Metastatic malignancies and the effect on arterial stiffness and blood pressure levels: the possible role of chemotherapy

Figures & data

Table 1 Treatment regimen by cancer type

Cancer type	Drug	n	Number of cycles median (range)	Dose (mg) median (range)
Kidney	Sunitinib	49	6 (3–6)	50 (25–50)
	Pazopanib	11	6 (2–6)	800 (400–800)
GIST	Imatinib	18	6 (6–6)	400 (400–400)
Bowel	Panitumumab	93	8 (3–8)	530 (250–900)
	Oxaliplatin	44	8 (4–8)	190 (140–480)
	Irinotecan	28	8 (6–8)	343 (240–410)
	Capecitabine	21	6 (3–8)	1,300 (200–2,000)

Abbreviation: GIST, gastrointestinal stromal tumor.

Table 2 Patient baseline characteristics

Characteristics	Entire cohort (n=171)	Kidney (n=60)	GIST (n=18)	Bowel (n=93)
Age (years)
Mean (SD)	62.9 (10.7)	57.9 (10.0)	67.4 (6.7)	65.2 (10.7)
Median	65	55.5	68.5	67
Range	29–80	38–75	54–79	29–80
Sex
Male	124 (72.5%)	42 (70%)	11 (61.1%)	71 (76.3%)
Female	47 (27.5%)	18 (30%)	7 (38.9%)	22 (23.7%)
Surgery
Inoperable	102 (59.6%)	13 (21.7%)	18 (100%)	89 (95.7%)
Operable	69 (40.4%)	47 (78.3%)	–	4 (4.3%)
Waist:hip ratio
Mean (SD)	0.88 (0.06)	0.89 (0.05)	0.86 (0.06)	0.88 (0.07)
Median	0.9	0.9	0.88	0.9
Range	0.7–0.95	0.76–0.95	0.70–0.94	0.70–0.95
Body-mass index
Mean (SD)	27.3 (6.5)	26.8 (6.0)	25.2 (7.7)	28 (6.5)
Median	27.8	26.4	24.9	28.5
Range	14.3–45.7	15.4–42.5	15.5–45.7	14.3–42.5
Cycles of chemotherapy
Mean (SD)	6.43 (1.5)	5.5 (1.2)	6.0 (–)	7.1 (1.5)
Median	6	6	6	8
Range	2–8	2–6	6–6	3–8

Abbreviation: GIST, gastrointestinal stromal tumor.

Table 3 Selected study parameters before and after chemotherapy by cancer type

Parameters	Kidney (n=60)		GIST (n=18)		Bowel (n=93)
	Before	After	Before	After	Before	After
SBP (mmHg)
Mean (SD)	134.2 (17.4)	134.6 (18.9)	126.5 (12.7)	129.8 (15.8)	137.3 (12.3)	133.5 (11.7)
Median	135	130	121.5	130	140	135
Range	105–169	100–178	110–146	105–150	110–160	105–156
DBP (mmHg)
Mean (SD)	72.6 (8.9)	70.0 (5.8)	72.6 (7.6)	74.4 (9.7)	73.4 (8.3)	72.9 (8.2)
Median	74.5	70	70	70	70	70
Range	60–87	60–82	65–90	65–98	60–90	60–98
Pulse
Mean (SD)	69.5 (6.3)	71.6 (6.2)	72.3 (8.1)	72.8 (9.0)	71.6 (6.9)	73.3 (7.0)
Median	70	70	71	70.5	70	73
Range	52–86	52–80	55–92	60–96	55–92	60–96
EF (%)
Mean (SD)	59.8 (3.4)	57.8 (4.3)	58.1 (4.6)	57.5 (4.9)	59.1 (3.6)	58.4 (4.0)
Median	60	58	60	60	60	60
Range	55–65	40–65	50–65	45–65	50–65	45–65
AIx75 (%)
Mean (SD)	19.03 (2.42)	20.9 (2.8)	17.5 (2.2)	18.7 (2.8)	17.2 (2.7)	21.8 (4.4)
Median	18.95	21.3	17.3	18	17.2	21.5
Range	14.5–25.2	15.6–28.6	14.3–21.3	14.6–24	12.5–28	14.5–33
PWVc-r (m/s)
Mean (SD)	7.2 (0.5)	7.9 (0.7)	7.7 (0.8)	8.3 (1.0)	7.7 (0.7)	8.6 (1.0)
Median	7.2	7.9	7.7	8.1	7.6	8.5
Range	6.2–7.9	6.5–9.2	6.5–9.2	6.9–10.6	6.5–10.0	6.9–11.4
PWVc-f (m/s)
Mean (SD)	7.3 (0.7)	8.1 (0.7)	7.4 (0.6)	8.2 (0.6)	7.6 (0.6)	8.4 (0.6)
Median	7.2	8	7.3	8	7.5	8.3
Range	5.6–8.9	6.5–9.5	6.5–8.6	7.2–9.2	6.3–9.5	7.2–10.7
ESR
Mean (SD)	11.8 (10.7)	12.4 (12.0)	7.6 (2.1)	9.1 (2.7)	7.7 (2.9)	7.3 (2.6)
Median	10	10	7	9	7	7
Range	5–55	4–95	5–12	5–15	5–15	5–15
CRP
Mean (SD)	5.8 (3.3)	7.0 (4.6)	5.5 (1.0)	5.6 (0.9)	6.1 (7.6)	5.5 (2.9)
Median	5.3	6.1	5.3	5.3	5	5
Range	4–30	4–40.5	4.3–8	4.3–7.5	3.0–77.2	3–30
Neutrophils
Mean (SD)	6.7 (4.8)	4.9 (3.0)	5.7 (2.1)	4.3 (2.0)	5.5 (3.1)	4.3 (2.3)
Median	5.3	4.3	5.4	4	4.9	4
Range	2.4–28.2	1.2–15.6	1.8–8.9	1.2–8.1	1.6–17.3	1.2–12.5
Hb
Mean (SD)	12.2 (1.3)	11.4 (1.9)	12.3 (1.2)	11.0 (1.2)	12.8 (1.7)	11.6 (1.9)
Median	12.3	11	12.3	10.8	12.6	11.5
Range	9.1–14.8	7.5–15.6	10.6–14.6	8.6–13	9.1–17.6	7.9–15
Plt
Mean (SD)	253.3 (117.0)	230.1 (83.8)	270.3 (126.8)	203.9 (55.4)	259.4 (102.1)	229.9 (53.2)
Median	240	215	247.5	196.5	236	219
Range	116–729	110–446	145–729	145–350	124–729	130–350
CrCl
Mean (SD)	58.4 (11.9)	58.1 (11.7)	63.2 (10.9)	63.0 (9.9)	64.4 (12.4)	60.2 (18.0)
Median	58	56.5	59	62	60	60
Range	30–90	31–86	50.2–89	51.3–86	50.7–112	1.1–112
Cr
Mean (SD)	1.3 (0.4)	1.3 (0.4)	1.1 (0.2)	1.2 (0.2)	1.0 (0.2)	1.2 (1.0)
Median	1.2	1.3	1.1	1.2	1	1
Range	0.8–2.6	0.8–2.6	0.8–1.5	0.8–1.5	0.6–1.5	0.6–6
Bil
Mean (SD)	0.7 (0.4)	0.8 (0.4)	0.6 (0.3)	0.7 (0.3)	0.6 (0.4)	0.8 (0.4)
Median	0.6	0.6	0.6	0.6	0.5	0.7
Range	0.3–1.6	0.3–2.2	0.3–1.6	0.4–1.5	0.1–2.5	0.1–2.2
SGOT
Mean (SD)	24.2 (19.8)	34.0 (23.4)	20.5 (9.8)	21.9 (5.3)	24.2 (12.8)	22.8 (8.1)
Median	20	25	16	21.5	20	21
Range	10–125	14–120	10–42	15–32	10–86	10–38
SGPT
Mean (SD)	26.0 (24.4)	37.3 (30.9)	17.6 (5.2)	24.8 (6.7)	25.4 (18.0)	25.9 (9.2)
Median	20	28	16	24.5	17	28
Range	12–166	13–175	12–31	15–36	10–84	12–55
ALP
Mean (SD)	108.4 (47.9)	105.1 (42.0)	79.4 (23.4)	82.8 (21.4)	156.7 (155.8)	135.6 (95.7)
Median	98	93.5	78.5	77.5	111	110
Range	68–352	54–295	42–121	52–124	42–926	11–473
CEA
Mean (SD)	1.5 (1.6)	1.5 (1.6)	1.2 (0.4)	1.2 (0.3)	98.2 (427.0)	59.2 (149.1)
Median	1.2	1	1	1	7.2	5
Range	0.5–10	0.5–10	0.9–2.3	0.9–2	0.6–4,011.7	0.5–1,097

Abbreviations: AIx75, augmentation index (heart rate-corrected); ALP, alkaline phosphatase; Bil, bilirubin; CEA, carcinoembryonic antigen; Cr, creatinine; CrCl, Cr clearance; CRP, c-reactive protein; DBP, diastolic blood pressure; EF, ejection fraction; ESR, erythrocyte-sedimentation rate; GIST, gastrointestinal stromal tumor; Hb, hemoglobin; Plt, platelet; PWV, pulse wave velocity; PWVc-f, carotid–femoral PWV; PWVc-r, carotid–radial PWV; SBP, systolic BP; SGOT, serum glutamic-oxaloacetic; SGPT, serum glutamic pyruvic transaminase.

Table 4 Differences in SBP, DBP, EF, AIx75, PWVc-r, and PWVc-f before and after chemotherapy in the total cohort and by cancer type

Status	Median (range)			P-valuea	Adjusted P-value
	Kidney (n=60)	GIST (n=18)	Bowel (n=93)
Before chemotherapy
SBP	135 (105–169)	121.5 (110–146)	140 (110–160)	0.013	0.012b
DBP	74.5 (60–87)	70 (65–90)	70 (60–90)	0.83	0.84b
EF	60 (55–65)	60 (50–65)	60 (50–65)	0.34	0.16b
AIx75	18.95 (14.5–25.2)	17.3 (14.3–21.3)	17.2 (12.5–28)	<0.001	<0.001c
PWVc-r	7.15 (6.2–7.9)	7.65 (6.5–9.2)	7.6 (6.5–10)	<0.001	<0.001c
PWVc-f	7.2 (5.6–8.9)	7.25 (6.5–8.6)	7.5 (6.3–9.5)	0.018	0.022c
Difference postchemotherapy
SBP	0 (−25 to 33)	4.5 (−13 to 33)	−5 (−40 to 15)	0.054	0.021b
DBP	−3.5 (−24 to 17)	2 (−10 to 15)	0 (−25 to 15)	0.23	0.15b
EF	0 (−20 to 5)	0 (−5 to 5)	0 (−5 to 5)	0.026	0.029b
AIx75	1.75 (−1 to 11)	1.4 (−1.7 to 5.7)	3.6 (0.4–17.2)	<0.001	<0.001c
PWVc-r	0.6 (−0.4 to 2.2)	0.4 (0.1–1.4)	0.7 (0–4.2)	0.09	0.085c
PWVc-f	0.7 (−0.4 to 2.9)	0.7 (0.1–1.5)	0.8 (−0.1 to 2.4)	0.93	0.81c

Notes: Values in bold denote significance (P<0.05). Patients with metastatic colorectal cancer were divided into subgroups according to the type of chemotherapy they received: 44 oxaliplatin-based chemotherapy, 28 irinotecan-based chemotherapy, and 21 capecitabine-based chemotherapy. Further analysis of central hemodynamics was performed on the three subgroups, and results are presented in Table 5. Comparison of differences among the three subgroups of chemotherapy showed no significant difference between AIx and PWVc-r; however, PWVc-f exhibited higher mean change in the irinotecan subgroup compared to oxaliplatin and capecitabine in the adjusted model (0.95 [0.2–2.4] vs 0.8 [−0.1 to 1.6] vs 0.5 [0.1–1.7], P=0.024, respectively).

a Kruskal-Wallis p;

b p-value estimated using ANCOVA with gender and BMI as covariates;

c p-value estimated using ANCOVA with gender, BMI, SBP (at baseline) and DPB (at baseline) levels as covariates.

Abbreviations: AIx75, augmentation index (heart rate-corrected); DBP, diastolic blood pressure; EF, ejection fraction; PWV, pulse wave velocity; PWVc-f, carotid–femoral PWV; PWVc-r, carotid–radial PWV; SBP, systolic BP; GIST, gastrointestinal stromal tumor.

Table 5 Differences in SBP, DBP, EF, AIx75, PWVc-r, and PWVc-f before and after chemotherapy in the subgroup of bowel cancer patients by treatment regimen

Variables	Median (range)		P-value*
	Before	After
Overall (n=93)
SBP	140 (110–160)	135 (105–156)	0.007
DBP	70 (60–90)	70 (60–98)	0.63
EF	60 (50–65)	60 (45–65)	0.007
AIx75	17.2 (12.5–28)	21.5 (14.5–33)	<0.001
PWVc-r	7.6 (6.5–10)	8.5 (6.9–11.4)	<0.001
PWVc-f	7.5 (6.3–9.5)	8.3 (7.2–10.7)	<0.001
Oxaliplatin-based (n =44)
SBP	140 (110–160)	130 (105–156)	0.003
DBP	70 (60–90)	70 (60–85)	0.71
EF	60 (55–65)	60 (50–65)	0.072
AIx75	16.4 (12.5–28)	19.5 (15.6–32)	<0.001
PWVc-r	7.4 (6.5–8.6)	8.2 (7–11.4)	<0.001
PWVc-f	7.5 (6.3–8.8)	8.2 (7.2–9.1)	<0.001
Irinotecan-based (n =28)
SBP	145.5 (120–155)	140 (110–156)	0.21
DBP	80 (70–90)	70 (60–98)	0.002
EF	60 (50–65)	60 (55–65)	0.57
AIx75	18.5 (14.5–23)	23.9 (17.2–31.5)	<0.001
PWVc-r	8 (7.4–10)	8.9 (8.1–11)	<0.001
PWVc-f	7.95 (6.5–9.5)	8.6 (8.3–10.7)	<0.001
Capecitabine-based (n =21)
SBP	136 (120–145)	130 (112–150)	0.74
DBP	69 (60–80)	70 (60–85)	0.012
EF	60 (50–65)	60 (45–65)	0.057
AIx75	17.2 (12.5–20)	21.3 (14.5–33)	<0.001
PWVc-r	7.5 (6.9–8.1)	8.5 (6.9–9.8)	<0.001
PWVc-f	7.2 (6.3–8.1)	7.8 (7.5–9)	<0.001

Notes:

* Wilcoxon signed-rank test. Values in bold denote significance (P<0.05).

Abbreviations: AIx75, augmentation index (heart rate-corrected); DBP, diastolic blood pressure; EF, ejection fraction; SBP, systolic blood pressure; PWV, pulse wave velocity; PWVc-f, carotid–femoral PWV; PWVc-r, carotid–radial PWV.

Table 6 Multiple regression analysis with SBP, DBP, EF, AIx75, PWVc-f, and PWVc-r pre- and postchemotherapy as dependent variables

Variables	β	SE (β)	P-value
SBP difference (after – before)
GIST vs bowel	3.88	2.98	0.19
Kidney vs bowel	3.31	1.87	0.078
Sex (female)	3.52	1.94	0.071
BMI	0.20	0.13	0.14
SBP at baseline	−0.30	0.06	<0.001
SBP difference (after – before)
GIST vs bowel	1.86	1.89	0.33
Kidney vs bowel	−2.64	1.21	0.030
Sex (female)	−0.41	1.25	0.75
BMI	0.001	0.09	0.99
DBP at baseline	−0.70	0.07	<0.001
EF difference (after – before)
GIST vs bowel	−0.14	0.80	0.87
Kidney vs bowel	−1.19	0.51	0.021
Sex (female)	−0.96	0.53	0.071
BMI	−0.07	0.04	0.071
EF at baseline	−0.21	0.06	0.002
AIx75 difference (after – before)
GIST vs bowel	−3.28	0.72	<0.001
Kidney vs bowel	−2.66	0.49	<0.001
Sex (female)	−0.02	0.49	0.97
BMI	0.01	0.03	0.79
AIx75 at baseline	0.01	0.09	0.92
PWVc-r difference (after – before)
GIST vs bowel	−0.24	0.16	0.14
Kidney vs bowel	−0.19	0.11	0.089
Sex (female)	0.001	0.11	0.99
BMI	0.02	0.01	0.001
PWVc-r at baseline	−0.09	0.08	0.24
PWVc-f difference (after – before)
GIST vs bowel	−0.08	0.13	0.53
Kidney vs bowel	−0.06	0.08	0.44
Sex (female)	0.09	0.08	0.29
BMI	0.01	0.01	0.15
PWVc-f at baseline	−0.40	0.06	<0.001

Note: Values in bold denote significance (P<0.05).

Abbreviations: AIx75, augmentation index (heart rate-corrected); BMI, body-mass index; DBP, diastolic blood pressure; GIST, gastrointestinal stromal tumor; PWV, pulse wave velocity; PWVc-f, carotid–femoral PWV; PWVc-r, carotid–radial PWV; SBP, systolic BP; EF, ejection fraction.