. 2023 Aug 18;17(2):426–447. doi: 10.1007/s12265-023-10425-2

Table 4.

Association between NETosis components and MACE in patients with ACS

Study	Population	Reporting of effect	Endpoint and follow-up	Univariate analysis		Multivariate analysis
Study	Population	Reporting of effect	Endpoint and follow-up	Unadjusted effect (95% CI)	p-value	Adjusted effect (95% CI)	p-value
dsDNA
Langseth et al. (2020) [38]	n = 956 patients with STEMI	² Grouped by median ³Grouped by highest quartile vs. others	All-cause death^† and composite of death, MI, stroke, hospitalisation due to HF, or revascularisation > 3 months at median 4.6 years^†	HR 3.36 (1.95–5.78)³; log rank²; 460 (407–508) vs. 411 (370–466) ng/mL^‡, all-cause death	< 0.001³; < 0.001²; < 0.001^‡	HR 2.28 (1.19–4.36)	0.013
Langseth et al. (2020) [38]	n = 956 patients with STEMI			Log rank²; 429 (317–481) vs. 412 (372–466) ng/mL^‡, MACE	0.052²; 0.255^‡	HR 2.06 (1.08-3.93)	0.029
Helseth et al. (2019) [37]	n = 251 STEMI patients treated with PCI	Grouped by median	Composite of all-cause mortality, MI, revascularisation ≥3 months, stroke, or hospitalisation due to HF at 1 year^†	HR 5.9 (1.7–20.3)	0.005	HR 6.7 (1.9–23.2)	0.003
Wang et al. (2018) [55]	n = 142 STEMI patients treated with PCI	Grouped by ROC threshold	All-cause^† and CV death^† & composite of death, ACS, PCI or CABG, or stroke at mean 24.5 months^†	Log rank², MACE	0.04	OR 7.43 (1.25–4.07), MACE	0.027
MPO-DNA
Hally et al. (2021) [41]	n = 100 patients with MI	² Grouped by median ^§Median z-score ^§§Median z-score with sP-selectin	Composite of CV death, non-fatal MI, or ischemic stroke at 1 year^†	OR 1.13 (0.7–1.83)²; OR 1.28 (0.72–2.1)^§; OR 1.86 (1.13–3.08)^§§	0.62; 0.33^§; 0.015^§§	No multivariate analysis
Hally et al. (2021) [41]	n = 100 patients with MI				0.62; 0.33^§; 0.015^§§	OR 1.94 (1.16–3.25)^§§	0.011
Langseth et al. (2020) [38]	n = 956 patients with STEMI	²Grouped by median	See Langseth et al. (2020)	Log rank²; 0.167 (0.14–0.25) vs. 0.18 (0.14–0.26) OD^‡, all-cause death	0.36²; 0.91^‡	No multivariate analysis
Langseth et al. (2020) [38]	n = 956 patients with STEMI	²Grouped by median	See Langseth et al. (2020)	Log rank²; 0.17 (0.14–0.24) vs. 0.18 (0.14–0.27) OD^‡, MACE	0.16²; 0.33^‡	No multivariate analysis
Helseth et al. (2019) [37]	n = 251 STEMI patients treated with PCI	Grouped by median	See Helseth et al. (2019)	HR NR	NS	No multivariate analysis
NE-DNA
Hally et al. (2021) [41]	n = 100 patients with MI	Grouped by median	See Hally et al. (2021)	OR 1.06 (0.66–1.72)	0.81	No multivariate analysis
Citrullinated histone 3
Hally et al. (2021) [41]	n = 100 patients with MI	Grouped by median	See Hally et al. (2021)	OR 1.43 (0.89–2.33)	0.14	No multivariate analysis
Langseth et al. (2020) [38]	n = 956 patients with STEMI	² Grouped by median	See Langseth et al. (2020)	Log rank²; 10.25 (4.96–17.32) vs. 9.07 (4.83–17.24) ng/mL^‡, all-cause death	0.092²; 0.6^‡	No multivariate analysis
Langseth et al. (2020) [38]	n = 956 patients with STEMI	² Grouped by median	See Langseth et al. (2020)	Log rank²; 92 (4.48–16.52) vs. 9.32 (4.91–17.30) ng/mL^‡, MACE	0.88²; 0.46^‡	No multivariate analysis

Abbreviations: BMI, body mass index; BNP, brain natriuretic protein; BP, blood pressure; CABG, coronary artery bypass graft; CAD, coronary artery disease; CitH3, citrullinated histone H3; H3(cit), see CitH3; CRP, C-reactive protein; cTnI, cardiac Troponin I; cTnT, cardiac Troponin T; CV, cardiovascular; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; FBG, fasting blood glucose; GOT, glutamic oxalacetic transaminase; GRACE, Global Registry of Acute Coronary Events; HF, heart failure; HFpEF, HF with preserved ejection fraction; HFrEF, HF with reduced ejection fraction; HR, hazard ratio; hsCRP, high-sensitivity CRP; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NE, neutrophil elastase; NGAL, neutrophil gelatinase-associated lipocalin; NR, not reported; NS, not significant (p < 0.05); OR, odds ratio; PCI, percutaneous coronary intervention; S, p-value is statistically significant (unspecified); SA, stable angina; 95% CI, 95% confidence interval; TIMI, Thrombolysis in Myocardial Infarction; WBC, white blood cell. ^†Indicates a primary endpoint; ^‡indicates concentration is represented as median (IQR) or mean ± SD for cases vs. controls, respectively; ¹denotes continuous variables assessed per unit change in concentration, as specified; ²denotes endpoints compared in patients stratified according to median biomarker concentration; ³denotes endpoints compared in patients stratified according to pre-specified categories of biomarker concentration. ^§Denotes effect size was calculated using the composite NET z-score (comprising z-scores of MPO-DNA% of NET standard, NE-DNA% of pooled serum standard and H3 (cit)% of NET standard) with platelet count; ^§§denotes effect parameter was calculated using composite NET z-score with platelet count and sP-selectin. Statistical significance was considered as two-tailed p ≤ 0.05 (bolded)