Preventive Cardiology

Lipoprotein(a)’s High (and Uneven) Cardiovascular Risks

Harvard researchers strengthened the link between high Lipoprotein(a) levels and greater risks of future cardiovascular events, including among patients who haven’t been diagnosed with ASCVD.

The researchers analyzed 12-year outcomes from 16,419 people in the Mass General Brigham Lp(a) Registry who had their Lp(a) measured between 2000 to 2019, including 62% with a history of ASCVD (prior MI, revascularization, ischemic stroke).

Patients with ASCVD histories generally had higher Lp(a) levels than those without ASCVD (37.8 vs 31.1 nmol/L), but Lp(a)’s future MACE risks increased at a far steeper rate among the patients without ASCVD. 

Compared to patients in the 1st to 50th percentile of Lp(a) levels, patients in the…

  • 51st to 70th Lp(a) percentiles had a 14% greater MACE risk if they also had ASCVD, and a 9% greater MACE risk if they didn’t have ASCVD.
  • 71st to 90th Lp(a) percentiles had a 21% greater MACE risk if they also had ASCVD, and a 17% greater MACE risk if they didn’t have ASCVD.
  • 91st to 100th Lp(a) percentiles had a 26% greater MACE risk if they also had ASCVD, and a 93% greater MACE risk if they didn’t have ASCVD.

Annual MACE rates were still highest among the patients with ASCVD compared to those without ASCVD across the four Lp(a) percentile levels (annual MACE rates: 4.1%, 4.9%, 5.3%, 5.3% vs. 1.1%, 1.2%, 1.3%, and 2.2%).

  • However, the ASCVD patients’ saw their risk plateau beyond the 70th percentile, while the non-ASCVD patients’ risk significantly increased at the 90th Lp(a) percentile.

Those differences in Lp(a) risk thresholds could have a significant impact on patient screening decisions and patient selection for future Lp(a) trials, especially considering that many patients with high Lp(a) levels wouldn’t be included in the current Lp(a) Phase 3 trials.

The Takeaway

Using real world data, this study further confirms conclusions from previous Lp(a) studies, while revealing that Lp(a)-related MACE risk thresholds can be quite different among primary and secondary prevention patients. That could have a big influence on future trials, which could in turn have a big influence on future Lp(a) testing and treatment guidelines.

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