Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance

Abstract

Statins are one of the most important medications in cardio-vascular diseases since they block cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase and thus reduce low density lipoprotein concentrations. In the last years, numerous pleiotropic properties of statins have been described, beyond their well-known lipid lowering function. In particular, they are able to modulate inflammation, which plays a pivotal role in the atherosclerotic process. Several trials have shown a direct correlation between statin therapy and lower C-reactive protein concentrations. Moreover, a large body of pathophysiological studies has demonstrated that statins lower cytokine concentrations and inhibit recruitment, migration and cell adhesion to endothelium by attenuating chemokine production. They also inhibit inflammatory pathways regulated by proteins as Ras and Rho, and increase nitric oxide production which exerts a protective effect on endothelium. In addition to reducing inflammation in coronary atherosclerosis, statins also have beneficial effects in chronic inflammatory and autoimmune diseases, such as psoriasis, and they could induce clinical improvement. Statins seem to exert benefits even in settings of infection. These results suggest that initiating and monitoring statin therapy on the basis of inflammatory markers, in particular C-reactive protein, may improve cardiovascular prevention and treatment.

Clinical utility of inflammatory markers and advanced lipoprotein testing: Advice from an expert panel of lipid specialists

“…9 Finally, the use of generic statins has made the cost of treatment very low and, therefore, enhanced the cost-effectiveness of the use of biomarkers to identify additional patients at increased absolute risk of CV events for whom more aggressive intervention may ultimately improve morbidity and mortality. 10,11 The National Lipid Association convened a panel of clinical experts to evaluate the use of selected biomarkers in clinical practice as either tools to improve risk assessment or as markers to adjust therapy once a decision to treat had been made (Table 1). Five clinical scenarios were considered by the panel that accounted for the vast majority of patients in whom clinicians would consider the use of biomarkers.…”

Atherosclerosis, Biological and Pathological Basis

“…These drugs block the cholesterol synthesis acting on the 3-hydroxy-3-methylglutaryl coenzyme A reductase at the hepatic level, but it has also been evidenced that they act directly at the level of the plaque inhibiting some inflammatory processes, diminishing the recruitment of inflammatory cells inside the lesion, and increasing the production of NO [22].…”

Atherosclerosis: pathogenesis and pathology

“…An additional function is inhibition of inflammatory pathways regulated by Ras and Rho, and increase of NO production, which subsequently enhances endothelium protection. 23 Statins also lower cytokine production and inhibit recruitment, migration and cell adhesion to endothelium. 23 The West of Scotland Coronary Prevention Study and the Prospective Study of Pravastatin in the Elderly at Risk both demonstrated reductions in LDL concentrations, cardiac mortality and coronary events at a dose of 40 mg/day.…”