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Association between body mass index and high-sensitivity C-reactive protein in male Japanese
Obesity Research & Clinical Practice (2013) 7, e297—e300
SHORT REPORT
Association between body mass index and high-sensitivity C-reactive protein in male Japanese Naoko Nishitani a,∗, Hisataka Sakakibara b a
Sugiyama Jogakuen University, Department of Nursing, 17-3 Hoshigaoka-motomachi, Chikusa-ku, Nagoya 464-8662, Japan b Nagoya University School of Health Sciences, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-8673, Japan Received 25 October 2011 ; received in revised form 2 February 2012; accepted 8 February 2012
KEYWORDS hs-CRP; BMI; Male worker
Summary We divided subjects into hs-CRP of ≤1.0 mg/l and >1.0 mg/l, and investigated the relationship between hs-CRP and basic attributes, lifestyle and health checkup test results. In particular, hs-CRP increased significantly as BMI increased, and hs-CRP of >1.0 mg/l was seen in about 40% of people with BMI of ≥25 kg/m2 and 75% with BMI of ≥30 kg/m2 . Persons with 3 or more abnormalities in BMI, blood pressure, serum lipid and glucose were found in 20.0% of those with hs-CRP >1.0 mg/l, while 4.3% in hs-CRP ≤ 1.0 mg/l. The present findings have suggested that hs-CRP > 1.0 mg/l can be an indicator for obesity-related risks in male Japanese. © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
C-reactive protein (CRP) is produced mainly in the liver, and increases rapidly in the blood when inflammation occurs in the body. Stimulation from inflammatory cytokines such as IL-1 and IL-6 is reported to be involved in its production [1]. Among previous studies on CRP, it is known from follow-up surveys in healthy men that CRP is an independent risk indicator for cardiovascular disease [2]. In the USA, hs-CRP of >3.0 mg/l is thought to be a high risk for heart disease [3]. Meanwhile, in Japan, ∗ Corresponding author. Tel.: +81 052 781 9268; fax: +81 052 781 9268. E-mail address: [email protected] (N. Nishitani).
hs-CRP of >1.0 mg/l is considered to be an indicator for the risk of future heart disease [4]. In the study, following up about 2500 subjects for over 14 years, the onset of heart disease was higher in those with hs-CRP of >1.02 mg/l than in those with hs-CRP of <0.21 mg/l, with a hazard risk of 2.98. Hence, with subjects divided into those having hsCRP of ≤1.0 mg/l and >1.0 mg/l, we conducted a cross-sectional survey to investigate factors related to hs-CRP >1.0 mg/l among male workers. Tests of hs-CRP were performed concurrently with a 2007 workplace health checkup in all the 212 male workers at a manufacturing plant. A self-completed questionnaire survey was also
1871-403X/$ — see front matter © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2012.02.004
e298
N. Nishitani, H. Sakakibara
Table 1
Characteristics of ≤1.0 mg/l hs-CRP and >1.0 mg/l hs-CRP subjects.
Characteristics
Age (year) BMI (kg/m2 ) Sift work (Yes) Overtime work (Yes) Overtime work (h/week) Smoke (Yes) Drink alcohol (≥5 days/week) Exercise (No) Sleeping (h) White blood cell (×103 cells/l) Systolic BP (mmHg) Diastolic BP (mmHg) HDL-cholesterol (mg/dl) Triglycerides (mg/dl) Fasting blood sugar (mg/dl) 3 or more abnormalities in 1—4 item 1. BMI (≥25 kg/m2 ) 2. Systolic BP (≥130 mmHg) or Diastolic BP (≥85 mmHg) 3. HDL-cholesterol (≤39 mg/dl) or Triglycerides (≥150 mg/dl) 4. Fasting blood sugar (≥110 mg/dl) a b c * **
hs-CRP
p value
≤1.0 mg/l n = 138
>1.0 mg/l n = 45
37.3 ± 12.8 23.1 ± 3.2 61 (44.2) 90 (65.2) 4.0 ± 3.7 86 (62.3) 41 (29.7) 78 (56.5) 6.4 ± 0.9 6.5 ± 1.6 115.9 ± 17.9 66.9 ± 12.8 58.0 ± 15.3 119.7 ± 95.8 90.9 ± 15.0 6 (4.3)
41.1 ± 12.8 26.0 ± 5.2 17 (37.8) 30 (66.7) 3.3 ± 3.1 25 (55.6) 10 (22.2) 23 (51.1) 6.2 ± 1.0 6.9 ± 1.3 119.6 ± 19.4 71.1 ± 12.0 52.5 ± 13.5 137.6 ± 78.5 97.1 ± 21.3 9 (20.0)
0.021a,* 0.001b,** 0.449c 0.859c 0.309a 0.420c 0.331c 0.526c 0.140a 0.103b 0.244b 0.050b 0.031b,* 0.258b 0.031b,* 0.001c
Mann—Whitney U test. t-test. 2 test. p < 0.05. p < 0.01.
conducted. Basic attributes and lifestyle were investigated, including age, work pattern (daytime work or shift work), whether living with family, job type, mean overtime working hours (working days in a week), mean sleeping hours (working days in the last one month), regular exercise (days in a week), smoking habits (present, past, never, and quantity in a day), and alcohol consumption (days in a week). The questionnaires were collected from workers who consented to participate in the study and signed an informed consent form. Questionnaires were collected from 210 workers (response rate 99.1%). Fasting blood including hs-CRP was collected during the morning of daytime work (08:30—17:00) from daytime workers, and from shift workers during the morning of afternoon shift among three shifts of morning shift (07:00—14:00), afternoon shift (14:00—22:00), and night shift (22:00—07:00). All blood samples were analyzed at the Medical Examination Center of Handa City Medical Association in Aichi Prefecture, where hs-CRP was measured using latex agglutination turbidimetric immunoassay with an automatic analyzer (Hitachi 7700, Japan). People
being treated for diabetes or other inflammatory conditions were excluded. People who could not undergo blood tests in a fasting state on the day of the health checkup were also excluded from analysis. As a result, the subjects for analysis were 183 men (age, 19—62 years; mean, 38.2 ± 12.9 years). All participants consented to the study and signed a consent form. This study was approved by the ethics committee of the Nagoya University School of Medicine. Among daytime workers, the median hs-CRP was 0.32 mg/l with the interquartile range (IQR) of 0.12—1.06 mg/l. Among shift workers, the median was 0.32 mg/l (IQR; 0.12—0.83 mg/l). The levels did not differ statistically between the groups. With subjects divided into those having hs-CRP of ≤1.0 mg/l and >1.0 mg/l, basic attributes and lifestyle were investigated by Mann—Whitney U test, 2 test and t-test. The results showed that the subjects with hs-CRP >1.0 mg/l had significantly higher BMI (p < 0.01), age (p < 0.05) and fasting blood glucose (p < 0.05), and significantly lower HDL-cholesterol (p < 0.05), when compared to those with hs-CRP ≤ 1.0 mg/l (Table 1). The levels of
BMI and hs-CRP Table 2
e299
Hs-CRP score, and >1.0 mg/l hs-CRP n (%) by BMI group.
Hs-CRP (mg/l)
BMI (kg/m2 )
(0—5.0)
<18.5
Median Inter quartile range (IQR) >1.0 hs-CRP n (%)
P
n = 11 0.14
≥18.5 to <22.0 n = 52 0.21
≥22.0 to <25.0 n = 65 0.28
≥25.0 to <30.0 n = 47 0.82
≥30.0 n=8 2.35
(0.05, 0.31) 1 (9.1)
(0.06, 0.50) 7 (13.5)
(0.10, 0.78) 13 (20.0)
(0.29, 1.26) 18 (38.3)
(0.88, 2.94) 6 (75.0)
<0.001
Kruskal—Wallis test.
hs-CRP increased with an increase in BMI (p < 0.001); hs-CRP > 1.0 mg/l was seen in 38% of subjects with BMI ≥ 25 kg/m2 and 75% with BMI ≥ 30 kg/m2 (Table 2). Obesity or BMI is shown to be associated with CRP [5—9]. In the present study the level of hs-CRP increased with BMI. In addition, when the cutoff value of hs-CRP was set at 1.0 mg/l, which is considered to be a risk for heart disease in Japanese population [4], hs-CRP of >1.0 mg/l was found in about 40% of subjects with BMI ≥ 25 kg/m2 , and 75% with BMI ≥ 30 kg/m2 . The findings have suggested that male Japanese workers with BMI ≥25 kg/m2 are more likely to be at risk for heart disease. This agrees with the obesity guidelines of BMI ≥ 25 kg/m2 for Japanese people. Obesity is known to be linked to metabolic syndrome. The present results showed that subjects with hs-CRP > 1.0 mg/l had higher fasting blood glucose and lower HDL-cholesterol, when compared to those with hs-CRP ≤ 1.0 mg/l. The prevalence of cases with 3 or more abnormalities in BMI, blood pressure, serum lipid and fasting glucose (Table 1) was 20.0% in those with hs-CRP > 1.0 mg/l, while 4.3% in those with hs-CRP ≤ 1.0 mg/l. It is, hence, considered that hs-CRP > 1.0 mg/l can be an indicator for metabolic syndrome. In this study, Spearman’s correlation coefficient for hsCRP showed positive correlations with triglycerides (r = 0.22), fasting blood sugar (r = 0.20), systolic blood pressure (r = 0.18), and diastolic blood pressure (r = 0.15), and a negative correlation with HDL-cholesterol (r = 0.28). These results were similar to previous studies [5]. The present findings have suggested that hs-CRP > 1.0 mg/l can be an indicator for obesityrelated risks in male Japanese. Further studies will be necessary with individuals in other types of work and in larger numbers.
Conflicts of interest statement The authors declare that there are no conflicts of interest associated with the present study.
Acknowledgements This study was conducted with aid for the health promotion field from a medical research and health promotion activities grant for 2006 from the Aichi Health Promotion Foundation.
References [1] Calabro P, Golia E, Yeh ETH. CRP and the risk of atherosclerotic events. Semin Immunopathol 2009;31:79—94. [2] Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New Engl J Med 1997;336:973—9. [3] Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon 3rd RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the Am Heart Association. Circulation 2003;107:499—511. [4] Arima H, Kubo M, Yonemoto K, Doi Y, Ninomiya T, Tanizaki Y, et al. High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study. Arterioscler Thromb Vasc Biol 2008;28: 1385—91. [5] Tamakoshi K, Yatsuya H, Kondo T, Hori Y, Ishikawa M, Zhang H, et al. The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state. Int J Obes Relat Metab Disord 2003;27:443—9. [6] Fredrikson GN, Hedblad B, Nilsson JA, Alm R, Berglund G, Nilsson J. Association between diet, lifestyle, metabolic cardiovascular risk factors, and plasma C-reactive protein levels. Metabolism 2004;53:1436—42. [7] Yamamoto K, Okazaki A, Ohmori S. The relationship between psychosocial stress, age, BMI, CRP, lifestyle, and the metabolic syndrome in apparently healthy subjects. J Physiol Anthropol 2011;30:15—22.
e300
N. Nishitani, H. Sakakibara
[8] Tamakoshi K, Yatsuya H, Kondo T, Ishikawa M, Zhang H, Murata C, et al. Long-term body weight variability is associated with elevated C-reactive protein independent of current body mass index among Japanese men. Int J Obes Relat Metab Disord 2003;27:1059—65.
[9] Homma M, Mori K, Funatsu K, Yamashita T, Kondo S, Yokoyama M, et al. Usefulness of assessing hs-CRP in health survey program (2) annual variation. JHD 2002;17:77—80 [in Japanese].
Available online at www.sciencedirect.com
SHORT REPORT
Association between body mass index and high-sensitivity C-reactive protein in male Japanese Naoko Nishitani a,∗, Hisataka Sakakibara b a
Sugiyama Jogakuen University, Department of Nursing, 17-3 Hoshigaoka-motomachi, Chikusa-ku, Nagoya 464-8662, Japan b Nagoya University School of Health Sciences, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-8673, Japan Received 25 October 2011 ; received in revised form 2 February 2012; accepted 8 February 2012
KEYWORDS hs-CRP; BMI; Male worker
Summary We divided subjects into hs-CRP of ≤1.0 mg/l and >1.0 mg/l, and investigated the relationship between hs-CRP and basic attributes, lifestyle and health checkup test results. In particular, hs-CRP increased significantly as BMI increased, and hs-CRP of >1.0 mg/l was seen in about 40% of people with BMI of ≥25 kg/m2 and 75% with BMI of ≥30 kg/m2 . Persons with 3 or more abnormalities in BMI, blood pressure, serum lipid and glucose were found in 20.0% of those with hs-CRP >1.0 mg/l, while 4.3% in hs-CRP ≤ 1.0 mg/l. The present findings have suggested that hs-CRP > 1.0 mg/l can be an indicator for obesity-related risks in male Japanese. © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
C-reactive protein (CRP) is produced mainly in the liver, and increases rapidly in the blood when inflammation occurs in the body. Stimulation from inflammatory cytokines such as IL-1 and IL-6 is reported to be involved in its production [1]. Among previous studies on CRP, it is known from follow-up surveys in healthy men that CRP is an independent risk indicator for cardiovascular disease [2]. In the USA, hs-CRP of >3.0 mg/l is thought to be a high risk for heart disease [3]. Meanwhile, in Japan, ∗ Corresponding author. Tel.: +81 052 781 9268; fax: +81 052 781 9268. E-mail address: [email protected] (N. Nishitani).
hs-CRP of >1.0 mg/l is considered to be an indicator for the risk of future heart disease [4]. In the study, following up about 2500 subjects for over 14 years, the onset of heart disease was higher in those with hs-CRP of >1.02 mg/l than in those with hs-CRP of <0.21 mg/l, with a hazard risk of 2.98. Hence, with subjects divided into those having hsCRP of ≤1.0 mg/l and >1.0 mg/l, we conducted a cross-sectional survey to investigate factors related to hs-CRP >1.0 mg/l among male workers. Tests of hs-CRP were performed concurrently with a 2007 workplace health checkup in all the 212 male workers at a manufacturing plant. A self-completed questionnaire survey was also
1871-403X/$ — see front matter © 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2012.02.004
e298
N. Nishitani, H. Sakakibara
Table 1
Characteristics of ≤1.0 mg/l hs-CRP and >1.0 mg/l hs-CRP subjects.
Characteristics
Age (year) BMI (kg/m2 ) Sift work (Yes) Overtime work (Yes) Overtime work (h/week) Smoke (Yes) Drink alcohol (≥5 days/week) Exercise (No) Sleeping (h) White blood cell (×103 cells/l) Systolic BP (mmHg) Diastolic BP (mmHg) HDL-cholesterol (mg/dl) Triglycerides (mg/dl) Fasting blood sugar (mg/dl) 3 or more abnormalities in 1—4 item 1. BMI (≥25 kg/m2 ) 2. Systolic BP (≥130 mmHg) or Diastolic BP (≥85 mmHg) 3. HDL-cholesterol (≤39 mg/dl) or Triglycerides (≥150 mg/dl) 4. Fasting blood sugar (≥110 mg/dl) a b c * **
hs-CRP
p value
≤1.0 mg/l n = 138
>1.0 mg/l n = 45
37.3 ± 12.8 23.1 ± 3.2 61 (44.2) 90 (65.2) 4.0 ± 3.7 86 (62.3) 41 (29.7) 78 (56.5) 6.4 ± 0.9 6.5 ± 1.6 115.9 ± 17.9 66.9 ± 12.8 58.0 ± 15.3 119.7 ± 95.8 90.9 ± 15.0 6 (4.3)
41.1 ± 12.8 26.0 ± 5.2 17 (37.8) 30 (66.7) 3.3 ± 3.1 25 (55.6) 10 (22.2) 23 (51.1) 6.2 ± 1.0 6.9 ± 1.3 119.6 ± 19.4 71.1 ± 12.0 52.5 ± 13.5 137.6 ± 78.5 97.1 ± 21.3 9 (20.0)
0.021a,* 0.001b,** 0.449c 0.859c 0.309a 0.420c 0.331c 0.526c 0.140a 0.103b 0.244b 0.050b 0.031b,* 0.258b 0.031b,* 0.001c
Mann—Whitney U test. t-test. 2 test. p < 0.05. p < 0.01.
conducted. Basic attributes and lifestyle were investigated, including age, work pattern (daytime work or shift work), whether living with family, job type, mean overtime working hours (working days in a week), mean sleeping hours (working days in the last one month), regular exercise (days in a week), smoking habits (present, past, never, and quantity in a day), and alcohol consumption (days in a week). The questionnaires were collected from workers who consented to participate in the study and signed an informed consent form. Questionnaires were collected from 210 workers (response rate 99.1%). Fasting blood including hs-CRP was collected during the morning of daytime work (08:30—17:00) from daytime workers, and from shift workers during the morning of afternoon shift among three shifts of morning shift (07:00—14:00), afternoon shift (14:00—22:00), and night shift (22:00—07:00). All blood samples were analyzed at the Medical Examination Center of Handa City Medical Association in Aichi Prefecture, where hs-CRP was measured using latex agglutination turbidimetric immunoassay with an automatic analyzer (Hitachi 7700, Japan). People
being treated for diabetes or other inflammatory conditions were excluded. People who could not undergo blood tests in a fasting state on the day of the health checkup were also excluded from analysis. As a result, the subjects for analysis were 183 men (age, 19—62 years; mean, 38.2 ± 12.9 years). All participants consented to the study and signed a consent form. This study was approved by the ethics committee of the Nagoya University School of Medicine. Among daytime workers, the median hs-CRP was 0.32 mg/l with the interquartile range (IQR) of 0.12—1.06 mg/l. Among shift workers, the median was 0.32 mg/l (IQR; 0.12—0.83 mg/l). The levels did not differ statistically between the groups. With subjects divided into those having hs-CRP of ≤1.0 mg/l and >1.0 mg/l, basic attributes and lifestyle were investigated by Mann—Whitney U test, 2 test and t-test. The results showed that the subjects with hs-CRP >1.0 mg/l had significantly higher BMI (p < 0.01), age (p < 0.05) and fasting blood glucose (p < 0.05), and significantly lower HDL-cholesterol (p < 0.05), when compared to those with hs-CRP ≤ 1.0 mg/l (Table 1). The levels of
BMI and hs-CRP Table 2
e299
Hs-CRP score, and >1.0 mg/l hs-CRP n (%) by BMI group.
Hs-CRP (mg/l)
BMI (kg/m2 )
(0—5.0)
<18.5
Median Inter quartile range (IQR) >1.0 hs-CRP n (%)
P
n = 11 0.14
≥18.5 to <22.0 n = 52 0.21
≥22.0 to <25.0 n = 65 0.28
≥25.0 to <30.0 n = 47 0.82
≥30.0 n=8 2.35
(0.05, 0.31) 1 (9.1)
(0.06, 0.50) 7 (13.5)
(0.10, 0.78) 13 (20.0)
(0.29, 1.26) 18 (38.3)
(0.88, 2.94) 6 (75.0)
<0.001
Kruskal—Wallis test.
hs-CRP increased with an increase in BMI (p < 0.001); hs-CRP > 1.0 mg/l was seen in 38% of subjects with BMI ≥ 25 kg/m2 and 75% with BMI ≥ 30 kg/m2 (Table 2). Obesity or BMI is shown to be associated with CRP [5—9]. In the present study the level of hs-CRP increased with BMI. In addition, when the cutoff value of hs-CRP was set at 1.0 mg/l, which is considered to be a risk for heart disease in Japanese population [4], hs-CRP of >1.0 mg/l was found in about 40% of subjects with BMI ≥ 25 kg/m2 , and 75% with BMI ≥ 30 kg/m2 . The findings have suggested that male Japanese workers with BMI ≥25 kg/m2 are more likely to be at risk for heart disease. This agrees with the obesity guidelines of BMI ≥ 25 kg/m2 for Japanese people. Obesity is known to be linked to metabolic syndrome. The present results showed that subjects with hs-CRP > 1.0 mg/l had higher fasting blood glucose and lower HDL-cholesterol, when compared to those with hs-CRP ≤ 1.0 mg/l. The prevalence of cases with 3 or more abnormalities in BMI, blood pressure, serum lipid and fasting glucose (Table 1) was 20.0% in those with hs-CRP > 1.0 mg/l, while 4.3% in those with hs-CRP ≤ 1.0 mg/l. It is, hence, considered that hs-CRP > 1.0 mg/l can be an indicator for metabolic syndrome. In this study, Spearman’s correlation coefficient for hsCRP showed positive correlations with triglycerides (r = 0.22), fasting blood sugar (r = 0.20), systolic blood pressure (r = 0.18), and diastolic blood pressure (r = 0.15), and a negative correlation with HDL-cholesterol (r = 0.28). These results were similar to previous studies [5]. The present findings have suggested that hs-CRP > 1.0 mg/l can be an indicator for obesityrelated risks in male Japanese. Further studies will be necessary with individuals in other types of work and in larger numbers.
Conflicts of interest statement The authors declare that there are no conflicts of interest associated with the present study.
Acknowledgements This study was conducted with aid for the health promotion field from a medical research and health promotion activities grant for 2006 from the Aichi Health Promotion Foundation.
References [1] Calabro P, Golia E, Yeh ETH. CRP and the risk of atherosclerotic events. Semin Immunopathol 2009;31:79—94. [2] Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New Engl J Med 1997;336:973—9. [3] Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon 3rd RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the Am Heart Association. Circulation 2003;107:499—511. [4] Arima H, Kubo M, Yonemoto K, Doi Y, Ninomiya T, Tanizaki Y, et al. High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study. Arterioscler Thromb Vasc Biol 2008;28: 1385—91. [5] Tamakoshi K, Yatsuya H, Kondo T, Hori Y, Ishikawa M, Zhang H, et al. The metabolic syndrome is associated with elevated circulating C-reactive protein in healthy reference range, a systemic low-grade inflammatory state. Int J Obes Relat Metab Disord 2003;27:443—9. [6] Fredrikson GN, Hedblad B, Nilsson JA, Alm R, Berglund G, Nilsson J. Association between diet, lifestyle, metabolic cardiovascular risk factors, and plasma C-reactive protein levels. Metabolism 2004;53:1436—42. [7] Yamamoto K, Okazaki A, Ohmori S. The relationship between psychosocial stress, age, BMI, CRP, lifestyle, and the metabolic syndrome in apparently healthy subjects. J Physiol Anthropol 2011;30:15—22.
e300
N. Nishitani, H. Sakakibara
[8] Tamakoshi K, Yatsuya H, Kondo T, Ishikawa M, Zhang H, Murata C, et al. Long-term body weight variability is associated with elevated C-reactive protein independent of current body mass index among Japanese men. Int J Obes Relat Metab Disord 2003;27:1059—65.
[9] Homma M, Mori K, Funatsu K, Yamashita T, Kondo S, Yokoyama M, et al. Usefulness of assessing hs-CRP in health survey program (2) annual variation. JHD 2002;17:77—80 [in Japanese].
Available online at www.sciencedirect.com