Supplementary Table 1.ICD-8 and 10-codes and ATC used to identify outcome and co-morbidity

Co-morbidity indicator / ICD-8 / ICD-10
Congestive heart failure
- Incompensatio cordis
- Heart failure/Asthma cordiale
- OedemeaPulmonum cordiale acutum
- Insufficiencia cordis sinistri
- Pericarditis acutaidiopathica
- Hemopericardia
- Dilated cardiomyopathy / 42709
42710
42711
42719 / I11.0
I50
I13.0
I13.2
I42.0
Stroke / 43309 43399 43409 43499 43601 43690 / I63I64
Systemic embolism / 444 / I74
Intracranial bleeding* / I60I61I62
Gastrointestinal bleeding* / K250K260K270K280K290
Traumatic intracranial bleeding* / S063CS064S065S066
Other bleedings leading to hospitalization: *
- Retinal bleeding
- Epitaxis or haemoptysis
- Anemia (acute)
- Haemothorax
- Postmenopausal haemorrhage
- Hematuria
- Conjunctival haemorrhage
- Vitreous haemorrhage
- Haemorrhage (non specified) / H356
R040R042
D62
J942
N95
N02R31
H113
H431
R58
Myocardial infarction / 41009 41099 / I21
Peripheral arterial disease / 44020 44399 44441 / I702I739I745
Atrial Fibrillation / 42793 42794 / I48
Aortic plaque / 44009 / I70.0
Diabetes mellitus / 24900 24909 25008 25009 / E10E11E14
Renal impairment / 403 404 580 581 582 583 59009 59319 792 / I12I13N00N01N02N03N04N05N07N11N14N17N18N19Q61
Medical treatment / ATC-Code
Statins / C10
Antiplatelet Drugs / B01AC
VKA treatment / B01AA
Alfa adrenic block# / C02AC02BC02C
Non-loop diuretics# / C02DAC02LC03AC03BC03DC03EC03XC07CC07DC08GC09BAC09DAC09XA52
Vasodilator# / C02DBC02DDC02DGC04C05
Beta blocker# / C07
Calcium channel blocker# / C07FC08C09BBC09DB
Renin-angiotensin inhibitor# / C09

*All included in endpoint Major bleeding.

# At least two groups present to assume hypertension treatment.

Supplementary Table 2 Crude and adjusted Cox regression hazard ratios (and 95% CIs) for pulse pressure for categorical model (quartiles, Q1 as reference) and linear effectsmodel (HR per 10 mmHg).

Stroke/systemic embolic event, major bleeding or death / Stroke/systemic embolic event / Major bleeding / Death
PP quartile
(range, mmHg)
Crude analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.94 (0.78-1.14) / 0.93 (0.61-1.43) / 1.06 (0.71-1.59) / 0.87 (0.70-1.09)
Q3 (62-73) / 1.01 (0.84-1.22) / 1.25 (0.85-1.85) / 1.44 (0.99-2.08) / 1.02 (0.82-1.26)
Q4 (74-144) / 1.26 (1.06-1.51) / 1.59 (1.09-2.32) / 1.33 (0.91-1.95) / 1.28 (1.04-1.57)
Linear effect (13-144) / 1.06 (1.02-1.10) / 1.12 (1.04-1.21) / 1.10 (1.02-1.18) / 1.06 (1.01-1.11)
Adjusted analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.92 (0.76-1.11) / 0.91 (0.59-1.40) / 1.05 (0.70-1.57) / 0.86 (0.69-1.08)
Q3 (62-73) / 0.95 (0.79-1.14) / 1.18 (0.79-1.74) / 1.38 (0.95-2.00) / 0.96 (0.78-1.19)
Q4 (74-144) / 1.11 (0.93-1.34) / 1.40 (0.94-2.06) / 1.19 (0.81-1.76) / 1.13 (0.91-1.39)
Linear effect (13-144) / 1.03 (0.99-1.07) / 1.09 (1.00-1.17) / 1.07 (0.99-1.16) / 1.03 (0.98-1.08)
Adjusted analysisinclSBP group
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.98 (0.77-1.26) / 0.92 (0.54-1.55) / 0.87 (0.54-1.39) / 0.99 (0.75-1.30)
Q3 (62-73) / 1.14 (0.85-1.53) / 1.19 (0.65-2.14) / 0.96 (0.55-1.65) / 1.20 (0.87-1.65)
Q4 (74-144) / 1.14 (0.80-1.62) / 0.98 (0.48-1.99) / 0.50 (0.26-1.00) / 1.24 (0.85-1.82)
Linear effect (13-144) / 0.99 (0.91-1.07) / 0.95 (0.81-1.10) / 0.89 (0.77-1.04) / 1.01 (0.93-1.10)

Supplementary table 3. Crude event rates by quartiles of the systolic, diastolic blood pressure and pulse pressure values in patients with incident heart failure, in patients with incident heart failure and no history of hypertension treatment (N=960).

Event rate per 100 PY (events)
Stroke/systemic embolic event, Major bleeding and Death / Stroke/systemic embolic event / Major bleeding / Death
SBPquartile
(range, mmHg)
Q1 (89-134) / 11.7% (135) / 2.5% (29) / 1.5% (19) / 8.1% (104)
Q2 (135-148) / 9.1% (103) / 1.5% (18) / 2.7% (32) / 6.2% (79)
Q3 (149-162) / 8.6% (97) / 1.6% (19) / 2.1% (24) / 6.4% (79)
Q4 (163-232) / 13.1% (86) / 3.7% (26) / 2.6% (19) / 8.8% (69)
DBPquartile
(range, mmHg)
Q1 (53-80) / 11.1% (157) / 2.3% (34) / 1.9% (28) / 8.1% (127)
Q2 (81-87) / 9.1% (96) / 2.1% (24) / 2.3% (26) / 5.5% (65)
Q3 (88-93) / 9.8% (89) / 1.7% (17) / 2.3% (22) / 7.7% (79)
Q4 (94-140) / 11.6% (79) / 2.3% (17) / 2.4% (18) / 7.5% (60)
PP quartile
(range, mmHg)
Q1 (13-50) / 10.5% (118) / 1.8% (21) / 1.8% (21) / 7.6% (94)
Q2 (51-61) / 10.0% (103) / 2.0% (22) / 2.0% (22) / 6.1% (73)
Q3 (62-73) / 9.6% (106) / 1.9% (22) / 2.6% (30) / 7.0% (86)
Q4 (74-144) / 11.7% (94) / 3.2% (27) / 2.4% (21) / 8.5% (78)

Supplementary Table 4.Crude and adjusted Cox regression hazard ratios (and 95% CIs) for systolic, diastolic blood pressure and pulse pressure for categorical model (quartiles, Q1 as reference) and linear effects model (HR per 10 mmHg). Only HF patients with no hypertension treatment history (N=960).

Stroke/systemic embolic event, major bleeding or death / Stroke/systemic embolic event / Major bleeding / Death
SBP quartile
(range, mmHg)
Crude analysis
Q1 (89-134) / Reference / Reference / Reference / Reference
Q2 (135-148) / 0.82 (0.63-1.06) / 0.64 (0.36-1.15) / 1.81 (1.02-3.19) / 0.79 (0.59-1.07)
Q3 (149-162) / 0.79 (0.61-1.03) / 0.70 (0.39-1.25) / 1.39 (0.76-2.53) / 0.84 (0.62-1.12)
Q4 (163-232) / 1.19 (0.91-1.57) / 1.62 (0.95-2.75) / 1.74 (0.92-3.29) / 1.17 (0.86-1.58)
Linear effect (89-232) / 1.03 (0.98-1.08) / 1.10 (1.00-1.21) / 1.09 (0.99-1.20) / 1.02 (0.96-1.07)
Adjusted analysis
Q1 (89-134) / Reference / Reference / Reference / Reference
Q2 (135-148) / 0.80 (0.62-1.03) / 0.56 (0.31-1.02) / 1.80 (1.02-3.18) / 0.78 (0.58-1.05)
Q3 (149-162) / 0.72 (0.56-0.94) / 0.55 (0.30-1.01) / 1.31 (0.71-2.40) / 0.79 (0.59-1.06)
Q4 (163-232) / 1.10 (0.84-1.45) / 1.42 (0.82-2.46) / 1.61 (0.85-3.05) / 1.06 (0.78-1.45)
Linear effect (89-232) / 1.01 (0.96-1.06) / 1.08 (0.97-1.20) / 1.08 (0.98-1.19) / 1.00 (0.95-1.06)
DSP quartile
(range, mmHg)
Crude analysis
Q1(53-80) / Reference / Reference / Reference / Reference
Q2 (81-87) / 0.86 (0.67-1.11) / 0.98 (0.58-1.65) / 1.26 (0.74-2.16) / 0.71 (0.53-0.96)
Q3 (88-93) / 0.93 (0.72-1.21) / 0.80 (0.45-1.44) / 1.25 (0.71-2.19) / 0.99 (0.75-1.32)
Q4 (94-140) / 1.09 (0.83-1.44) / 1.05 (0.59-1.88) / 1.32 (0.73-2.40) / 0.98 (0.72-1.33)
Linear effect (53-140) / 1.04 (0.95-1.15) / 1.09 (0.89-1.34) / 1.05 (0.86-1.29) / 1.01 (0.91-1.12)
Adjusted analysis
Q1(53-80) / Reference / Reference / Reference / Reference
Q2 (81-87) / 0.83 (0.64-1.07) / 0.92 (0.54-1.57) / 1.20 (0.70-2.05) / 0.69 (0.51-0.93)
Q3 (88-93) / 0.92 (0.71-1.20) / 0.67 (0.36-1.22) / 1.23 (0.70-2.17) / 1.03 (0.78-1.38)
Q4 (94-140) / 1.08 (0.82-1.42) / 0.93 (0.51-1.68) / 1.30 (0.71-2.38) / 0.99 (0.73-1.36)
Linear effect (53-140) / 1.05 (0.95-1.16) / 1.07 (0.86-1.33) / 1.06 (0.86-1.30) / 1.02 (0.91-1.15)
PP quartile
(range, mmHg)
Crude analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.95 (0.73-1.24) / 1.12 (0.62-2.04) / 1.12 (0.62-2.05) / 0.82 (0.60-1.11)
Q3 (62-73) / 0.95 (0.73-1.24) / 1.08 (0.60-1.97) / 1.49 (0.86-2.61) / 0.95 (0.71-1.27)
Q4 (74-144) / 1.18 (0.90-1.55) / 1.87 (1.05-3.30) / 1.39 (0.76-2.54) / 1.18 (0.88-1.60)
Linear effect (13-144) / 1.03 (0.97-1.09) / 1.12 (1.00-1.27) / 1.12 (1.00-1.26) / 1.02 (0.95-1.09)
Adjusted analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.93 (0.71-1.22) / 0.98 (0.53-1.80) / 1.12 (0.62-2.05) / 0.81 (0.60-1.11)
Q3 (62-73) / 0.88 (0.67-1.14) / 0.89 (0.48-1.64) / 1.43 (0.81-2.51) / 0.89 (0.66-1.20)
Q4 (74-144) / 1.07 (0.81-1.41) / 1.60 (0.89-2.89) / 1.30 (0.71-2.40) / 1.06 (0.78-1.44)
Linear effect (13-144) / 1.00 (0.94-1.07) / 1.09 (0.96-1.24) / 1.11 (0.98-1.25) / 0.99 (0.93-1.07)

Supplementary table 5. Crude event rates by quartiles of the systolic, diastolic blood pressure and pulse pressure values in patients with incident heart failure, in patients with incident heart failure and no history of atrial fibrillation diagnosis (N=1566).

Event rate per 100 PY (events)
Stroke/systemic embolic event, Major bleeding and Death / Stroke/systemic embolic event / Major bleeding / Death
SBPquartile
(range, mmHg)
Q1 (89-134) / 10.3% (162) / 2.0% (32) / 1.4% (23) / 7.3% (126)
Q2 (135-148) / 10.7% (161) / 2.0% (32) / 2.8% (46) / 7.1% (123)
Q3 (149-162) / 9.5% (147) / 1.9% (31) / 2.5% (40) / 6.6% (113)
Q4 (163-232) / 14.4% (202) / 3.4% (53) / 3.2% (49) / 9.2% (156)
DBPquartile
(range, mmHg)
Q1 (53-80) / 10.6% (208) / 2.1% (42) / 1.9% (39) / 7.8% (167)
Q2 (81-87) / 9.3% (136) / 1.9% (30) / 2.0% (31) / 6.3% (103)
Q3 (88-93) / 11.9% (157) / 2.7% (38) / 2.9% (42) / 7.7% (118)
Q4 (94-140) / 13.3% (171) / 2.6% (38) / 3.3% (46) / 8.3% (130)
PP quartile
(range, mmHg)
Q1 (13-50) / 10.1% (161) / 1.8% (30) / 1.8% (30) / 7.0% (123)
Q2 (51-61) / 10.2% (139) / 1.9% (28) / 2.1% (30) / 6.6% (103)
Q3 (62-73) / 10.9% (174) / 2.4% (41) / 3.0% (51) / 7.5% (137)
Q4 (74-144) / 13.4% (198) / 3.0% (49) / 3.0% (47) / 8.9% (155)

Supplementary Table 6.Crude and adjusted Cox regression hazard ratios (and 95% CIs) for systolic, diastolic blood pressure and pulse pressure for categorical model (quartiles, Q1 as reference) and linear effects model (HR per 10 mmHg). Only HF patients with no history of atrial fibrillationdiagnosis (N=1566).

Stroke/systemic embolic event, major bleeding or death / Stroke/systemic embolic event / Major bleeding / Death
SBP quartile
(range, mmHg)
Crude analysis
Q1 (89-134) / Reference / Reference / Reference / Reference
Q2 (135-148) / 1.03 (0.83-1.28) / 1.00 (0.61-1.64) / 2.07 (1.26-3.42) / 0.98 (0.76-1.25)
Q3 (149-162) / 0.93 (0.75-1.17) / 0.97 (0.59-1.58) / 1.85 (1.11-3.09) / 0.91 (0.71-1.17)
Q4 (163-232) / 1.39 (1.13-1.70) / 1.75 (1.13-2.71) / 2.31 (1.41-3.79) / 1.27 (1.01-1.61)
Linear effect (89-232) / 1.07 (1.03-1.10) / 1.12 (1.04-1.20) / 1.14 (1.06-1.22) / 1.04 (1.00-1.08)
Adjusted analysis
Q1 (89-134) / Reference / Reference / Reference / Reference
Q2 (135-148) / 0.97 (0.78-1.20) / 0.83 (0.51-1.37) / 2.03 (1.23-3.35) / 0.95 (0.74-1.22)
Q3 (149-162) / 0.85 (0.68-1.06) / 0.76 (0.46-1.25) / 1.78 (1.06-2.98) / 0.86 (0.66-1.11)
Q4 (163-232) / 1.20 (0.97-1.49) / 1.33 (0.84-2.10) / 2.09 (1.26-3.46) / 1.14 (0.89-1.44)
Linear effect (89-232) / 1.05 (1.01-1.08) / 1.08 (1.00-1.16) / 1.12 (1.05-1.21) / 1.03 (0.99-1.07)
DSP quartile
(range, mmHg)
Crude analysis
Q1(53-80) / Reference / Reference / Reference / Reference
Q2 (81-87) / 0.89 (0.71-1.10) / 0.96 (0.60-1.53) / 1.07 (0.67-1.72) / 0.82 (0.64-1.05)
Q3 (88-93) / 1.09 (0.89-1.35) / 1.30 (0.84-2.01) / 1.52 (0.98-2.35) / 0.98 (0.77-1.23)
Q4 (94-140) / 1.23 (1.00-1.50) / 1.27 (0.82-1.97) / 1.72 (1.12-2.64) / 1.07 (0.85-1.34)
Linear effect (53-140) / 1.11 (1.04-1.19) / 1.17 (1.01-1.35) / 1.25 (1.09-1.44) / 1.03 (0.95-1.12)
Adjusted analysis
Q1(53-80) / Reference / Reference / Reference / Reference
Q2 (81-87) / 0.84 (0.68-1.05) / 0.91 (0.57-1.46) / 1.03 (0.64-1.66) / 0.79 (0.62-1.01)
Q3 (88-93) / 1.04 (0.84-1.28) / 1.14 (0.73-1.78) / 1.46 (0.94-2.27) / 0.95 (0.75-1.21)
Q4 (94-140) / 1.17 (0.95-1.44) / 1.11 (0.71-1.74) / 1.65 (1.07-2.56) / 1.06 (0.84-1.34)
Linear effect (53-140) / 1.10 (1.02-1.18) / 1.12 (0.96-1.31) / 1.24 (1.08-1.44) / 1.03 (0.95-1.12)
PP quartile
(range, mmHg)
Crude analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.99 (0.79-1.24) / 1.05 (0.63-1.75) / 1.15 (0.69-1.90) / 0.94 (0.72-1.22)
Q3 (62-73) / 1.08 (0.87-1.34) / 1.33 (0.83-2.14) / 1.73 (1.10-2.72) / 1.09 (0.85-1.38)
Q4 (74-144) / 1.31 (1.07-1.62) / 1.68 (1.07-2.64) / 1.67 (1.06-2.64) / 1.28 (1.01-1.63)
Linear effect (13-144) / 1.07 (1.02-1.11) / 1.14 (1.04-1.24) / 1.13 (1.04-1.23) / 1.06 (1.01-1.11)
Adjusted analysis
Q1 (13-50) / Reference / Reference / Reference / Reference
Q2 (51-61) / 0.95 (0.75-1.19) / 0.94 (0.56-1.58) / 1.14 (0.69-1.90) / 0.92 (0.70-1.19)
Q3 (62-73) / 0.98 (0.79-1.22) / 1.10 (0.68-1.77) / 1.65 (1.05-2.60) / 1.00 (0.78-1.28)
Q4 (74-144) / 1.16 (0.94-1.43) / 1.34 (0.84-2.13) / 1.56 (0.98-2.48) / 1.15 (0.90-1.46)
Linear effect (13-144) / 1.04 (0.99-1.08) / 1.08 (0.98-1.18) / 1.12 (1.02-1.22) / 1.03 (0.98-1.09)

Supplementary Figure 1 Estimated restricted cubic splines of the adjusted effects of systolic, diastolic blood pressure and pulse pressure. Reference levelsare 120 mmHg systolic, 80 mmHg diastolic, and 40 mmHg pulse pressure. Individual blood pressure measurements are marked on the horizontal axes. Only HF patients with no hypertension treatment history (N=960).

Supplementary Figure 2 Estimated restricted cubic splines of the adjusted effects of systolic, diastolic blood pressure and pulse pressure. Reference levelsare 120 mmHg systolic, 80 mmHg diastolic, and 40 mmHg pulse pressure. Individual blood pressure measurements are marked on the horizontal axes. Only HF patients with no history of atrial fibrillationdiagnosis (N=1566).