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The characteristics of the participants with and without CKD are listed in Table 1. Overall, the mean age of the study population was 57.9 ± 8.9 years, and 38.7% (n = 817) participants were men. A total of 9.5% (n = 200) participants had CKD. Compared with participants without CKD, those with CKD were more likely to be older and have higher levels of BMI, waist circumference, FPG, BP, UACR, and lower levels of eGFR (all P < 0.05). The proportions of hypertension, diabetes, antidiabetic medications, and antihypertensive medications were significantly higher in those with CKD (both P < 0.001). In addition, CVs of FPG, SBP, DBP, TC, and LDL-c significantly increased in participants with CKD compared with those without (all P < 0.05). No significant differences in sex distribution, proportions of current smoking, current drinking, being physically active, dyslipidemia, lipid-lowering medications, and the levels of lipids and CVs of TG and HDL-c were found between the two groups (all P > 0.05).
Characteristics Total Without CKD With CKD P value Participants, n 2,109 1,909 200 Age (years) 57.9 ± 8.9 57.5 ± 8.7 61.9 ± 9.9 < 0.001* Men, n (%) 817 (38.7) 751 (39.3) 66 (33.0) 0.080 BMI (kg/m2) 25.1 ± 3.5 24.9 ± 3.5 26.2 ± 3.8 < 0.001* Waist circumference (cm) 84.2 ± 9.6 83.9 ± 9.6 87.1 ± 9.9 < 0.001* Lifestyle factors, n (%) Current smoking 503 (23.9) 465 (24.4) 38 (19.0) 0.091 Current drinking 368 (17.4) 334 (17.5) 34 (17.0) 0.860 Regular exercise 106 (5.0) 101 (5.3) 5 (2.5) 0.086 FPG (mg/dL) 101.2 ± 32.8 99.6 ± 31.2 115.8 ± 42.8 < 0.001* Blood pressure (mmHg) SBP 131 ± 21 130 ± 20 142 ± 24 < 0.001* DBP 79 ± 10 79 ± 10 83 ± 11 < 0.001* Lipid profiles (mg/dL) TG 105.3 (75.2–154.1) 104.5 (74.4–151.9) 118.8 (77.1–168.4) 0.073 TC 197.5 ± 36.0 197.3 ± 35.7 199.1 ± 38.7 0.513 HDL-c 53.8 ± 11.5 53.9 ± 11.5 53.4 ± 11.6 0.588 LDL-c 95.0 ± 25.8 95.1 ± 25.6 94.5 ± 27.3 0.784 eGFR at the second visit (mL/min per 1.73 m2) 91.0 ± 12.5 91.4 ± 12.3 87.6 ± 14.0 < 0.001* eGFR at the third visit (mL/min per 1.73 m2) 91.7 ± 11.9 92.6 ± 10.7 83.5 ± 18.6 < 0.001* UACR at the second visit (mg/g) 4.4 (2.0–10.6) 4.1 (2.0–10.0) 8.5 (2.9–16.7) < 0.001* UACR at the third visit (mg/g) 7.8 (5.2–12.9) 7.3 (5.0–10.8) 51.5 (37.4–84.1) < 0.001* Diabetes, n (%) 447 (21.2) 362 (19.0) 85 (42.5) < 0.001* Hypertension, n (%) 838 (39.7) 711 (37.2) 127 (63.5) < 0.001* Dyslipidemia, n (%) 597 (28.3) 532 (27.9) 65 (32.5) 0.167 Medications Antidiabetic medications at three visits, n (%) 398 (18.9) 319 (16.7) 79 (39.5) < 0.001* Antihypertensive medications at three visits, n (%) 504 (23.9) 427 (22.4) 77 (38.5) < 0.001* Lipid-lowering medications at three visits, n (%) 22 (1.0) 17 (0.9) 5 (2.5) 0.078 Variability, coefficient of variation FPG, % 12.4 ± 10.2 11.9 ± 9.5 17.7 ± 13.9 < 0.001* SBP, % 7.3 ± 4.2 7.2 ± 4.1 8.3 ± 4.5 < 0.001* DBP, % 6.6 ± 3.8 6.5 ± 3.8 7.4 ± 3.9 0.002* TG, % 26.7 ± 17.4 26.5 ± 17.3 28.5 ± 17.5 0.124 TC, % 9.5 ± 6.3 9.3 ± 6.1 11.0 ± 7.8 0.004* HDL-c, % 10.7 ± 7.5 10.6 ± 7.4 11.5 ± 8.4 0.141 LDL-c, % 20.7 ± 11.1 20.5 ± 10.9 22.6 ± 12.7 0.028* Note. Data are means ± SDs and medians (IQRs) for continuous variables, or numbers (percentages) for categorical variables. *Statistically significant. BMI, Body mass index; CKD, chronic kidney disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HDL-c, high-density lipoprotein cholesterol; IQR, interquartile range; LDL-c, low-density lipoprotein cholesterol; SBP, systolic blood pressure; SD, standard deviation; TC, total cholesterol; TG, triglyceride; UACR, urinary albumin-to-creatinine ratio. Table 1. Characteristics of participants with and without CKD
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Table 2 shows the associations of VVV of FPG with the risk of CKD. After adjustment for confounding factors including mean FPG, the risk of CKD increased with increasing CV quartiles of FPG (P value for trend = 0.017). Participants in the highest quartile of CV-FPG had a 70% increased risk for CKD than those in the lowest quartile (OR = 1.70, 95% CI 1.06–2.72). In addition, the risk increased by 2% for each 1 increment in CV-FPG (OR = 1.02, 95% CI 1.00–1.03).
Measures of variability Cases/
No. of participantsCumulative incidence (%) OR (95% CI) Model 1 Model 2 Model 3 Quartiles of CV-FPG (%) Q1 (0–6.22) 33/529 6.2 1 (ref.) 1 (ref.) 1 (ref.) Q2 (6.22–9.65) 34/526 6.5 0.99 (0.60–1.63) 1.00 (0.60–1.66) 0.97 (0.58–1.61) Q3 (9.65–14.96) 43/527 8.2 1.30 (0.81–2.10) 1.19 (0.73–1.93) 1.10 (0.68–1.79) Q4 (14.96–78.23) 90/527 17.1 2.78 (1.81–4.27) 2.06 (1.30–3.26) 1.70 (1.06–2.72) P for trend < 0.001* < 0.001* 0.017* Each 1 increment 1.04 (1.03–1.05) 1.03 (1.01–1.04) 1.02 (1.00–1.03) Note. Model 1: adjusted for age, sex, waist circumference, current drinking, current smoking, and regular exercise. Model 2: adjusted for model 1 plus antidiabetic medications, baseline SBP, LDL-c, log10TG, and eGFR at the second visit. Model 3: adjusted for model 2 plus mean FPG. *Statistically significant. CI, Confidence interval; CKD, chronic kidney disease; CV, coefficient of variation; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; VVV, visit-to-visit variability; OR, odds ratios. Table 2. Odds ratios and 95% confidence intervals of CKD by the VVV of FPG
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Table 3 shows the associations of VVV of BP with the risk of CKD. After adjustment for confounding factors including mean SBP, participants in the highest quartile of CV-SBP had a 62% increased risk for CKD than those in the lowest quartile (OR = 1.62, 95% CI 1.04–2.50). In addition, the risk increased by 4% for each 1 increment in CV-SBP (OR = 1.04, 95% CI 1.01–1.08). However, no significant association with the risk of CKD was found for higher quartiles of CV-DBP than for the lowest quartile.
Measures of variability Cases/
No. of participantsCumulative incidence (%) OR (95% CI) Model 1 Model 2 Model 3 Quartiles of CV-SBP (%) Q1 (0–4.29) 38/528 7.2 1 (ref.) 1 (ref.) 1 (ref.) Q2 (4.29–6.65) 52/526 9.9 1.38 (0.88–2.15) 1.31 (0.84–2.07) 1.31 (0.83–2.06) Q3 (6.65–9.83) 43/528 8.1 1.07 (0.67–1.70) 1.07 (0.67–1.71) 1.05 (0.66–1.69) Q4 (9.83–31.87) 67/527 12.7 1.76 (1.15–2.70) 1.69 (1.10–2.62) 1.62 (1.04–2.50) P for trend 0.027* 0.041* 0.072 Each 1 increment 1.05 (1.02–1.09) 1.05 (1.01–1.08) 1.04 (1.01–1.08) Quartiles of CV-DBP (%) Q1 (0–3.91) 38/528 7.2 1 (ref.) 1 (ref.) 1 (ref.) Q2 (3.91–6.06) 40/526 7.6 1.01 (0.63–1.61) 1.02 (0.64–1.64) 1.02 (0.64–1.65) Q3 (6.06–8.70) 54/528 10.2 1.34 (0.86–2.08) 1.32 (0.84–2.06) 1.34 (0.85–2.10) Q4 (8.70–32.39) 68/527 12.9 1.61 (1.05–2.47) 1.41 (0.91–2.18) 1.47 (0.95–2.28) P for trend 0.011* 0.069 0.044* Each 1 increment 1.04 (1.00–1.08) 1.02 (0.98–1.06) 1.02 (0.99–1.06) Note. Model 1: adjusted for age, sex, waist circumference, current drinking, current smoking, and regular exercise. Model 2: adjusted for model 1 plus antihypertensive medications, baseline DBP (for the CV of SBP), SBP (for the CV of DBP), FPG, LDL-c, log10TG, and eGFR at the second visit. Model 3: adjusted for model 2 plus mean SBP (for the CV of SBP) or DBP (for the CV of DBP). *Statistically significant. CI, Confidence interval; CKD, chronic kidney disease; CV, coefficient of variation; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; VVV, visit-to-visit variability; OR, odds ratios; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride. Table 3. Odds ratios and 95% confidence intervals of CKD by the VVV of BP
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Table 4 shows the associations of VVV of lipids with the risk of CKD. After adjustment for confounding factors including mean LDL-c, participants in the highest quartile of CV-LDL had an 85% increased risk for CKD compared with the lowest quartile (OR = 1.85, 95% CI 1.23–2.80). In addition, the risk increased by 2% for each 1 increment in CV-LDL (OR = 1.02, 95% CI 1.00–1.03). However, no significant associations with the risk of CKD were found for higher quartiles of CV-TG, CV-TC, and CV-HDL compared with their lowest quartiles.
Measures of variability Cases/
No. of participantsCumulative incidence (%) OR (95% CI) Model 1 Model 2 Model 3 Quartiles of CV-TG (%) Q1 (0–14.62) 34/527 6.5 1 (ref.) 1 (ref.) 1 (ref.) Q2 (14.62–23.21) 59/528 11.2 1.83 (1.17–2.86) 1.76 (1.11–2.77) 1.75 (1.11–2.77) Q3 (23.21–34.29) 50/527 9.5 1.63 (1.03–2.58) 1.63 (1.02–2.60) 1.62 (1.02–2.59) Q4 (34.29–137.16) 57/527 10.8 1.78 (1.14–2.80) 1.56 (0.98–2.47) 1.54 (0.96–2.45) P for trend 0.035* 0.130 0.148 Each 1 increment 1.01 (1.00–1.02) 1.01 (1.00–1.01) 1.01 (1.00–1.01) Quartiles of CV-TC (%) Q1 (0–5.20) 51/526 9.7 1 (ref.) 1 (ref.) 1 (ref.) Q2 (5.20–8.11) 31/529 5.9 0.58 (0.37–0.94) 0.60 (0.37–0.96) 0.60 (0.37–0.96) Q3 (8.11–12.08) 52/527 9.9 1.04 (0.69–1.57) 0.98 (0.64–1.49) 0.98 (0.64–1.49) Q4 (12.08–59.43) 66/527 12.5 1.35 (0.91–2.01) 1.26 (0.84–1.89) 1.26 (0.84–1.90) P for trend 0.026* 0.088 0.090 Each 1 increment 1.04 (1.01–1.06) 1.03 (1.01–1.05) 1.03 (1.01–1.05) Quartiles of CV-HDL (%) Q1 (0–5.74) 51/528 9.7 1 (ref.) 1 (ref.) 1 (ref.) Q2 (5.74–9.13) 42/526 8.0 0.83 (0.54–1.28) 0.79 (0.51–1.24) 0.79 (0.51–1.23) Q3 (9.13–13.85) 46/527 8.7 0.87 (0.57–1.33) 0.88 (0.57–1.36) 0.87 (0.56–1.35) Q4 (13.85–68.96) 61/528 11.6 1.18 (0.79–1.77) 1.14 (0.75–1.71) 1.11 (0.74–1.68) P for trend 0.375 0.445 0.505 Each 1 increment 1.01 (0.99–1.03) 1.01 (0.99–1.03) 1.01 (0.99–1.03) Quartiles of CV-LDL (%) Q1 (0–13.05) 48/528 9.1 1 (ref.) 1 (ref.) 1 (ref.) Q2 (13.05–19.08) 44/527 8.3 0.91 (0.59–1.41) 0.87 (0.56–1.36) 0.87 (0.56–1.36) Q3 (19.08–26.73) 33/526 6.3 0.75 (0.47–1.19) 0.70 (0.43–1.13) 0.70 (0.43–1.13) Q4 (26.73–79.55) 75/528 14.2 1.91 (1.28–2.84) 1.86 (1.24–2.79) 1.85 (1.23–2.80) P for trend 0.003* 0.005* 0.007* Each 1 increment 1.02 (1.01–1.03) 1.02 (1.00–1.03) 1.02 (1.00–1.03) Note. Model 1: adjusted for age, sex, waist circumference, current drinking, current smoking, and regular exercise. Model 2: adjusted for model 1 plus lipid-lowering medications, baseline SBP, FPG, LDL-c (for the CV of TG), log10TG (for the CV of TC, HDL-c, and LDL-c), and eGFR at the second visit. Model 3: adjusted for model 2 plus mean TG (for the CV of TG), mean TC (for the CV of TC), mean HDL-c (for the CV of HDL-c), or mean LDL-c (for the CV of LDL-c). *Statistically significant. CI, Confidence interval; CKD, chronic kidney disease; CV, coefficient of variation; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; OR, odds ratios; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; VVV, visit-to-visit variability. Table 4. Odds ratios and 95% confidence intervals of CKD by the VVV of lipids
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The CV-FPG, CV-SBP, and CV-LDL significantly associated with CKD were used to calculate the variability score. Therefore, the variability score had a range of 0–3. The cumulative incidence of CKD was 5.5%, 10.0%, 16.6%, and 32.0% in participants with a variability score of 0, 1, 2, and 3, respectively (Figure 2). Using participants with a variability score of 0 as the reference, the risk of CKD increased by 58% (OR = 1.58, 95% CI 1.08–2.32), 121% (OR = 2.21, 95% CI 1.40–3.49), and 548% (OR = 6.48, 95% CI 3.18–13.21) for participants with a variability score of 1, 2, and 3, respectively, after adjusting for traditional risk factors including mean FPG, mean SBP, and mean LDL-c (P value for trend < 0.001). The graded relationship between the variability score and the risk of CKD was consistent among subgroups of men and women, age < 65 and ≥ 65 years, BMI < 25 and ≥ 25 kg/m2, with and without current smoking, with and without current drinking, and with and without diabetes (all P values for interaction > 0.05; Figure 3).
Figure 2. Cumulative incidence of CKD and the association between variability score and CKD risk. The hollow columns indicate a cumulative incidence of CKD. The black circles and bars indicate ORs and 95% CIs of CKD risk using participants with a score = 0 as the reference. The regression analysis was adjusted for age, sex, waist circumference, current drinking, current smoking, regular exercise, antidiabetic medications, antihypertensive medications, lipid-lowering medications, baseline log10TG, eGFR at the second visit, mean FPG, mean SBP, and mean LDL-c. OR: odds ratio; CI: confidence interval; FPG: fasting plasma glucose; SBP: systolic blood pressure; LDL-c: low-density lipoprotein cholesterol.
Figure 3. Associations of variability score with the risks of CKD stratified by sex (A), age (B), BMI (C), current smoking (D), current drinking (E), and diabetes status (F). The regression analysis was adjusted for age, sex, waist circumference, current drinking, current smoking, regular exercise, antidiabetic medications, antihypertensive medications, lipid-lowering medications, baseline log10TG, eGFR at the second visit, mean FPG, mean SBP, and mean LDL-c. OR: odds ratio; CI: confidence interval; BMI: body mass index; FPG: fasting plasma glucose; SBP: systolic blood pressure; LDL-c: low-density lipoprotein cholesterol.
Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai
doi: 10.3967/bes2021.106
- Received Date: 2020-12-16
- Accepted Date: 2021-05-17
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Key words:
- Chronic kidney disease /
- Cohort /
- Metabolic factor /
- Visit-to-visit variability
Abstract:
Citation: | LI Ling, WANG Fei, XU Min, LU Jie Li, ZHAO Zhi Yun, LI Mian, WANG Tian Ge, WANG Shuang Yuan, BI Yu Fang, XU Yu, CAI Wei Min, NING Guang. Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai[J]. Biomedical and Environmental Sciences, 2021, 34(10): 761-772. doi: 10.3967/bes2021.106 |