24 - Anti-inflammatory Therapy for Cardiovascular Disease

Abstract

Atherosclerosis is a disease driven by lipid accumulation and chronic low-grade systemic inflammation. Yet, clinicians often focus attention solely on “residual cholesterol risk” without paying adequate attention to “residual inflammatory risk” despite the fact that the latter group of patients are three times as common as the former. In statin-treated patients, data from multiple randomized trials now demonstrate that targeting inflammation is at least as effective as further targeting of low-density lipoprotein (LDL) cholesterol. Further, the availability of colchicine, an inexpensive generic anti-inflammatory therapy, now allows clinicians to move beyond lipid strategies alone to reduce major adverse cardiovascular event rates in their patients. Thus, to effectively practice today, clinical lipidologists need to measure high-sensitivity C-reactive protein (hsCRP) as well as LDL cholesterol in order to differentiate patients with “residual inflammatory risk” from those with “residual cholesterol risk.” While statin therapy lowers both LDL cholesterol and hsCRP and is thus appropriate initial treatment for virtually all individuals with atherosclerotic risk, the selection of a second agent should be tailored by a better understanding as to whether the underlying pathophysiological defect in a given patient requires further inflammation inhibition or further lipid-lowering. In the future, it can be anticipated that all atherosclerosis patients will receive aggressive lipid-lowering and inflammation-inhibiting therapy, in addition to behavioral and lifestyle interventions. Future targets for inflammatory atheroprotection include upstream inhibition of the nucleotide-binding oligomerization domain–like receptor family pyrin domain containing 3 (NLRP3) inflammasome as well as direct downstream targeting of interleukin-6, the central cytokine driving atherosclerotic disease progression.