Infection with hepatitis B virus (HBV) may be a risk factor for cardiovascular disease. We investigated the relationship between HBV infection and metabolic syndrome.
We performed a cross-sectional study of 9,474 Korean men and women who were at least 20 years old and who underwent a routine health check-up at Ulsan University Hospital in Ulsan, South Korea between March 2008 and February 2009. The associations of hepatitis B surface antigen (HBsAg) seropositivity with the presence of metabolic syndrome and its components were investigated by logistic regression analysis. Data were analyzed separately for males and females.
HBsAg seropositivity was significantly negatively associated with hypertriglyceridemia and metabolic syndrome in men (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.29 to 0.50; P < 0.001 and OR, 0.75; 95% CI, 0.57 to 0.98, P = 0.033). In women, HBsAg seropositivity was also significantly negatively associated with hypertriglyceridemia, but not with metabolic syndrome (OR, 0.40; 95% CI, 0.17 to 0.91; P = 0.029 and OR, 0.80; 95% CI, 0.38 to 1.66, P = 0.545).
HBV infection was significantly negatively associated with hypertriglyceridemia and metabolic syndrome in men and hypertriglyceridemia in women.
Metabolic syndrome refers to a constellation of metabolic abnormalities that increase the risk of diabetes and cardiovascular disease, including central obesity, hypertriglyceridemia, low high density lipoprotein (HDL) cholesterol, hypertension, and hyperglycemia.
Around the world, an estimated 350 million persons are chronically infected with the hepatitis B virus (HBV), resulting in 600,000 deaths annually from cirrhosis, liver failure, and hepatocellular carcinoma.
A large body of experimental and epidemiologic evidence suggests that infectious agents contribute to atherosclerosis, which ultimately leads to cardiovascular disease.
A few studies have explored whether HBV is associated with atherosclerosis or cardiovascular disease, but most studies failed to show a significant association.
Recently, three studies investigated the association between HBV infection and metabolic syndrome, with inconsistent results. Two studies reported a negative association between the two,
Data were obtained from 9,474 (i.e., 7,602 men and 1,872 women) subjects who were at least 20 years old and who underwent a routine health check-up at the Ulsan University Hospital Heath Promotion Center (UUH-HPC) in Ulsan, South Korea, between March 2008 and February 2009. A total of 17,816 subjects were examined during this period, of whom 6,081 had missing values in their characteristics, 3,054 were taking medicine, and 405 had chronic diseases such as thyroid disease, lung disease, kidney disease, rheumatoid arthritis, psychiatric disorder, or malignancy. These 8,342 subjects were excluded from the study, but 491 men and women who were taking medicine for dyslipidemia, hypertension, or diabetes were included. 9,474 subjects were finally included in the analysis. Although the excluded subjects were more likely to be younger and have a slightly worse lifestyle, HBsAg seropositivity was comparable between the excluded and included subjects (data not shown). More than 90% of the subjects were employed by, or had family members who were employed by, manufacturing companies that paid for the health check-ups. Most subjects did not present with symptoms. The subjects' average family income was consistent with that of South Korea. The study protocol was approved by the institutional review board of UUH.
Subjects who visited UUH-HPC were asked to complete a questionnaire about lifestyle, medical history, and family income. Lifestyle data included alcohol intake, smoking, and exercise. Medical history data included current diseases and medication. Height, weight, waist circumference (WC), and blood pressure (BP) were measured by trained nurses, and blood tests for lipid profiles, fasting plasma glucose (FPG), alanine aminotransferase (ALT), and a serologic test for HBsAg were performed.
Body weight and height were measured in subjects wearing light indoor clothing without shoes, consistent with a standard protocol. Body mass index (BMI) was defined as body weight in kilograms divided by the square of the height in meters. WC was measured at the midpoint between the lowest ribs and the ileac crest. BP was measured by trained nurses using a mercury sphygmomanometer according to a standard protocol.
Alcohol intake was scored as <1, 1-2, or ≥3, according to the number of days per week of alcohol consumption. Smoking status was scored as 'never smoked,' 'former smoker,' and 'current smoker.' Physical exercise was scored as <1, 1-2, or ≥3, according to the number of days per week of exercise. Family income was scored as <1,500, 1,500-3,000, or >3,000 US dollars per month. The average monthly income per household in Korea was 2,625 US dollars in 2008.
Consistent with 2001 criteria established by the National Cholesterol Education Program's Adult Treatment Panel III,
We analyzed the association between HBV infection and metabolic syndrome, using HBsAg seropositivity as an independent variable regardless of chronic hepatitis B or low activity HBV carrier and using metabolic syndrome and its five components as dependent variables. Data were analyzed separately for males and females. The characteristics of the study subjects in HBsAg seropositive and seronegative groups were compared using Student t-tests for continuous variables and chi-square tests for categorical variables. Triglyceride, HDL cholesterol, FPG, and ALT levels were log transformed because their distribution was skewed to the right of the normal distribution. The odds ratios of metabolic syndrome and its components were calculated using a logistic regression model. Age, BMI, ALT, alcohol intake, smoking, exercise, family income, and education level were included in the multivariate analysis. P-values of less than 0.05 were considered to indicate statistical significance. All statistical analyses were performed using Stata SE ver. 10.0 (Stata Co., College Station, TX, USA).
The prevalence of HBV infection in men was 5.7%. Triglyceride levels were significantly lower in HBsAg-positive than in HBsAg-negative men (4.59 ± 0.48 [SD] versus 4.75 ± 0.52 mg/dL, P < 0.001) and HDL cholesterol levels were also significantly lower in HBsAg-positive than in HBsAg-negative men (3.81 ± 0.26 [SD] versus 3.84 ± 0.25 mg/dL, P = 0.039) (
In women, the prevalence of HBV infection was 4.5%. Triglyceride levels were lower in HBsAg-positive than in HBsAg-negative women, but this difference was not statistically significant (4.45 ± 0.39 [SD] versus 4.50 ± 0.50 mg/dL, P = 0.328). ALT level was significantly higher in HBsAg-positive than in HBsAg-negative women (3.11 ± 0.56 [SD] versus 2.81 ± 0.43 mg/dL, P < 0.001]. ALT abnormality was significantly higher in HBsAg-positive than in HBsAg-negative women (11.9% versus 3.5%, P < 0.001). Age, BMI, WC, HDL cholesterol, systolic BP, diastolic BP, and FPG were not significantly different in HBsAg-positive and HBsAg-negative women and there was no significant difference in distribution between HBsAg-positive and HBsAg-negative women with regards to in alcohol intake, smoking, exercise, family income, and education level.
Multiple logistic regression analysis of men, with metabolic syndrome as a dependent variable revealed a significant negative association between HBsAg positivity and metabolic syndrome (adjusted odds ratio [OR], 0.75; 95% confidence interval [CI], 0.57 to 0.98; P = 0.033) (
Our cross-sectional study of Korean adults revealed that, in both sexes, HBV infection is significantly negatively associated with hypertriglyceridemia among the five components of metabolic syndrome (adjusted OR, 0.39; 95% CI, 0.29 to 0.50; P < 0.001 in men; adjusted OR, 0.40; 95% CI, 0.17 to 0.91; P = 0.029 in women), and significantly negatively associated with metabolic syndrome (adjusted OR, 0.75; 95% CI, 0.57 to 0.98; P = 0.033) in men but not in women (adjusted OR, 0.80; 95% CI, 0.38 to 1.66; P = 0.545).
Previous studies have consistently shown a significant negative association between HBV infection and triglyceride levels.
Although ALT abnormality was more in HBsAg-positive than in HBsAg-negative subjects and positively associated with hypertriglyceridemia (data not shown), HBV infection was negatively associated with hypertriglyceridemia in our study. This suggests that HBV infection has an effect on the decrease in serum triglyceride levels, which was stronger than the positive relationship between ALT abnormality and hypertriglyceridemia. Kang et al.
The association between HBV infection and HDL cholesterol remains controversial. Su et al.
Three studies explored the direct association between HBV infection and metabolic syndrome. Consistent with the present findings, Jan et al.
Our study had some advantages. We were able to take age, BMI, alcohol intake, smoking, exercise, family income, education level, and ALT level into consideration and examine the effects of HBV infection independently of potential confounders in the analysis with results reported by sex. In addition, HBsAg rather than anti-HBc was used to demonstrate HBV infection because the interpretation of positive anti-HBc varies with the presence of HBsAg or anti-HBs.
The present study had several limitations. First, the population may not be representative of all Koreans because over 90% of the study subjects were employed by, or were related to persons employed by, world-class industrial companies that provided stable living conditions and a generous family income. However, 5.7% of the male and 4.5% of the female study subjects had HBsAg, consistent with other epidemiological studies of the prevalence of HBsAg carriers in Korea.
This cross-sectional study of Korean adults showed that HBV infection is significantly negatively associated with metabolic syndrome in men, but not in women, even though HBV infection is negatively associated with hypertriglyceridemia in both men and women. These findings are incompatible with the fact that most previous reports over the past decade found no significant relationship between HBV infection and atherosclerosis or cardiovascular disease.
No potential conflict of interest relevant to this article was reported.
Characteristics of study subjects with regards to sex and hepatitis B virus infection
Values are presented as mean ± SD or %.
HBsAg: hepatitis B surface antigen, ALT: alanine aminotransferase.
*Based on t-tests for continuous variables and chi-square tests for categorical variables. †Log-transformed data. ‡Percentages may not total 100 because of rounding.
Crude and adjusted ORs* and 95% CIs for metabolic syndrome and its components according to the seropositivity of HBV infection in men
OR: odds ratios, CI: confidence intervals, HBV: hepatitis B virus, HBsAg: hepatitis B surface antigen.
*Determined via logistic regression. †Adjusted for age, body mass index, alanine aminotransferase, alcohol intake, smoking, exercise, family income, and educational status. ‡≥130 mm Hg systolic blood pressure or ≥85 mm Hg diastolic blood pressure.
Crude and adjusted ORs* and 95% CIs for metabolic syndrome and its components according to the seropositivity of HBV infection in women
OR: odds ratios, CI: confidence intervals, HBV: hepatitis B virus, HBsAg: hepatitis B surface antigen.
*Determined via logistic regression. †Adjusted for age, body mass index, alanine aminotransferase, alcohol intake, smoking, exercise, family income, and educational status. ‡≥130 mm Hg systolic blood pressure or ≥85 mm Hg diastolic blood pressure.