Elevated lipoprotein(a) [Lp(a)] is associated with accelerated progression of coronary plaques, a higher prevalence of thin-cap fibroatheroma, and an increased risk of spontaneous myocardial infarction. However, Lp(a)'s impact on coronary artery disease (CAD) and the resulting coronary flow dynamics have yet to be fully determined.

To evaluate the effects of elevated Lp(a) levels on epicardial coronary flow and endoluminal disease pattern (focal or diffuse).

In a propensity-score matched (PSM) cohort from the ongoing PIONEER IV trial (NCT04923191), participants with de novo CAD and elevated Lp(a) (>50 mg/dL or 120 nmol/L) were matched to controls based on traditional CAD risk factors. Epicardial flow velocity was assessed using the Quantitative Flow Ratio (QFR), with the virtual QFR-Pressure Pullback Gradient Index (QFR-PPGi) characterizing the endoluminal disease phenotype. A QFR ≤ 0.80 indicated significant epicardial flow limitation.

Among 672 consecutively enrolled participants with available Lp(a) measurements, elevated levels were observed in 23 % (152/672). Complete risk profiles for traditional CAD risk factors were available for 391 participants with de novo CAD, of whom 75 had elevated Lp(a) levels. After propensity matching, 75 pairs (150 participants) were eligible for analyses. QFR analyses were completed in 392/450 (87 %) vessels. The median difference in baseline QFR between matched vessels was −0.045 (p = 0.005), while the mean difference in QFR-PPGi was −0.028 (p = 0.013). Vessels from participants with elevated Lp(a) demonstrated significantly higher rates of QFR ≤ 0.80 compared to matched controls (31 % vs. 19 %, absolute risk difference 12 %; 95 % CI: 2.7 %–21 %, p = 0.011).