Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Atherosclerosis

Nature Reviews Disease Primers volume 5, Article number: 56 (2019) Cite this article

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. World Health Organization. Cardiovascular diseases (CVDs) Fact Sheet. 2017.

  2. Benjamin, E. J. et al. Heart disease and stroke statistics–2017 update: a report from the American Heart Association. Circulation 136, e146–e603 (2017).

    Google Scholar 

  3. Centers for Disease Control and Prevention. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol–United States, 1999–2002 and 2005–2008. MMWR Morb. Mortal. Wkly Rep. 60, 109–114 (2011).

    Google Scholar 

  4. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1545–1602 (2016).

    Article  Google Scholar 

  5. Herrington, W., Lacey, B., Sherliker, P., Armitage, J. & Lewington, S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res. 118, 535–546 (2016).

    Article  CAS  PubMed  Google Scholar 

  6. Roth, G. A. et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation 132, 1667–1678 (2015).

    Article  PubMed  Google Scholar 

  7. WHO. Cardiovascular disease: Global Hearts Initiative. (World Health Organization, Geneva, 2018).

    Google Scholar 

  8. Goldstein, J. L. & Brown, M. S. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 161, 161–172 (2015). A telling of the cholesterol tale from two luminaries in the field.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Libby, P. The forgotten majority: unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 46, 1225–1228 (2005).

    Article  PubMed  Google Scholar 

  10. Hochholzer, W. & Giugliano, R. P. Lipid lowering goals: back to nature? Ther. Adv. Cardiovasc. Dis. 4, 185–191 (2010).

    CAS  Google Scholar 

  11. Giugliano, R. P. et al. Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT trial. JAMA Cardiol. 2, 547–555 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hopstock, L. A. et al. Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905–1977 in the population-based Tromso study 1979–2016. BMJ Open. 7, e015001 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schreiner, P. J., Jacobs, D. R. Jr., Wong, N. D. & Kiefe, C. I. Twenty-five year secular trends in lipids and modifiable risk factors in a population-based biracial cohort: the Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985–2011. J. Am. Heart. Assoc. 5, e003384 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ference, B. A. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 38, 2459–2472 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nordestgaard, B. G. et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur. Heart J. 34, 3478–3490 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr. & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Miller, Y. I. et al. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ. Res. 108, 235–248 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Navab, M. et al. The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J. Lipid Res. 45, 993–1007 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Gistera, A. & Hansson, G. K. The immunology of atherosclerosis. Nat. Rev. Nephrol. 13, 368–380 (2017).

    Article  PubMed  CAS  Google Scholar 

  20. Libby, P., Hansson, G. K. & Lichtman, A. H. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38, 1092–1104 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tardif, J. C. et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 371, 1761–1768 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Ketelhuth, D. F. J. & Hansson, G. K. Adaptive response of T and B cells in atherosclerosis. Circ. Res. 118, 668–678 (2016). A summary of the roles of adaptive immunity in atherosclerosis.

    Article  CAS  PubMed  Google Scholar 

  23. Boren, J. & Williams, K. J. The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity. Curr. Opin. Lipidol. 27, 473–483 (2016).

    Article  CAS  PubMed  Google Scholar 

  24. Llorente-Cortes, V., Martinez-Gonzalez, J. & Badimon, L. LDL receptor-related protein mediates uptake of aggregated LDL in human vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 20, 1572–1579 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Musunuru, K. & Kathiresan, S. Surprises from genetic analyses of lipid risk factors for atherosclerosis. Circ. Res. 118, 579–585 (2016). A window into novel aspects of lipids and atherosclerosis emerging from contemporary human genetics.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Libby, P. Triglycerides on the rise: should we swap seats on the seesaw? Eur. Heart J. 36, 774–776 (2015).

    Article  PubMed  Google Scholar 

  27. Nordestgaard, B. G. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ. Res. 118, 547–563 (2016). A rethinking of the contributions of triglyceride-rich lipoproteins to human atherogenesis based on observational epidemiology and human genetics studies.

    Article  CAS  PubMed  Google Scholar 

  28. Burgess, S. et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 3, 619–627 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kranzhofer, R., Browatzki, M., Schmidt, J. & Kubler, W. Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes. Biochem. Biophys. Res. Commun. 257, 826–828 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. McMaster, W. G., Kirabo, A., Madhur, M. S. & Harrison, D. G. Inflammation, immunity, and hypertensive end-organ damage. Circ. Res. 116, 1022–1033 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rocha, V. Z. & Libby, P. Obesity, inflammation, and atherosclerosis. Nat. Rev. Cardiol. 6, 399–409 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Despres, J. P. Body fat distribution and risk of cardiovascular disease: an update. Circulation 126, 1301–1313 (2012).

    Article  PubMed  Google Scholar 

  33. Libby, P., Nahrendorf, M. & Swirski, F. K. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease. J. Am. Coll. Cardiol. 67, 1091–1103 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Libby, P. et al. Inflammation, immunity, and infection in atherothrombosis: JACC Review Topic of the Week. J Am Coll Cardiol. 72, 2071–2081 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ridker, P. M. A test in context: high-sensitivity C-reactive protein. J. Am. Coll. Cardiol. 67, 712–723 (2016).

    Article  PubMed  Google Scholar 

  36. Nus, M. & Mallat, Z. Immune-mediated mechanisms of atherosclerosis and implications for the clinic. Expert Rev. Clin. Immunol. 12, 1217–1237 (2016).

    Article  CAS  PubMed  Google Scholar 

  37. Ignarro, L. J. & Napoli, C. Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis. Curr. Diab. Rep. 5, 17–23 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Cybulsky, M. I. & Gimbrone, M. A. Jr. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 251, 788–791 (1991).

    Article  CAS  PubMed  Google Scholar 

  39. Li, H., Cybulsky, M. I., Gimbrone, M. A. Jr. & Libby, P. An atherogenic diet rapidly induces VCAM-1, a cytokine regulatable mononuclear leukocyte adhesion molecule, in rabbit endothelium. Arterioscler. Thromb. 13, 197–204 (1993).

    Article  PubMed  Google Scholar 

  40. SenBanerjee, S. et al. KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J. Exp. Med. 199, 1305–1315 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gimbrone, M. A. & García-Cardeña, G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 118, 620–636 (2016). An up-to-date summary of the roles of endothelial cells in atherosclerosis from a pioneering investigator.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chatzizisis, Y. S. et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J. Am. Coll. Cardiol. 49, 2379–2393 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Bennett, M. R., Sinha, S. & Owens, G. K. Vascular smooth muscle cells in atherosclerosis. Circ. Res. 118, 692–702 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Robbins, C. S. et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19, 1166–1172 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wanschel, A. et al. Neuroimmune guidance cue semaphorin 3E is expressed in atherosclerotic plaques and regulates macrophage retention. Arterioscler. Thromb. Vasc. Biol. 33, 886–93 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Swirski, F. K., Nahrendorf, M. & Libby, P. The ins and outs of inflammatory cells in atheromata. Cell. Metab. 15, 135–136 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. Libby, P. & Hansson, G. K. Inflammation and immunity in diseases of the arterial tree: players and layers. Circ. Res. 116, 307–311 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gistera, A. et al. Transforming growth factor-β signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway. Sci. Transl. Med. 5, 196ra100 (2013).

    Article  PubMed  CAS  Google Scholar 

  49. Grabner, R. et al. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J. Exp. Med. 206, 233–248 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Geng, Y.-J. & Libby, P. Evidence for apoptosis in advanced human atheroma. Co-localization with interleukin-1 beta-converting enzyme. Am. J. Pathol. 147, 251–266 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Clarke, M. C., Talib, S., Figg, N. L. & Bennett, M. R. Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis. Circ. Res. 106, 363–372 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Tabas, I., Garcia-Cardena, G. & Owens, G. K. Recent insights into the cellular biology of atherosclerosis. J. Cell. Biol. 209, 13–22 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yurdagul, A., Doran, A. C., Cai, B., Fredman, G. & Tabas, I. A. Mechanisms and consequences of defective efferocytosis in atherosclerosis. Front. Cardiovasc. Med. 8, 4–86 (2018).

    Google Scholar 

  54. Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Fuster, J. J. et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355, 842–847 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wolach, O. et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci. Transl. Med. 10, eaan8292 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Libby, P. & Ebert, B. CHIP (clonal hematopoiesis of indeterminate potential): potent and newly recognized contributor to cardiovascular risk. Circulation 138, 666–668 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ruiz, J. L., Hutcheson, J. D. & Aikawa, E. Cardiovascular calcification: current controversies and novel concepts. Cardiovasc. Pathol. 24, 207–212 (2015).

    Article  CAS  PubMed  Google Scholar 

  59. Ruiz, J. L., Weinbaum, S., Aikawa, E. & Hutcheson, J. D. Zooming in on the genesis of atherosclerotic plaque microcalcifications. J. Physiol. 594, 2915–2927 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Huang, H. et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 103, 1051–1056 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Irkle, A. et al. Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography. Nat. Commun. 6, 7495 (2015).

    Article  PubMed  Google Scholar 

  62. Galis, Z. et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ. Res. 75, 181–189 (1994).

    Article  CAS  PubMed  Google Scholar 

  63. Alexander, M. R. et al. Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice. J. Clin. Invest. 122, 70–79 (2012).

    Article  CAS  PubMed  Google Scholar 

  64. Libby, P. Mechanisms of acute coronary syndromes and their implications for therapy. N. Engl. J. Med. 368, 2004–2013 (2013). A consideration of the cellular and molecular mechanisms that underlie the acute coronary syndromes.

    Article  CAS  PubMed  Google Scholar 

  65. Bentzon, J. F., Otsuka, F., Virmani, R. & Falk, E. Mechanisms of plaque formation and rupture. Circ. Res. 114, 1852–1866 (2014). An authoritative review of the pathological findings that provide insight into the mechanisms of atherogenesis and its thrombotic complications.

    Article  CAS  PubMed  Google Scholar 

  66. Libby, P. & Pasterkamp, G. Requiem for the ‘vulnerable plaque’. Eur. Heart J. 36, 2984–2987 (2015).

    PubMed  Google Scholar 

  67. Pasterkamp, G., den Ruijter, H. M. & Libby, P. Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease. Nat. Rev. Cardiol. 14, 21–29 (2017).

    Article  CAS  PubMed  Google Scholar 

  68. Amento, E. P., Ehsani, N., Palmer, H. & Libby, P. Cytokines and growth factors positively and negatively regulate intersitial collagen gene expression in human vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 11, 1223–1230 (1991).

    Article  CAS  Google Scholar 

  69. Galis, Z., Sukhova, G., Lark, M. & Libby, P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin. Invest. 94, 2493–2503 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Galis, Z., Sukhova, G., Kranzhöfer, R., Clark, S. & Libby, P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc. Natl. Acad. Sci. USA 92, 402–406 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Martinod, K. & Wagner, D. D. Thrombosis: tangled up in NETs. Blood 123, 2768–2776 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Franck, G. et al. Roles of PAD4 and NETosis in experimental atherosclerosis and arterial injury: implications for superficial erosion. Circ. Res. 123, 33–42 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Folco, E. J. et al. Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1α and cathepsin G. Arterioscler. Thromb. Vasc. Biol. 38, 1901–1912 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bevilacqua, M. P., Schleef, R., Gimbrone, M. A. J. & Loskutoff, D. J. Regulation of the fibrinolytic system of cultured human vascular endothelium by IL-1. J. Clin. Invest. 78, 587–591 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. van Lammeren, G. W. et al. Time-dependent changes in atherosclerotic plaque composition in patients undergoing carotid surgery. Circulation 129, 2269–2276 (2014).

    Article  PubMed  CAS  Google Scholar 

  76. Quillard, T., Franck, G., Mawson, T., Folco, E. & Libby, P. Mechanisms of erosion of atherosclerotic plaques. Curr. Opin. Lipidol. 28, 434–441 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Quillard, T. et al. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur. Heart J. 36, 1394–1404 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Franck, G. et al. Flow perturbation mediates neutrophil recruitment and potentiates endothelial injury via TLR2 in mice: implications for superficial erosion. Circ. Res. 121, 31–42 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Fernandez-Friera, L. et al. Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) study. Circulation 131, 2104–2113 (2015).

    Article  PubMed  Google Scholar 

  80. Doukky, R. et al. Promoting appropriate use of cardiac imaging: no longer an academic exercise. Ann. Intern. Med. 166, 438–440 (2017).

    Article  PubMed  Google Scholar 

  81. Gould, K. L. & Lipscomb, K. Effects of coronary stenoses on coronary flow reserve and resistance. Am. J. Cardiol. 34, 48–55 (1974).

    Article  CAS  PubMed  Google Scholar 

  82. Rumberger, J. A. Coronary artery disease: a continuum, not a threshold. Mayo Clin. Proc. 92, 323–326 (2017).

    Google Scholar 

  83. Topol, E. J. & Nissen, S. E. Our preoccupation with coronary luminology. The dissociation between clincial and angiographic findings in ischemic heart disease. Circulation 92, 2333–2342 (1995).

    Article  CAS  PubMed  Google Scholar 

  84. Tonino, P. A. L. et al. Angiographic versus functional severity of coronary artery stenoses in the fame study. J. Am. Coll. Cardiol. 55, 2816–2821 (2010).

    Article  PubMed  Google Scholar 

  85. Falk, E., Shah, P. K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. Bittencourt, M. S. et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ. Cardiovasc. Imaging. 7, 282–291 (2014).

    Article  PubMed  Google Scholar 

  87. Maddox, T. M. et al. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA 312, 1754–1763 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wilson, J. M. & Jungner, Y. G. Principles and practice of mass screening for disease [article in Spanish]. Bol. Oficina Sanit. Panam. 65, 281–393 (1968).

    CAS  PubMed  Google Scholar 

  89. Piepoli, M. F. et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 37, 2315–2381 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  90. US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA 316, 1997–2007 (2016).

    Article  Google Scholar 

  91. Goff, D. C. et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129, S49–S73 (2014).

    Article  PubMed  Google Scholar 

  92. Stone, N. J. et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129, S1–S45 (2014).

    Article  PubMed  Google Scholar 

  93. Nasir, K. et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J. Am. Coll. Cardiol. 66, 1657–1668 (2015).

    Article  CAS  PubMed  Google Scholar 

  94. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376, 1713–1722 (2017).

    Article  CAS  PubMed  Google Scholar 

  95. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Eikelboom, J. W. et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N. Engl. J. Med. 377, 1319–1330 (2017).

    Article  CAS  PubMed  Google Scholar 

  97. Roth, G. A. et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol. 70, 1–25 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Heidenreich, P. A. et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation 123, 933–944 (2011).

    Article  PubMed  Google Scholar 

  99. McConnachie, A. et al. Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study. Eur. Heart J. 35, 290–298 (2014).

    Article  CAS  PubMed  Google Scholar 

  100. Lloyd-Jones, D. M. et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 113, 791–798 (2006).

    Article  PubMed  Google Scholar 

  101. Falaschetti, E. et al. Adiposity and cardiovascular risk factors in a large contemporary population of pre-pubertal children. Eur. Heart J. 31, 3063–3072 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Victora, C. G. et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 371, 340–357 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Juonala, M. et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N. Engl. J. Med. 365, 1876–1885 (2011).

    Article  CAS  PubMed  Google Scholar 

  104. Vedanthan, R. et al. Family-based approaches to cardiovascular health promotion. J. Am. Coll. Cardiol. 67, 1725–1737 (2016).

    Article  PubMed  Google Scholar 

  105. Ference, B. A. Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps. Curr. Opin. Lipidol. 26, 566–571 (2015).

    Article  CAS  PubMed  Google Scholar 

  106. Pahkala, K. et al. Ideal cardiovascular health in adolescence: effect of lifestyle intervention and association with vascular intima-media thickness and elasticity (the Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] study). Circulation 127, 2088–2096 (2013).

    Article  PubMed  Google Scholar 

  107. Koskinen, J. et al. Arterial structure and function after recovery from the metabolic syndrome. The Cardiovascular Risk in Young Finns Study. Circulation 121, 392–400 (2010).

    Article  PubMed  Google Scholar 

  108. Tonetti, M. S. et al. Treatment of periodontitis and endothelial function. N. Engl. J. Med. 356, 911–920 (2007).

    Article  CAS  PubMed  Google Scholar 

  109. Baena-Diez, J. M. et al. Association between chronic immune-mediated inflammatory diseases and cardiovascular risk. Heart 104, 119–126 (2017).

    Article  PubMed  CAS  Google Scholar 

  110. D’Aiuto, F. et al. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol. 6, 954–965 (2018).

    Article  PubMed  Google Scholar 

  111. D’Aiuto, F. & Deanfield, J. E. Intensive periodontal therapy and type 2 diabetes - Authors’ reply. Lancet Diabetes Endocrinol. 7, 175–176 (2019).

    Article  PubMed  Google Scholar 

  112. Marma, A. K., Berry, J. D., Ning, H., Persell, S. D. & Lloyd-Jones, D. M. Distribution of 10-year and lifetime predicted risks for cardiovascular disease in US adults: findings from the National Health and Nutrition Examination Survey 2003 to 2006. Circ. Cardiovasc. Qual. Outcomes. 3, 8–14 (2010).

    Article  PubMed  Google Scholar 

  113. Berry, J. D. et al. Prevalence and progression of subclinical atherosclerosis in younger adults with low short-term but high lifetime estimated risk for cardiovascular disease. The Coronary Artery Risk Development in Young Adults Study and Multi-Ethnic Study of Atherosclerosis. Circulation 119, 382–389 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Patel, R. S. et al. Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study. BMJ Open 6, e011511 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  115. JBS3 Board. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 100 (Suppl. 2), ii1–ii67 (2014).

    Article  CAS  Google Scholar 

  116. Lopez-Gonzalez, A. A. et al. Effectiveness of the heart age tool for improving modifiable cardiovascular risk factors in a Southern European population: a randomized trial. Eur. J. Prev. Cardiol. 22, 389–396 (2015).

    Article  Google Scholar 

  117. Kivipelto, M. et al. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 5, 735–741 (2006).

    Article  PubMed  Google Scholar 

  118. Gottesman, R. F. et al. Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol. 71, 1218–1227 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Rovio, S. P. et al. Cardiovascular risk factors from childhood and midlife cognitive performance: the Young Finns study. J. Am. Coll. Cardiol. 69, 2279–2289 (2017).

    Article  PubMed  Google Scholar 

  120. Ngandu, T. et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 385, 2255–2263 (2015).

    Article  PubMed  Google Scholar 

  121. Turakhia, M. P. et al. Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: the Apple Heart Study. Am. Heart J. 207, 66–75 (2019).

    Article  PubMed  Google Scholar 

  122. Wilkins E. W. L. et al. European Cardiovascular Disease Statistics 2017. (European Heart Network, 2017).

  123. Moran, A. E. et al. Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: the Global Burden of Disease 2010 study. Circulation 129, 1483–1492 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Mora, S., Ames, J. M. & Manson, J. E. Low-dose aspirin in the primary prevention of cardiovascular disease: shared decision making in clinical practice. JAMA 316, 709–710 (2016).

    Article  PubMed  Google Scholar 

  125. Mora, S. & Manson, J. E. Aspirin for primary prevention of atherosclerotic cardiovascular disease: advances in diagnosis and treatment. JAMA Intern. Med. 176, 1195–1204 (2016).

    Article  PubMed  Google Scholar 

  126. Dugani, S., Ames, J. M., Manson, J. E. & Mora, S. Weighing the anti-ischemic benefits and bleeding risks from aspirin therapy: a rational approach. Curr. Atheroscler. Rep. 20, 15 (2018).

    Article  PubMed  CAS  Google Scholar 

  127. Ridker, P. M. Should aspirin be used for primary prevention in the post-statin era? N. Engl. J. Med. 379, 1572–1574 (2018).

    Article  PubMed  Google Scholar 

  128. Raber, I. et al. The rise and fall of aspirin in the primary prevention of cardiovascular disease. Lancet 393, 2155–2167 (2019).

    Article  PubMed  Google Scholar 

  129. Betsholtz, C. et al. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature 320, 695–699 (1986).

    Article  CAS  PubMed  Google Scholar 

  130. Chow, C. K. et al. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 121, 750–758 (2010).

    Article  PubMed  Google Scholar 

  131. Law, M. R., Morris, J. K. & Wald, N. J. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 338, b1665 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Duckworth, W. et al. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360, 129–139 (2009).

    Article  CAS  PubMed  Google Scholar 

  133. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).

    Article  CAS  Google Scholar 

  134. Collins, R. et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388, 2532–2561 (2016).

    Article  CAS  PubMed  Google Scholar 

  135. Ridker, P. M. What works and in whom? A simple, easily applied, evidence-based approach to guidelines for statin therapy. Circ. Cardiovasc. Qual. Outcomes. 5, 592–593 (2012).

    Article  PubMed  Google Scholar 

  136. Ridker P. M., Libby P. and Buring J. E. in Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 10th Edition (ed. Braunwald, E.) 891–933 (Saunders, 2014).

  137. Grundy, S. M. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 139, e1082–e1143 (2019).

    PubMed  Google Scholar 

  138. Di Angelantonio, E. et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302, 1993–2000 (2009).

    Article  PubMed  Google Scholar 

  139. Saely, C. H., Rein, P. & Drexel, H. Combination lipid therapy in type 2 diabetes. N. Engl. J. Med. 363, 692 (2010). author reply 694–695.

    Article  Google Scholar 

  140. Department of Health and Human Services. Food and Drug Aministration. AbbVie Inc. et al. Withdrawal of approval of indications related to the coadministration with statins in applications for niacin extended-release tablets and fenofibric acid delayed-release capsules. Fed. Regist. 81, 22612–22613 (2016).

    Google Scholar 

  141. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).

    Article  CAS  Google Scholar 

  142. Stone, N. J. et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129, S1–S45 (2014).

    Article  PubMed  Google Scholar 

  143. [No authors listed].The Lipid Research Clinics Coronary Primary Prevention Trial results II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251, 365–374 (1984).

    Article  Google Scholar 

  144. Hammersley, D. & Signy, M. Ezetimibe: an update on its clinical usefulness in specific patient groups. Ther. Adv. Chronic Dis. 8, 4–11 (2017).

    Article  CAS  PubMed  Google Scholar 

  145. Cannon, C. P. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372, 2387–2397 (2015).

    Article  CAS  PubMed  Google Scholar 

  146. Robinson, J. G. et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1489–1499 (2015).

    Article  CAS  PubMed  Google Scholar 

  147. Sabatine, M. S. et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1500–1509 (2015).

    Article  CAS  PubMed  Google Scholar 

  148. Nicholls, S. J. et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV Randomized Clinical Trial. JAMA 316, 2373–2384 (2016).

    Article  CAS  PubMed  Google Scholar 

  149. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376, 1713–1722 (2017).

    Article  CAS  PubMed  Google Scholar 

  150. Ridker, P. M. et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N. Engl. J. Med. 376, 1527–1539 (2017).

    Article  CAS  PubMed  Google Scholar 

  151. Ray, K. K. et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N. Engl. J. Med. 376, 1430–1440 (2017).

    Article  CAS  PubMed  Google Scholar 

  152. Giugliano, R. P. et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 390, 1962–1971 (2017).

    Article  CAS  PubMed  Google Scholar 

  153. Landmesser, U. et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur. Heart J. 38, 2245–2255 (2017). A masterful review of an important innovation in anti-atherosclerotic therapy with an emphasis on its practical application.

    CAS  PubMed  Google Scholar 

  154. Annemans, L., Packard, C. J., Briggs, A. & Ray, K. K. ‘Highest risk-highest benefit’ strategy: a pragmatic, cost-effective approach to _targeting use of PCSK9 inhibitor therapies. Eur. Heart J. 39, 2546–2550 (2018).

    Article  PubMed  Google Scholar 

  155. Sabatine, M. S. et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease. Circulation 138, 756–766 (2018).

    Article  CAS  PubMed  Google Scholar 

  156. Bhatt, D. L. et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N. Engl. J. Med. 380, 11–22 (2018).

    Article  PubMed  Google Scholar 

  157. Antithrombotic Trialists’ Collaboration Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324, 71–86 (2002).

    Article  Google Scholar 

  158. Zheng, S. L. & Roddick, A. J. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA 321, 277–287 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Roffi, M. et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting Without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur. Heart J. 37, 267–315 (2016).

    Article  CAS  PubMed  Google Scholar 

  160. Ridker, P. M. et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390, 1833–1842 (2017).

    Article  CAS  PubMed  Google Scholar 

  161. Bevilacqua, M. P., Pober, J. S., Majeau, G. R., Cotran, R. S. & Gimbrone, M. A. Jr. Interleukin-1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes and related leukocyte cell lines. J. Clin. Invest. 76, 2003–2011 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Ridker, P. M. et al. Low-dose methotrexate for the prevention of atherosclerotic events. N. Engl. J. Med. 380, 752–762 (2019).

    Article  CAS  PubMed  Google Scholar 

  163. Nissen S. E. et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N. Engl. J. Med. 375, 2519–2529 (2016).

  164. Ricciotti, E. & FitzGerald, G. A. Prostaglandins and inflammation. Arterioscler. Thromb. Vasc. Biol. 31, 986–1000 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Benner JS, G. R., Mogun, H., Neumann, P. J., Weinstein, M. C. & Avorn, J. Long-term persistence in use of statin therapy in elderly patients. JAMA 288, 455–461 (2002).

    Article  PubMed  Google Scholar 

  166. Kim, M. C. et al. Impact of postdischarge statin withdrawal on long-term outcomes in patients with acute myocardial infarction. Am. J. Cardiol. 115, 1–7 (2015).

    Article  PubMed  Google Scholar 

  167. Zhang, H., Plutzky, J., Shubina, M. & Turchin, A. Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study. Ann. Intern. Med. 167, 221–227 (2017).

    Article  PubMed  Google Scholar 

  168. Stroes, E. S. et al. Statin-associated muscle symptoms: impact on statin therapy–European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur. Heart J. 36, 1012–1022 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Newman, C. B. et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler. Thromb. Vasc. Biol. 39, e38–e81 (2019).

    Article  CAS  PubMed  Google Scholar 

  170. Vaishnava, P. & Lewis, E. F. Assessment of quality of life in severe heart failure. Curr. Heart Fail. Rep. 4, 170–177 (2007).

    Article  PubMed  Google Scholar 

  171. Mark, D. B. Assessing quality-of-life outcomes in cardiovascular clinical research. Nat. Rev. Cardiol. 13, 286–308 (2016).

    Article  PubMed  Google Scholar 

  172. Muhammad, I., He, H. G., Kowitlawakul, Y. & Wang, W. Narrative review of health-related quality of life and its predictors among patients with coronary heart disease. Int. J. Nurs. Pract. 22, 4–14 (2016).

    Article  PubMed  Google Scholar 

  173. Lewis, E. F. et al. Impact of cardiovascular events on change in quality of life and utilities in patients after myocardial infarction: a VALIANT study (valsartan in acute myocardial infarction). JACC Heart Fail. 2, 159–165 (2014).

    Article  PubMed  Google Scholar 

  174. Thomas, S. B. et al. Racial differences in the association between self-rated health status and objective clinical measures among participants in the BARI 2D trial. Am. J. Public Health 100 (Suppl. 1), S269–S276 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Sajobi, T. T. et al. Trajectories of health-related quality of life in coronary artery disease. Circ. Cardiovasc. Qual. Outcomes 11, e003661 (2018).

    Article  PubMed  Google Scholar 

  176. De Smedt, D. et al. Validity and reliability of three commonly used quality of life measures in a large European population of coronary heart disease patients. Int. J. Cardiol. 167, 2294–2299 (2013).

    Article  PubMed  Google Scholar 

  177. Hlatky, M. A. et al. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am. J. Cardiol. 64, 651–654 (1989).

    Article  CAS  PubMed  Google Scholar 

  178. Kroenke, K., Spitzer, R. L. & Williams, J. B. The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern. Med. 16, 606–613 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Kulik, A. Quality of life after coronary artery bypass graft surgery versus percutaneous coronary intervention: what do the trials tell us? Curr. Opin. Cardiol. 32, 707–714 (2017).

    Article  PubMed  Google Scholar 

  180. Gomes-Neto, M. et al. High-intensity interval training versus moderate-intensity continuous training on exercise capacity and quality of life in patients with coronary artery disease: a systematic review and meta-analysis. Eur. J. Prev. Cardiol. 24, 1696–1707 (2017).

    Article  PubMed  Google Scholar 

  181. Allen, J. K. & Dennison, C. R. Randomized trials of nursing interventions for secondary prevention in patients with coronary artery disease and heart failure: systematic review. J. Cardiovasc. Nurs. 25, 207–220 (2010).

    Article  PubMed  Google Scholar 

  182. De Smedt, D. et al. The association between self-reported lifestyle changes and health-related quality of life in coronary patients: the EUROASPIRE III survey. Eur. J. Prev. Cardiol. 21, 796–805 (2014).

    Article  PubMed  Google Scholar 

  183. Thomas L. The Lives of a Cell. New York: Penguin Books; 1974: 31–36.

  184. Libby, P., Pasterkamp, G., Crea, F. & Jang, I. K. Reassessing the mechanisms of acute coronary syndromes. Circ. Res. 124, 150–160 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Peter Libby & Eldrin F. Lewis

  2. Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Julie E. Buring

  3. Centre d’Investigació Cardiovascular CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Lina Badimon

  4. Center for Molecular Medicine, Karolinska Universitetssjukhuset, Stockholm, Sweden

    Göran K. Hansson

  5. Institute of Cardiovascular Sciences, University College London, London, UK

    John Deanfield

  6. Center for Clinical and Epidemiological Research, University Hospital, University of São Paulo, São Paulo, Brazil

    Márcio Sommer Bittencourt

  7. Faculdade Israelita de Ciencias da Saude Albert Einstein, São Paulo, Brazil

    Márcio Sommer Bittencourt

  8. DASA, São Paulo, Brazil

    Márcio Sommer Bittencourt

  9. Hacettepe University, Ankara, Turkey

    Lale Tokgözoğlu

Authors
  1. Peter Libby
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julie E. Buring
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lina Badimon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Göran K. Hansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Deanfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Márcio Sommer Bittencourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lale Tokgözoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eldrin F. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.).

Corresponding author

Correspondence to Peter Libby.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Libby, P., Buring, J.E., Badimon, L. et al. Atherosclerosis. Nat Rev Dis Primers 5, 56 (2019). https://doi.org/10.1038/s41572-019-0106-z

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-019-0106-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing
  NODES
admin 2
Association 17
chat 1
Idea 1
idea 1
innovation 1
INTERN 5
Project 1
twitter 1