Supplementary Fig. 1
Hazard ratio (HR) and 95% confidence interval (CI) for standard deviation (SD) of systolic blood pressure (SBP) with cardiovascular disease by using restricted cubic splines with four knots placed at 5, 7.5, 10, 15 mm Hg. Data were adjusted for age, sex, smoking status, alcohol drinking status, duration of diabetes mellitus, body mass index, usage of blood glucose treatment, usage of antihypertensive treatment, usage of lipid lowering treatment. The red line represented HR and the blue lines represented 95% CIs.
dmj-43-350-s005.pdf
Fig. 1Study design for the investigation of the association of visit-to-visit variability (VVV) in blood pressure (BP) and cardiovascular disease (CVD). The BP measurements during the measurement period (0, 3, 6, 9, 12, 15, 18, 21, 24 months after baseline) were used to calculate the mean and VVV. The median follow-up period was 49.5 months.
Fig. 2Hazard ratio (95% confidence interval [CI]) for cardiovascular disease of Q5 compared to Q1 of standard deviation of systolic blood pressure (SBP) in different subgroups. Data were adjusted for sex, age, smoking status, alcohol drinking status, duration of diabetes mellitus, body mass index, baseline fasting plasma glucose, use of blood glucose treatment, use of antihypertensive drugs, use of lipid lowering drugs and mean SBP values. Baseline low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol, and triglycerides were further adjusted when patients without baseline lipid profiles were excluded. BP, blood pressure; DM, diabetes mellitus.
Table 1Baseline characteristics of included patients in the present study
Characteristic |
Total |
SD of SBP Quintile 1 (<4.51 mm Hg) |
SD of SBP Quintile 2 (≥4.51 and <5.98 mm Hg) |
SD of SBP Quintile 3 (≥5.98 and <7.62 mm Hg) |
SD of SBP Quintile 4 (≥7.62 and <10.28 mm Hg) |
SD of SBP Quintile 5 (≥10.28 mm Hg) |
P value for difference |
No. of patients |
10,163 |
2,035 |
2,023 |
2,040 |
2,032 |
2,033 |
|
No. of cases |
894 |
162 |
127 |
159 |
168 |
278 |
|
Cumulative incidence rate, <0.001 |
8.8 |
8.0 |
6.3 |
7.8 |
8.3 |
13.7 |
<0.001 |
Median follow-up time, mo, median (IQR) |
49.5 (13.1) |
49.2 (13.6) |
49.3 (11.1) |
49.4 (13.0) |
49.4 (12.1) |
50.4 (14.0) |
<0.001 |
Person-years |
60,420 |
12,067 |
12,040 |
12,145 |
12,036 |
12,133 |
|
Incidence density, case/1,000 person-yr |
14.8 |
13.4 |
10.5 |
13.1 |
14.0 |
22.9 |
<0.001 |
Patients characteristics |
|
|
|
|
|
|
|
Age |
61.3±10.5 |
60.7±10.4 |
60.5±10.9 |
61.4±10.2 |
62.1±10.6a
|
64.1±10.0a
|
<0.001 |
Female sex |
6,185 (60.9) |
1,206 (59.3) |
1,179 (58.3) |
1,219 (59.8) |
1,262 (62.1)a
|
1,319 (64.9)a
|
<0.001 |
Body mass index, kg/m2
|
24.1±2.6 |
24.2±2.4 |
24.1±2.6 |
24.0±2.7 |
24.1±2.6 |
24.2±2.6a
|
0.967 |
Duration of diabetes mel- litus, mo, median (IQR) |
40.1 (9.3) |
36.3 (7.9) |
38.7 (8.2) |
39.4 (9.1) |
40.6 (10.8)a
|
45.4 (11.7)a
|
<0.001 |
Smoking |
2,373 (23.3) |
510 (25.1) |
491 (24.3) |
483 (23.7) |
467 (23.0) |
422 (20.8)a
|
0.016 |
Alcohol drinking |
1,317 (13.0) |
267 (13.1) |
251 (12.4) |
265 (13.0) |
267 (13.1) |
267 (13.1) |
0.950 |
Education |
|
|
|
|
|
|
<0.001 |
Illiterate |
485 (4.8) |
111 (5.5) |
106 (5.2) |
103 (5.0) |
100 (4.9) |
65 (3.2) |
|
Literate |
2,146 (21.1) |
462 (22.7) |
443 (21.9) |
468 (22.9) |
424 (20.9) |
349 (17.2) |
|
Elementary school |
5,417 (53.3) |
1,131 (55.6) |
1,088 (53.8) |
1,064 (52.2) |
1,043 (51.3) |
1,091 (53.7) |
|
High school |
1,945 (19.1) |
302 (14.8) |
346 (17.1) |
379 (18.6) |
424 (20.9) |
494 (24.3) |
|
College or above |
169 (1.7) |
29 (1.4) |
40 (2.0) |
26 (1.3) |
40 (2.0) |
34 (1.7) |
|
Fasting plasma glucose, mmol/L |
8.1±4.0 |
8.0±3.8 |
7.7±3.7a
|
8.0±4.4 |
8.4±4.7 |
8.6±3.3a
|
<0.001 |
Lipid profile |
6.7±1.4 |
7.6±1.7 |
6.9±1.5 |
6.3±1.4a
|
6.0±1.3a
|
6.6±1.4a
|
<0.001 |
Total cholesterol, mmol/L Triglycerides, mmol/L |
2.6±1.3 |
2.5±1.2 |
2.6±1.4 |
2.4±1.2 |
2.2±1.1a
|
2.2±1.3a
|
<0.001 |
High-density lipoprotein, mmol/L |
2.1±0.6 |
2.3±0.7 |
2.2±0.6 |
2.1±0.6a
|
1.9±0.5a
|
2.2±0.6a
|
<0.001 |
Low-density lipoprotein, mmol/L |
4.6±0.8 |
4.8±1.6 |
4.6±1.4 |
4.5±1.4a
|
4.2±1.3a
|
4.7±1.5a
|
<0.001 |
Any use of blood glucose treatment |
9,625 (94.7) |
1,929 (94.8) |
1,926 (95.2) |
1,929 (94.6) |
1,915 (94.2) |
1,926 (94.7) |
0.736 |
Any use of BP lowering treatment |
4,981 (49.0) |
876 (43.0) |
892 (44.1) |
963 (47.2)a
|
1,048 (51.6)a
|
1,202 (59.1)a
|
<0.001 |
Any use of lipid lowering treatment |
925 (9.1) |
160 (7.9) |
148 (7.3) |
183 (9.0)a
|
206 (10.1)a
|
228 (11.1)a
|
<0.001 |
Blood pressure at baseline |
|
|
|
|
|
|
|
SBP, mm Hg |
130.1±11.7 |
129.8±6.4 |
129.6±7.4 |
129.9±9.2 |
131.4±11.4a
|
134.7±18.8a
|
<0.001 |
DBP, mm Hg |
80.2±13.0 |
80.3±6.0 |
80.4±15.0 |
80.5±12.3 |
80.9±7.1 |
82.2±19.6a
|
<0.001 |
Blood pressure during measurement period |
|
|
|
|
|
|
|
SBP, mm Hg |
131.1±7.1 |
129.4±5.0 |
128.9±5.0 |
129.1±5.3 |
130.2±6.6a
|
132.9±10.9a
|
<0.001 |
DBP, mm Hg |
80.9±6.5 |
80.2±6.7 |
79.8±6.0 |
79.9±5.7 |
80.2±6.5 |
80.9±7.4a
|
<0.001 |
Table 2HRs and 95% CIs for cardiovascular disease, associated with visit-to-visit SBP variability
Variable |
Model Ia
|
Model IIb
|
Adjusted HR (95% CI) |
P for trend |
Adjusted HR (95% CI) |
P for trend |
SD SBP, mm Hg |
|
<0.001 |
|
<0.001 |
Q1 (<4.51) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥4.51 and <5.98) |
0.76 (0.60–1.02) |
0.77 (0.61–1.03) |
Q3 (≥5.98 and <7.62) |
0.92 (0.74–1.15) |
0.95 (0.76–1.18) |
Q4 (≥7.62 and <10.28) |
0.90 (0.72–1.12) |
0.90 (0.72–1.12) |
Q5 (≥10.28) |
1.29 (1.06–1.57)c
|
1.24 (1.01–1.52)c
|
CV SBP, mm Hg |
|
<0.001 |
|
0.026 |
Q1 (<3.49) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥3.49 and <4.62) |
0.77 (0.61–1.02) |
0.79 (0.62–1.01) |
Q3 (≥4.62 and <5.89) |
0.96 (0.77–1.19) |
0.98 (0.79–1.22) |
Q4 (≥5.89 and <7.84) |
0.89 (0.71–1.10) |
0.90 (0.72–1.11) |
Q5 (≥7.84) |
1.24 (1.02–1.51)c
|
1.23 (1.01–1.50)c
|
VIM SBP, mm Hg |
|
0.007 |
|
0.027 |
Q1 (<1.72) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥1.72 and <2.27) |
0.74 (0.58–1.05) |
0.79 (0.60–1.04) |
Q3 (≥2.27 and <2.90) |
0.93 (0.75–1.16) |
0.95 (0.77–1.18) |
Q4 (≥2.90 and <3.85) |
0.89 (0.72–1.11) |
0.91 (0.73–1.12) |
Q5 (≥3.85) |
1.20 (0.99–1.47) |
1.20 (1.04–1.46)c
|
ARV SBP, mm Hg |
|
0.031 |
|
0.025 |
Q1 (<4.00) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥4.00 and <5.71) |
1.05 (0.84–1.30) |
1.06 (0.85–1.32) |
Q3 (≥5.71 and <7.63) |
0.95 (0.76–1.19) |
0.97 (0.77–1.21) |
Q4 (≥7.63 and <10.57) |
0.95 (0.77–1.19) |
0.96 (0.77–1.20) |
Q5 (≥10.57) |
1.29 (1.06–1.58)c
|
1.24 (1.01–1.52)c
|
SV SBP, mm Hg |
|
0.046 |
|
0.037 |
Q1 (<5.45) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥5.45 and <7.46) |
0.94 (0.75–1.17) |
0.96 (0.77–1.20) |
Q3 (≥7.46 and <9.74) |
0.86 (0.69–1.07) |
0.89 (0.71–1.11) |
Q4 (≥9.74 and <13.44) |
0.88 (0.70–1.09) |
0.89 (0.72–1.11) |
Q5 (≥13.44) |
1.26 (1.03–1.54)c
|
1.24 (1.01–1.52)c
|
Table 3HRs and 95% CIs for cardiovascular disease, associated with visit-to-visit DBP variability
Variable |
Model Ia
|
Model IIb
|
Adjusted HR (95% CI) |
P for trend |
Adjusted HR (95% CI) |
P for trend |
SD DBP, mm Hg |
|
0.006 |
|
0.007 |
Q1 (<3.50) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥3.50 and <4.46) |
1.01 (0.80–1.26) |
1.01 (0.81–1.26) |
Q3 (≥4.46 and <5.39) |
0.92 (0.73–1.15) |
0.92 (0.74–1.16) |
Q4 (≥5.39 and <6.78) |
1.08 (0.87–1.35) |
1.09 (0.88–1.35) |
Q5 (≥6.78) |
1.23 (1.00–1.51)c
|
1.22 (0.99–1.50) |
CV DBP, mm Hg |
|
0.020 |
|
0.018 |
Q1 (<4.35) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥4.35 and <5.59) |
1.11 (0.89–1.38) |
1.11 (0.89–1.38) |
Q3 (≥5.59 and <6.80) |
1.01 (0.81–1.27) |
1.02 (0.81–1.28) |
Q4 (≥6.80 and <8.47) |
1.03 (0.83–1.29) |
1.04 (0.84–1.30) |
Q5 (≥8.47) |
1.24 (1.00–1.52)c
|
1.24 (1.01–1.53)c
|
VIM DBP, mm Hg |
|
0.099 |
|
0.070 |
Q1 (<0.74) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥0.74 and <0.97) |
1.01 (0.81–1.25) |
1.01 (0.81–1.26) |
Q3 (≥0.97 and <1.20) |
1.02 (0.82–1.27) |
1.03 (0.83–1.28) |
Q4 (≥1.20 and <1.49) |
0.99 (0.80–1.23) |
1.01 (0.81–1.25) |
Q5 (≥1.49) |
1.11 (0.90–1.37) |
1.12 (0.91–1.38) |
ARV DBP |
|
0.684 |
|
0.719 |
Q1 (<3.13) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥3.13 and <4.29) |
1.11 (0.90–1.36) |
1.11 (0.90–1.36) |
Q3 (≥4.29 and <5.57) |
0.92 (0.74–1.15) |
0.92 (0.74–1.15) |
Q4 (≥5.57 and <7.14) |
0.92 (0.74–1.14) |
0.92 (0.74–1.14) |
Q5 (≥7.14) |
1.12 (0.92–1.38) |
1.12 (0.91–1.37) |
SV DBP |
|
0.183 |
|
0.194 |
Q1 (<4.25) |
1.00 (reference) |
1.00 (reference) |
Q2 (≥4.25 and <5.67) |
1.24 (0.99–1.54) |
1.25 (0.99–1.54) |
Q3 (≥5.67 and <7.07) |
0.99 (0.79–1.24) |
1.00 (0.80–1.25) |
Q4 (≥7.07 and <9.06) |
0.97 (0.78–1.21) |
0.98 (0.78–1.22) |
Q5 (≥9.06) |
1.29 (1.05–1.58)c
|
1.28 (1.04–1.58)c |