The Optimal Haemoglobin Target in Dialysis Patients May Be Determined by Its Contrasting Effects on Arterial Stiffness and Pressure Pulsatility

Figures & data

Table 1 Recorded Patient Characteristics in 48 Dialysis Patients

Demographics
Age (years)	55.8 (14.3)	Dialysis duration (months)	24 (12–36)
Female sex	22 (45.8)	Phosphate (mmol/l)	1.4 (0.9–1.8)
Black	27 (56.25)	Calcium (mmol/l)	2.3 (2.1–2.4)
Asian	11 (22.92)	Calcium x phosphate	3.0 (2.2–4.0)
Mixed	6 (12.5)	Phosphate binder use	35 (79.5)
White	4 (8.33)	High phosphate	44 (83.3)
Lifestyle		IPTH	470.3 (182.0–785.8)
Alcohol use (units per week)	1 (2.1)	High sensitivity CRP (mg/l)	8.9 (2.5–29.9)
Current smoker	0 (0)	Haemoglobin (g/dl)	10.8 (1.7)
Ex-smoker	4 (8.3)	Transferrin saturation (%)	22.9 (19.1–28.9)
Anthropometry		Ferritin (ng/mL)	361 (128–654)
Body mass index (kg/m^2)	26.8 (5.6)	Albumin (g/l)	37.9 (6.5)
Waist (cm)	99 (16)	Vitamin D (nmol/l)	19.7 (9.0)
Waist-hip ratio	0.98 (0.09)	Uric acid (mmol/l)	0.28 (0.12)
Weight (kg)	74.7 (14.7)	ESA use	43 (89.6)
Height (m)	1.67 (0.11)	Cardiovascular disease	14 (29.2)
Waist-height ratio	0.60 (0.11)	Heart Failure	7 (14.6)
Major traditional risk factors		Arterial function
Hypertension	44 (91.7)	Pulse wave velocity (m/sec)	11.2 (7.8–14.9)
Systolic BP (mmHg)	146 (22)	Augmentation index (%)	27.1 (16.2)
Diastolic BP (mmHg)	85 (14)	Reflected wave pressure (mmHg)	25.0 (15.0–29.5)
Mean BP	105 (14)	Reflection magnitude (%)	67.0 (16.6)
Heart rate (beats/min)	75 (17)	Central systolic BP (mmHg)	136 (22)
Dyslipidemia	30 (71.4)	Central pulse pressure (mmHg)	49 (17)
Total cholesterol (mmol/l)	4.3 (1.1)	Pulse pressure amplification	132 (29)
LDL cholesterol (mmol/l)	2.4 (1.0)	Forward wave pressure (mmHg)	35 (11)
HDL cholesterol (mmol/l)	1.13 (0.90–1.55)	Other hemodynamics
Non-HDL cholesterol (mmol/l)	3.1 (1.0)	Stroke volume (mL/beat)	71.4 (26.0)
Triglycerides (mmol/l)	1.33 (0.88–1.80)	Cardiac output (l/min)	5.5 (2.2)
Diabetes	19 (39.6)	Stroke work (gram-meters/beat)	153.2 (66.8)
ACEI/ARB therapy	37 (77.1)	Left ventricular mass index (g/m2)	103.4 (51.0)
Non-traditional/renal risk factors		SVR (mmHg/l/min)	20.4 (15.2–24.3)

Notes: Data are expressed as mean (SD), median (interquartile range) or number (%).

Abbreviations: BP, blood pressure; LDL, low density lipoprotein; HDL, high density lipoprotein; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; iPTH, intact parathyroid hormone; CRP, C-reactive protein; ESA, erythropoietin stimulating agent; SVR, systemic vascular resistance.

Table 2 Associations of Haemoglobin Concentrations with Arterial Function in 48 Dialysis Patients

	Model 1^a				Model 2^b				Model 3^c				Model 4^d				Model 5^e
Arterial Function Parameter	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2
Log PWV	0.030(0.015)	0.329	0.05	0.314	0.031(0.014)	0.366	0.03	0.450	0.031(0.014)	0.378	0.03	0.476	0.031(0.014)	0.375	0.03	0.468	0.031(0.014)	0.374	0.03	0.461
Aix	1.835(1.215)	0.232	0.1	0.552	1.920(1.183)	0.284	0.1	0.589	1.954(1.192)	0.291	0.1	0.589	1.946(1.220)	0.293	0.1	0.588	1.920(1.192)	0.238	0.1	0.597
Log RWP	−0.027(0.014)	−0.322	0.07	0.552	−0.026(0.014)	−0.323	0.07	0.586	−0.026(0.014)	−0.321	0.08	0.587	−0.020(0.014)	−0.262	0.2	0.613	−0.026(0.014)	−0.324	0.08	0.588
Rm	1.951(1.226)	0.275	0.1	0.430	2.044(1.184)	0.301	0.1	0.592	2.076(1.194)	0.307	0.09	0.599	1.995(1.224)	0.299	0.1	0.582	2.052(1.190)	0.305	0.1	0.601
CSBP	−2.231(1.035)	−0.347	0.03	0.798	−2.150(1.022	−0.344	0.04	0.809	−2.151(1.038)	−0.344	0.04	0.809	−1.514(1.091)	−0.246	0.1	0.816	−2.153(1.039)	−0.344	0.04	0.810
CPP	−3.126(1.227)	−0.400	0.01	0.541	−3.005(1.189)	−0.403	0.01	0.583	−3.004(1.208)	−0.402	0.01	0.583	−2.357(1.208)	−0.336	0.06	0.480	−3.003(1.208)	−0.402	0.01	0583
PPP	−5.828(1.616)	−0.510	0.001	0.390	−5.831(1.589)	−0.521	0.001	0.426	−5.807(1.612)	−0.520	0.001	0.426	−5.570(1.670)	−0.502	0.002	0.424	−5.599(1.611)	−0.506	0.001	0.43
PPamp	−2.838(2.138)	−0.222	0.2	0.502	−2.856(2.173)	−0.223	0.2	0.502	−2.851(2.206)	−0.223	0.2	0.503	−3.531(2.280)	−0.272	0.1	−0.530	−2.939(2.160)	−0.234	0.1	0.524
FWP	−3.111(0.862)	−0.544	0.001	0.480	−3.087(0.870)	−0.544	0.001	0.489	−3.080(0.884)	−0.543	0.002	0.490	−2.658(0.858)	−0.512	0.005	0.546	−3.091(0.880)	−0.546	0.001	0.49

Notes: Significant associations are shown in bold. ^aAdjusted for age, sex, race, height, weight, mean arterial pressure and heart rate. ^bAdjusted for age, sex, race, height, weight, mean arterial pressure, heart rate and diabetes. ^cAdjusted for age, sex, race, height, weight, mean arterial pressure, heart rate, diabetes and heart failure. ^dAdjusted for age, sex, race, height, weight, mean arterial pressure, heart rate, diabetes and angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy. ^eAdjusted for age, sex, race, height, weight, mean arterial pressure, heart rate, diabetes and erythropoietin stimulating agent therapy.

Abbreviations: β, regression coefficient; Log, logarithmically transformed; PWV, pulse wave velocity; Aix, augmentation index; RWP, reflected wave pressure; Rm, reflection; magnitude; CSBP, central systolic blood pressure; CPP, central pulse pressure; PPP, peripheral pulse pressure; PPamp, pulse pressure amplification; FWP, forward wave pressure.

Table 3 Associations of Haemoglobin Concentrations with Arterial Function in Sensitivity Analyses Among Patients Without Heart Failure and on ACEI or ARB and ESA Agent Therapy

	Patients without Heart Failure (n=41)				Patients on ACEI or ARB Therapy (n=37)				Patients on ESA Therapy (n=43)
Arterial Function Parameter	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2	β (SD)	Partial R	P	Model R^2
Log PWV	0.037 (0.015)	0.435	0.01	0.390	0.031 (0.017)	0.357	0.07	0.440	0.031 (0.014)	0.376	0.03	0.409
Aix	2.347 (1.212)	0.355	0.06	0.621	1.792 (1.399)	0.269	0.2	0.519	2.097 (1.030)	0.365	0.05	0.677
Log RWP	−0.020 (0.014)	−0.264	0.2	0.550	−0.027 (0.016)	−0.350	0.1	0.643	−0.026 (0.014)	−0.327	0.08	0.537
Rm	2.509 (1.203)	0.378	0.04	0.626	1.861 (1.405)	0.278	0.2	0.512	2.225 (1.015)	0.389	0.03	0.687
CSBP	1.971 (1.017)	−0.334	0.07	0.796	−1.994 (1.159)	−0.338	0.09	0.824	−2.149 (1.051)	0.239	0.1	0.773
CPP	−2.809 (1.212)	−0.407	0.02	0.555	−2.697 (1.230)	−0.416	0.03	0.644	−3.011 (1.244	0.404	0.02	0.535
PPP	−5.476 (1.723)	−0.508	0.004	0.382	−6.344 (1.807)	−0.567	0.002	0.447	−5.406 (1.763)	−0.482	0.004	0.336
PPamp	−2.862 (2.484)	−0.216	0.3	0.496	−4.199 (2.764)	−0.302	0.1	0.525	−3.149 (2.091)	−0.265	0.1	0.557
FWP	−2.888 (0.922)	−0.524	0.004	0.437	−2.190 (2.008)	−0.588	0.003	0.587	−3.125 (0.903)	−0.554	0.002	0.445

Notes: Associations were assessed in age, sex, race, weight, height, heart rate, mean arterial pressure and diabetes adjusted linear regression models. Significant associations are shown in bold.

Abbreviations: β, regression coefficient; Log, logarithmically transformed; PWV, pulse wave velocity; Aix, augmentation index; RWP, reflected wave pressure; Rm, reflection magnitude; CSBP, central systolic blood pressure; CPP, central pulse pressure; PPP, peripheral pulse pressure; PPamp, pulse pressure amplification; FWP, forward wave pressure.

Figure 1 Receiver operator characteristic curves showing the accuracy of haemoglobin concentrations in predicting the presence of arterial stiffness (pulse wave velocity >10 m/sec) (A) and a normal central pulse pressure (<50 mmHg) (B).

Abbreviation: AUC, area under the curve.

Table 4 Bivariate Associations Among Haemoglobin Concentrations and Hemodynamic Variables

	Haemoglobin	Log SVR	Stroke Volume	Cardiac Output	Stroke Work	LVMI
Haemoglobin	–
Log SVR	0.285 (0.05)	–
Stroke volume	−0.290 (0.05)	−0.869 (<0.0001)	–
Cardiac output	−0.319 (0.03)	−0.926 (<0.0001)	0.910 (<0.0001)	–
Stroke work	−0.367 (0.01)	−0.732 (<0.0001)	0.925 (<0.0001)	0.867 (<0.0001)
LVMI	−0.154 (0.3)	−0.359 (0.01)	0.346 (0.01)	0.409 (0.005)	0.337 (0.02)	–

Notes: Results are expressed as Pearson correlation (p). Significant associations are shown in bold.

Abbreviations: Log, logarithmically transformed; SVR, systemic vascular resistance; LVMI, left ventricular mass index.