Atherosclerosis

Abstract

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease.

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Fig. 1: The contribution of cardiovascular diseases to the global burden of death in 2016.
Fig. 2: Initiation and progression of atherosclerosis.
Fig. 3: The progression of atherosclerotic lesions: cellular birth and death.
Fig. 4: Atheroma complication: disruption and healing.
Fig. 5: Clinical manifestations of atherosclerosis.
Fig. 6: Relationship between luminal diameter narrowing and relative coronary artery flow/reserve at rest and under stress conditions.

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Acknowledgements

P.L. receives funding support from the National Heart, Lung, and Blood Institute (R01HL080472), the American Heart Association (18CSA34080399), and the RRM Charitable Fund. We thank C. Swallom for her editorial assistance.

Peer review information

Nature Reviews Disease Primers thanks G. Fredman, R. A. Hegele and A. S. Wierzbicki for their contribution to the peer review of this work.

Author information

Introduction (P.L.); Epidemiology (J.E.B.); Mechanisms/pathophysiology (L.B. and G.K.H.); Diagnosis, screening and prevention (J.D. and M.S.B.); Management (L.T.); Quality of life (E.F.L.); Outlook (P.L.); Overview of Primer (P.L.).

Correspondence to Peter Libby.

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Competing interests

P.L. is an unpaid consultant to, or involved in clinical trials for, Amgen, AstraZeneca, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Novartis, Pfizer, Sanofi-Regeneron and XBiotech, Inc. P.L. is a member of scientific advisory boards for Amgen, Corvidia Therapeutics, DalCor Pharmaceuticals, IFM, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune and Novartis. P.L.’s laboratory has received research funding in the last 2 years from Novartis. L.B. has performed lectures and advisory board work in 2017 for Sanofi, Amgen and Astrazeneca. L.B. receives research grant support from AstraZeneca and research funding and grants from Fondo de Investigaciones Sanitarias (FIS), Plan Nacional-Retos MINECO and the EU. G.K.H. is the inventor of patents regarding immune therapy in atherosclerosis. G.K.H. is also the recipient of grants for research on immune mechanisms in atherosclerosis from the Swedish Research Council, the Swedish Heart-Lung Foundation and the EU. J.D. has received CME honoraria and/or consulting fees from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk and Bayer. J.D. is a member of a Study Steering Committee for Novo Nordisk and has received research grants from the British Heart Foundation, MRC(UK), NIHR, PHE, MSD, Pfizer, Aegerion, Colgate and Roche. M.S.B. has received research support funding from Sanofi and consulting fees from Boston Scientific. L.T. is a member of the scientific advisory boards for Merck, Abbott, Amgen, Sanofi and Daichi Sankyo. L.T. also performed lectures for Abbott, Astra, Actelion, Merck, Servier, Recordati, Mylan, Amgen, Novartis, Sanofi, Pfizer, Bayer, Novo Nordisk and Sanovel. E.F.L. reports institutional research grant and consulting from Novartis, and institutional research grants from Amgen and Sanofi. J.E.B. declares no competing interests.

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