The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review

Abstract

Vascular calcification (VC) is a complex process of calcium deposition on the arterial wall and atherosclerotic plaques and involves interaction between vascular smooth muscle cells, inflammatory and VC mediators. The latter are independent predictors of cardiovascular morbidity and mortality and potential targets of pharmaceutical therapy. This paper is a narrative review of the complex mechanisms of VC development and in this context the potential anti-atherosclerotic effects of statins. At the initial stages of atherosclerosis VC correlates with atherosclerosis burden and in the long-term with cardiovascular morbidity and mortality. A plethora of animal and clinical studies have proposed statins as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Based on coronary computed tomography data, high doses of statins may have negligible or even positive effects on the progression of coronary artery calcification. Growing data support an increase in atherosclerotic plaque calcification in peripheral arteries (e.g., carotids), after long-term, statin-therapy. Despite the paradox of increasing VC, those effects of statins have been associated with higher plaque stability, reducing the risk of consequent adverse events. Statins seem to promote a "favorable" atherosclerotic calcification, suppressing atherosclerotic lesion expansion and their vulnerability. More studies are required to clarify the underlying mechanisms.

Keywords: arterial calcification; atherosclerotic plaque; atherosclerotic plaque calcification; plaque vulnerability; statins.

Fig. 1.

Pathophysiologic mechanisms of statins on vascular calcification. (A) Anti-inflammatory effect and vascular calcification promotion. (B) Direct vascular calcification promotion. OPN, osteopontin; OPG, osteoprotegerin; NF-$\kappa$B, nuclear factor kappa light chain enhancer of activated B cells; IL-1$\beta$, interleukin-1$\beta$; RUNX2, runt-related transcription factor 2; RANKL, receptor activator of nuclear factor kappa-$\beta$ ligand; ALP, alkaline phosphatase.