Blood Pressure Control Unmasks the Cardiovascular Risk Associated With Lipoprotein(a): Insights From the Gaelp(a) Study

Objective: To assess the relationship between Lp(a), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and blood pressure control in predicting major adverse cardiovascular events (MACE) in the Argentine multicenter GAELp(a) cohort.Design and method: We analyzed 2,864 patients with available data on Lp(a), LDL-C, and blood pressure. ApoB measurements, however, were available in 1,816 out of 3,652 participants (49.7%). All analyses including ApoB were therefore restricted to this subset. Among hypertensive patients, 1,051/2,052 (51.2%) had ApoB values available. Lp(a) values were standardized to nmol/L (conversion factor 2.5 if mg/dL). Controlled blood pressure (BP_control) was defined as systolic <130 mmHg and/or diastolic <80 mmHg among hypertensive patients. MACE was defined as ischemic heart disease, peripheral artery disease, or prior ischemic stroke. Logistic regression models were adjusted for age, sex, LDL-C, ApoB, statin use, and blood pressure control. Incremental value was assessed using AUC, NRI, IDI, Brier score, spline modeling, heatmaps, and decision curve analysis. Results: Lp(a) provided incremental predictive value over LDL-C and ApoB (Lp(a) improved model discrimination metrics (AUC, NRI, IDI); Brier < 0). The association between Lp(a) and MACE was stronger in patients with controlled blood pressure, suggesting a residual risk independent of hemodynamic load. In contrast, in uncontrolled hypertension, the Lp(a)-MACE association was attenuated. Decision curve analysis demonstrated greater net benefit for the model including Lp(a) across risk thresholds of 5–20%. Conclusions: Elevated Lp(a) is associated with residual cardiovascular risk beyond LDL-C and ApoB, particularly in patients with well-controlled blood pressure. These findings highlight the relevance of Lp(a) screening to identify high-risk individuals despite optimal hypertension management.