Serum Phosphate and Microvascular Function in a Population-Based Cohort

Charles Ginsberg; Alfons J.H.M. Houben; Rakesh Malhotra; Tos T.J.M. Berendschot; Pieter C. Dagnelie; Jeroen P. Kooman; Caroll A. Webers; Coen D.A. Stehouwer; Joachim H. Ix

doi:10.2215/CJN.02610319

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Figure 1.
Maastricht population for each microvascular end point. BMI, body mass index; LDF, laser-Doppler flowmetry.
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Figure 2.
Percentage capillary recruitment during postocclusive reactive hyperemia is lower at higher phosphate quartiles. Phosphate quartile ranges were (Q1) 1.6–2.8 mg/dl, (Q2) 2.9–3.2 mg/dl, (Q3) 3.2–3.6 mg/dl, and (Q4) 3.6–5.2 mg/dl. Values presented are adjusted for age, sex, smoking status, 24-hour ambulatory systolic BP, use of antihypertensives, use of lipid modifying agents, diabetes status, eGFR, and serum calcium.

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Table 1.

Baseline characteristics of participants by serum phosphate quartiles

Characteristics	Phosphate Quartiles (Range)
	Q1 (1.6–2.8 mg/dl)	Q2 (2.9–3.2 mg/dl)	Q3 (3.2–3.6 mg/dl)	Q4 (3.6–5.2 mg/dl)
	n=809	n=855	n=781	n=744
Age (yr [±SD])	60 (9)	60 (8)	60 (8)	59 (8)
Male (n [%])	644 (80)	549 (64)	307(39)	159 (21)
BMI (kg/m² [±SD])	28 (4.2)	27 (4.3)	27 (4.5)	26 (5.1)
Smoking (n [%])
Never	283 (35)	297 (36)	260 (34)	226 (31)
Former	433 (54)	429 (51)	394 (51)	375 (52)
Current	82 (10)	110 (13)	118 (15)	123 (17)
Diabetes status (n [%])^a
Normal	424 (52)	462 (54)	453 (58)	438 (59)
Prediabetes	152 (19)	119 (14)	104 (13)	92 (12)
Type 2 diabetes	233 (29)	274 (32)	224 (29)	214 (29)
HbA1C (% [±SD])	5.9 (0.9)	5.9 (0.9)	5.9 (0.9)	6.0 (1.0)
Retinopathy (n [%])	10 (1)	12 (2)	12 (2)	16 (2)
Cardiovascular disease (n [%])	117 (15)	145 (17)	131 (17)	118 (17)
BP (mm Hg [±SD])
Office systolic BP	139 (17)	136 (18)	134 (18)	130 (18)
Office diastolic BP	79 (10)	76 (10)	75 (10)	74 (10)
24-h systolic BP	122 (11)	120 (12)	118 (12)	116 (11)
24-h diastolic BP	76 (7)	74 (7)	73 (7)	72 (7)
BP medication (n [%])	331 (41)	380 (45)	304 (39)	270 (36)
Hyperlipidemia medication (n [%])	303 (37)	337 (40)	273 (35)	257 (35)
eGFR (ml/min per 1.73 m² [±SD])	81 (18)	82 (17)	81 (16)	80 (17)
CKD stage (n [%])
None (eGFR >60 ml/min per 1.73 m²)	760 (94)	782 (91)	722 (92)	695 (93)
CKD stage 3a	45 (6)	63 (7)	54 (7)	39 (5)
CKD stage 3b	4 (0.5)	10 (1)	5 (1)	8 (1)
CKD stage 4	0 (0)	0 (0)	0 (0)	2 (0.3)
Urine albumin/creatinine ratio (mg/g [±IQR])	4 (2–8)	5 (3–9)	5 (3–10)	5 (2–8)
Calcium (mg/dl [±SD])	9.3 (0.4)	9.3 (0.3)	9.4 (0.3)	9.4 (0.3)

The upper range of Q2 was 3.19, the lower range of Q3 was 3.22, the upper range of Q3 was 3.56, and the lower range of Q4 was 3.60.
BMI, body mass index; HbA1C, hemoglobin A1c; IQR, interquartile range.
↵a Glucose metabolism status was assessed by an oral glucose tolerance test and defined according to the World Health Organization 2006 criteria as normal glucose metabolism, impaired fasting glucose, impaired glucose tolerance (combined as prediabetes), and type 2 diabetes mellitus.

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Table 2.

Association of phosphate with microvascular measurements

Measurement Used (% [95% CI])	Measurement Results per Phosphate Range Quartile				Per 1 mg/dl Higher Serum Phosphate	P^a
Measurement Used (% [95% CI])	Q1 (1.6–2.8 mg/dl)	Q2 (2.9–3.2 mg/dl)	Q3 (3.2–3.6 mg/dl)	Q4 (3.6–5.2 mg/dl)	Per 1 mg/dl Higher Serum Phosphate	P^a
Capillary recruitment during postocclusive reactive hyperemia (n=659)
Model 1	Reference	−7.1 (−13.3 to −0.8)	−7.1 (−13.6 to −0.6)	−8.7 (−15.9 to −1.6)	−5.2 (−10.1 to −0.4)	0.04
Model 2	Reference	−6.6 (−12.8 to −0.3)	−6.3 (−12.8 to 0.3)	−8.4 (−15.6 to −1.1)	−5.0(−10.0 to −0.1)	0.04
Capillary recruitment during venous congestion (n=659)
Model 1	Reference	−5.6 (−12.3 to 1.0)	−6.0 (−12.9 to 0.90)	−8.1 (−15.7 to −0.5)	−4.7 (−9.8 to 0.5)	0.08
Model 2	Reference	−5.2 (−11.7 to 1.6)	−5.0 (−11.9 to 2.0)	−7.9 (−15.6 to −0.1)	−4.5 (−9.8 to 0.7)	0.09
Heat-induced skin hyperemic response (n=1306)
Model 1	Reference	−132 (−242 to −22)	−112 (−230 to 6)	−120 (−249 to 8)	−53 (−140 to 35)	0.24
Model 2	Reference	−117 (−226 to −7)	−92 (−211 to 27)	−81 (−211 to 415)	−25 (−113 to 63)	0.57
Retinal arteriolar dilation (n=1834)
Model 1	Reference	−0.18 (−0.53 to 0.18)	−0.12 (−0.50 to 0.25)	−0.21 (−0.61 to 0.20)	−0.19 (−0.47 to 0.07)	0.15
Model 2	Reference	−0.11 (−0.46 to 0.24)	−0.05 (−0.43 to 0.33)	−0.09 (−0.50 to 0.32)	−0.12 (−0.30 to 0.15)	0.39
Retinal venular dilation (n=1834)
Model 1	Reference	−0.02 (−0.29 to 0.26)	−0.25 (−0.54 to 0.05)	−0.41 (−0.73 to −0.10)	−0.26 (−0.47 to −0.05)	0.01
Model 2	Reference	0.03 (−0.24 to 0.31)	−0.20 (−0.49 to 0.10)	−0.35 (−0.66 to −0.03)	−0.23 (−0.44 to −0.02)	0.03

The upper range of Q2 was 3.19, the lower range of Q3 was 3.22, the upper range of Q3 was 3.56, and the lower range of Q4 was 3.60.
Model 1 adjusted for age and sex; model 2 additionally adjusted for body mass index, smoking status, 24-h ambulatory systolic BP, use of antihypertensives, use of lipid-modifying agents, glucose metabolism status, eGFR, and serum calcium.
↵a P values reported for the continuous analysis.

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Table 3.
Association of serum phosphate with heat-induced skin hyperemic response, stratified by sex
Sex Change per 1 mg/dl Higher Phosphate (% [95% CI])^a P Value P Interaction
Men −149 (−260 to −38) 0.01 0.01
Women 88 (−55 to 230) 0.23
↵a Adjusted for age, sex, body mass index, smoking status, 24-h ambulatory systolic BP, use of antihypertensives, use of lipid-modifying agents, diabetes status, eGFR, and serum calcium.