Predictors and Clinical Significance of Myocardial Injury in Elderly Patients Under the COVID-19 Pandemic

Figures & data

Table 1 Baseline Demographics and Clinical Characteristics According to Myocardial Injury

	Total (n=347)	Myocardial Injury (n=202)	Without Myocardial Injury (n=145)	p value
Age (years)	80.5 (66.8–89.3)	85.0 (78.3–89.0)	67.0 (65.0–76.0)	<0.001
Male	159 (45.8)	102 (50.5)	57 (39.3)	0.039
Body mass index	22.3 (20.3–25.3)	20.9 (19.5–23.8)	24.9 (21.5–27.0)	0.014
Hypertension	199 (57.3)	135 (66.8)	64 (44.1)	<0.001
Diabetes mellitus	76 (21.9)	52 (25.7)	24 (16.6)	0.041
Coronary artery disease	62 (17.9)	47 (23.3)	15 (10.3)	0.002
COPD	20 (5.8)	9 (4.5)	11 (7.6)	0.217
Oral antivirals	95 (27.4)	54 (26.7)	41 (28.3)	0.751
Hospitalization days	9 (6–13)	10 (6.5–14)	7 (6–12)	0.370
Vaccination
0	256 (73.8)	175 (86.6)	81 (55.9)	<0.001
1	3 (0.9)	1 (0.5)	2 (1.4)	0.574
2	34 (9.8)	12 (5.9)	22 (15.2)	0.033
Booster dose	54 (15.6)	14 (6.9)	40 (27.6)	<0.001
Disease severity status
Mild	265 (76.4)	143 (70.8)	122 (84.2)	0.043
Moderate	47 (13.5)	30 (14.9)	17 (11.7)	0.401
Severe	15 (4.3)	12 (5.9)	3 (2.1)	0.108
Critical	20 (5.8)	17 (8.4)	3 (2.1)	0.017
Creatinine (μmol/L)	71 (57–83)	78 (58–96)	68 (57–72)	<0.001
hs-CRP (mg/L)	7.3 (1.3–22.2)	10.5 (2.6–27.7)	2.6 (1.1–11.5)	<0.001
D-dimer (mg/L)	0.39 (0.74–2.51)	1.05 (0.57–5.42)	0.38 (0.24–0.72)	<0.001
White Blood Cell Count (x10^9/L)	5.3 (4.1–6.6)	5.1 (4.1–8.2)	5.4 (4.3–6.1)	0.196
Neutrophil /lymphocyte ratio (%)	2.3 (1.4–3.9)	3.2 (1.5–5.0)	2.0 (1.4–2.3)	<0.001
Platelet (x10^9/L)	211 (142–261)	209 (127–285)	213 (176–245)	0.231
Hemoglobin (g/L)	125 (110–133)	121 (104–132)	130 (120–139)	<0.001
Albumin (g/L)	38 (34–41)	34 (31–39)	40 (39–41)	<0.001
NT-proBNP (pg/mL)	195.5 (78.9–487.0)	449.0 (207.0–790.0)	57.1 (30.7–136.0)	<0.001
Cardiac troponin T (ng/mL)	0.021 (0.009–0.031)	0.029 (0.023–0.044)	0.007 (0.006–0.011)	<0.001
Cardiac Troponin T changes* (ng/mL)	0.010±0.077	0.017±0.101	0.001±0.005	0.668
Cardiac troponin T variation^# (%)	24.1±179.2	37.3±230.4	5.9±53.3	0.696
NYHA class III–IV	7 (2.0)	5 (2.4)	2 (1.3)	0.704
LMWH	69 (19.9)	45 (22.2)	24 (16.6)	0.188
Aspirin	102 (29.3)	68 (33.6)	34 (23.4)	0.039
Clopidogrel	84 (24.2)	57 (28.2)	27 (18.6)	0.040
OAC	21 (0.061)	16 (7.9)	5 (3.4)	0.085
HFNC/BiPAP	20 (5.8)	15 (7.4)	5 (3.4)	0.117
Invasive mechanical ventilation	7 (2.0)	7 (3.5)	0 (0.0)	0.024
ICU admission	19 (5.5)	16 (7.9)	3 (2.1)	0.018
Death	18 (5.2)	15 (7.4)	3 (2.1)	0.026

Notes: Data are shown as median (interquartile range), mean±standard deviation or n (%). *The highest absolute gap between the baseline and follow-up hs-cTnT values. ^#The ratio of cardiac troponin T changes to baseline values.

Abbreviations: BiPAP, bilevel non-invasive ventilation; COPD, chronic obstructive pulmonary disease; HFNC, high flow nasal cannulas; hs-CRP, high-sensitivity C-reactive protein; ICU, intensive care unit; LMWH, low molecular weight heparin; NYHA, New York Heart Association; NT-proBNP, N-terminal pro-B-type natriuretic peptide; OAC, oral anti-coagulation.

Table 2 Baseline Demographics and Clinical Characteristics According to Survival

	Total (n=347)	Non-Survivors (n=18)	Survivors (n=329)	p value
Age (years)	80.5 (66.8–89.3)	91.0 (79.5–95.5)	79.0 (66.0–88.0)	0.004
Male	159 (45.8)	8 (44.4)	151 (45.9)	0.904
Body mass index	22.3 (20.3–25.3)	19.5 (18.5–21.0)	22.6 (20.5–25.4)	0.058
Hypertension	199 (57.3)	10 (55.6)	189 (57.4)	0.874
Diabetes mellitus	76 (21.9)	6 (33.3)	70 (21.3)	0.228
Coronary artery disease	62 (17.9)	6 (33.3)	56 (17.0)	0.079
COPD	20 (5.8)	1 (5.6)	19 (5.8)	0.969
Use of oral antivirals	95 (27.4)	7 (38.9)	88 (26.7)	0.261
Hospitalization days	9 (6–13)	9 (4.5–12)	10 (6–13)	0.312
Vaccination
0	256 (73.8)	16 (88.9)	240 (72.9)	0.173
1	3 (0.9)	0 (0.0)	3 (0.9)	0.852
2	34 (9.8)	1 (5.6)	33 (10.0)	0.534
Booster dose	54 (15.6)	1 (5.6)	53 (16.1)	0.328
Disease severity status
Mild	265 (76.4)	1 (5.6)	264 (80.2)	<0.001
Moderate	47 (13.5)	1 (5.6)	46 (14.0)	0.486
Severe	15 (4.3)	2 (11.1)	13 (4.0)	0.179
Critical	20 (5.8)	14 (77.8)	6 (1.8)	<0.001
Creatinine (μmol/L)	71 (57–83)	145 (99–376)	71 (57–78)	0.007
hs-CRP (mg/L)	7.3 (1.3–22.2)	29.8 (16.2–150.8)	6.9 (1.2–21.0)	<0.001
D-dimer (mg/L)	0.39 (0.74–2.51)	12.54 (4.89–17.51)	0.63 (0.38–1.78)	<0.001
White Blood Cell Count (x10^9/L)	5.3 (4.1–6.6)	10.0 (6.35–12.9)	5.1 (4.1–6.4)	<0.001
Neutrophil /lymphocyte ratio (%)	2.3 (1.4–3.9)	13.7 (4.5–18.3)	2.1 (1.4–3.6)	<0.001
Platelet (x10^9/L)	211 (142–261)	128 (62–264)	213 (161–262)	0.026
Hemoglobin (g/L)	125 (110–133)	111 (101–149)	127 (110–133)	0.002
NT-proBNP (pg/mL)	195.5 (78.9–487.0)	2203.0 (931.0–15,100.0)	173.0 (53.7–424.0)	<0.001
Cardiac troponin T (ng/mL)	0.021 (0.009–0.031)	0.065 (0.061–0.185)	0.019 (0.008–0.029)	<0.001
Albumin (g/L)	38 (34–41)	31 (28–33)	39 (34–41)	<0.001
HFNC/BiPAP	20 (5.8)	14 (77.8)	6 (1.8)	<0.001
Invasive mechanical ventilation	7 (2.0)	1 (5.6)	6 (1.8)	0.314
ICU admission	19 (5.5)	8 (44.4)	11 (3.3)	<0.001

Note: Data are shown as median (interquartile range) or n (%).

Abbreviations: BiPAP, bilevel non-invasive ventilation; COPD, chronic obstructive pulmonary disease; HFNC, high flow nasal cannulas; hs-CRP, high-sensitivity C-reactive protein; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

Figure 1 Cardiac troponin values and odds ratio of mortality.

Notes: Distribution of hs-cTnT values in patients was colored in blue. Spline curve of the odds ratio of in-hospital death was plotted according to the values of hs-cTnT. Dashed black lines are 95% confidence intervals. Dashed grey line indicates odds ratio = 1.

Abbreviation: hs-cTnT, high-sensitivity cardiac troponin T.

Figure 2 Temporal changes in cycle threshold values from admission.

Notes: Figure shows temporal changes in Ct values of SARS-CoV-2 between patients with and without myocardial injury. Ct values in the y axis were the average of simultaneously tested Ct values of ORF1ab and N since they were parallel and approximate. 95% confidence interval was indicated by the ribbon.

Abbreviations: Ct, cycle threshold; ORF1ab, open reading frame 1ab; N, nucleocapsid protein.

Figure 3 Odds ratio of risk factors of myocardial injury.

Notes: Multivariate model was adjusted with age (per 5-year increase), hypertension, diabetes, coronary artery disease, severity of COVID-19, vaccination, creatinine, D-dimer and neutrophil-to-lymphocyte ratio.

Table 3 Predictors of Mortality in Multivariate Logistic Regression Models

Risk Factors	Univariate Model		Model 1		Model 2
	Odds Ratio (95% CI)	p value	Odds Ratio (95% CI)	p value	Odds Ratio (95% CI)	p value
hs-cTnT > URL^#	3.80 (1.22–16.62)	0.038	0.66 (0.09–5.92)	0.680
hs-cTnT > 3xURL	12.4 (4.30–34.93)	<0.001			13.21 (2.11–87.1)	0.005
Neutrophil/lymphocyte ratio	1.15 (1.07–1.24)	<0.001	1.06 (0.98–1.12)	0.050	1.05 (0.95–1.11)	0.228
Age (per 5-year increase)	1.42 (1.10–1.94)	0.011	0.99 (0.64–1.63)	0.989	0.98 (0.64–1.60)	0.937
Creatinine	1.01 (1.01–1.02)	0.010	1.01 (1.01–1.03)	0.037	1.01 (0.99–1.02)	0.511
Albumin	0.80 (0.73–0.88)	<0.001	0.76 (0.65–0.87)	0.001	0.77 (0.66–0.89)	0.001
D-dimer	1.09 (1.01–1.15)	<0.001	1.11 (1.01–1.20)	0.017	1.10 (1.01–1.20)	0.034

Note: ^#The 99th percentile URL for hs-cTnT was 0.014 ng/mL.

Abbreviations: hs-cTnT, high-sensitivity cardiac troponin T; URL, upper reference limit.

Figure 4 Hs-cTnT and clinical endpoints.

Notes: (A) Receiver operating characteristic curve of hs-cTnT for the prediction of mortality. hs-cTnT = 0.052 ng/mL (3 × URL) had most balanced sensitivity and specificity. (B) The cumulative incidence of in-hospital mortality in patients with hs-cTnT > URL and those who did not. (C) The cumulative incidence of in-hospital mortality in patients with hs-cTnT > 3 × URL and those who did not.

Abbreviations: hs-cTnT, high-sensitivity cardiac troponin T; URL, upper reference limit.