients is not well understood. This makes it difficult to provide risk assessment and secondary prevention plans for this population.

Aim of the study

The study aim was to provide novel insights into the associated risk of elevated versus normal Lp(a) levels with the occurrence of MACE in an incident ASCVD cohort representative of an acute setting.

Methods

In this retrospective observational cohort study, 32,537 adults who were newly diagnosed with ASCVD after their enrollment in the UK Biobank between March 2006 and December 2010 were included. ASCVD was defined as any of the following diagnoses: MI, ischemic stroke, TIA, coronary artery disease, cerebrovascular disease, stent placement and/or revascularization, peripheral artery disease, and stable or unstable angina. Median follow-up duration was 4.7 years. Of the 32,537 patients, 22,257 (68.4%) had normal (<65 nmol/L) and 5204 (16.0%) had elevated (>150 nmol/L) Lp(a) levels. To assess the association between Lp(a) and post-index MACE, a complete-case analysis was conducted in 30,510 patients, of whom 20,887 (68.5%) had normal and 4885 (16.0%) had elevated Lp(a) levels.

Outcome

The primary endpoint was the occurrence of MACE (time to first event and all events). MACE was defined as a composite outcome of CV death, nonfatal MI, nonfatal ischemic stroke, or coronary revascularization.

Main results

Incidence of MACE by Lp(a) status

  • Of the incident ASCVD patients with elevated Lp(a) levels, 41.2% had subsequent MACE (25.9% nonfatal MI and 16.4% coronary revascularization), compared with 35.6% of those with normal Lp(a) levels (22.6% nonfatal MI and 10.9% coronary revascularization).
  • During the entire follow-up period, the incidence rate of composite MACE was 22.85 per 100 person-years (95%CI: 22.28–23.42) in patients with elevated Lp(a) levels and 19.94 per 100 person-years (95%CI: 19.68–20.21) in those with normal Lp(a) levels (incidence rate difference: 2.90 per 100 person-years; incidence rate ratio (IRR): 1.17; 95%CI: 1.14–1.20; P<0.001). This difference was mainly caused by increased incidence rates of nonfatal MI (IRR: 1.14; 95%CI: 1.10–1.18) and coronary revascularization (IRR: 1.48; 95%CI: 1.38–1.59).
  • In the first year of follow-up, the incidence rate of MACE was also higher in patients with elevated Lp(a) levels (43.68 per 100 person-years; 95%CI: 41.81–45.55) compared with those with normal Lp(a) levels (36.89 per 100 person-years; 95%CI: 36.06–37.73; incidence rate difference: 6.79 per 100 person-years; IRR: 1.19; 95%CI: 1.13–1.25; P<0.001). Again, the increased MACE incidence rate was mainly driven by nonfatal MI (IRR: 1.11; 95%CI: 1.04–1.19) and coronary revascularization (IRR: 1.47; 95%CI: 1.34–1.60).

Association between Lp(a) and MACE

  • Over the entire follow-up period, a 100-nmol/L continuous increase in Lp(a) was associated with increased risks of coronary revascularization (adjusted HR: 1.19; 95%CI: 1.14–1.23; P<0.001), nonfatal ischemic stroke (adjusted HR: 1.10; 95%CI: 1.01–1.19; P=0.021), composite MACE (adjusted HR: 1.08; 95%CI: 1.06–1.10; P<0.001), and nonfatal MI (adjusted HR: 1.03; 95%CI: 1.00–1.06; P=0.042) but not CV death (adjusted HR: 1.03; 95%CI: 0.97–1.09; P=0.327).

Conclusion

In this retrospective observational cohort study from the UK Biobank, elevated Lp(a) levels were associated with increased risk of subsequent MACE (in particular nonfatal MI and coronary revascularization) in patients with incident ASCVD, compared with normal Lp(a) levels.

The authors believe the “increased rate of subsequent MACE and coronary revascularization highlights an acute population who may benefit from earlier and more targeted intervention for Lp(a) and other CV risk factors, particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help to identify and better manage these high-risk individuals.”

Find this article online at Atherosclerosis.

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