Major adverse cardiovascular events

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.{{cite journal | vauthors=de Jong M, van der Worp HB, van der Graaf Y, Visseren FL, Westerink J | title=Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials | journal= Cardiovascular Diabetology | volume=16 | issue=1 | pages=134 | year=2017 | doi= 10.1186/s12933-017-0617-4 | pmc=5644073 | pmid = 29037211 | doi-access=free }}{{cite journal |vauthors=Arnott C, Li Q, Kang A, Neuen BL, Bompoint S, Lam CS, Rodgers A, Mahaffey KW, Cannon CP, Perkovic V, Jardine MJ, Neal B | title=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= Journal of the American Heart Association | volume=9 | issue=3 | pages=e014908 | year=2020 | doi= 10.1161/JAHA.119.014908 | pmc=7033896 | pmid = 31992158 }} Another study similarly defined MACE as a composite of nonfatal stroke, nonfatal acute coronary syndrome, and death from vascular causes.{{cite journal |vauthors=Neal B, Wu Y, Feng X, Elliott P | title=Effect of Salt Substitution on Cardiovascular Events and Death| journal= The New England Journal of Medicine | volume=185 | issue=12 | pages=1067-1077 | year=2021 | doi= 10.1056/NEJMoa2105675 | pmid = 34459569 | hdl=1959.4/unsworks_77679 | hdl-access=free }} But another study defines MACE as "CVD events, admission for HF (heart failure), ischemic cardiovascular [CV] events, cardiac death".{{cite journal | vauthors=Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L | title=Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies | journal= Journal of the American Heart Association | volume=6 | issue=7 | pages=e004947 | year=2017 | doi= 10.1161/JAHA.116.004947 | pmc=5586261 | pmid = 28663251 }} Yet another study defined MACE as "CV death, hospitalization for HF, or myocardial infarction (MI)".{{cite journal | vauthors=Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM | title=Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease | journal=PLOS One | volume=13 | issue=6 | pages=e0198144 | year=2018 | doi = 10.1371/journal.pone.0198144 | pmc=5999069 | pmid=29897923| bibcode=2018PLoSO..1398144R | doi-access=free }}

The heterogeneity of the sets defining MACE, hampering systematic reviews and meta-analyses, has been repeatedly criticized.{{cite journal |last1=Poudel |first1=I |last2=Tejpal |first2=C |last3=Rashid |first3=H |last4=Jahan |first4=N |title=Major Adverse Cardiovascular Events: An Inevitable Outcome of ST-elevation myocardial infarction? A Literature Review. |journal=Cureus |date=30 July 2019 |volume=11 |issue=7 |pages=e5280 |doi=10.7759/cureus.5280 |doi-access=free |pmid=31423405|pmc=6695291 |s2cid=201040946 }}{{cite journal |last1=Bonsu |first1=JM |last2=Guha |first2=A |last3=Charles |first3=L |last4=Yildiz |first4=VO |last5=Wei |first5=L |last6=Baker |first6=B |last7=Brammer |first7=JE |last8=Awan |first8=F |last9=Lustberg |first9=M |last10=Reinbolt |first10=R |last11=Miller |first11=ED |last12=Jneid |first12=H |last13=Ruz |first13=P |last14=Carter |first14=RR |last15=Milks |first15=MW |last16=Paskett |first16=ED |last17=Addison |first17=D |title=Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies. |journal=Journal of the American College of Cardiology |date=18 February 2020 |volume=75 |issue=6 |pages=620–628 |doi=10.1016/j.jacc.2019.11.059 |pmid=32057377|pmc=7860639 }}{{cite journal |last1=Bosco |first1=E |last2=Hsueh |first2=L |last3=McConeghy |first3=KW |last4=Gravenstein |first4=S |last5=Saade |first5=E |title=Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review. |journal=BMC Medical Research Methodology |date=6 November 2021 |volume=21 |issue=1 |pages=241 |doi=10.1186/s12874-021-01440-5 |pmid=34742250|pmc=8571870 |s2cid=243767377 |doi-access=free }}

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,{{cite journal |last1=Robertson |first1=T |last2=Beveridge |first2=G |last3=Bromley |first3=C |title=Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey. |journal=PLOS ONE |date=2017 |volume=12 |issue=8 |pages=e0183297 |doi=10.1371/journal.pone.0183297 |pmid=28813505 |pmc=5559080 |bibcode=2017PLoSO..1283297R |doi-access=free }} high-sensitivity C-reactive protein, d-dimer level,{{cite journal |last1=Zhao |first1=X |last2=Liu |first2=C |last3=Zhou |first3=P |last4=Sheng |first4=Z |last5=Li |first5=J |last6=Zhou |first6=J |last7=Chen |first7=R |last8=Wang |first8=Y |last9=Chen |first9=Y |last10=Song |first10=L |last11=Zhao |first11=H |last12=Yan |first12=H |title=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. |journal=Frontiers in Cardiovascular Medicine |date=2020 |volume=7 |pages=603621 |doi=10.3389/fcvm.2020.603621 |pmid=33330667 |pmc=7728669 |doi-access=free }} renal failure,{{cite journal |last1=Neumann |first1=Johannes T. |last2=Thao |first2=Le T. P. |last3=Callander |first3=Emily |last4=Chowdhury |first4=Enayet |last5=Williamson |first5=Jeff D. |last6=Nelson |first6=Mark R. |last7=Donnan |first7=Geoffrey |last8=Woods |first8=Robyn L. |last9=Reid |first9=Christopher M. |last10=Poppe |first10=Katrina K. |last11=Jackson |first11=Rod |last12=Tonkin |first12=Andrew M. |last13=McNeil |first13=John J. |title=Cardiovascular risk prediction in healthy older people |journal=GeroScience |date=February 2022 |volume=44 |issue=1 |pages=403–413 |doi=10.1007/s11357-021-00486-z |pmid=34762275|pmc=8810999 }} consumption of salt as sodium chloride, and altered thyroid function.{{cite journal |last1=Chaker |first1=L |last2=van den Berg |first2=ME |last3=Niemeijer |first3=MN |last4=Franco |first4=OH |last5=Dehghan |first5=A |last6=Hofman |first6=A |last7=Rijnbeek |first7=PR |last8=Deckers |first8=JW |last9=Eijgelsheim |first9=M |last10=Stricker |first10=BH |last11=Peeters |first11=RP |title=Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study. |journal=Circulation |date=6 September 2016 |volume=134 |issue=10 |pages=713–22 |doi=10.1161/CIRCULATIONAHA.115.020789 |pmid=27601558|s2cid=207711411 |doi-access=free }}{{cite journal |last1=Chaker |first1=L |last2=Baumgartner |first2=C |last3=den Elzen |first3=WP |last4=Collet |first4=TH |last5=Ikram |first5=MA |last6=Blum |first6=MR |last7=Dehghan |first7=A |last8=Drechsler |first8=C |last9=Luben |first9=RN |last10=Portegies |first10=ML |last11=Iervasi |first11=G |last12=Medici |first12=M |last13=Stott |first13=DJ |last14=Dullaart |first14=RP |last15=Ford |first15=I |last16=Bremner |first16=A |last17=Newman |first17=AB |last18=Wanner |first18=C |last19=Sgarbi |first19=JA |last20=Dörr |first20=M |last21=Longstreth WT |first21=Jr |last22=Psaty |first22=BM |last23=Ferrucci |first23=L |last24=Maciel |first24=RM |last25=Westendorp |first25=RG |last26=Jukema |first26=JW |last27=Ceresini |first27=G |last28=Imaizumi |first28=M |last29=Hofman |first29=A |last30=Bakker |first30=SJ |last31=Franklyn |first31=JA |last32=Khaw |first32=KT |last33=Bauer |first33=DC |last34=Walsh |first34=JP |last35=Razvi |first35=S |last36=Gussekloo |first36=J |last37=Völzke |first37=H |last38=Franco |first38=OH |last39=Cappola |first39=AR |last40=Rodondi |first40=N |last41=Peeters |first41=RP |last42=Thyroid Studies |first42=Collaboration |title=Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis. |journal=The Journal of Clinical Endocrinology and Metabolism |date=November 2016 |volume=101 |issue=11 |pages=4270–4282 |doi=10.1210/jc.2016-2255 |pmid=27603906|pmc=5095234 }}{{cite journal |last1=Müller |first1=P |last2=Dietrich |first2=JW |last3=Lin |first3=T |last4=Bejinariu |first4=A |last5=Binnebößel |first5=S |last6=Bergen |first6=F |last7=Schmidt |first7=J |last8=Müller |first8=SK |last9=Chatzitomaris |first9=A |last10=Kurt |first10=M |last11=Gerguri |first11=S |last12=Clasen |first12=L |last13=Klein |first13=HH |last14=Kelm |first14=M |last15=Makimoto |first15=H |title=Usefulness of Serum Free Thyroxine Concentration to Predict Ventricular Arrhythmia Risk in Euthyroid Patients With Structural Heart Disease. |journal=The American Journal of Cardiology |date=15 April 2020 |volume=125 |issue=8 |pages=1162–1169 |doi=10.1016/j.amjcard.2020.01.019 |pmid=32087999|s2cid=211261823 }}{{cite journal |last1=Müller |first1=P |last2=Leow |first2=MK |last3=Dietrich |first3=JW |title=Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence. |journal=Frontiers in Cardiovascular Medicine |date=2022 |volume=9 |pages=942971 |doi=10.3389/fcvm.2022.942971 |pmid=36046184 |pmc=9420854 |doi-access=free }}

Two reviews have concluded that SGLT2 inhibitors benefit patients with atherosclerotic MACE.{{cite journal | vauthors=Zelniker TA, Wiviott SD, abatine MS | title=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 | journal=The Lancet | volume=393 | issue=10166 | pages=31–39 | year=2019 | doi = 10.1016/S0140-6736(18)32590-X | pmid=30424892 | s2cid=53277899 }}{{cite journal | vauthors=Xu D, Chandler O, Xiao H | title=Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial? | journal=Frontiers in Medicine | volume=8 | pages=712671 | year=2021 | doi = 10.3389/fmed.2021.712671 | pmc=8419219 | pmid=34497814 | doi-access=free }} 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.{{cite journal | vauthors=Tippetts TS, Holland WL, Summers SA | title=Cholesterol - the devil you know; ceramide - the devil you don't | journal=Trends in Pharmacological Sciences | volume=42 | issue=12 | pages=1082–1095 | year=2021 | doi = 10.1016/j.tips.2021.10.001 | pmc=8595778 | pmid=34750017}}

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Category:Cardiovascular system