1 O'Gara, P. T. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 61, e78–e140 (2013).

2 Steg, P. G. et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur. Heart J. 33, 2569–2619 (2012).

3 Krumholz, H. M. et al. Reduction in acute myocardial infarction mortality in the United States: risk-standardized mortality rates from 1995–2006. JAMA 302, 767–773 (2009).

4 Larose, E. et al. Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction: traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance. J. Am. Coll. Cardiol. 55, 2459–2469 (2010).

5 Javadov, S. & Karmazyn, M. Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell. Physiol. Biochem. 20, 1–22 (2007).

6 Ibanez, B. et al. The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion. Int. J. Cardiol. 147, 428–432 (2011).

7 Murry, C. E., Jennings, R. B. & Reimer, K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124–1136 (1986).

8 Bøtker, H. E. et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375, 727–734 (2010).

9 Sloth, A. D. et al. Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur. Heart J. 35, 168–175 (2014).

10 Breivik, L., Helgeland, E., Aarnes, E. K., Mrdalj, J. & Jonassen, A. K. Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion. Basic Res. Cardiol. 106, 135–145 (2011).

11 Piot, C. et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N. Engl. J. Med. 359, 473–481 (2008).

12 US National Library of Medicine. ClinicalTrials.gov[online], (2014).

13 Opie, L. H. Metabolic management of acute myocardial infarction comes to the fore and extends beyond control of hyperglycemia. Circulation 117, 2172–2177 (2008).

14 Díaz, R. et al. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA 298, 2399–2405 (2007).

15 Selker, H. P. et al. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA 307, 1925–1933 (2012).

16 Chen, Z. et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 366, 1622–1632 (2005).

17 Ibanez, B. et al. Early metoprolol administration before coronary reperfusion results in increased myocardial salvage analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation 115, 2909–2916 (2007).

18 Ibanez, B. et al. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation 128, 1495–1503 (2013).

19 Lunar, I. G. et al. Pre-reperfusion metoprolol administration diminishes CMR-quantified microvascular obstruction in STEMI patients undergoing PCI: role of neutrophil-platelet coaggregates inhibition [abstract]. J. Am. Coll. Cardiol. 63 (Suppl.), A35 (2014).

20 Pizarro, G. et al. Long term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial. J. Am. Coll. Cardiol. 63, 2356–2362 (2014).

21 Aragón, J. P. et al. Beta3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation. J. Am. Coll. Cardiol. 58, 2683–2691 (2011).

22 Passamani, E., Davis, K. B., Gillespie, M. J. & Killip, T. A randomized trial of coronary artery bypass surgery. Survival of patients with a low ejection fraction. N. Engl. J. Med. 312, 1665–1671 (1985).

23 Detre, K. M., Takaro, T., Hultgren, H. & Peduzzi, P. Long-term mortality and morbidity results of the Veterans Administration randomized trial of coronary artery bypass surgery. Circulation 72, V84–V89 (1985).

24 Varnauskas, E. Survival, myocardial infarction, and employment status in a prospective randomized study of coronary bypass surgery. Circulation 72, V90–V101 (1985).

25 Kovacic, J. C., Castellano, J. M. & Fuster, V. Cardiovascular defense challenges at the basic, clinical, and population levels. Ann. N. Y. Acad. Sci. 1254, 1–6 (2012).

26 Serruys, P. W. et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N. Engl. J. Med. 360, 961–972 (2009).

27 Mohr, F. W. et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 381, 629–638 (2013).

28 Tonino, P. A. et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N. Engl. J. Med. 360, 213–224 (2009).

29 Farkouh, M. E. et al. Strategies for multivessel revascularization in patients with diabetes. N. Engl. J. Med. 367, 2375–2384 (2012).

30 Magnuson, E. A. et al. Cost-effectiveness of percutaneous coronary intervention with drug eluting stents versus bypass surgery for patients with diabetes mellitus and multivessel coronary artery disease results from the FREEDOM trial. Circulation 127, 820–831 (2013).

31 Boden, W. E. et al. Optimal medical therapy with or without PCI for stable coronary disease. N. Engl. J. Med. 356, 1503–1516 (2007).

32 The BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N. Engl. J. Med. 360, 2503–2515 (2009).

33 Farkouh, M. E. et al. Risk factor control for coronary artery disease secondary prevention in large randomized trials. J. Am. Coll. Cardiol. 61, 1607–1615 (2013).

34 Gaur, S. et al. Reproducibility of invasively measured and non-invasively computed fractional flow reserve [abstract]. J. Am. Coll. Cardiol. 63 (Suppl.), A999 (2014).

35 Ahmadi, A. et al. Does prognosis change depending on number and composition of non obstructive plaques? Results from the multinational coronary CT angiography evaluation for clinical outcome: an international multicenter registry (CONFIRM) [abstract]. J. Am. Coll. Cardiol. 63 (Suppl.), A980 (2014).

36 Sanz, G. & Fuster, V. Prevention: Polypills for cardiovascular prevention: a step forward? Nat. Rev. Cardiol. 10, 683–684 (2013).

37 Yusuf, S. et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE study): a prospective epidemiological survey. Lancet 378, 1231–1243 (2011).

38 Bosworth, H. B. et al. Medication adherence: a call for action. Am. Heart J. 162, 412–424 (2011).

39 Epstein, R. S. Medication adherence: hope for improvement? Mayo Clinic Proc. 86, 268–270 (2011).

40 Wald, N. J. & Law, M. R. A strategy to reduce cardiovascular disease by more than 80%. BMJ 326, 1419 (2003).

41 Thom, S. et al. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA 310, 918–929 (2013).

42 Sanz, G. et al. The fixed-dose combination drug for secondary cardiovascular prevention project: improving equitable access and adherence to secondary cardiovascular prevention with a fixed-dose combination drug: study design and objectives. Am. Heart J. 162, 811.e1–817.e1 (2011).

43 Muntner, P. et al. Projected impact of polypill use among US adults: medication use, cardiovascular risk reduction, and side effects. Am. Heart J. 161, 719–725 (2011).

44 Yusuf, S. et al. Combination pharmacotherapy to prevent cardiovascular disease: present status and challenges. Eur. Heart J. 35, 353–364 (2014).

45 Andersen, H., Knudsen, L. & Hasenkam, J. Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur. Heart J. 13, 704–708 (1992).

46 Cribier, A. et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis first human case description. Circulation 106, 3006–3008 (2002).

47 Bourantas, C. V. & Serruys, P. W. Evolution of transcatheter aortic valve replacement. Circ. Res. 114, 1037–1051 (2014).

48 Leon, M. B. et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N. Engl. J. Med. 363, 1597–1607 (2010).

49 Popma, J. J. et al. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J. Am. Coll. Cardiol. 63, 1972–1981 (2014).

50 Smith, C. R. et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N. Engl. J. Med. 364, 2187–2198 (2011).

51 Adams, D. H. et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N. Engl. J. Med. 370, 1790–1798 (2014).

52 Grube, E., Sinning, J.-M. & Vahanian, A. The Year in Cardiology 2013: valvular heart disease (focus on catheter-based interventions). Eur. Heart J. 35, 490–495 (2014).

53 Alfieri, O. et al. The double-orifice technique in mitral valve repair: a simple solution for complex problems. J. Thorac. Cardiovasc. Surg. 122, 674–681 (2001).

54 Munkholm-Larsen, S. et al. A systematic review on the safety and efficacy of percutaneous edge-to-edge mitral valve repair with the MitraClip system for high surgical risk candidates. Heart 100, 473–478 (2013).

55 Feldman, T. et al. Percutaneous repair or surgery for mitral regurgitation. N. Engl. J. Med. 364, 1395–1406 (2011).

56 Mauri. et al. 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J. Am. Coll. Cardiol. 62, 317–328 (2013).

57 O'Gara, P., Calhoon, J., Moon, M. & Tommaso, C. Transcatheter therapies for mitral regurgitation: a professional society overview from the American College of Cardiology, the American Association for Thoracic Surgery, Society for Cardiovascular Angiography and Interventions Foundation, and the Society of Thoracic Surgeons. J. Thorac. Cardiovasc. Surg. 147, 837–849 (2014).

58 Fanning, J. P. et al. Characterization of neurological injury in transcatheter aortic valve implantation: how clear is the picture? Circulation 129, 504–515 (2014).

59 Van Belle, E. et al. Postprocedural aortic regurgitation in balloon-expandable and self-expandable transcatheter aortic valve replacement procedures: analysis of predictors and impact on long-term mortality: insights from the FRANCE2 registry. Circulation 129, 1415–1427 (2014).

60 Tuzcu, E. M. & Kapadia, S. R. Selection of valves for TAVR: is the CHOICE clear? JAMA 311, 1500–1502 (2014).

61 US National Library of Medicine. ClinicalTrials.gov[online], (2014).

62 US National Library of Medicine. ClinicalTrials.gov[online], (2014).

63 Mack, M. J. et al. The outcomes of transcatheter aortic valve replacement in patients with end-stage renal disease: a report from the STS/ACC TVT Registry [abstract]. J. Am. Coll. Cardiol. 63 (Suppl.), A1714 (2014).

64 US National Library of Medicine. ClinicalTrials.gov[online], (2014).

65 US National Library of Medicine. ClinicalTrials.gov[online], (2014).

66 Chugh, S. S., Roth, G. A., Gillum, R. F. & Mensah, G. A. Global burden of atrial fibrillation in developed and developing bations. Global Heart 9, 113–119 (2014).

67 January, C. et al. AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation http://dx.doi.org/10.1161/CIR.0000000000000041.

68 Kirchhof, P. et al. Atrial fibrillation guidelines across the Atlantic: a comparison of the current recommendations of the European Society of Cardiology/European Heart Rhythm Association/European Association of Cardiothoracic Surgeons, the American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society, and the Canadian Cardiovascular Society. Eur. Heart J. 34, 1471–1474 (2013).

69 Magnani, J. W. et al. Genetic loci associated with atrial fibrillation: relation to left atrial structure in the Framingham Heart Study. J. Am. Heart Assoc. 3, e000616 (2014).

70 Lubitz, S. A. et al. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese. J. Am. Coll. Cardiol. 63, 1200–1210 (2014).

71 Nakanishi, K. et al. Peri-atrial epicardial adipose tissue is associated with new-onset nonvalvular atrial fibrillation. Circ. J. 76, 2748–2754 (2011).

72 Abed, H. S. et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA 310, 2050–2060 (2013).

73 Kottkamp, H. Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy. Eur. Heart J. 34, 2731–2738 (2013).

74 Yoon, J. H. et al. Left atrial function assessed by Doppler echocardiography rather than left atrial volume predicts recurrence in patients with paroxysmal atrial fibrillation. Clin. Cardiol. 36, 235–240 (2013).

75 Russo, C. et al. LA volumes and reservoir function are associated with subclinical cerebrovascular disease: the CABL (Cardiovascular Abnormalities and Brain Lesions) study. JACC Cardiovasc. Imaging 6, 313–323 (2013).

76 Gaita, F. et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J. Am. Coll. Cardiol. 62, 1990–1997 (2013).

77 Di Biase, L. et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J. Am. Coll. Cardiol. 60, 531–538 (2012).

78 Lee, J. M. et al. Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation. Am. J. Cardiol. 113, 963–969 (2014).

79 Moran, A. E., Roth, G. A., Narula, J. & Mensah, G. A. 1990–2010 global cardiovascular disease atlas. Global Heart 9, 3–16 (2014).

80 Go, A. S. et al. Executive summary: Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129, 399–410 (2014).

81 Jaffe, M. G., Lee, G. A., Young, J. D., Sidney, S. & Go, A. S. Improved blood pressure control associated with a large-scale hypertension program. JAMA 310, 699–705 (2013).

82 Centers for Disease Control and Prevention. Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003–2010. MMWR Morb. Mortal. Wkly Rep. 61, 703–709 (2012).

83 James, P. A. et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311, 507–520 (2014).

84 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 http://dx.doi.org/10.1161/01.cir.0000437738.63853.7a.

85 Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8, 445–544 (2012).

86 Mancia, G. et al. 2013 practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J. Hypertens. 31, 1925–1938 (2013).

87 Wright, J. T. Jr, Fine, L. J., Lackland, D. T., Ogedegbe, G. & Dennison Himmelfarb, C. R. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann. Intern. Med. 160, 499–503 (2014).

88 Peterson, E. D., Gaziano, J. M. & Greenland, P. Recommendations for treating hypertension what are the right goals and purposes? JAMA 311, 474–476 (2013).

89 Cook, N., Appel, L. J. & Whelton, P. K. Lower levels of sodium intake and reduced cardiovascular risk. Circulation 129, 981–989 (2014).

90 Aburto, N. J. et al. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ 346, f1326 (2013).

91 Fuster, V. & Kelly, B. B. (Eds) Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health (National Academies Press, 2010).

92 Appel, L. J. et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke a call to action from the American Heart Association. Circulation 123, 1138–1143 (2011).

93 Mozaffarian, D. & Ludwig, D. S. Dietary guidelines in the 21st century—a time for food. JAMA 304, 681–682 (2010).

94 Cogswell, M. E. et al. Sodium and potassium intakes among US adults: NHANES 2003–2008. Am. J. Clin. Nutr. 96, 647–657 (2012).

95 Beaglehole, R. et al. Priority actions for the non-communicable disease crisis. Lancet 377, 1438–1447 (2011).

96 He, F. J., Brinsden, H. C. & MacGregor, G. A. Salt reduction in the United Kingdom: a successful experiment in public health. J. Hum. Hypertens. 28, 345–352 (2013).

97 Wyness, L. A., Butriss, J. L. & Stanner, S. A. Reducing the population's sodium intake: the UK Food Standards Agency's salt reduction programme. Public Health Nutr. 15, 254–261 (2012).

98 Papademetriou, V., Rashidi, A. A., Tsioufis, C. & Doumas, M. Renal nerve ablation for resistant hypertension: how did we get here, present status, and future directions. Circulation 129, 1440–1451 (2014).

99 Schmieder, R. E. et al. Updated ESH position paper on interventional therapy of resistant hypertension. EuroIntervention 9 (Suppl. R), R58–R66 (2013).

100 Mahfoud, F. et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur. Heart J. 34, 2149–2157 (2013).

101 Bhatt, D. L. et al. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 370, 1393–1401 (2014).

102 Seidah, N. G., Awan, Z., Chrétien, M. & Mbikay, M. PCSK9: a key modulator of cardiovascular health. Circ. Res. 114, 1022–1036 (2014).

103 Gutierrez, M. J. et al. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler. Thromb. Vasc. Biol. 34, 676–683 (2014).

104 Nissen, S. E. et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290, 2292–2300 (2003).

105 Diditchenko, S. et al. Novel formulation of a reconstituted high-density lipoprotein (CSL112) dramatically enhances ABCA1-dependent cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. 33, 2202–2211 (2013).

106 Waksman, R. et al. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high density lipoprotein plasma infusions in patients with acute coronary syndrome. J. Am. Coll. Cardiol. 55, 2727–2735 (2010).

107 Dadu, R. T. & Ballantyne, C. M. Lipid lowering with PCSK9 inhibitors. Nat. Rev. Cardiol. 11, 563–575 (2014).

108 Selvin, E., Parrinello, C. M., Sacks, D. B. & Coresh, J. Trends in prevalence and control of diabetes in the United States, 1988–1994 and 1999–2010. Ann. Intern. Med. 160, 517–525 (2014).

109 Gregg, E. W. et al. Changes in diabetes-related complications in the United States, 1990–2010. N. Engl. J. Med. 370, 1514–1523 (2014).

110 Schauer, P. R. et al. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N. Engl. J. Med. 370, 2002–2013 (2014).

111 Loy, C. T., Schofield, P. R., Turner, A. M. & Kwok, J. B. Genetics of dementia. Lancet 383, 828–840 (2013).

112 Kovacic, J. C. & Fuster, V. Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease. Mt Sinai J. Med. 79, 664–673 (2012).

113 Launer, L. J., Hughes, T. M. & White, L. R. Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann. Neurol. 70, 774–780 (2011).

114 Toledo, J. B. et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain 136, 2697–2706 (2013).

115 Qureshi, A. I. & Caplan, L. R. Intracranial atherosclerosis. Lancet 383, 984–998 (2014).

116 Hassell, M. E. et al. Silent cerebral infarcts associated with cardiac disease and procedures. Nat. Rev. Cardiol. 10, 696–706 (2013).

117 Russo, C. et al. Subclinical left ventricular dysfunction and silent cerebrovascular disease: the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Circulation 128, 1105–1111 (2013).

118 Yaffe, K. et al. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation 129, 1560–1567 (2014).

119 Larson, E. B., Yaffe, K. & Langa, K. M. New insights into the dementia epidemic. N. Engl. J. Med. 369, 2275–2277 (2013).

120 Kovacic, J. C., Moreno, P., Nabel, E. G., Hachinski, V. & Fuster, V. Cellular senescence, vascular disease, and aging: part 2 of a 2-part review: clinical vascular disease in the elderly. Circulation 123, 1900–1910 (2011).

121 Afilalo, J. et al. Frailty assessment in the cardiovascular care of older adults. J. Am. Coll. Cardiol. 63, 747–762 (2013).

122 Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966–972 (2013).

123 Fyhrquist, F., Saijonmaa, O. & Strandberg, T. The roles of senescence and telomere shortening in cardiovascular disease. Nat. Rev. Cardiol. 10, 274–283 (2013).

124 Mapstone, M. et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat. Med. 20, 415–418 (2014).

125 Céspedes, J. et al. Promotion of cardiovascular health in preschool children: 36-month cohort follow-up. Am. J. Med. 126, 1122–1126 (2013).

126 WHO. Noncommunicable diseases and mental health. Global status report on noncommunicable diseases 2010 [online], (WHO, 2011).

127 Cannon, B. Cardiovascular disease: biochemistry to behaviour. Nature 493, S2–S3 (2013).

128 Fuster, V., Narula, J., Vedantahan, R. & Kelly, B. B. (eds) Promoting Cardiovascular Health Worldwide: Perspectives on the 12 Recommendations from the Institute of Medicine [online], (2014).

129 Jenks, S. Gene therapy death—“everyone has to share in the guilt”. J. Natl Cancer Inst. 92, 98–100 (2000).

130 Grines, C. The AGENT clinical trials programme. Eur. Heart J. Suppl. 6, E18–E23 (2004).

131 Jessup, M. et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124, 304–313 (2011).

132 Greenberg, B. et al. Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease Phase 2b). JACC Heart Fail. 2, 84–92 (2014).

133 Perin, E. C. et al. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA 307, 1717–1726 (2012).

134 Traverse, J. H. et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA 306, 2110–2119 (2011).

135 Traverse, J. H. et al. Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA 308, 2380–2389 (2012).

136 Sheridan, C. Amgen announces oncolytic virus shrinks tumors. Nat. Biotech. 31, 471–472 (2013).

137 Delewi, R. et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a meta-analysis of randomised controlled clinical trials. Heart 99, 225–232 (2013).

138 Jeevanantham, V. et al. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters a systematic review and meta-analysis. Circulation 126, 551–568 (2012).

139 Bolli, R. et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378, 1847–1857 (2011).

140 Hare, J. M. et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308, 2369–2379 (2012).

141 Makkar, R. R. et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 379, 895–904 (2012).

142 Yaniz-Galende, E. et al. Stem cell factor gene transfer promotes cardiac repair after myocardial infarction via in situ recruitment and expansion of c-kit+ cells. Circ. Res. 111, 1434–1445 (2012).

143 Nagata, N. & Yamanaka, S. Perspectives for induced pluripotent stem cell technology: new insights into human physiology involved in somatic mosaicism. Circ. Res. 114, 505–510 (2014).