Current concepts in atherosclerosis

Mohammad Alkhalil,Robin P. Choudhury

doi:10.1007/s12055-018-0699-y

Abstract

Atherosclerosis is a complex disease process. It is increasingly recognised that both lipoprotein retention and inflammatory cellular components are intricately related in the initiation and development of atherosclerotic plaque. LDL-c (cholesterol) has been long established as a cause for atherosclerosis; additionally, inflammatory cells such as monocytes and subsequently foam cells have also been directly linked to the progression of atherosclerotic disease. Emerging data suggest that structures outside vascular intima and media are also closely related to atherosclerosis. Perivascular adipose tissue (PVAT) may be a determinant of the inflammatory status of the atherosclerotic plaque. All these features are becoming extremely relevant as therapies against atherosclerosis are targeting both lipid retention and inflammation. Recently, there has been some success in these novel therapies, such as the proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitor evolocumab and the interleukin-1ß neutralising antibody, canakinumab, in reducing cardiovascular events when added to standard therapy such as statin. This review will discuss the pathogenesis of atherosclerosis, including some novel features, and its management using new anti-atherosclerotic drugs.

Highlights

Atherosclerosis is a complex disease with multiple processes implicated in early atherogenesis
Lipoprotein retention within the intima of the vascular wall coupled with inflammatory flux of monocytes and lymphocytes in addition to changes in endothelial function and migration of vascular smooth muscle cells leads to the formation of atherosclerotic plaque [1]
Inflammatory response and are coupled with increased rate of lipoprotein accumulation and extracellular matrix deposition leading to intimal thickening and facilitating the process of atherosclerotic plaque formation [5]

Summary

Introduction

Atherosclerosis is a complex disease with multiple processes implicated in early atherogenesis. The Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Treating to New Targets (TNT) studies [46, 48] demonstrated incremental benefits from reducing LDL-c using intensive statin treatments This relationship between statin-induced LDL-c reduction and vascular events was borne out in a large meta-analysis, including 170,000 patients from 26 randomised trials. The recent relative success of novel therapies in reducing cardiovascular events has promoted an important debate as to whether these drugs are applicable for the real world These drugs have typically produced an absolute risk reduction of 1–2% of combined clinical outcomes, including death, myocardial infarction, stroke, unstable angina and coronary revascularisation. This strategy is yet to be tested in the future to assess whether it would be effective, but undoubtedly, it would decrease the sample size to prove efficacy, reduce costs and follow-up duration but more importantly would spare low-risk individuals from unnecessary risks

Conclusion

Findings

Compliance with ethical standards