Concept used in cardiovascular research
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.
[18] Other studies have shown MACE to be potently predicted by levels of
ceramide found in patients.
[20]
References
^ Bonora BM, Avogaro A, Fadini GP (2020).
"Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence" .
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy . 13 : 161–174.
doi :
10.2147/DMSO.S233538 .
PMC
6982447 .
PMID
32021362 .
^ Chong WH, Yanoff LB, Andraca-Carrera E, Hai MT (2020). "Assessing the Safety of Glucose-Lowering Drugs - A New Focus for the FDA".
The New England Journal of Medicine . 383 (13): 1199–1202.
doi :
10.1056/NEJMp2004889 .
PMID
32966719 .
S2CID
221888300 .
^ Kip KE, Hollabaugh K, Marroquin OC, Williams DO (2008).
"The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention" .
Journal of the American College of Cardiology . 51 (7): 701–707.
doi :
10.1016/j.jacc.2007.10.034 .
PMID
18279733 .
^ de Jong M, van der Worp HB, van der Graaf Y, Visseren FL, Westerink J (2017).
"Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials" .
Cardiovascular Diabetology . 16 (1): 134.
doi :
10.1186/s12933-017-0617-4 .
PMC
5644073 .
PMID
29037211 .
^ Arnott C, Li Q, Kang A, Neuen BL, Bompoint S, Lam CS, Rodgers A, Mahaffey KW, Cannon CP, Perkovic V, Jardine MJ, Neal B (2020).
"Sodium-Glucose Cotransporter 2 Inhibition for the Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis" .
Journal of the American Heart Association . 9 (3): e014908.
doi :
10.1161/JAHA.119.014908 .
PMC
7033896 .
PMID
31992158 .
^ Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L (2017).
"Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies" .
Journal of the American Heart Association . 6 (7): e004947.
doi :
10.1161/JAHA.116.004947 .
PMC
5586261 .
PMID
28663251 .
^ Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM (2018).
"Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease" .
PLOS One . 13 (6): e0198144.
Bibcode :
2018PLoSO..1398144R .
doi :
10.1371/journal.pone.0198144 .
PMC
5999069 .
PMID
29897923 .
^ Poudel, I; Tejpal, C; Rashid, H; Jahan, N (30 July 2019).
"Major Adverse Cardiovascular Events: An Inevitable Outcome of ST-elevation myocardial infarction? A Literature Review" . Cureus . 11 (7): e5280.
doi :
10.7759/cureus.5280 .
PMC
6695291 .
PMID
31423405 .
S2CID
201040946 .
^ 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 (18 February 2020).
"Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies" . Journal of the American College of Cardiology . 75 (6): 620–628.
doi :
10.1016/j.jacc.2019.11.059 .
PMC
7860639 .
PMID
32057377 .
^ Bosco, E; Hsueh, L; McConeghy, KW; Gravenstein, S; Saade, E (6 November 2021).
"Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review" . BMC Medical Research Methodology . 21 (1): 241.
doi :
10.1186/s12874-021-01440-5 .
PMC
8571870 .
PMID
34742250 .
S2CID
243767377 .
^ Robertson, T; Beveridge, G; Bromley, C (2017).
"Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey" . PLOS ONE . 12 (8): e0183297.
Bibcode :
2017PLoSO..1283297R .
doi :
10.1371/journal.pone.0183297 .
PMC
5559080 .
PMID
28813505 .
^ Zhao, X; Liu, C; Zhou, P; Sheng, Z; Li, J; Zhou, J; Chen, R; Wang, Y; Chen, Y; Song, L; Zhao, H; Yan, H (2020).
"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 . 7 : 603621.
doi :
10.3389/fcvm.2020.603621 .
PMC
7728669 .
PMID
33330667 .
^ 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. (February 2022).
"Cardiovascular risk prediction in healthy older people" . GeroScience . 44 (1): 403–413.
doi :
10.1007/s11357-021-00486-z .
PMC
8810999 .
PMID
34762275 .
^ Chaker, L; van den Berg, ME; Niemeijer, MN; Franco, OH; Dehghan, A; Hofman, A; Rijnbeek, PR; Deckers, JW; Eijgelsheim, M; Stricker, BH; Peeters, RP (6 September 2016).
"Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study" . Circulation . 134 (10): 713–22.
doi :
10.1161/CIRCULATIONAHA.115.020789 .
PMID
27601558 .
S2CID
207711411 .
^ 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 (November 2016).
"Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis" . The Journal of Clinical Endocrinology and Metabolism . 101 (11): 4270–4282.
doi :
10.1210/jc.2016-2255 .
PMC
5095234 .
PMID
27603906 .
^ 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 (15 April 2020). "Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease". The American Journal of Cardiology . 125 (8): 1162–1169.
doi :
10.1016/j.amjcard.2020.01.019 .
PMID
32087999 .
S2CID
211261823 .
^ Müller, P; Leow, MK; Dietrich, JW (2022).
"Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence" . Frontiers in Cardiovascular Medicine . 9 : 942971.
doi :
10.3389/fcvm.2022.942971 .
PMC
9420854 .
PMID
36046184 .
^
a
b Zelniker TA, Wiviott SD, abatine MS (2019). "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".
The Lancet . 393 (10166): 31–39.
doi :
10.1016/S0140-6736(18)32590-X .
PMID
30424892 .
S2CID
53277899 .
^ Xu D, Chandler O, Xiao H (2021).
"Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?" .
Frontiers in Medicine . 8 : 712671.
doi :
10.3389/fmed.2021.712671 .
PMC
8419219 .
PMID
34497814 .
^ Tippetts TS, Holland WL, Summers SA (2021).
"Cholesterol - the devil you know; ceramide - the devil you don't" .
Trends in Pharmacological Sciences . 42 (12): 1082–1095.
doi :
10.1016/j.tips.2021.10.001 .
PMC
8595778 .
PMID
34750017 .