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Table 1 shows the baseline characteristics of the participants stratified according to quartiles of NLR. The proportion of men, current smokers, and current drinkers increased with increased NLR quartiles (P < 0.05). With the increment of NLR, participants tended to be with lower levels of LDL-c, HDL-c, TC, and higher levels of waist circumference, SBP, and DBP (all P < 0.05; Table 1). Moreover, the baseline prevalence of baPWV and albuminuria increased with NLR quartiles. There was no significant difference between NLR levels and the proportion of participants in high school or above and those doing moderate to vigorous physical activity (both P > 0.05; Table 1).
CharacteristicsNLR Quartiles Q1 Q2 Q3 Q4 P value N (%) 1,566 (24.4) 1,620 (25.2) 1,623 (25.2) 1,621 (25.2) Age (years) 58.10 ± 8.14 57.77 ± 8.39 57.84 ± 8.97 58.39 ± 9.37 0.16 Male sex, n (%) 453 (28.9) 530 (32.7) 628 (38.7) 738 (45.5) < 0.0001 ≥ 9 years of Education, n (%) 997 (63.9) 1,051 (65.2) 1,055 (65.3) 1,027 (63.7) 0.93 Current drinking, n (%) 119 (7.8) 142 (9.0) 179 (11.4) 184 (11.8) < 0.0001 Current smoking, n (%) 229 (15.1) 296 (19.0) 334 (21.3) 386 (24.7) < 0.0001 Ideal physical activity, n (%) 1,136 (72.5) 1,150 (71.0) 1,160 (71.5) 1,156 (71.3) 0.53 BMI (kg/m2) 25.06 ± 3.25 25.41 ± 3.34 25.32 ± 3.26 25.10 ± 3.15 0.01 Waist circumference (cm) 87.22 ± 6.13 87.73 ± 6.15 88.14 ± 6.04 88.11 ± 6.08 < 0.0001 SBP (mmHg) 140.09 ± 18.93 141.52 ± 19.99 141.68 ± 19.79 142.40 ± 20.46 0.01 DBP (mmHg) 82.36 ± 10.14 82.84 ± 10.23 83.23 ± 10.18 83.77 ± 10.60 0.001 HbA1c (%) 5.82 ± 0.84 5.84 ± 0.93 5.84 ± 0.91 5.85 ± 0.99 0.74 Triglycerides (mmol/L) 1.40 (0.98–1.91) 1.41 (1.00–2.02) 1.39 (1.02–2.00) 1.33 (0.95–1.89) 0.01 LDL-c (mmol/L) 3.34 ± 0.89 3.25 ± 0.86 3.19 ± 0.86 3.07 ± 0.83 < 0.0001 HDL-c (mmol/L) 1.36 ± 0.32 1.33 ± 0.31 1.30 ± 0.32 1.31 ± 0.32 < 0.0001 TC (mmol/L) 5.51 ± 1.01 5.43 ± 1.06 5.32 ± 0.97 5.20 ± 0.96 < 0.0001 Baseline abnormal ABI, n (%) 101 (6.6) 99 (6.3) 112 (7.1) 120 (7.6) 0.19 Baseline elevated baPWV, n (%) 318 (21.1) 335 (21.5) 373 (24.1) 426 (27.3) < 0.0001 Baseline albuminuria, n (%) 76 (4.9) 108 (6.7) 117 (7.2) 116 (7.2) 0.007 Note. Data are expressed as mean ± SD, median (interquartile range), or n (%). NLR, neutrophil-to-lymphocyte ratio; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; TC, total cholesterol; ABI, ankle-brachial index; baPWV, brachial-ankle pulse wave velocity; SD, standard deviation. Table 1. Baseline characteristics according to quartiles of NLR (n = 6,430)
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Table 2 shows the risk of new-onset abnormal ABI, elevated baPWV, or albuminuria according to baseline NLR quartiles. On Poisson regression analysis, NLR was significantly associated with increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. The incidence of abnormal ABI was 1.4%, 1.5%, 1.9%, and 3.1%, the incidence of elevated baPWV was 14.8%, 15.3%, 17.1%, and 17.2%, and the incidence of albuminuria was 7.8%, 8.1%, 8.5%, and 9.8% from the lowest to highest NLR quartiles. After full adjustment for age, sex, educational attainment, physical activity, smoking status, drinking status, and metabolic risk factors, the RRs and related 95% CIs for quartile 2 to quartile 4 compared with the lowest quartile for abnormal ABI analysis were 1.07 (95% CI 0.57–2.01), 1.35 (95% CI 0.75–2.44) and 2.05 (95% CI 1.17–3.57), respectively (Table 2). Similarly, participants in the highest NLR quartile presented an increased risk of new-onset albuminuria (RR: 1.37; 95% CI 1.06–1.77). Furthermore, compared with the lowest quartile of NLR, quartiles 3 and 4 presented a significantly higher risk of new-onset elevated baPWV (RR: 1.25; 95% CI 1.01–1.54 for quartile 3; RR: 1.25; 95% CI 1.01–1.55 for quartile 4). In addition, the multivariable-adjusted RR per SD increment of NLR was 1.32 (95% CI 1.15–1.50) for new-onset abnormal ABI, 1.11 (95% CI 1.03–1.19) for new-onset elevated baPWV, and 1.13 (95% CI 1.04–1.23) for new-onset albuminuria.
NLR
No. of participants
Cases, n (%)RR (95% CI) Model 1 Model 2 Abnormal ABI Quartile 1 1,389 20 (1.4) 1.00 (ref.) 1.00 (ref.) Quartile 2 1,366 20 (1.5) 1.07 (0.57−2.01) 1.07 (0.57−2.01) Quartile 3 1,415 27 (1.9) 1.38 (0.76−2.48) 1.35 (0.75−2.44) Quartile 4 1,370 43 (3.1) 2.02 (1.16−3.51) 2.05 (1.17−3.57) Per SD increase 1.31 (1.15−1.50) 1.32 (1.15−1.50) Elevated baPWV Quartile 1 1,162 172 (14.8) 1.00 (ref.) 1.00 (ref.) Quartile 2 1,160 178 (15.3) 1.07 (0.86−1.33) 1.04 (0.84−1.29) Quartile 3 1,149 196 (17.1) 1.26 (1.02−1.56) 1.25 (1.01−1.54) Quartile 4 1,162 200 (17.2) 1.28 (1.03−1.58) 1.25 (1.01−1.55) Per SD increase 1.10 (1.03−1.18) 1.11 (1.03−1.19) Albuminuria Quartile 1 1,471 114 (7.8) 1.00 (ref.) 1.00 (ref.) Quartile 2 1,493 121 (8.1) 1.11 (0.86−1.44) 1.09 (0.84−1.41) Quartile 3 1,468 124 (8.5) 1.15 (0.88−1.49) 1.13 (0.87−1.47) Quartile 4 1,474 144 (9.8) 1.38 (1.07−1.78) 1.37 (1.06−1.77) Per SD increase 1.13 (1.04−1.22) 1.13 (1.04−1.23) Note. Model 1: Adjusted for age, sex, educational attainment, physical activity, smoking status, and drinking status. Model 2: Further adjusted for metabolic risk factors (HbA1c, SBP, DBP, LDL-c, HDL-c, and triglycerides, BMI) based on model 1. NLR, neutrophil-to-lymphocyte ratio; ABI, ankle-brachial index; baPWV, brachial-ankle pulse wave velocity; SD, standard deviation BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol, RR, risk ratio; CI, confidence interval. Table 2. Association of NLR with subclinical macrovascular and microvascular diseases
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We further conducted a stratified analysis to see the association between NLR and new-onset abnormal ABI, elevated baPWV, and albuminuria according to BMI categories (BMI < 24 kg/m2 or BMI ≥ 24 kg/m2). Figure 2 shows the incidence of each outcome according to quartiles of NLR by BMI category. In particular, in participants with normal weight, the incidence of abnormal ABI, elevated baPWV, and albuminuria increased gradually with NLR level, compared to that in those with a BMI ≥ 24 kg/m2. After fully adjusting covariates and using the Poisson regression model, we found that the association between NLR and subclinical vascular abnormalities was much stronger in participants with normal weight. The increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria per SD increment of NLR was 57% (RR 1.57; 95% CI 1.28–1.91), 17% (RR 1.17; 95% CI 1.05–1.30), and 26% (RR 1.26; 95% CI 1.10–1.44), respectively (Figure 3). However, no significant association was found among participants with BMI ≥ 24 kg/m2. Furthermore, we found an interaction between the NLR and BMI on the risk of new-onset abnormal ABI (P for interaction = 0.01) and a borderline significant interaction on new-onset albuminuria (P for interaction = 0.08).
Figure 2. Incidence of each outcome by NLR/BMI category. Incidence of (A) abnormal ABI, (B) elevated baPWV, and (C) albuminuria. NLR, neutrophil-to-lymphocyte ratio; ABI, ankle-brachial index; baPWV, brachial-ankle pulse wave velocity.
Figure 3. Association of NLR quartiles with subclinical macrovascular and microvascular diseases by BMI categories. NLR, neutrophil-to-lymphocyte ratio; BMI, body mass index; ABI, ankle-brachial index; baPWV, brachial-ankle pulse wave velocity; SD, standard deviation; RR, risk ratio; CI, confidence interval.
In addition, we explored the association between NLR and new-onset abnormal ABI, elevated baPWV, and albuminuria on the basis of the waist circumference categories (Supplementary Table S1 available in www.besjournal.com). We also found a statistically significant relationship between NLR and subclinical atherosclerosis abnormalities in participants with normal waist circumference. A higher NLR quartile was associated with a higher incidence of abnormal ABI (RR 2.31; 95% CI 1.10–3.00) and albuminuria (RR 1.70; 95% CI 1.13–3.11). However, we did not find the modified effect of waist circumference on such relationships.
NLR Abnormal ABI Elevated baPWV Albuminuria Model 1 Model 2 Model 1 Model 2 Model 1 Model 2 WC < 90 cm (men)/80 cm (women) (n = 3,428) Quartile 1 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) Quartile 2 0.74 (0.28−1.32) 0.75 (0.29−1.33) 0.91 (0.65−1.91) 0.89 (0.63−1.88) 1.42 (0.93−2.53) 1.45 (0.94−2.57) Quartile 3 0.90 (0.37−1.45) 0.91 (0.38−1.46) 1.39 (1.04−2.82) 1.32 (0.97−2.65) 1.28 (0.84−2.31) 1.24 (0.81−2.24) Quartile 4 2.27 (1.09−2.98) 2.31 (1.10−3.00) 1.29 (0.95−2.59) 1.21 (0.89−2.44) 1.72 (1.16−3.17) 1.70 (1.13−3.11) Per SD increase 1.35 (1.14−3.13) 1.36 (1.15−3.15) 1.13 (1.03−2.81) 1.11 (1.01−2.75) 1.19 (1.07−2.91) 1.19 (1.07−2.91) WC ≥ 90 cm (men)/80 cm (women) (n = 3,002) Quartile 1 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) 1.00 (ref.) Quartile 2 1.43 (0.61−1.84) 1.46 (0.62−1.87) 1.17 (0.88−2.41) 1.13 (0.85−2.33) 0.93 (0.67−1.95) 0.92 (0.66−1.93) Quartile 3 2.03 (0.90−2.46) 2.01 (0.89−2.43) 1.12 (0.83−2.29) 1.15 (0.84−2.33) 1.09 (0.78−2.19) 1.09 (0.78−2.18) Quartile 4 1.57 (0.66−1.93) 1.58 (0.66−1.93) 1.27 (0.94−2.55) 1.27 (0.94−2.55) 1.20 (0.86−2.36) 1.17 (0.84−2.32) Per SD increase 1.24 (1.01−2.74) 1.24 (1.00−2.71) 1.08 (0.98−2.66) 1.10 (0.99−2.70) 1.08 (0.96−2.62) 1.08 (0.96−2.60) P for interactiona 0.52 0.68 0.27 Note. Model 1: Adjusted for age, sex, education attainment, physical activity, smoking status and drinking status. Model 2: Further adjusted for metabolic risk factors (HbA1c, SBP, DBP, LDL-c, HDL-c, and triglycerides) based on model 1. aThe interactions of WC category with NLR (per SD increase) on risks of diseases was examined by including respective multiplicative interaction term in the final model 2. NLR, neutrophil-to lymphocyte ratio; ABI, ankle brachial index; baPWV, brachial-ankle pulse wave velocity; SD, standard deviation BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; LDL-c, low density lipoprotein cholesterol; HDL-c, high density lipoprotein cholesterol; WC, waist circumference. Table S1. Association of NLR quartiles with subclinical macrovascular and microvascular diseases by waist circumference categories
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Characteristics of Enrolled Participants
NLR and Risk of New-onset Abnormal ABI, Elevated BaPWV, and Albuminuria
Stratified Analysis for the Association between NLR and New-onset Abnormal ABI, Elevated BaPWV, and Albuminuria
Supplementary Materials21126.pdf |