Haptoglobin and risk of myocardial infarction, stroke, and congestive heart failure in 342,125 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Figures & data

Table

AMI	acute myocardial infarction
AMORIS	Apolipoprotein MOrtality RISk study
AP	attributable proportion of risk due to interaction
apoA-1	apolipoprotein A-1
ApoB	apolipoprotein B
DM	diabetes mellitus
HF	congestive heart failure
Hp	haptoglobin
HR	hazard ratio
HS	haemorrhagic stroke
HsCRP	high sensitive C-reactive protein
ICD	International Classification of Diseases
IS	ischaemic stroke
ISP	inflammation-specific plasma protein
RERI	relative excess risk due to interaction
S	synergistic index of Rothman
SD	standard deviation
TC	total serum cholesterol
TG	triglycerides

Table I.  Base-line characteristics (mean (SD)) by gender and quartiles ^a of Hp in AMORIS population free of AMI, stroke and HF.

Female	Q1	Q2	Q3	Q4	All
Hp categories	≤0.9	0.9–1.0	1.0–1.2	>1.2
No. of patients	33,864	44,771	40,985	38,244	157,864
No. of strokes (%)	845 (2.5)	1,378 (3.1)	1,669 (4.1)	2,180 (5.7)	6,072 (3.8)
No. of AMI (%)	522 (1.5)	807 (1.8)	1,074 (2.6)	1,888 (4.9)	4,291 (2.7)
No. of HF (%)	508(1.5)	710 (1.6)	928 (2.3)	1,488 (3.9)	3,634 (2.3)
Age, years	46.7 (11.4)	47.8 (11.7)	49.4 (12.2)	51.8 (12.7)	49.0 (12.1)
Haptoglobin g/L	0.72 (0.10)	0.95 (0.05)	1.14 (0.05)	1.50 (0.27)	1.08 (0.31)
Total cholesterol mmol/L	5.53 (1.12)	5.62 (1.12)	5.77 (1.15)	5.92 (1.22)	5.71 (1.16)
Triglycerides mmol/L	0.92 (0.51)	1.00 (0.56)	1.13 (0.62)	1.31 (0.70)	1.09 (0.62)
Hypertension (%)	139 (0.4)	207 (0.5)	232 (0.6)	339 (0.9)	917 (0.6)
DM (%)	498 (1.5)	735 (1.6)	880 (2.1)	1,452 (3.8)	3,565 (2.3)
Male
Hp categories	≤0.8	0.8–1.0	1.0–1.3	>1.3
No. of patients	42,507	47,154	45,054	49,546	184,261
No. of strokes (%)	1,334 (3.1)	1,673 (3.5)	2,186 (4.9)	3,270 (6.6)	8,463 (4.6)
No. of AMI (%)	1,542 (3.6)	2,157 (4.6)	2,852 (6.3)	4,665 (9.4)	11,216 (6.1)
No. of HF (%)	614 (1.4)	902 (1.9)	1,077 (2.4)	2,077 (4.2)	4,670 (2.5)
Age, years	45.2 (10.4)	46.6 (10.7)	47.9 (10.9)	49.5 (11.1)	47.4 (10.9)
Haptoglobin g/L	0.70 (0.11)	0.95 (0.05)	1.14 (0.06)	1.53 (0.29)	1.09 (0.35)
Total cholesterol mmol/L	5.60 (1.05)	5.69 (1.05)	5.80 (1.08)	5.86 (1.13)	5.74 (1.09)
Triglycerides mmol/L	1.28 (0.75)	1.37 (0.77)	1.47 (0.81)	1.57 (0.84)	1.43 (0.80)
Hypertension (%)	177 (0.4)	201 (0.4)	255 (0.6)	416 (0.8)	1,049 (0.6)
DM (%)	1,025 (2.4)	1,349 (2.9)	1,654 (3.7)	2,444 (4.9)	6,472 (3.5)

^a Distribution into quartiles could not be done exactly since Hp was measured with 1 decimal only.

Hp = haptoglobin; SD = standard deviation; AMI = acute myocardial infarction; HF = heart failure; DM= diabetes mellitus; Q = quartile.

Figure 1.  Hazard ratios of acute myocardial infarction (AMI) by deciles of haptoglobin and gender adjusted for age, total cholesterol (TC), triglycerides (TG), hospital-recorded hypertension, and diabetes. Reference point not included as basis for fit of regression lines.

Table II.  Hazard ratio of ischaemic, haemorrhagic, and total stroke by quartiles of Hp per gender. Adjusted for age; and adjusted for age, TC, TG, hypertension, and DM.

Haptoglobin quartiles ^a (g/L)	Ischaemic stroke HR (95% CI)	Haemorrhagic stroke HR (95% CI)	Total stroke HR (95% CI)
Men, adjusted for age:
≤ Q1 (≤0.8)	1	1
Q1–Q2 (0.8–1.0)	1.09 (1.00–1.19)	0.97 (0.82–1.15)	1.03 (0.96–1.11)
Q2–Q3 (1.0–1.3)	1.33 (1.23–1.45)	1.15 (0.98–1.35)	1.25 (1.17–1.34)
> Q3 (>1.3)	1.58 (1.47–1.71)	1.20 (1.03–1.41)	1.49 (1.40–1.59)
Men, adjusted for age, TC, TG, hypertension and DM:
≤ Q1 (≤0.8)	1	1	1
Q1–Q2 (0.8–1.0)	1.07 (0.98–1.17)	0.97 (0.82–1.15)	1.01 (0.94–1.09)
Q2–Q3 (1.0–1.3)	1.26 (1.16–1.37)	1.14 (0.97–1.34)	1.20 (1.12–1.28)
> Q3 (>1.3)	1.46 (1.35–1.58)	1.18 (1.01–1.38)	1.40 (1.31–1.49)
Women, adjusted for age:
< Q1 (≤0.9)	1	1	1
Q1–Q2 (0.9–1.0)	1.24 (1.12–1.38)	0.89 (0.71–1.10)	1.18 (1.08–1.28)
Q2–Q3 (1.0–1.2)	1.39 (1.25–1.53)	1.04 (0.85–1.28)	1.31 (1.21–1.43)
> Q3 (>1.2)	1.56 (1.42–1.72)	0.90 (0.73–1.11)	1.46 (1.35–1.58)
Women, adjusted for age, TC, TG, hypertension and DM:
< Q1 (≤0.9)	1	1	1
Q1–Q2 (0.9–1.00)	1.22 (1.10–1.35)	0.88 (0.71–1.09)	1.16 (1.07–1.27)
Q2–Q3 (1.00–1.20)	1.32 (1.20–1.46)	1.02 (0.83–1.25)	1.26 (1.16–1.37)
> Q3 (>1.20)	1.43 (1.30–1.57)	0.86 (0.70–1.06)	1.34 (1.24–1.46)

^a Distribution into quartiles could not be done exactly since Hp was measured with 1 decimal only.

Hp = haptoglobin; HR = hazard ratio; TC = total cholesterol; TG = triglycerides; CI = confidence interval, DM = diabetes mellitus; Q = quartile.

Table III.  Hazard ratio of AMI by gender specific quartiles ^a of Hp. Adjusted for age; and adjusted for age, TC, TG, hypertension, and DM.

	Men	Women
Haptoglobin quartiles g/L	HR (95% CI)	HR (95% CI)
Adjusted for age:
≤ Q1	1	1
Q1–Q2	1.16 (1.09–1.24)	1.11 (0.99–1.24)
Q2–Q3	1.45 (1.36–1.55)	1.35 (1.22–1.50)
> Q3	1.92 (1.81–2.03)	1.99 (1.81–2.20)
Adjusted for age, TC, TG, hypertension, and DM:
≤ Q1	1	1
Q1–Q2	1.12 (1.05–1.20)	1.08 (0.97–1.20)
Q2–Q3	1.33 (1.25–1.42)	1.25 (1.12–1.38)
> Q3	1.70 (1.60–1.80)	1.72 (1.56–1.90)

^a Distribution into quartiles (as in Table II) could not be done exactly since Hp was measured with 1 decimal only.

AMI = acute myocardial infarction; HR = hazard ratio; Hp = haptoglobin; TC = total cholesterol; TG = triglycerides; CI = confidence interval, DM = diabetes mellitus; Q = quartile.

Table IV.  Hazard ratio of HF by gender specific quartiles ^a of Hp. Adjusted for age; and adjusted for age, TC, TG, hypertension and DM.

	Men	Women
Haptoglobin quartiles (g/L)	HR (95% CI)	HR (95% CI)
Adjusted for age:
≤ Q1	1	1
Q1–Q2	1.16 (1.05–1.29)	0.95 (0.85–1.07)
Q2–Q3	1.25 (1.13–1.38)	1.10 (0.99–1.23)
> Q3	1.86 (1.70–2.03)	1.38 (1.25–1.53)
Adjusted for age, TC, TG, hypertension, and DM:
≤ Q1	1	1
Q1–Q2	1.14 (1.03–1.26)	0.95 (0.85–1.06)
Q2–Q3	1.19 (1.08–1.32)	1.06 (0.95–1.19)
> Q3	1.71 (1.56–1.88)	1.28 (1.16–1.42)

^a Distribution into quartiles (as in Table II) could not be done exactly since Hp was measured with 1 decimal only.

HF = heart failure; Hp = haptoglobin; HR = hazard ratio; TC = total cholesterol; TG = triglycerides; CI = confidence interval, DM = diabetes mellitus.

Table V.  Comparisons of AMI, ischaemic, haemorrhagic and all stroke and HF HRs for 1 SD difference in Hp by age and gender, adjusted for age, and adjusted for age, TC, TG, hypertension and DM.

	AMI HR (95% CI)	All stroke HR (95% CI)	Ischaemic stroke HR (95% CI)	Haemorrhagic stroke HR (95% CI)	HF HR (95% CI)
Adjusted for age:
Age (adjusted for gender):
≤ 65	1.25 (1.24–1.27)	1.17 (1.15–1.19)	1.18 (1.16–1.21)	1.06 (1.02–1.11)	1.27 (1.24–1.29)
> 65	1.07 (1.04–1.10)	1.01 (0.98–1.04)	1.00 (0.97–1.04)	0.94 (0.86–1.03)	1.05 (1.02–1.08)
Gender:
Men	1.20 (1.19–1.22)	1.14 (1.12–1.16)	1.14 (1.12–1.17)	1.07 (1.02–1.12)	1.20 (1.17–1.22)
Women	1.21 (1.18–1.23)	1.09 (1.07–1.11)	1.10 (1.07–1.13)	0.96 (0.90–1.02)	1.10 (1.07–1.13)
Adjusted for age, TC, TG, hypertension and DM:
Age (adjusted for gender):
≤ 65	1.22 (1.20–1.24)	1.15 (1.13–1.17)	1.15 (1.13–1.18)	1.05 (1.00–1.09)	1.23 (1.20–1.26)
> 65	1.06 (1.02–1.09)	1.00 (0.97–1.03)	0.99 (0.96–1.03)	0.94 (0.86–1.03)	1.04 (1.00–1.07)
Gender:
Men	1.18 (1.16–1.20)	1.12 (1.10–1.14)	1.12 (1.10–1.14)	1.06 (1.01–1.11)	1.17 (1.15–1.20)
Women	1.18 (1.15–1.20)	1.07 (1.04–1.09)	1.07 (1.05–1.10)	0.94 (0.88–1.01)	1.07 (1.05–1.10)

AMI = acute myocardial infarction; HF = heart failure; Hp = haptoglobin; HR = hazard ratio; SD = standard deviation; CI = confidence interval; TC = total cholesterol; TG = triglycerides; DM = diabetes mellitus.

Figure 2.  Hazard ratios of acute myocardial infarction (AMI) by cross-classification of quartiles of haptoglobin and total cholesterol with lowest joint quartile as reference category, adjusted for age, gender, triglycerides, hospital-recorded hypertension, and diabetes.

Figure 3.  Hazard ratios of acute ischaemic stroke (IS) by cross-classification of quartiles of haptoglobin and total cholesterol with lowest joint quartile as reference category, adjusted for age, gender, triglycerides, hospital-recorded hypertension, and diabetes.

Figure 4.  Hazard ratios of heart failure (HF) by cross-classification of quartiles of haptoglobin and total cholesterol with lowest joint quartile as reference category, adjusted for age, gender, triglycerides, hospital-recorded hypertension, and diabetes.