Major adverse cardiovascular events explained

Major adverse cardiovascular events (MACE, or major adverse cardiac events) is a composite endpoint frequently used in cardiovascular research.[1] [2] Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult.[3]

Definition

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.[4] [5] But another study defines MACE as "CVD events, admission for HF (Heart Failure), ischemic cardiovascular [CV] events, cardiac death, or MACE".[6] Yet another study defined MACE as "CV death, hospitalization for HF, or myocardial infarction (MI)".[7]

The heterogeneity of the sets defining MACE, hampering systematic reviews and meta-analyses, has been repeatedly criticized.[8] [9] [10]

Risk factors for MACE

Which conditions are risk factors for MACE depends on some characteristics of the investigated cohort. Established risk indicators in the general population include age, pre-existing cardiovascular disease, smoking, diabetes mellitus, elevated concentrations of triglycerides and non-HDL cholesterol concentration, reduced HDL concentration and hypertension, as, e. g., demonstrated by the Framingham Heart Study. More recently, additional risk indicators have been identified, e. g. type 2 allostatic load,[11] high-sensitivity C-reactive protein, d-dimer level,[12] renal failure[13] and altered thyroid function.[14] [15] [16] [17]

Therapeutic interventions

Two reviews have concluded that SGLT2 inhibitors benefit patients with atherosclerotic MACE.[18] [19] One of those studies defined MACE as the composite of myocardial infarction, stroke, or cardiovascular death. Other studies have shown MACE to be potently predicted by levels of ceramide found in patients.[20]

Notes and References

  1. Bonora BM, Avogaro A, Fadini GP . Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence . . 13 . 161–174 . 2020 . 10.2147/DMSO.S233538 . 6982447 . 32021362 . free .
  2. Chong WH, Yanoff LB, Andraca-Carrera E, Hai MT . Assessing the Safety of Glucose-Lowering Drugs - A New Focus for the FDA . . 383 . 13 . 1199–1202 . 2020 . 10.1056/NEJMp2004889 . 32966719. 221888300 .
  3. Kip KE, Hollabaugh K, Marroquin OC, Williams DO . The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention . . 51 . 7 . 701–707 . 2008 . 10.1016/j.jacc.2007.10.034 . 18279733 . free .
  4. de Jong M, van der Worp HB, van der Graaf Y, Visseren FL, Westerink J . Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials . . 16 . 1 . 134 . 2017 . 10.1186/s12933-017-0617-4 . 5644073 . 29037211 . free .
  5. Arnott C, Li Q, Kang A, Neuen BL, Bompoint S, Lam CS, Rodgers A, Mahaffey KW, Cannon CP, Perkovic V, Jardine MJ, Neal B . Sodium-Glucose Cotransporter 2 Inhibition for the Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis . . 9 . 3 . e014908 . 2020 . 10.1161/JAHA.119.014908 . 7033896 . 31992158 .
  6. Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L . Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies . . 6 . 7 . e004947 . 2017 . 10.1161/JAHA.116.004947 . 5586261 . 28663251 .
  7. Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM . Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease . . 13 . 6 . e0198144 . 2018 . 10.1371/journal.pone.0198144 . 5999069 . 29897923. 2018PLoSO..1398144R . free .
  8. Poudel . I . Tejpal . C . Rashid . H . Jahan . N . Major Adverse Cardiovascular Events: An Inevitable Outcome of ST-elevation myocardial infarction? A Literature Review. . Cureus . 30 July 2019 . 11 . 7 . e5280 . 10.7759/cureus.5280 . free . 31423405. 6695291 . 201040946 .
  9. Bonsu . JM . Guha . A . Charles . L . Yildiz . VO . Wei . L . Baker . B . Brammer . JE . Awan . F . Lustberg . M . Reinbolt . R . Miller . ED . Jneid . H . Ruz . P . Carter . RR . Milks . MW . Paskett . ED . Addison . D . Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies. . Journal of the American College of Cardiology . 18 February 2020 . 75 . 6 . 620–628 . 10.1016/j.jacc.2019.11.059 . 32057377. 7860639 .
  10. Bosco . E . Hsueh . L . McConeghy . KW . Gravenstein . S . Saade . E . Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review. . BMC Medical Research Methodology . 6 November 2021 . 21 . 1 . 241 . 10.1186/s12874-021-01440-5 . 34742250. 8571870 . 243767377 . free .
  11. Robertson . T . Beveridge . G . Bromley . C . Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey. . PLOS ONE . 2017 . 12 . 8 . e0183297 . 10.1371/journal.pone.0183297 . 28813505 . 5559080 . 2017PLoSO..1283297R . free .
  12. Zhao . X . Liu . C . Zhou . P . Sheng . Z . Li . J . Zhou . J . Chen . R . Wang . Y . Chen . Y . Song . L . Zhao . H . Yan . H . Estimation of Major Adverse Cardiovascular Events in Patients With Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Risk Prediction Score Model From a Derivation and Validation Study. . Frontiers in Cardiovascular Medicine . 2020 . 7 . 603621 . 10.3389/fcvm.2020.603621 . 33330667 . 7728669 . free .
  13. Neumann . Johannes T. . Thao . Le T. P. . Callander . Emily . Chowdhury . Enayet . Williamson . Jeff D. . Nelson . Mark R. . Donnan . Geoffrey . Woods . Robyn L. . Reid . Christopher M. . Poppe . Katrina K. . Jackson . Rod . Tonkin . Andrew M. . McNeil . John J. . Cardiovascular risk prediction in healthy older people . GeroScience . February 2022 . 44 . 1 . 403–413 . 10.1007/s11357-021-00486-z . 34762275. 8810999 .
  14. Chaker . L . van den Berg . ME . Niemeijer . MN . Franco . OH . Dehghan . A . Hofman . A . Rijnbeek . PR . Deckers . JW . Eijgelsheim . M . Stricker . BH . Peeters . RP . Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study. . Circulation . 6 September 2016 . 134 . 10 . 713–22 . 10.1161/CIRCULATIONAHA.115.020789 . 27601558. 207711411 . free .
  15. Chaker . L . Baumgartner . C . den Elzen . WP . Collet . TH . Ikram . MA . Blum . MR . Dehghan . A . Drechsler . C . Luben . RN . Portegies . ML . Iervasi . G . Medici . M . Stott . DJ . Dullaart . RP . Ford . I . Bremner . A . Newman . AB . Wanner . C . Sgarbi . JA . Dörr . M . Longstreth WT . Jr . Psaty . BM . Ferrucci . L . Maciel . RM . Westendorp . RG . Jukema . JW . Ceresini . G . Imaizumi . M . Hofman . A . Bakker . SJ . Franklyn . JA . Khaw . KT . Bauer . DC . Walsh . JP . Razvi . S . Gussekloo . J . Völzke . H . Franco . OH . Cappola . AR . Rodondi . N . Peeters . RP . Thyroid Studies . Collaboration . Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis. . The Journal of Clinical Endocrinology and Metabolism . November 2016 . 101 . 11 . 4270–4282 . 10.1210/jc.2016-2255 . 27603906. 5095234 .
  16. Müller . P . Dietrich . JW . Lin . T . Bejinariu . A . Binnebößel . S . Bergen . F . Schmidt . J . Müller . SK . Chatzitomaris . A . Kurt . M . Gerguri . S . Clasen . L . Klein . HH . Kelm . M . Makimoto . H . Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease. . The American Journal of Cardiology . 15 April 2020 . 125 . 8 . 1162–1169 . 10.1016/j.amjcard.2020.01.019 . 32087999. 211261823 .
  17. Müller . P . Leow . MK . Dietrich . JW . Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence. . Frontiers in Cardiovascular Medicine . 2022 . 9 . 942971 . 10.3389/fcvm.2022.942971 . 36046184 . 9420854 . free .
  18. Zelniker TA, Wiviott SD, abatine MS . SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials . . 393 . 10166 . 31–39 . 2019 . 10.1016/S0140-6736(18)32590-X . 30424892 . 53277899 .
  19. Xu D, Chandler O, Xiao H . Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial? . . 8 . 712671 . 2021 . 10.3389/fmed.2021.712671 . 8419219 . 34497814 . free .
  20. Tippetts TS, Holland WL, Summers SA . Cholesterol - the devil you know; ceramide - the devil you don't . . 42 . 12 . 1082–1095 . 2021 . 10.1016/j.tips.2021.10.001 . 8595778 . 34750017.

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