Parasite Immunology, 2015, 37, 333–339
DOI: 10.1111/pim.12187
The potential long-term effect of previous schistosome infection reduces the risk of metabolic syndrome among Chinese men S.-W. SHEN,1* Y. LU,2* F. LI,2* Z.-H. SHEN,2* M. XU,3 W.-F. YAO,1 Y.-B. FENG,2 J.-T. YUN,2 Y.-P. WANG,1 W. LING,2 H.-J. QI2 & D.-X. TONG2 1 Wuxi No. 2 People’s Hospital Affiliated to Nanjing Medical University, Wuxi City, Jiangsu Province, China, 2Jiangsu Provincial Taihu Cadre’s Sanatorium of Jiangsu Provincial People’s Hospital Group, Wuxi City, Jiangsu Province, China, 3Jiangsu Institute of Parasitic Diseases, Wuxi City, Jiangsu Province,China
SUMMARY The association between potential long-term effects of previous schistosome infection (PSI) and the development of metabolic syndrome remains unknown. Therefore, we aimed to evaluate the association between them. Participants were from regions which were all reportedly heavily endemic for S. japonicum in China 40 years ago. One thousand five hundred and ninety-seven men were enrolled. Among these, 465 patients with PSI were selected as study subjects and 1132 subjects served as controls. We found PSI significantly correlated with lower prevalences of metabolic syndrome and its components, including central obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol, which indicates that the potential long-term effects of PSI may reduce the risk of metabolic syndrome. However, further studies are needed to investigate the protective immune effects of PSI. Keywords men, metabolic syndrome, negative regulation of immune response, previous schistosome infection Abbreviations: BMI, body mass index; FBG, fasting blood glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MS, metabolic syndrome; PSI, previous schistosome infection; TC, total cholesterol; TG, triglyceride; UA, uric acid; WC, waist circumstance
INTRODUCTION Metabolic syndrome is a condition that includes the presence of a cluster of risk factors specific for cardiovascular disease. A meta-analysis of longitudinal studies revealed a significantly higher risk of cardio-cerebro-vascular diseases and death in patients with MS compared with non-MS subjects (1). MS is therefore recognized as a major public health concern. Recently, some studies have shown an inverse association between helminth infections and inflammatory diseases, including MS and cardiovascular diseases, and specific immune responses might contribute at least partly to this issue (2–5). Schistosomiasis is regarded as both a helminth infection and an immunological disease (6). Schistosome antigens have been found to induce metabonomic alterations and mediate the host immune response (7–10), which produce a strong anti-inflammatory response to help suppress the development of arteriosclerosis in mice (11). Greatly illuminated by these studies, we are going to evaluate the association between the potential long-term effects of previous schistosome infection (PSI) and the risk of developing MS components in Chinese men, to provide evidence for the development of new strategies for the prevention and control of MS.
MATERIALS AND METHODS Subjects
Correspondence: Zhen-Hai Shen, Jiangsu Provincial Taihu Cadre’s Sanatorium of Jiangsu Provincial People’s Hospital Group, Wuxi City, Jiangsu Province 214086, China (e-mail: shentaihu@126. com). *Co-first authors. Received: 9 November 2014 Accepted for publication: 13 March 2015 © 2015 John Wiley & Sons Ltd
The collected records of 11 782 consecutive healthy males presenting at our unit for health management from April and June (2013) were reviewed retrospectively. Analyses were confined to men resided in suburban areas of Shanghai Municipality or the cities of Suzhou and Wuxi in Jiangsu Province, China, which used to be heavily endemic for S. japonicum (6258 cases) (12). And only men aged
333
S.-W. Shen et al.
≥45 years (2036 cases) were included as the transmission of schistosomiasis has been controlled for 40 years. We further excluded those with a history of viral hepatitis (131 subjects), decompensated cirrhosis (13 subjects), alcohol consumption of >25 g/day (197 subjects), malignant tumours (24 subjects), use of statin drugs (60 subjects) or incomplete medical records (14 subjects). The remaining 1597 males were included in the present analysis, including 465 subjects (aged 47–92 years) in the PSI group and 1132 subjects (aged 45–93 years) in the control group. All of the participants underwent faecal examination by Kato– Katz method and were confirmed parasite free at the time of sampling. None of them suffered liver or kidney dysfunction or ascites. The study protocol was approved by the Ethics Review Committee of our sanatorium. Informed consent was obtained from all participants following a detailed description of the purpose and potential benefits of this study.
Methods All data were collected using a questionnaire administered by well-trained medical professionals. Health examinations included measurements of blood pressure, blood lipid and glucose levels, height and body weight. Waist circumstance (WC) was measured using the method recommended by the World Health Organization. Briefly, each subject was instructed to stand with the feet 25– 30 cm apart and with the back straight to allow even distribution of body weight on two legs, and then, the waist measurement was taken with a tape measure in a horizontal plane, midway between the inferior margin of the ribs and the superior border of the iliac crest. All participants fasted for 8–12 h prior to collection of 5 mL of venous blood from the cubital vein on the following morning. Levels of fasting blood glucose (FBG) were determined using the hexokinase method, triglycerides (TG) by the glycerol phosphate oxidase method, total cholesterol (TC) by the oxidase method, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) by antibody-based homogeneous assays and uric acid (UA) using the uricase-/peroxidasecoupled method with a fully automatically biochemical analyzer (Hitachi 7600; Hitachi, Ltd., Tokyo, Japan). Ultrasound examination of the liver was performed using an iU22 ultrasound system (Philips Healthcare, Andover, MA, USA).
Parasite Immunology
90 cm) and any two of the following four criteria: (i) TG level ≥17 mmol/L or specific treatment for this lipid abnormality; (ii) HDL-C level 13 cm), with a thickened luminal wall, and enlargement of the left lobe of the liver and atrophy of the right lobe, with the external left lobe appearing blunt and round (15, 16). The accumulation of MS components was grouped according to the number of MS components: (i) MS0 = absence of any MS component; (ii) MS1 = presence of one MS component; (iii) MS2 = development of two MS components; (iv) MS3 = development of three MS components; and (v) MS4 = presence of four or more MS components.
Statistical analysis All data were expressed as mean standard deviation (SD), and all statistical analyses were performed using the statistical software SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). Variables were compared across PSI categories using Student’s t-tests for continuous variables and chisquared test for categorical variables, and correlations between PSI and MS and its components were evaluated by logistic regression analysis. A P value 005) (Table 1).
334
© 2015 John Wiley & Sons Ltd, Parasite Immunology, 37, 333–339
Diagnostic criteria
WC, waist circumference; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid; FPG, fasting blood glucose. All continuous variables were presented as means SD. P values were calculated from Student’s t-tests for continuous variables.
1913 0056 2223 0027 1321 0187 0794 0427 1731 084
9535 0000
9533 0000
1765 0078
3465 0001
7753 0000
10455 0000
621 160 638 150 37245 8704 38272 7568 298 076 303 068 136 034 118 024 490 092 493 080 136 102 183 124 8144 1055 8340 1013 13722 1903 13902 1709 8425 831 8848 741 6567 789 6494 709
With PSI Without PSI T P
465 1132
2403 285 2549 263
TC (mmol/L) TG (mmol/L) SBP (mmHg) BMI (kg/m2) WC (cm) AGE (year) N Groups
Table 1 Comparison of biochemical markers for MS between groups
Previous schistosome infection and MS
DBP (mmHg)
HDL-C (mmol/L)
LDL-C (mmol/L)
UA (lmol/L)
FPG (mmol/L)
Volume 37, Number 7, July 2015
© 2015 John Wiley & Sons Ltd, Parasite Immunology, 37, 333–339
Comparison of prevalences and age-stratified prevalences of MS and its components between groups The prevalences of MS (P < 0001) and its components including central obesity (P < 0001), hypertriglyceridemia (P < 0001), low HDL-C (P < 0001), hypertension (P < 001) and hyperglycaemia (P < 001) were significantly lower in the PSI group than in the control group. After age stratification, apart from the prevalence of hypertension in study subjects aged >65 years, the changes in the prevalences of MS and its components between the PSI and control groups were consistent with those before age stratification (all P < 005) (Table 2).
Different accumulation profiles of MS components The prevalences of MS0 (P < 0001) and MS1 (P < 0001) were significantly higher, and those of MS3 (P < 001) and ≥MS4 (P < 0001) were significantly lower in the PSI group compared with the control group. There was no significant difference in the prevalence of MS2 between the two groups (P > 005). The percentage of patients with three or more MS components was significantly lower in the PSI group (2645%) than in the control group (4638%) (v2 = 51346, P < 0001) (Table 3).
Correlation between PSI and risk of MS Logistic regression analysis revealed significant negative associations between PSI and MS (odds ratio [OR] = 0434, 95% confidence interval [CI]: 0333–0566, P < 0001) and its components including central obesity (OR = 0447, 95% CI: 0351–0570, P < 0001), hypertriglyceridemia (OR = 0423, 95% CI: 0329–0545, P < 0001), low HDL-C (OR = 053, 95% CI: 0388–0725, P < 0001), hypertension (OR = 0691, 95% CI: 0549–087, P < 0001) and hyperglycaemia (OR = 0683, 95% CI: 0545–0857, P = 0001) (model 1). After adjustment for age, BMI, TC, LDL-C and UA levels, PSI was still correlated with a lower prevalence of MS (OR = 0667, 95% CI: 0477–0931, P < 005) and its components including central obesity (OR = 0724, 95% CI: 0525– 0999, P < 005), hypertriglyceridemia (OR = 0444, 95% CI: 0332–0594, < 0001) and low HDL-C (OR = 0634, 95% CI: 0457–088, P < 001). However, no associations were detected between PSI and hypertension (OR = 0842, 95% CI: 0659–1077, P > 005) and hyperglycaemia (OR = 0871, 95% CI: 0685–1108, P > 005) (model 3) (Table 4).
DISCUSSION The immune response induced by schistosome infection is an important host defence mechanism against pathogens.
335
S.-W. Shen et al.
Parasite Immunology
Table 2 Comparison of prevalence and age-stratified prevalence of MS and its components between groups
47–92 years 45–93 years
≤65 years
>65 years
Groups
No.
With PSI Without PSI v2 P With PSI Without PSI v2 P With PSI Without PSI v2 P
465 1132
254 713
211 419
MS No. (%)
Central obesity No. (%)
Hypertriglyceridemia No. (%)
Low HDL-C No. (%)
Hypertension No. (%)
Hyperglycaemia No. (%)
85 (1828) 385 (3401) 33940
DOI: 10.1111/pim.12187
The potential long-term effect of previous schistosome infection reduces the risk of metabolic syndrome among Chinese men S.-W. SHEN,1* Y. LU,2* F. LI,2* Z.-H. SHEN,2* M. XU,3 W.-F. YAO,1 Y.-B. FENG,2 J.-T. YUN,2 Y.-P. WANG,1 W. LING,2 H.-J. QI2 & D.-X. TONG2 1 Wuxi No. 2 People’s Hospital Affiliated to Nanjing Medical University, Wuxi City, Jiangsu Province, China, 2Jiangsu Provincial Taihu Cadre’s Sanatorium of Jiangsu Provincial People’s Hospital Group, Wuxi City, Jiangsu Province, China, 3Jiangsu Institute of Parasitic Diseases, Wuxi City, Jiangsu Province,China
SUMMARY The association between potential long-term effects of previous schistosome infection (PSI) and the development of metabolic syndrome remains unknown. Therefore, we aimed to evaluate the association between them. Participants were from regions which were all reportedly heavily endemic for S. japonicum in China 40 years ago. One thousand five hundred and ninety-seven men were enrolled. Among these, 465 patients with PSI were selected as study subjects and 1132 subjects served as controls. We found PSI significantly correlated with lower prevalences of metabolic syndrome and its components, including central obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol, which indicates that the potential long-term effects of PSI may reduce the risk of metabolic syndrome. However, further studies are needed to investigate the protective immune effects of PSI. Keywords men, metabolic syndrome, negative regulation of immune response, previous schistosome infection Abbreviations: BMI, body mass index; FBG, fasting blood glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MS, metabolic syndrome; PSI, previous schistosome infection; TC, total cholesterol; TG, triglyceride; UA, uric acid; WC, waist circumstance
INTRODUCTION Metabolic syndrome is a condition that includes the presence of a cluster of risk factors specific for cardiovascular disease. A meta-analysis of longitudinal studies revealed a significantly higher risk of cardio-cerebro-vascular diseases and death in patients with MS compared with non-MS subjects (1). MS is therefore recognized as a major public health concern. Recently, some studies have shown an inverse association between helminth infections and inflammatory diseases, including MS and cardiovascular diseases, and specific immune responses might contribute at least partly to this issue (2–5). Schistosomiasis is regarded as both a helminth infection and an immunological disease (6). Schistosome antigens have been found to induce metabonomic alterations and mediate the host immune response (7–10), which produce a strong anti-inflammatory response to help suppress the development of arteriosclerosis in mice (11). Greatly illuminated by these studies, we are going to evaluate the association between the potential long-term effects of previous schistosome infection (PSI) and the risk of developing MS components in Chinese men, to provide evidence for the development of new strategies for the prevention and control of MS.
MATERIALS AND METHODS Subjects
Correspondence: Zhen-Hai Shen, Jiangsu Provincial Taihu Cadre’s Sanatorium of Jiangsu Provincial People’s Hospital Group, Wuxi City, Jiangsu Province 214086, China (e-mail: shentaihu@126. com). *Co-first authors. Received: 9 November 2014 Accepted for publication: 13 March 2015 © 2015 John Wiley & Sons Ltd
The collected records of 11 782 consecutive healthy males presenting at our unit for health management from April and June (2013) were reviewed retrospectively. Analyses were confined to men resided in suburban areas of Shanghai Municipality or the cities of Suzhou and Wuxi in Jiangsu Province, China, which used to be heavily endemic for S. japonicum (6258 cases) (12). And only men aged
333
S.-W. Shen et al.
≥45 years (2036 cases) were included as the transmission of schistosomiasis has been controlled for 40 years. We further excluded those with a history of viral hepatitis (131 subjects), decompensated cirrhosis (13 subjects), alcohol consumption of >25 g/day (197 subjects), malignant tumours (24 subjects), use of statin drugs (60 subjects) or incomplete medical records (14 subjects). The remaining 1597 males were included in the present analysis, including 465 subjects (aged 47–92 years) in the PSI group and 1132 subjects (aged 45–93 years) in the control group. All of the participants underwent faecal examination by Kato– Katz method and were confirmed parasite free at the time of sampling. None of them suffered liver or kidney dysfunction or ascites. The study protocol was approved by the Ethics Review Committee of our sanatorium. Informed consent was obtained from all participants following a detailed description of the purpose and potential benefits of this study.
Methods All data were collected using a questionnaire administered by well-trained medical professionals. Health examinations included measurements of blood pressure, blood lipid and glucose levels, height and body weight. Waist circumstance (WC) was measured using the method recommended by the World Health Organization. Briefly, each subject was instructed to stand with the feet 25– 30 cm apart and with the back straight to allow even distribution of body weight on two legs, and then, the waist measurement was taken with a tape measure in a horizontal plane, midway between the inferior margin of the ribs and the superior border of the iliac crest. All participants fasted for 8–12 h prior to collection of 5 mL of venous blood from the cubital vein on the following morning. Levels of fasting blood glucose (FBG) were determined using the hexokinase method, triglycerides (TG) by the glycerol phosphate oxidase method, total cholesterol (TC) by the oxidase method, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) by antibody-based homogeneous assays and uric acid (UA) using the uricase-/peroxidasecoupled method with a fully automatically biochemical analyzer (Hitachi 7600; Hitachi, Ltd., Tokyo, Japan). Ultrasound examination of the liver was performed using an iU22 ultrasound system (Philips Healthcare, Andover, MA, USA).
Parasite Immunology
90 cm) and any two of the following four criteria: (i) TG level ≥17 mmol/L or specific treatment for this lipid abnormality; (ii) HDL-C level 13 cm), with a thickened luminal wall, and enlargement of the left lobe of the liver and atrophy of the right lobe, with the external left lobe appearing blunt and round (15, 16). The accumulation of MS components was grouped according to the number of MS components: (i) MS0 = absence of any MS component; (ii) MS1 = presence of one MS component; (iii) MS2 = development of two MS components; (iv) MS3 = development of three MS components; and (v) MS4 = presence of four or more MS components.
Statistical analysis All data were expressed as mean standard deviation (SD), and all statistical analyses were performed using the statistical software SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). Variables were compared across PSI categories using Student’s t-tests for continuous variables and chisquared test for categorical variables, and correlations between PSI and MS and its components were evaluated by logistic regression analysis. A P value 005) (Table 1).
334
© 2015 John Wiley & Sons Ltd, Parasite Immunology, 37, 333–339
Diagnostic criteria
WC, waist circumference; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid; FPG, fasting blood glucose. All continuous variables were presented as means SD. P values were calculated from Student’s t-tests for continuous variables.
1913 0056 2223 0027 1321 0187 0794 0427 1731 084
9535 0000
9533 0000
1765 0078
3465 0001
7753 0000
10455 0000
621 160 638 150 37245 8704 38272 7568 298 076 303 068 136 034 118 024 490 092 493 080 136 102 183 124 8144 1055 8340 1013 13722 1903 13902 1709 8425 831 8848 741 6567 789 6494 709
With PSI Without PSI T P
465 1132
2403 285 2549 263
TC (mmol/L) TG (mmol/L) SBP (mmHg) BMI (kg/m2) WC (cm) AGE (year) N Groups
Table 1 Comparison of biochemical markers for MS between groups
Previous schistosome infection and MS
DBP (mmHg)
HDL-C (mmol/L)
LDL-C (mmol/L)
UA (lmol/L)
FPG (mmol/L)
Volume 37, Number 7, July 2015
© 2015 John Wiley & Sons Ltd, Parasite Immunology, 37, 333–339
Comparison of prevalences and age-stratified prevalences of MS and its components between groups The prevalences of MS (P < 0001) and its components including central obesity (P < 0001), hypertriglyceridemia (P < 0001), low HDL-C (P < 0001), hypertension (P < 001) and hyperglycaemia (P < 001) were significantly lower in the PSI group than in the control group. After age stratification, apart from the prevalence of hypertension in study subjects aged >65 years, the changes in the prevalences of MS and its components between the PSI and control groups were consistent with those before age stratification (all P < 005) (Table 2).
Different accumulation profiles of MS components The prevalences of MS0 (P < 0001) and MS1 (P < 0001) were significantly higher, and those of MS3 (P < 001) and ≥MS4 (P < 0001) were significantly lower in the PSI group compared with the control group. There was no significant difference in the prevalence of MS2 between the two groups (P > 005). The percentage of patients with three or more MS components was significantly lower in the PSI group (2645%) than in the control group (4638%) (v2 = 51346, P < 0001) (Table 3).
Correlation between PSI and risk of MS Logistic regression analysis revealed significant negative associations between PSI and MS (odds ratio [OR] = 0434, 95% confidence interval [CI]: 0333–0566, P < 0001) and its components including central obesity (OR = 0447, 95% CI: 0351–0570, P < 0001), hypertriglyceridemia (OR = 0423, 95% CI: 0329–0545, P < 0001), low HDL-C (OR = 053, 95% CI: 0388–0725, P < 0001), hypertension (OR = 0691, 95% CI: 0549–087, P < 0001) and hyperglycaemia (OR = 0683, 95% CI: 0545–0857, P = 0001) (model 1). After adjustment for age, BMI, TC, LDL-C and UA levels, PSI was still correlated with a lower prevalence of MS (OR = 0667, 95% CI: 0477–0931, P < 005) and its components including central obesity (OR = 0724, 95% CI: 0525– 0999, P < 005), hypertriglyceridemia (OR = 0444, 95% CI: 0332–0594, < 0001) and low HDL-C (OR = 0634, 95% CI: 0457–088, P < 001). However, no associations were detected between PSI and hypertension (OR = 0842, 95% CI: 0659–1077, P > 005) and hyperglycaemia (OR = 0871, 95% CI: 0685–1108, P > 005) (model 3) (Table 4).
DISCUSSION The immune response induced by schistosome infection is an important host defence mechanism against pathogens.
335
S.-W. Shen et al.
Parasite Immunology
Table 2 Comparison of prevalence and age-stratified prevalence of MS and its components between groups
47–92 years 45–93 years
≤65 years
>65 years
Groups
No.
With PSI Without PSI v2 P With PSI Without PSI v2 P With PSI Without PSI v2 P
465 1132
254 713
211 419
MS No. (%)
Central obesity No. (%)
Hypertriglyceridemia No. (%)
Low HDL-C No. (%)
Hypertension No. (%)
Hyperglycaemia No. (%)
85 (1828) 385 (3401) 33940
