George Thanassoulis

Should not yet guide clinical decisions; leaves open prospective validation of ΔHR for autonomic risk assessment.

ASXL1-mutant CHIP was associated with aortic stenosis and calcification; extends prior CHIP observations and leaves IL-1/IL-6 inhibition hypothesis-generating.

Emerging targeted therapies, particularly Lp(a)-lowering RNA-based agents, offer a promising novel pharmacological approach to potentially slow the progression of calcific aortic stenosis.

May identify higher valvular calcification risk; leaves open causal role or clinical utility of dp-ucMGP.

High lipoprotein(a) is highlighted as a key driver of residual cardiovascular risk in patients who have achieved very low LDL cholesterol levels.

Recalibration of the Framingham Risk Score using contemporary population data significantly reduces risk overestimation and improves the targeting of statin therapy, whereas the Pooled Cohort Equations continue to overestimate risk even after recalibration.

High HDL-C is associated with lower ASCVD risk independent of apoB and attenuates the effect of high apoB on ASCVD risk, suggesting its role in primary prevention warrants re-evaluation.

Elevated Lipoprotein(a) is independently associated with increased carotid intima-media thickness, and the combination of both markers identifies patients at the highest risk for incident ASCVD.

This JACC Scientific Statement outlines the current challenges and future needs for accurate, lifespan-spanning clinical risk assessment in congenital heart disease.

A robust pipeline of novel Lp(a)-lowering therapies is currently in development and clinical trials, which may fundamentally alter the cardiovascular risk prevention paradigm.

The Canadian Lp(a) Registry provides real-world baseline data showing that while most patients with elevated Lp(a) are on lipid-lowering therapy, nearly half do not achieve LDL-C <2.0 mmol/L.

Early lipid monitoring before age 40 can identify individuals with a high likelihood of lifetime elevated non-HDL-C and significantly increased long-term risk for CVD.

Polygenic risk scores for coronary artery disease, systolic blood pressure, LDL-C, and Lipoprotein(a) are significantly associated with prevalent aortic valve calcification, suggesting shared genetic pathways between CAD and AVC and highlighting systolic blood pressure as an underrecognized risk factor.

This NHLBI working group report outlines critical knowledge gaps and provides recommendations to advance research on Lipoprotein(a) as a causal mediator of cardiovascular disease and calcific aortic valve disease.

In patients with triglycerides >400 mg/dL, none of the current LDL-C equations perform adequately compared to beta-quantification, indicating LDL-C should be directly measured rather than calculated in this population.