The Curious Case of Synergy between Lipoprotein (a), Coronary Calcification, and Cardiovascular Disease Risk.

Abstract

Despite recent advances in cardiovascular interventions and preventive therapies, there remains a substantial residual risk of atherosclerotic cardiovascular disease (ASCVD), even among patients on maximal guideline-directed medical therapy. Growing epidemiological and genetic evidence supports the causal role that lipoprotein(a) [Lp(a)], an apolipoprotein-B–containing lipoprotein, plays in increasing the risk of ASCVD morbidity and mortality, and an elevated Lp(a) (≥50 mg/dL or ≥125 nmol/L) is considered a risk enhancer in recent national guidelines (1). Multiple proinflammatory, proatherogenic, procalcific, and cellular signaling mechanisms have been described that could mediate the association of Lp(a) with ASCVD clinical events, in particular due to the oxidized phospholipid content of Lp(a) (2). An intriguing finding has been that elevated Lp(a) concentrations do not associate with prevalent coronary artery calcification (CAC) despite being associated with more rapid progression of CAC and atherosclerotic plaque (3). But while prior studies have shown no association between prevalent Lp(a) and CAC, the joint association of Lp(a) and CAC with the risk of future ASCVD events is not well understood (4). CAC, measured on computed tomography, is an established risk enhancer incorporated into recent guidelines to favor initiation or intensification of statin therapy in patients with uncertain ASCVD risk. On the other hand, the absence of CAC has been used to favor withholding or delaying statin use in certain patients (1).