Serum Anion Gap is Associated with Risk of All-Cause Mortality in Critically Ill Patients with Acute Myocardial Infarction

Figures & data

Table 1 Baseline Characteristics of AMI Patients According to AG

AG (mmol/L)
Characteristics	Quartile 1 <12.0	Quartile 2 ≥12.0,<14.1	Quartile 3 ≥14.1,<16.7	Quartile 4 ≥16.7	p-value
Number of patients	443	446	463	454	-
Age(years)	67.1±13.0	66.5±14.5	67.66±14.7	69.9±14.5	0.001
Male, n(%)	297(67.0)	291(65.2)	313(67.6)	283(62.3)	0.334
Weight(kg)	80.28±17.00	82.32±18.93	81.84±20.45	80.32±22.16	0.102
Mean heart rate(bpm)	79.81±14.23	79.22±13.69	80.82±14.13	86.28±16.91	<0.001
Creatinine(mg/dL)	0.89±0.41	0.98±0.46	1.15±0.70	1.96±1.82	<0.001
BUN(mg/dL)	16.99±8.02	19.23±10.04	22.21±12.71	34.72±23.64	<0.001
Hemoglobin(g/dL)	11.28±2.13	12.15±1.96	12.09±2.04	11.88±2.29	<0.001
Platelet(×10^9/L)	210.78±98.11	225.64±79.26	237.40±91.71	244.87±104.83	<0.001
WBC(×10^9/L)	11.52±5.08	11.50±4.05	12.45±4.82	15.21±6.81	<0.001
Sodium(mmol/L)	136.89±4.14	138.20±3.43	137.90±3.78	138.04±4.73	<0.001
Potassium(mmol/L)	4.15±0.69	4.12±0.64	4.22±0.65	4.37±0.87	<0.001
Chloride(mmol/L)	106.38±5.00	105.02±4.56	103.96±4.39	103.30±5.62	<0.001
Bicarbonate(mmol/L)	25.09±3.36	24.32±3.12	22.97±3.15	19.44±4.46	<0.001
SOFA score	3.17±2.76	2.81±2.61	3.21±2.75	5.65±3.75	<0.001
SAPS II score	32.08±12.13	30.46±12.26	32.50±13.50	43.95±16.90	<0.001
Hypertension, n(%)	244(55.1)	232(52.0)	229(49.5)	168(37.0)	<0.001
AF, n(%)	102(23.0)	110(24.7)	103(22.2)	148(32.6)	0.001
CHF, n(%)	114(25.7)	161(36.1)	182(39.3)	247(54.4)	<0.001
Diabetes, n(%)	96(21.7)	100(22.4)	114(24.6)	155(34.1)	<0.001
Chronic renal disease, n(%)	20(4.5)	23(5.2)	36(7.8)	52(11.5)	<0.001
CS, n(%)	29(6.5)	61(13.7)	71(15.3)	142(31.3)	<0.001
30-day mortality, n(%)	18(4.1)	40(9.0)	58(12.5)	154(33.9)	<0.001
180-day mortality, n(%)	35(7.9)	57(12.8)	84(18.1)	198(43.6)	<0.001
1-year mortality, n(%)	41(9.3)	68(15.2)	95(20.5)	214(47.1)	<0.001

Abbreviations: BUN, blood urea nitrogen; WBC, white blood cell; SOFA, sequential organ failure assessment; SAPS II, simplified acute physiology score II; AF, atrial fibrillation; CHF, congestive heart failure; CS, cardiogenic shock.

Table 2 Hazard Ratio of AG (Continuous) for Mortality

	30-Day Mortality		180-Day Mortality		1-Year Mortality
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
Unadjusted	1.198 (1.173,1.225)	<0.001	1.192 (1.169,1.216)	<0.001	1.189 (1.166,1.212)	<0.001
Model 1	1.190 (1.164,1.216)	<0.001	1.181 (1.158,1.205)	<0.001	1.178 (1.155,1.201)	<0.001
Model 2	1.108 (1.076,1.141)	<0.001	1.098 (1.070,1.126)	<0.001	1.093 (1.066,1.120)	<0.001
Model 3	1.083 (1.051,1.117)	<0.001	1.077 (1.049,1.105)	<0.001	1.074 (1.047,1.101)	<0.001

Notes: Model 1: adjusted for age and sex; Model 2: adjusted for model 1 plus SOFA score, creatinine, blood urea nitrogen, platelet, white blood cell, hemoglobin, and heart rate; Model 3: adjusted for model 2 plus hypertension, atrial fibrillation, congestive heart failure, diabetes, renal disease, cardiogenic shock and SAPS II score.

Abbreviations: HR, hazard ratio; CI, confidence interval; SOFA, sequential organ failure assessment; SAPS II, simplified acute physiology score II.

Figure 1 Associations between AG on a continuous scale and adjusted-risk of mortality in AMI patients. Hazard ratio (line) and 95% confidence interval (grey area) from adjusted Cox regression for 30-day mortality (A), 180-day mortality (B) and 1-year mortality (C). 12mmo/L of AG concentration were used as reference. Cox regression was adjusted for Age, sex, SOFA score, creatinine, BUN, platelet, WBC, hemoglobin, mean heart rate, SAPS II score and comorbidities of hypertension, AF, CHF, diabetes and renal disease as Model 3 described in Tables 2 and 3.

Abbreviations: AG, anion gap; HR, hazard ratio.

Table 3 Hazard Ratio of AG (Quartile) for Mortality

AG, mmol/L	Unadjusted		Model 1		Model 2		Model 3
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
30-day mortality
<12.0	1.0 (ref)		1.0 (ref)		1.0 (ref)		1.0 (ref)
≥12.0,<14.1	2.248(1.289, 3.920)	0.004	2.236(1.282,3.900)	0.005	2.424(1.380,4.256)	0.002	2.243(1.273,3.955)	0.005
≥14.1,<16.7	3.211(1.892,5.449)	<0.001	3.162(1.863,5.366)	<0.001	3.054(1.785,5.224)	<0.001	3.026(1.763,5.194)	<0.001
≥16.7	10.086(6.189,16.437)	<0.001	9.287(5.694,15.146)	<0.001	5.090(3.017,8.586)	<0.001	4.402(2.573,7.531)	<0.001
P for trend	<0.001		<0.001		<0.001		<0.001
180-day mortality
<12.0	1.0 (ref)		1.0 (ref)		1.0 (ref)		1.0 (ref)
≥12.0,<14.1	1.662(1.091,2.531)	0.018	1.647(1.081,2.510)	<0.001	1.877(1.224,2.880)	0.004	1.719(1.118,2.645)	0.014
≥14.1,<16.7	2.418(1.630,3.587)	<0.001	2.388(1.609,3.542)	<0.001	2.376(1.588,3.553)	<0.001	2.362(1.575,3.542)	<0.001
≥16.7	7.036(4.911,10.088)	<0.001	6.468(4.511,9.273)	<0.001	3.674(2.476,5.452)	<0.001	3.116(2.077,4.676)	<0.001
P for trend	<0.001		<0.001		<0.001		<0.001
1-year mortality
<12.0	1.0 (ref)		1.0 (ref)		1.0 (ref)		1.0 (ref)
≥12.0,<14.1	1.696(1.151,2.498)	0.008	1.647(1.136,2.467)	<0.001	1.873(1.262,2.778)	0.002	1.700(1.143,2.528)	0.009
≥14.1,<16.7	2.342(1.623,3.377)	<0.001	2.315(1.605,3.339)	<0.001	2.265(1.558,3.294)	<0.001	2.239(1.536,3.264)	<0.001
≥16.7	6.622(4.740,9.251)	<0.001	6.098(4.362,8.525)	<0.001	3.398(2.349,4.915)	<0.001	2.876(1.969,4.201)	<0.001
P for trend	<0.001		<0.001		<0.001		<0.001

Notes: Model 1: adjusted for age and sex; Model 2: adjusted for model 1 plus SOFA score, creatinine, blood urea nitrogen, platelet, white blood cell, hemoglobin, and heart rate; Model 3: adjusted for model 2 plus hypertension, atrial fibrillation, congestive heart failure, diabetes, renal disease, cardiogenic shock and SAPS II score.

Abbreviations: HR, hazard ratio; CI, confidence interval; SOFA, sequential organ failure assessment; SAPS II, simplified acute physiology score II.

Figure 2 Adjusted survival rate by quartiles of AG. Risk-adjusted survival plots for 30-day mortality (A), 180-day mortality (B) and 1-year mortality (C). Cox regression was adjusted for age, sex, SOFA score, creatinine, BUN, platelet, WBC, hemoglobin, mean heart rate, SAPS II score and comorbidities of hypertension, AF, CHF, diabetes and renal disease as Model 3 described in Tables 2 and 3. The HRs and 95% CI were presented using the bottom quartile as reference.

Abbreviation: AG, anion gap.

Figure 3 Associations between AG and risk of death in subgroups. Forest plot and adjusted hazard ratios with 95% CI for 30-day, 180-day and 1-year mortality.

Abbreviations: AF, atrial fibrillation; CHF, congestive heart failure; AKI, acute kidney injury.