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Physical Activity is Associated With Elevated Arterial Stiffness in Patients With Lumbar Disk Herniation Gang Jin, MD,*w Zhi-gang Cao, MD, PhD,z Yi-na Zhang, MD,y Ying Li, BS,y8 and Bao-zhong Shen, MD, PhD*

Study Design: A cross-sectional study in a general health examination. Objective: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and lumbar disk herniation (LDH). Summary of Background Data: Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Various vascular risk factors such as obesity, diabetes mellitus, and smoking have been reported to be associated with LDH. BaPWV is an early indicator of subclinical atherosclerosis. Methods: A total of 490 participants with LDH and 490 participants without LDH were selected for the evaluation of baPWV. BaPWV was measured using an automatic device. The prevalence of LDH was calculated by the quartiles of baPWV levels. Multiple linear regression analysis was performed to evaluate the risk factors for baPWV. Results: LDH patients had significantly higher readings of baPWV compared with non-LDH subjects (P < 0.001). The prevalence rate of LDH gradually increased according to baPWV quartiles. In addition, the levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis showed that body mass index, low-density lipoprotein cholesterol, physical activity, and systolic blood pressure contributed to increased baPWV. Conclusions: The findings showed that LDH patients had higher baPWV levels. In addition, reduced physical activity was a risk factor contributing to increased baPWV. Further studies are warranted to determine the role of baPWV in LDH. Key Words: lumbar disk herniation, brachial-ankle pulse wave velocity, arterial stiffness, arteriosclerosis, physical activity (J Spinal Disord Tech 2015;28:E30–E34) Received for publication December 22, 2013; accepted May 27, 2014. From the *Department of Medical Imaging and Nuclear Medicine, The Fourth Affiliated Hospital, Harbin Medical University; wDepartment of Medical Imaging, NO. 211 Hospital of the People’s Liberation Army; Departments of zMedical Imaging; yGeriatrics; and 8International Physical Examination and Healthy Center, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China. G.J. and Z.-G.C. contributed equally. The authors declare no conflict of interest. Reprints: Bao-zhong Shen, MD, PhD, Department of Medical Imaging and Nuclear Medicine, The Affiliated Fourth Hospital, Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, Heilongjiang, China (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.

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L

ow back disorders are a major public health problem that causes individual suffering and economic loss. Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Much progress has been made toward finding etiological factors of LDH. Heredity is an important risk factor for developing LDH.1 In addition, acquired factors, including obesity,2 diabetes mellitus,3 smoking, and physical loading related to occupations and sports,4 have also been associated with LDH. Lumbar disk abnormalities were frequently found in asymptomatic individuals.5 Only 4%–6% of LDHs became symptomatic.6 Early detection of LDH is of great importance for the subjects with the clustering of vascular risk factors. The lumbar intervertebral disk is the largest avascular tissue in adults and its main source of nutrition is from diffusion from blood vessels in the surrounding structures. Insufficient nutrition in intervertebral disk tissue has been suggested to be one of the primary causes of the degenerative disk.7 Recent studies have shown that atherosclerosis is associated with LDH.8 Atherosclerosis diminishes nutrition through reduced blood flow. Moreover, the abdominal aorta, particularly the aortoiliac junction, has been reported to be one of the most common sites of arteriosclerosis. Elevated arterial stiffness is an early indicator of subclinical atherosclerosis. Pulse wave velocity (PWV), the best noninvasive method for assessing arterial stiffness, is an index of vascular damage and prognosis of cardiovascular diseases.9 Brachial-ankle PWV (baPWV) measurement is a quicker approach and is easier to manipulate than PWV measurement. In addition, baPWV is highly correlated with aortic PWV.10 Previous studies have documented that baPWV is a marker of atherosclerosis progress in hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease.11,12 The aim of this study was to evaluate the association between baPWV and LDH.

MATERIALS AND METHODS Study Population The study included 980 subjects (538 men and 442 women) who visited International Physical Examination and Healthy Center from January 2009 to December 2010 and underwent CT of the spine as part of their routine J Spinal Disord Tech



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Elevated baPWV in LDH

health check. Our study recruited 490 subjects with a history of LDH (mean age, 44.9 ± 5.5 y; range, 33–61 y). They had visited the Department of Orthopaedics of the Fourth or Second Affiliated Hospital before they came to International Physical Examination and Healthy Center, because of conditions such as back leg pain, diagnosis of LDH by MRI, and with sciatica. A total of 490 subjects in the control group (mean age, 44.8 ± 5.3 y; range, 33–60 y) were randomly selected from the participants of medical examination. The control and case groups were matched in age, sex, and smoking status. We obtained informed consent from all subjects. The study protocol was approved by the Ethics Committee of the Second Hospital of Harbin Medical University, China.

was used to determine the degree of agreement between the 2 researchers. Subjects meeting any of the following criteria were excluded: spinal tumor, spinal infection, vertebral fracture, a history of lumbar spinal surgery, spinal stenosis, disk bulging, systemic inflammatory disorders, cancer, baPWV < 0.9 to rule out peripheral arterial occlusion, a history of arrhythmia, a history of thyroid disease, hypertension, diabetes, atrial fibrillation, and medical treatment with lipid-lowering agents and anticoagulant medication.



Clinical Examination Clinical data including medical history, smoking status, physical activity, and medication use were recorded for each participant. Cigarette smoking was defined as having smoked at least 100 cigarettes in one’s lifetime. Regular leisure-time physical activity was defined as participation in moderate or vigorous activity for Z30 minutes per day at least 3 days a week. The validity of the physical activity questionnaire is supported by objective measures of activity using accelerometry devices in 106 British adults from the general population.13 All the subjects underwent physical examination that includes anthropometric and blood pressure measurements. Blood pressure was determined using a mercury-gravity sphygmomanometer in a sitting position after a 15-minute resting period. Body weight was measured in light clothing, without shoes, to the nearest 0.5 kg. Height was measured to the nearest 0.5 cm. Body mass index (BMI) was calculated as weight (kg) divided by height (m2).

Biochemical Analyses All subjects were studied on an outpatient basis. Fasting venous blood samples were drawn for the analysis. The values included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and fasting plasma glucose (FPG). All assays were performed at the Laboratory of Analytical Biochemistry at the Second Affiliated Hospital, Harbin, using a biochemical analyzer (Modular Analytics; Roche, Mannheim, Germany).

Diagnosis and Exclusion Criteria The diagnosis of LDH was based on history and clinical manifestations by a spine surgeon according to the recommendations of the combined task forces of The North American Spine Society, American Society of Spine Radiology, and The American Society of Neuroradiology.14 A computed tomography (Light Speed VCT-XT; GE) scan was undertaken in each subject. Two radiologists blinded to the clinical and laboratory data performed the examination. The interobserver reliability was analyzed by calculating the k coefficient in a sample of 140 LDH patients. The k coefficient of the agreement Copyright

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Measurement of baPWV BaPWV was measured using an automatic device (model MB3000; M&B Electronic Instruments, Beijing, China). Subjects were in the supine position Z10 minutes before measurement. Bilateral arm and ankle blood pressure, and pulse volumes of the brachial and posterior tibial arteries were measured. The baPWV was automatically calculated according to the formula (L/PTT), where L is the difference between the length from the heart to ankle and the length from the heart to brachium. PTT was the pulse transit time between the brachial and tibial arterial waveform. The coefficients of variation were 2.3% for interobserver reproducibility and 3.7% for intraobserver reproducibility, respectively. We used the mean value of bilateral baPWV in our analyses. All measurements were performed by a single examiner who was blinded to the clinical data. The method was validated in a previous report.15

Statistical Analysis All data were expressed as means ± SD or medians (with interquartile ranges) or percentage. The w2 test was used for all categorical variables, whereas the Student t test was used for continuous variables. The prevalence rate of LDH was compared according to baPWV quartiles (Q1r1160, Q2 = 1161–1267, Q3 = 1268–1379, Q4Z1380 cm/s, respectively). Multiple linear regression analysis was used to evaluate the risk factors for baPWV. All the above tests were considered significant at P < 0.05 (2-tailed). Statistical analyses were performed using the SPSS software package version 17.0 (SPSS Inc., Chicago, IL).

RESULTS Clinical and laboratory data of those with and without LDH are shown in Table 1. The patients with LDH had higher BMI, TG, LDL, FPG, baPWV, and lower HDL and physical activity levels compared with the subjects without LDH. There were no significant differences in age, sex, smoking status, SBP, DBP, and TC between the 2 groups. The interobserver reliability was analyzed by calculating the k coefficient. k coefficient was 0.83 for LDH (95% CI, 0.737–0.921; P < 0.001). A k coefficient of 1.0 indicates a perfect association and 0 indicates no association. Median of baPWV in subjects with the different levels of moderate/vigorous physical activity (bars mean www.jspinaldisorders.com |

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TABLE 1. Baseline Characteristics of the Analyzed Participants According to LDH Status Variables

With LDH

Without LDH

N 490 Age (y) 44.9 (5.5) 44.8 Sex, male [n (%)] 258 (52.7) 280 Smoking [n (%)] 144 (29.4) 136 25.7 (2.2) 24.0 BMI (kg/m2) Moderate/vigorous physical activity [n (%)] None 396 (80.8) 359 > 0– < 3/wk 62 (12.7) 89 Z3/wk 32 (6.5) 52 SBP (mm Hg) 130.0 (6.7) 129.5 DBP (mm Hg) 74.8 (6.6) 74.2 TC (mmol/L) 4.80 (0.93) 4.77 TG (mmol/L) 1.68 (1.20–2.46) 1.58 HDL (mmol/L) 1.45 (1.24–1.66) 1.51 LDL (mmol/L) 3.22 (0.73) 3.05 FPG (mmol/L) 5.53 (5.15–6.01) 5.33 BaPWV (cm/s) 1321.4 (160.8) 1225.8

P

490 (5.3) (57.1) (27.8) (1.8)

0.841 0.158 0.572 < 0.001

(73.3) (18.2) (10.6) (7.2) (6.5) (1.05) (1.05–2.25) (1.34–1.76) (0.70) (4.86–5.81) (153.6)

0.005 0.017 0.022 0.779 0.134 0.701 0.014 < 0.001 < 0.001 < 0.001 < 0.001

Data are shown as means (SD) or percentage. baPWV indicates brachial-ankle pulse wave velocity; BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoprotein cholesterol; LDH, lumbar disk herniation; LDL, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride.

maximum and minimum value) are shown in Figure 1. BaPWV values according to the frequency of moderate to vigorous leisure-time physical activities in different subjects were 1284.8 ± 165.4, 1266.5 ± 161.3, and 1188.9 ± 132.5 cm/s, respectively (P < 0.001). The prevalence of LDH was calculated by the quartiles of baPWV levels. The prevalence rate of LDH in Q2, Q3, and Q4 was significantly higher than that in Q1. The PR% of LDH in Q1, Q2, Q3, and Q4 was 28.5% (70/ 246), 46.1% (113/245), 58.9% (146/248), and 66.8% (161/ 241), respectively. The prevalence ratio for the subjects in Q2, Q3, and Q4 were 1.62, 2.07, and 2.34, respectively,

FIGURE 1. Median of baPWV in subjects with the different levels of moderate/vigorous physical activity (bars mean maximum and minimum value). Statistical comparison among groups is shown (P < 0.001). BaPWV indicates brachial-ankle pulse wave velocity.

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compared with the participants in Q1. There was a significant difference of the prevalence rate in different quartiles (for Q2 vs. Q1, w2 = 16.388, P < 0.001; for Q3 vs. Q1, w2 = 46.431, P < 0.001; for Q4 vs. Q1, w2 = 71.805, P < 0.001). The results showed that the prevalence rate of LDH tended to increase according to baPWV quartiles (Fig. 2). Multiple linear regression analysis was performed to evaluate the risk factors for baPWV. Twelve variables including age, sex, BMI, physical activity, smoking, SBP, DBP, TC, TG, HDL, LDL, and FPG were entered into the original equation. The risk factors found to be significantly associated with baPWV in the regression analysis were BMI, LDL, SBP, and physical activity (Table 2).

DISCUSSION The main findings of our study are the following: LDH patients had higher baPWV levels. The levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis further showed that BMI, LDL, SBP, and physical activity contributed to increased baPWV. Our study indicated that baPWV has a correlation with LDH. Inflammation plays an important role in herniated intervertebral disk tissues.16 The loss of the extracellular matrix constituents in the nucleus pulposus results in nucleus herniation.17 Increased expression of tumor necrosis factor-a and monocyte chemoattractant protein induce macrophage infiltration. The activated macrophages further secrete proinflammatory cytokines, such as tumor necrosis factor-a, interleukin 6, and interleukin 1b, which activate the expression of matrix metalloproteinase.18 Elevated MMPs contributes to the pathogenesis of human disk herniation by promoting matrix degradation.19 In addition, upregulation of matrix metalloproteinase 2 and 9 is associated with arterial stiffness.20 Recent studies demonstrated that baPWV is related to cerebrovascular, cardiovascular, and peripheral arterial disease and is a good surrogate marker of early atherosclerosis. The abdominal aorta, and particularly

FIGURE 2. The association between baPWV levels and prevalence rate of LDH (%). Participants were stratified into quartiles according to their baPWV levels. P < 0.001. BaPWV indicates brachial-ankle pulse wave velocity; LDH, lumbar disk herniation. Copyright

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TABLE 2. Multivariate Linear Regression Analysis With baPWV (cm/s) as the Dependent Variable Variables 2

BMI (kg/m ) LDL (mmol/L) Physical activity SBP (mm Hg)

b

P

0.394 0.118 0.104 0.058

< 0.001 < 0.001 < 0.001 0.047

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investigate baPWV changes in patients with LDH in a larger sample. The results will call for the attention of potential vascular lesions in patients with LDH. In conclusion, LDH patients had higher baPWV levels. Multiple linear regression analysis further revealed that reduced physical activity was a risk factor contributing to increased baPWV. Further studies are warranted to determine the role of baPWV in LDH.

b, standardized regression coefficients. Adjusted R2 = 0.202, P < 0.001. baPWV indicates brachial-ankle pulse wave velocity; BMI, body mass index; LDL, low-density lipoprotein cholesterol; SBP, systolic blood pressure.

REFERENCES

the aortoiliac junction, has been shown to be one of the most common sites of arteriosclerosis, and atherosclerosis of arteries supplying the lumbar region has been regarded as one of the mechanisms leading to intervertebral disk degeneration.21 Atherosclerosis decreases the blood supply in the lumbar arteries, resulting in ischemia of the disk area, thus render the disks more vulnerable to mechanical stress. A study addressed that vascular changes occurred before degeneration of the disk at every lumbar level, suggesting that disturbances in the nutritional supply may precede degeneration.7 Another report also indicated that impaired flow in lumbar arteries is markedly associated with reduced diffusion in lumbar disks and may play an important role as an accelerator of disk degeneration. Recently, a study confirmed that vascular risk factors such as TC and TGs are increased in patients with LDH.22 Further analysis found that high cholesterol and TGs could be responsible for the reduced blood supply to the already poorly vascularized intervertebral disk.23 Our study revealed that LDH was correlated with increased baPWV. Moreover, some risk factors of LDH such as obesity, diabetes mellitus, and smoking are associated with baPWV.24–26 Dyslipidaemia, BMI, SBP, and inactivity accelerate the development of atherosclerosis in a synergistic manner. Our results showed that reduced physical activity is correlated with baPWV in patients with LDH. Physical activity is important for the maintenance of musculoskeletal health. Moreover, physical activity participation leads to higher bone mass.27,28 Sedentary lifestyle can easily result in slowing down of blood flow and is an independent risk factor for atherosclerosis and cardiovascular diseases. Previous studies have demonstrated that regular aerobic exercise is efficacious in preventing and reversing arterial stiffness in healthy adults.29 Recent data found the direct effects of inactivity on vascular remodeling and vascular function.30 This study has limitations. First, our study is a crosssectional study, so the order of causality must be confirmed in prospective studies. It remains possible that other, yet undiscovered, factors may exist. Second, the level and type of herniation were not evaluated. Finally, we did not observe the signal changes and disk degeneration in our study. Further studies are warranted to explore the correlation between the changes of disk abnormality and baPWV. Despite these limitations, our study was the first study to

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Physical activity is associated with elevated arterial stiffness in patients with lumbar disk herniation.

A cross-sectional study in a general health examination...
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