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Association between serum lipids and low back pain among a middle-aged Japanese population: a large-scale cross-sectional study

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Lipids in Health and Disease201817:266

https://doi.org/10.1186/s12944-018-0907-1

  • Received: 12 September 2018
  • Accepted: 8 November 2018
  • Published:

Abstract

Background

Abnormal lipid levels have been suggested as a mechanism leading to atherosclerosis of the lumbar vessels, resulting in low back pain (LBP). This study examined whether abnormal lipid levels were associated with LBP among middle-aged adults in Japan.

Methods

The present study included adults between 40 and 64 years old who underwent an annual health checkup. A total of 258,367 eligible participants were analyzed to investigate associations of LBP with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and LDL-C/HDL-C ratio. Participants were categorized into two groups according to each of LDL-C, HDL-C, and LDL-C/HDL-C ratio (LDL-C: ≥ 140 vs. < 140 mg/dL; HDL-C: ≥ 40 vs. < 40 mg/dL; LDL-C/HDL-C ratio: ≥ 2.5 vs. < 2.5). Information on LBP was obtained using a self-administered questionnaire. Logistic regression modeling was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for LBP.

Results

The prevalence of LBP was 2.2% in men and 2.1% in women. Multivariable analysis adjusting for age, body mass index, and lifestyle factors found significant associations for HDL-C <  40 mg/dL (OR, 1.34; 95%CI, 1.20–1.48 in men; OR, 1.32; 95%CI, 1.02–1.72 in women) and LDL-C/HDL-C ratio ≥ 2.5 (OR, 1.17; 95%CI, 1.09–1.26 in men; OR, 1.15; 95%CI, 1.03–1.29 in women) with LBP.

Conclusions

Low HDL-C and high LDL-C/HDL-C ratio were significantly associated with LBP in a middle-aged Japanese population. These findings might support the atherosclerosis-LBP hypothesis.

Keywords

  • Low back pain
  • Lipid
  • HDL cholesterol
  • LDL cholesterol
  • LDL-C/HDL-C ratio

Background

Low back pain (LBP) is a common musculoskeletal health problem worldwide, and the leading cause of years lived with disability [1]. Moreover, LBP has been linked to considerable socio-economic loss, impairing the health of employees, and reducing work productivity [2, 3]. Effective strategies for prevention of LBP are thus urgently required.

The etiology of LBP is multifactorial, including individual, physical, and psychosocial factors [4]. As one of the mechanisms underlying LBP, it has been suggested that atherosclerosis of the lumbar arteries could reduce the blood supply to the lumbar region, leading to disc degeneration and LBP [5, 6]. LBP has been found more frequently in subjects with missing or narrowed lumbar or sacral arteries [7, 8] or calcification in the abdominal aorta [9]. Considering that LBP could be influenced by arterial degeneration, risk factors for atherosclerosis may also be associated with LBP. Several studies have investigated associations of LBP with high levels of blood cholesterol, which are involved in the development of atherosclerosis [1013]. However, the results have been inconsistent and mostly from Western countries. Given the ethnic differences in lifestyles and the development of metabolic disorders [14], research targeted at the Japanese population is essential to clarify the risk factors for LBP and to explore effective interventions for preventing LBP in this population.

The aim of the present study was to investigate the association between serum lipids (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and LDL-C/HDL-C ratio) and LBP in a Japanese population using large-scale data from health checkups.

Methods

Study population

Subjects in the present study were adults between 40 and 64 years old who underwent an annual health checkup during the period from April 2013 to March 2014 and conducted by the All Japan Labor Welfare Foundation, a health checkup center in Japan. Of the total of 310,577 participants in health checkups during this period, 310,498 subjects participated in this study. Of these, we excluded from the present study 7525 participants who took medication for dyslipidemia at the time of the checkup, and 44,606 participants with missing data on variables. As a result, data from 258,367 participants were analyzed. Informed consent for the use of personal information in this study was obtained from each participant. The present study complies with the ethical guidelines of the Declaration of Helsinki, and received approval from the medical ethics committee of Showa University School of Medicine (Approval No. 2407) and the Ethics Committee of the All Japan Labor Welfare Foundation (Approval No. 9-1-0007).

Measurements

A self-administered questionnaire was distributed to each subject who underwent the health checkup. The subject was asked to complete the questionnaire, which included questions on age, sex, and lifestyle. Question items on lifestyle included smoking status (none, former, current), alcohol intake (none, sometimes, everyday), and physical activity equal to walking at least 60 min/day (yes or no), as information recommended to assess health conditions in health checkups by the Ministry of Health, Labour and Welfare in Japan [15]. LBP was self-reported in the following question: “Do you have LBP under treatment including follow-up?” [16]. Measurements of height and weight were performed by trained staff. Height and weight were measured to the nearest 0.1 cm using a stadiometer, and to the nearest 0.1 kg using a scale, respectively. Body mass index (BMI) was calculated as the weight in kilograms divided by the square of the height in meters. Age was classified into strata of 40–49, 50–59, and 60–64 years [11]. BMI was categorized into three groups of < 18.5, 18.5–24.9, and ≥ 25 kg/m2 [17].

A venous blood sample was collected and analyzed at an external laboratory (SRL, Tokyo, Japan) within 24 h of being drawn. LDL-C and HDL-C were determined using a direct method (AU5400; Beckman Coulter, Tokyo, Japan). LDL-C and HDL-C were categorized based on the definitions of dyslipidemia by the Japan Atherosclerosis Society Guidelines [18] as follows: LDL-C, high (≥ 140 mg/dL) or normal (< 140 mg/dL); HDL-C, low (< 40 mg/dL) or normal (≥ 40 mg/dL). LDL-C/HDL-C ratio was categorized according to a previous study [19] as high (≥ 2.5) or low (< 2.5).

Statistical analysis

We compared the characteristics of participants by sex and by the presence or absence of LBP using Pearson’s chi-square test for categorical variables, and the unpaired t-test for continuous variables. To evaluate the relationship between serum lipids and LBP, logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for LBP. In the model, age, BMI, smoking status, alcohol intake, and physical activity, were included to control for potential confounders because such lifestyle factors have been recognized as important factors contributing to LBP [2022]. Statistical analyses were performed using JMP version 13.0 (SAS Institute Japan, Tokyo, Japan). A value of p <  0.05 was considered statistically significant, and all reported p values are two sided.

Results

Mean age of participants in the present study was 50.9 years (standard deviation, 7.2 years), and 65.6% of participants were men. The prevalence of LBP was 2.2% for the overall cohort. Participant characteristics by sex in the present study are shown in Table 1. The prevalence of LBP was 2.2% in men, and 2.1% in women.
Table 1

Baseline characteristics of study participants by sex (n = 258,367)

 

Men (n = 169,606)

Women (n = 88,761)

p valuea

n

%

n

%

Age (years)

 40–49

80,774

47.6

40,029

45.1

<  0.001

 50–59

61,948

36.5

34,912

39.3

 

 60–64

26,884

15.9

13,820

15.6

 

Height (cm)

169.1 (6.4)

157.2 (6.3)

<  0.001

Weight (kg)

68.5 (11.6)

55.7 (10.3)

<  0.001

Body mass index (kg/m2)

 <  18.5

3783

2.2

6241

7.0

<  0.001

 18.5–24.9

110,236

65.0

63,475

71.5

 

 ≥ 25

55,587

32.8

19,045

21.5

 

Physical activity (min/day)

 ≥ 60

58,183

34.3

27,453

30.9

<  0.001

 <  60

111,423

65.7

61,308

69.1

 

Smoking status

 None

58,054

34.2

65,547

73.8

<  0.001

 Former

31,525

18.6

5884

6.6

 

 Current

80,027

47.2

17,330

19.5

 

Alcohol intake

 None

48,457

28.6

50,406

56.8

<  0.001

 Sometimes

48,965

28.9

24,558

27.7

 

 Everyday

72,184

42.6

13,797

15.5

 

Low back pain

 +

3726

2.2

1889

2.1

0.256

 –

165,880

97.8

86,872

97.9

 

LDL-C (mg/dL)

 Normal (<  140)

119,824

70.6

63,407

71.4

<  0.001

 High (≥ 140)

49,782

29.4

25,354

28.6

 

HDL-C (mg/dL)

 Normal (≥ 40)

154,412

91.0

86,920

97.9

<  0.001

 Low (<  40)

15,194

9.0

1841

2.1

 

LDL-C/HDL-C ratio

 Low (<  2.5)

105,067

61.9

70,748

79.7

<  0.001

 High (≥ 2.5)

64,539

38.1

18,013

20.3

 

Data are presented as number and percentage, or mean (standard deviation)

LDL-C: Low-density lipoprotein-cholesterol, HDL-C: High-density lipoprotein-cholesterol

a Pearson chi-square test or unpaired t test

Tables 2 and 3 show comparisons of characteristics between participants with and without LBP in men and in women. Among men, proportions of low HDL-C level and high LDL-C/HDL-C ratio were significantly higher in participants with LBP than in those without LBP (Table 2). Proportions of low HDL-C level and high LDL-C level and LDL-C/HDL-C ratio were significantly higher in women with LBP than in women without LBP (Table 3).
Table 2

Comparison of characteristics between participants with and without low back pain among men

 

Low back pain (+) (n = 3726)

Low back pain (−) (n = 165,880)

p valuea

Age (years)

 40–49

1478

39.7

79,296

47.8

<  0.001

 50–59

1455

39.0

60,493

36.5

 60–64

793

21.3

26,091

15.7

Height (cm)

169.1 (6.6)

169.1 (6.4)

0.486

Weight (kg)

69.3 (12.0)

68.5 (11.6)

<  0.001

Body mass index (kg/m2)

 <  18.5

129

3.5

6029

3.6

<  0.001

 18.5–24.9

2261

60.7

105,600

63.7

 ≥ 25

1336

35.8

54,251

32.7

Physical activity (min/day)

 ≥ 60

1244

33.4

56,939

34.3

0.233

 <  60

2482

66.6

108,941

65.7

Smoking status

 None

1249

33.5

56,805

34.2

<  0.001

 Former

813

21.8

30,712

18.5

 Current

1664

44.7

78,363

47.2

Alcohol intake

 None

1085

29.1

47,372

42.5

0.054

 Sometimes

1010

27.1

47,955

28.9

 Everyday

1631

43.8

70,553

28.6

LDL-C (mg/dL)

 Normal (<  140)

2605

69.9

117,219

70.7

0.320

 High (≥ 140)

1121

30.1

48,661

29.3

HDL-C (mg/dL)

 Normal (≥ 40)

3294

88.4

151,118

91.1

<  0.001

 Low (<  40)

432

11.6

14,762

8.9

LDL-C/HDL-C ratio

 Low (<  2.5)

2178

58.5

102,889

62.0

<  0.001

 High (≥ 2.5)

1548

41.5

62,991

38.0

Data are presented as number and percentage, or mean (standard deviation)

LDL-C: Low-density lipoprotein-cholesterol, HDL-C: High-density lipoprotein-cholesterol

aPearson chi-square test or unpaired t test

Table 3

Comparison of characteristics between participants with and without low back pain among women

 

Low back pain (+) (n = 1889)

Low back pain (−) (n = 86,872)

p valuea

Age (years)

 40–49

626

33.1

39,403

45.4

<  0.001

 50–59

863

45.7

34,049

39.2

 60–64

400

21.2

13,420

15.4

Height (cm)

156.9 (6.5)

157.2 (6.3)

0.062

Weight (kg)

57.7 (10.8)

55.7 (10.3)

<  0.001

Body mass index (kg/m2)

 <  18.5

138

7.3

9474

10.9

<  0.001

 18.5–24.9

1200

63.5

58,904

67.8

 ≥ 25

551

29.2

18,494

21.3

Physical activity (min/day)

 ≥ 60

643

34.0

26,810

30.9

0.003

 <  60

1246

66.0

60,062

69.1

Smoking status

 None

1327

70.2

64,220

73.9

0.001

 Former

149

7.9

5735

6.6

 Current

413

21.9

16,917

19.5

Alcohol intake

 None

1099

58.2

49,307

56.7

0.250

 Sometimes

521

27.6

24,037

27.7

 Everyday

269

14.2

13,528

15.6

LDL-C (mg/dL)

 Normal (<  140)

1278

67.7

62,129

71.5

<  0.001

 High (≥ 140)

611

32.3

24,743

28.5

HDL-C (mg/dL)

 Normal (≥ 40)

1828

96.8

85,092

98.0

<  0.001

 Low (<  40)

61

3.3

1780

2.0

LDL-C/HDL-C ratio

 Low (<  2.5)

1398

74.0

69,350

79.8

<  0.001

 High (≥ 2.5)

491

26.0

17,522

20.2

Data are presented as number and percentage, or mean (standard deviation)

LDL-C: Low-density lipoprotein-cholesterol, HDL-C: High-density lipoprotein-cholesterol

a Person chi-square test or unpaid t test

Crude and adjusted ORs of serum lipids for LBP are shown in Table 4. Univariate analysis showed that low HDL-C level and high LDL-C/HDL-C ratio were significantly associated with LBP in both sexes. Even when adjusted for age, BMI, smoking status, alcohol intake, and physical activity in multivariable analysis, associations of HDL-C (OR, 1.34; 95%CI, 1.20–1.48 in men; OR, 1.32; 95%CI, 1.02–1.72 in women) and LDL-C/HDL-C ratio (OR, 1.17; 95%CI, 1.09–1.26 in men; OR, 1.15; 95%CI, 1.03–1.29 in women) with LBP remained significant.
Table 4

Crude and adjusted odds ratios of serum lipids for low back pain by sex

 

Total

Low back pain

Crude

Adjusteda

N

n (%)

OR

95%CI

OR

95%CI

Men

 LDL-C (mg/dL)

  Normal (<  140)

119,824

2605 (2.2)

1.00

 

1.00

 

  High (≥ 140)

49,782

1121 (2.3)

1.04

0.97–1.11

1.04

0.96–1.11

 HDL-C (mg/dL)

  Normal (≥ 40)

154,412

3294 (2.1)

1.00

 

1.00

 

  Low (<  40)

15,194

432 (2.8)

1.34

1.21–1.49

1.34

1.20–1.48

 LDL-C/HDL-C ratio

  Low (<  2.5)

105,067

2178 (2.1)

1.00

 

1.00

 

  High (≥ 2.5)

64,539

1548 (2.4)

1.16

1.09–1.24

1.17

1.09–1.26

Women

 LDL-C (mg/dL)

  Normal (<  140)

63,407

1278 (2.0)

1.00

 

1.00

 

  High (≥ 140)

25,354

611 (2.4)

1.20

1.09–1.32

1.02

0.92–1.13

 HDL-C (mg/dL)

  Normal (≥ 40)

86,920

1828 (2.1)

1.00

 

1.00

 

  Low (<  40)

1841

61 (3.3)

1.59

1.23–2.07

1.32

1.02–1.72

 LDL-C/HDL-C ratio

  Low (<  2.5)

70,748

1398 (2.0)

1.00

 

1.00

 

  High (≥ 2.5)

18,013

491 (2.7)

1.39

1.25–1.54

1.15

1.03–1.29

OR: Odds ratio, CI: Confidence interval, LDL-C: Low-density lipoprotein-cholesterol, HDL-C: High-density lipoprotein-cholesterol

a Adjusted for age, body mass index, smoking status, alcohol intake, and physical activity

Discussion

This study investigated the association between serum lipids and LBP using large-scale data from annual health checkups in Japan. Our results showed that low HDL-C level and high LDL-C/HDL-C ratio were significantly associated with LBP after adjusting for potential confounders. To the best of our knowledge, this represents the first study to demonstrate significant associations between serum lipids and LBP in middle-aged Japanese adults.

Our study indicated that prevalence of LBP under treatment was 2.2% in total participants. Myojin et al. have reported that the prevalence of backache under treatment was 5.25% based on the Comprehensive Survey of Living Conditions, collected by the Ministry of Health, Labour and Welfare of Japan, and with participants including elderly individuals [16]. Considering that older people show a higher prevalence of LBP [23], it may be reasonable for the prevalence of LBP to be lower in our study. In a previous study with more than 5000 health examinees [24], prevalence of LBP treated among 40–59 years old was 3.2%, similar to our results.

The present study found a significant association between low HDL-C level and LBP. Low HDL-C level is considered as an independent risk factor for cardiovascular events [25, 26]. Heuch et al. found that the prevalence of LBP was inversely associated with HDL-C among women in a nationally representative sample study [11]. Moreover, in a cohort study, low HDL-C level could represent a risk factor for chronicity of LBP in men with LBP at baseline [27]. Such results suggest that our study findings in a Japanese population were reasonable.

A mechanism by which abnormality of serum lipid concentrations causes LBP might be explained through atherosclerosis of the involved arteries; the atherosclerosis obstructs blood supply to corresponding lumbar region, resulting in disc degeneration and damage to surrounding tissues [5, 28]. Several studies have indicated more frequent LBP in patients with various lesions in the arteries involved [7, 8, 29]. Because disorders of lipid metabolism are considered essential for initiating the long, drawn-out process of atherosclerosis development, our results are in accordance with the hypothesis that atherosclerosis of the lumbar vessels is significant as a mechanism leading to LBP. Although lipid levels may indirectly affect LBP through obesity, which has been considered to result in increased mechanical load on the lumbar structure [30], our results showed a significant relationship between LBP and lipid levels after adjustment of BMI. These results may imply the existence of another pathway contributing to the development of LBP other than obesity. Another mechanism might involve inflammation. Pro-inflammatory cytokines have been shown to influence lipid metabolism via stimulating fatty acid synthesis or lipolysis [31]. Chronic LBP patients have been shown to have higher levels of pro-inflammatory cytokines than those without LBP [32, 33]. Because information on pro-inflammatory cytokines was not obtained in our study, future studies will be needed to elucidate the mechanisms involved.

In the present study, a high LDL-C/HDL-C ratio was significantly associated with LBP. LDL-C/HDL-C ratio has recently gained attention as an index for cardiovascular disease risk [19, 34]. This study used a cutoff for LDL-C/HDL-C ratio of 2.5 according to the previous study related to cardiovascular risk [19]. The cutoff value of 2.5 is consistent with the value from an intravascular ultrasonographic study that indicated a drastic increase in plaque formation in the coronary artery [35]. In addition, as an optimal reference value for cholesterol, the National Cholesterol Education Program guidelines recommend levels of LDL-C and HDL-C that represent a ratio of about 2.5 [36]. Our results suggest that LDL-C/HDL-C ratio ≥ 2.5, which can be obtained from a standard lipid profile, may be useful as a marker to detect the risk of LBP from the standpoint of the atherosclerosis-LBP hypothesis.

A major strength in the present study was that the subject population was a large-scale sample in Japan. In contrast, our study has some limitations. First, information on LBP was obtained from a self-reported questionnaire in the health checkup, and was not based on specific clinical examinations or a disease-specific questionnaire. Distinguishing between localized pain and radicular pain, or acute and chronic pain was thus not possible. However, such assessments of LBP in detail may be difficult to achieve in large population-based research. Second, confounding by unmeasured variables such as occupation, psychosocial characteristics, or unhealthy lifestyles including sedentary behavior or sleep disturbance [3739] cannot be ruled out. These factors could contribute to both LBP and dyslipidemia without causal relationship between them. Finally, the direction of causality of the relationship was not able to be inferred because of the cross-sectional design used in this study. For example, it cannot deny the possibility that LBP would restrict physical activity over time which lead to dyslipidemia. Further longitudinal research is needed to clarify the causal relationship.

Conclusions

In conclusion, a low HDL-C level and high LDL-C/HDL-C ratio were significantly associated with LBP in a middle-aged Japanese population. The present study may have important implications for elucidation of the pathophysiological mechanisms of LBP.

Abbreviations

BMI: 

Body mass index

CI: 

Confidence interval

HDL-C: 

High-density lipoprotein-cholesterol

LBP: 

Low back pain

LDL-C: 

Low-density lipoprotein-cholesterol

OR: 

Odds ratio

Declarations

Acknowledgements

We would like to thank Dr. Nobuo Yanagisawa, Dr. Takeshi Kawaguchi, Mr. Takahiro Tamura, and Mr. Yutaka Hoshina in the All Japan Labor Welfare Foundation for supporting the study.

Funding

This study was supported in part by Grant-in-Aid for Young Scientists (JP18K17979) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Availability of data and materials

The data used in the current study are available on reasonable request and only after approval by the Ethics Committee of the All Japan Labor Welfare Foundation.

Authors’ contributions

TY, HO, and TS contributed to the study design, data interpretation, and manuscript preparation. TY conducted the data analysis, and drafted the manuscript. SN and MK contributed to the acquisition of data. AM (Minoura), AM (Miki), YC, and HH contributed to the data interpretation, and supported drafting the manuscript. AK made substantial contributions to the conception of this study and project administration. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

The present study was approved by the medical ethics committee of Showa University School of Medicine (Approval No. 2407) and the Ethics Committee of the All Japan Labor Welfare Foundation (Approval No. 9-1-0007). Informed consent for the use of personal information in this study was obtained from each participant.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku Tokyo, 142-8555, Japan
(2)
All Japan Labor Welfare Foundation, 6-16-11 Hatanodai, Shinagawa-ku Tokyo, 142-0064, Japan

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