High blood hemoglobin concentration as risk factor of major atherosclerotic cardiovascular events in 114,159 healthy men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Figures & data

Figure 1. Mean levels of hemoglobin (g/L) by 5-year age-groups and gender.

Table I. Gender-adjusted least square means (SE) of continuous and gender-specific categorical risk factors and atherosclerotic cardiovascular events by quartiles of hemoglobin. Total and subgroup with measured apolipoproteins.^a

Risk factors	Q1 (n = 28457)	Q2 (n = 28878)	Q3 (n = 28712)	Q4 (n = 28112)	Total (n = 114159)
Female/male	25893/2564	21767/7111	11509/17203	3594/24518	62763/51396
Age, years	50.1 (0.09)	51.3 (0.08)	51.5 (0.08)	50.6 (0.09)	50.9 (0.04)
Males, %	9.0	24.7	59.9	87.2	45.0
Hb, g/L	125.3 (0.03)	137.3 (0.03)	145.6 (0.03)	157.2 (0.04)	141.3 (0.001)
TC, mmol/L	5.37 (0.007)	5.65 (0.007)	5.84 (0.007)	6.00 (0.008)	5.72 (0.003)
TG, mmol/L	1.11 (0.006)	1.24 (0.006)	1.40 (0.006)	1.63 (0.007)	1.34 (0.001)
Hp, g/L	1.09 (0.003)	1.08 (0.002)	1.08 (0.002)	1.09 (0.003)	1.09 (0.001)
Uric acid, μmol/L	266.8 (0.4)	278.5 (0.4)	290.9 (0.4)	302.9 (0.5)	284.6 (0.23)
Diabetes, n (%)	818 (2.9)	980 (3.4)	1256 (4.4)	1813 (6.4)	4867 (4.3)
F	628 (2.4)	655 (3.0)	478 (4.2)	349 (9.7)	2110 (3.4)
M	190 (7.4)	325 (4.6)	778 (4.5)	1464 (6.0)	2757 (5.4)
Hypertension, n (%)	271 (1.0)	276 (1.0)	308 (1.1)	363 (1.3)	1218 (1.1)
F	223 (0.9)	195 (0.9)	159 (1.4)	102 (2.8)	679 (1.1)
M	48 (1.9)	81 (1.1)	149 (0.9)	261 (1.1)	539 (1.0)
Events:
AMI, n (%)	943 (3.3)	1076 (3.7)	1413 (4.9)	1843 (6.6)	5275 (4.6)
F	706 (2.7)	692 (3.2)	492 (4.3)	269 (7.5)	2159 (3.4)
M	237 (9.2)	384 (5.4)	921 (5.4)	1574 (6.4)	3116 (6.1)
IS, n (%)	791 (2.8)	932 (3.2)	1034 (3.6)	1102 (3.9)	3859 (3.4)
F	648 (2.5)	672 (3.1)	477 (4.1)	222 (6.2)	2019 (3.2)
M	143 (5.6)	260 (3.7)	557 (3.2)	880 (3.6)	1840 (3.6)
CHF, n (%)	924 (3.2)	864 (3.0)	889 (3.1)	992 (3.5)	3669 (3.2)
F	731 (2.8)	616 (2.8)	420 (3.6)	252 (7.0)	2019 (3.2)
M	193 (7.5)	248 (3.5)	469 (2.7)	740 (3.0)	1650 (3.2)
MACE, n (%)	2208 (7.8)	2417 (8.4)	2805 (9.8)	3300 (11.7)	10730 (9.4)
F	1742 (6.7)	1678 (7.7)	1176 (10.2)	602 (16.8)	5198 (8.3)
M	466 (18.2)	739 (10.4)	1629 (9.5)	2698 (11.0)	5532 (10.8)
Subgroup with apolipoproteins:	Q1 (n = 11001)	Q2 (n = 11910)	Q3 (n = 12141)	Q4 (n = 11639)	Total (n = 46691)
ApoB, g/L	1.14 (0.003)	1.21 (0.003)	1.28 (0.003)	1.34 (0.003)	1.24 (0.002)
ApoA-1, g/L	1.42 (0.002)	1.44 (0.002)	1.44 (0.992)	1.44 (0.002)	1.44 (0.001)
ApoB/apoA-1	0.82 (0.003)	0.86 (0.003)	0.91 (0.002)	0.95 (0.003)	0.89 (0.001)
LDL-C, mmol/L	3.47 (0.01)	3.66 (0.01)	3.81 (0.01)	3.90 (0.01)	3.72 (0.005)
HDL-C, mmol/L	1.58 (0.004)	1.58 (0.004)	1.55 (0.004)	1.51 (0.004)	1.55 (0.002)
TC/HDL-C	3.77 (0.02)	3.92 (0.01)	4.17 (0.01)	4.46 (0.02)	4.09 (0.008)

^aAll variables had a significant test of trend across the Hb quartiles (P < 0.001) except for Hp (P = 0.80).

SE = standard error of the mean; Hb = hemoglobin; Q = quartile; TC = total serum cholesterol; TG = triglycerides; Hp = haptoglobin; AMI = acute myocardial infarction; IS = ischemic stroke; CHF = congestive heart failure; MACE = major atherosclerotic cardiovascular event; apoB = apolipoprotein B; apoA-1 = apolipoprotein A-1; LDL-C = low-density lipoprotein; HDL-C = high-density lipoprotein; M = male; F = female.

Table II. HR (95% CI) of first occurrence of AMI by age and gender and by deciles of Hb, adjusted for risk factors^a and adjusted for time-dependent occurrence of IS or CHF prior to AMI.

Factors	Ref	D2	D3	D4	D5	D6	D7	D8	D9	D10	Per SD
Total	1.0	0.93	0.89	0.97	0.92	0.99	1.08	1.05	1.18	1.40	1.11
(AMI = 5275)		(0.81–1.07)	(0.78–1.03)	(0.85–1.11)	(0.81–1.05)	(0.86–1.13)	(0.94–1.23)	(0.92–1.20)	(1.04–1.35)	(1.23–1.59)	(1.07–1.14)
Age:^b
<65	1.0	1.03	0.98	1.22	1.10	1.24	1.34	1.50	1.54	1.92	1.24
(AMI = 2441)		(0.78–1.35)	(0.75–1.28)	(0.94–1.58)	(0.86–1.41)	(0.97–1.59)	(1.05–1.70)	(1.18–1.91)	(1.21–1.96)	(1.51–2.43)	(1.18–1.30)
≥65	1.0	0.90	0.82	0.88	0.89	0.92	0.90	0.92	0.88	1.05	1.01
(AMI = 2834)		(0.76–1.07)	(0.69–0.98)	(0.74–1.05)	(0.75–1.05)	(0.77–1.09)	(0.77–1.07)	(0.77–1.08)	(0.74–1.05)	(0.89–1.24)	(0.97–1.05)
Gender:^c
Male	1.0	0.89	0.99	1.01	1.00	1.09	1.10	1.15	1.31	1.44	1.10
(AMI = 3116)		(0.77–1.04)	(0.85–1.15)	(0.86–1.13)	(0.86–1.16)	(0.92–1.29)	(0.95–1.28)	(0.99–1.34)	(1.13–1.52)	(1.25–1.65)	(1.06–1.13)
Female	1.0	0.77	0.90	0.72	0.84	0.90	0.92	0.88	0.97	1.05	1.04
(AMI = 2159)		(0.63–0.94)	(0.57–1.10)	(0.85–0.90)	(0.70–1.02)	(0.73–1.11)	(0.76–1.11)	(0.73–1.07)	(0.80–1.17)	(0.89–1.25)	(1.00–1.08)

^aAdjustment factors: age, gender, total cholesterol, triglycerides, hospital recorded hypertension, and diabetes.

^bAge-group-specific deciles (Age <65 splits at: 126, 131, 135, 138, 142, 145, 149, 153, 158 g/L; Age ≥65 splits at: 124, 129, 133, 136.1, 139.1, 142.2, 146, 150, 155.9 g/L).

^cGender-specific deciles (Male splits at: 137, 142, 145, 147.7, 150, 152, 155, 158, 162 g/L; Female splits at: 122, 127, 130, 132, 135, 137, 140, 143, 147 g/L).

HR = hazard ratio; CI = confidence interval; AMI = acute myocardial infarction; Hb = hemoglobin; IS = ischemic stroke; CHF = congestive heart failure; D = decile; Ref = reference group (first decile); SD = standard deviation.

Table III. HR (95% CI) of first occurrence of IS by age and gender and by deciles of Hb, adjusted for risk factors^a and adjusted for time-dependent occurrence of AMI or CHF prior to IS.

Factors	Ref	D2	D3	D4	D5	D6	D7	D8	D9	D10	Per SD
Total	1.0	1.06	1.11	1.20	1.30	1.23	1.28	1.34	1.28	1.64	1.14
(IS = 3859)		(0.91–1.24)	(0.95–1.30)	(1.03–1.39)	(1.13–1.51)	(1.05–1.44)	(1.09–1.50)	(1.15–1.56)	(1.09–1.49)	(1.40–1.91)	(1.10–1.18)
Age:^b
<65	1.0	0.98	1.12	1.20	1.33	1.22	1.41	1.54	1.53	1.80	1.20
(IS = 1576)		(0.73–1.33)	(0.85–1.49)	(0.90–1.60)	(1.02–1.74)	(0.92–1.61)	(1.09–1.84)	(1.18–2.02)	(1.16–2.02)	(1.37–2.35)	(1.13–1.28)
≥65	1.0	1.28	1.17	1.28	1.29	1.33	1.21	1.18	1.22	1.37	1.08
(IS = 2283)		(1.06–1.56)	(0.96–1.43)	(1.05–1.56)	(1.06–1.57)	(1.09–1.62)	(1.00–1.47)	(0.97–1.43)	(1.00–1.50)	(1.12–1.67)	(1.03–1.13)
Gender:^b
Male	1.0	1.02	0.98	0.98	1.18	1.18	1.09	0.91	1.22	1.47	1.10
(IS = 1840)		(0.84–1.23)	(0.81–1.19)	(0.79–1.21)	(0.98–1.42)	(0.96–1.46)	(0.90–1.33)	(0.74–1.12)	(1.01–1.48)	(1.22–1.76)	(1.05–1.15)
Female	1.0	1.17	1.22	1.19	1.26	1.17	1.35	1.48	1.33	1.47	1.12
(IS = 2019)		(0.94–1.46)	(0.98–1.52)	(0.94–1.51)	(1.02–1.55)	(0.93–1.47)	(1.10–1.66)	(1.20–1.83)	(1.07–1.64)	(1.20–1.79)	(1.07–1.17)

^aSame adjustment factors as in Table II.

^bSee footnote to Table II.

HR = hazard ratio; CI = confidence interval; AMI = acute myocardial infarction; Hb = hemoglobin; IS = ischemic stroke; CHF = congestive heart failure; D = decile; SD = standard deviation.

Table IV. HR (95% CI) of first occurrence of CHF by age and gender and by deciles of Hb, adjusted for risk factors^a and adjusted for time-dependent occurrence of AMI or IS prior to CHF.

Factors	Ref	D2	D3	D4	D5	D6	D7	D8	D9	D10	Per SD
Total	1.0 (-)	0.86	0.90	0.84	0.99	0.92	0.95	1.07	1.13	1.33	1.10
(CHF = 3669)		(0.75–0.99)	(0.78–1.05)	(0.73–0.97)	(0.87–1.14)	(0.79–1.07)	(0.81–1.11)	(0.93–1.24)	(0.98–1.31)	(1.15–1.54)	(1.06–1.14)
Age:^b
<65	1.0 (-)	0.97	0.72	1.10	0.99	0.96	0.88	1.05	1.05	1.39	1.13
(CHF = 1012)		(0.68–1.38)	(0.50–1.03)	(0.78–1.54)	(0.72–1.37)	(0.69–1.35)	(0.63–1.23)	(0.76–1.45)	(0.75–1.47)	(1.01–1.91)	(1.04–1.22)
≥65	1.0 (-)	0.94	0.85	0.80	0.89	0.95	0.90	1.02	1.04	1.10	1.05
(CHF = 2657)		(0.80–1.10)	(0.72–1.01)	(0.67–0.96)	(0.75–1.06)	(0.80–1.12)	(0.76–1.06)	(0.86–1.21)	(0.88–1.24)	(0.93–1.30)	(1.01–1.10)
Gender:^b
Male	1.0 (-)	0.95	0.91	0.92	0.91	0.94	1.08	1.04	1.27	1.25	1.07
(CHF = 1650)		(0.78–1.14)	(0.75–1.11)	(0.74–1.14)	(0.75–1.11)	(0.74–1.18)	(0.89–1.32)	(0.84–1.29)	(1.04–1.54)	(1.04–1.50)	(1.02–1.12)
Female	1.0 (-)	0.80	0.86	0.82	0.70	0.86	0.98	0.90	0.90	1.17	1.08
(CHF = 2019)		(0.66–0.98)	(0.70–1.04)	(0.66–1.03)	(0.58–0.86)	(0.69–1.07)	(0.81–1.18)	(0.74–1.10)	(0.74–1.09)	(0.99–1.39)	(1.03–1.12)

^aSame adjustment factors as in Table II.

^bSee footnote to Table II.

HR = hazard ratio; CI = confidence interval; AMI = acute myocardial infarction; Hb = hemoglobin; IS = ischemic stroke; CHF = congestive heart failure; D = decile; SD = standard deviation.

Table V. HR (95% CI) of first occurrence of MACE by age and gender and by deciles of Hb, adjusted for risk factors.^a

Factors	Ref	D2	D3	D4	D5	D6	D7	D8	D9	D10	Per SD
Total	1.0 (-)	0.98	0.96	1.10	1.06	1.08	1.16	1.23	1.29	1.55	1.14
(MACE = 10628)		(0.89–1.07)	(0.87–1.05)	(0.92–1.10)	(0.98–1.16)	(0.98–1.19)	(1.05–1.27)	(1.12–1.34)	(1.18–1.41)	(1.42–1.70)	(1.12–1.17)
Age:^b
<65	1.0 (-)	1.00	0.95	1.15	1.17	1.20	1.32	1.44	1.56	1.85	1.23
(MACE = 4364)		(0.83–1.20)	(0.80–1.14)	(0.96–1.38)	(0.99–1.39)	(1.01–1.43)	(1.12–1.56)	(1.22–1.71)	(1.32–1.85)	(1.57–2.18)	(1.19–1.28)
≥65	1.0 (-)	1.05	0.94	0.98	1.03	1.03	1.02	1.15	1.09	1.27	1.07
(MACE = 6264)		(0.94–1.18)	(0.84–1.05)	(0.87–1.10)	(0.92–1.15)	(0.92–1.15)	(0.92–1.14)	(1.02–1.28)	(0.97–1.22)	(1.13–1.42)	(1.04–1.10)
Gender:^b
Male	1.0 (-)	0.90	0.97	0.98	1.06	1.08	1.09	1.14	1.29	1.43	1.11
(MACE = 5483)		(0.81–1.00)	(0.87–1.09)	(0.87–1.11)	(0.95–1.18)	(0.96–1.22)	(0.98–1.22)	(1.01–1.28)	(1.15–1.44)	(1.28–1.58)	(1.08–1.13)
Female	1.0 (-)	0.86	0.99	0.86	0.95	0.94	1.08	1.04	1.09	1.32	1.11
(MACE = 5145)		(0.75–0.98)	(0.85–1.05)	(0.74–0.99)	(0.84–1.07)	(0.82–1.08)	(0.96–1.22)	(0.92–1.18)	(0.96–1.23)	(1.18–1.48)	(1.08–1.14)

^aSame adjustment factors as in Table II.

^bSee footnote to Table II.

HR = hazard ratio; CI = confidence interval; Hb = hemoglobin; AMI = acute myocardial infarction; IS = ischemic stroke; CHF = congestive heart failure; MACE = major atherosclerotic cardiovascular events, including AMI, IS, or CHF; D = decile; SD = standard deviation.