Recently the incidence of gallstone disease in Korea has increased due to Western-style diet, obesity, and increasing age. Gallstones are mostly asymptomatic, hence it is often found by chance during abdomen ultrasonography. The prevalence of gallstone disease is different according to race and gender. Prevalence in Koreans has been reported as 3.1% in males and 3.4% in females.¹⁾ On the other hand, the prevalence in American Caucasians was 8.6% and 16.6% in males and females, respectively, and in American Hispanics it was 8.9%, 26.7% in males and females, respectively.²⁾ Gallstones can be classified into cholesterol stones, pigment stones, and mixed stones according to their composition. Cholesterol stones account for 90% or more in Western countries, whereas in Korea the proportion of pigment stones have been high, but recently there has been an increase in cholesterol stones. Generally black pigment stones and brown pigment stones have been classified as pigment stones. However, Kim et al.³⁾ reported that from the results of chemical analysis of black pigment stones and brown pigment stones, 45% of black pigment stones and 81% of brown pigment stones are cholesterol stones. Therefore the effect of cholesterol on gallstone formation may be greater in Koreans.

The established risk factors which cause cholesterol stones are old age, female, obesity^4,5,6) as well as pregnancy, oral contraceptives, alcohol, smoking, and diabetes.^7,8,9) Amongst these risk factors, age, obesity, smoking, and diabetes are the risk factors for atherosclerosis,^10,11,12,13) hence the proposed relationship between gallstones and atherosclerosis. Wysowski et al.¹⁴⁾ reported that the medical history of biliary disease is correlated with that of myocardial infarction, and Bortnichak et al.¹⁵⁾ reported that the risk for coronary artery disease is high in patients who had cholecystectomy. Thus, there are many studies which reported the relationship between biliary disease and atherosclerosis, but the relationship is still unclear.

Carotid ultrasonography is often used to assess the degree of atherosclerosis. Carotid intima media thickness (IMT) measured by ultrasound is an indicator for the degree of atherosclerosis of systemic and coronary arteries,^16,17) and several studies have reported it as a significant independent indicator for coronary artery disease and cerebral arterial disease. Cho et al.¹⁸⁾ reported that the maximum value of carotid IMT in Koreans is 0.69 ± 0.18 mm in males and 0.67 ± 0.16 mm in females, and Mannami et al.¹⁹⁾ reported that the mean carotid IMT in the Japanese population is 0.92 ± 0.13 mm in males and 0.89 ± 0.11 mm in females. Likewise, there have been efforts to gather IMT data by race and gender, but there are not enough data for the Korean population. In this study, we classified adult men under regular medical examination into a group who had discovered gallstones by chance and a group who did not have gallstones, and investigated the relationship between gallstones and atherosclerosis by comparing common carotid IMT.

The prevalence of gallstone disease in Korean males was found to be 3.1% in a report by Lee et al.¹⁾ in 1997, but it was 6.6% in this study. This is higher than the known prevalence and there are three possible reasons. First, the prevalence reported by Lee et al.¹⁾ was age-standardized prevalence, but in this study, the age and BMI were relatively high with a mean age of 50.3 years and a mean BMI of 24.2 kg/m². Second, the prevalence of gallstone disease in Koreans is increasing due to adoption of Western style diet and lifestyle.²¹⁾ In addition, selective bias may have been a factor, as the abdomen ultrasonography is optional for the medical examination.

The established risk factors for gallstone disease in the previous studies were old age, obesity and female,^4,5,6) as well as pregnancy, oral contraceptives, alcohol, smoking, and diabetes.^7,8,9) In this study, age and BMI in the gallstone group was higher than the non-gallstone group (Table 1). The relationship between cholesterol level and gallstone disease has not been established,²²⁾ and the two showed no association in this study. Also, there was a report about an increase in gallstone disease in type 2 diabetes,¹⁾ but the correlation was not found in this study.

Increase in carotid IMT is known as an independent factor for coronary artery disease, and recently, correlation to cerebrovascular disease has been reported. A meta-analysis of Lorenz et al.²³⁾ reported that an increase in carotid IMT by 0.10 mm increased the incidence of myocardial infarction by 1.15 (95% confidence interval [CI], 1.12 to 1.17), and stroke by 1.18 (95% CI, 1.16 to 1.21), when age and gender were adjusted. Age, systolic blood pressure, and BMI are known factors that increase carotid IMT,^18,24,25) but in this study, age, BMI, gallstone, and fasting glucose showed correlation with the maximum value of carotid IMT.

Recently Mendez-Sanchez et al.²⁶⁾ reported that carotid IMT increased in gallstone patients and a 0.1 mm increase in carotid IMT increased the prevalence of gallstone disease by 1.25 times (95% CI, 1.02 to 1.53; P = 0.027). Also Mendez-Sanchez et al.²⁷⁾ reported that patients with coronary artery disease were at higher risk for gallstone disease (odds ratio, 2.84), and Chavez-Tapia et al.²⁸⁾ reported that patients undergoing cholecystectomy were at greater risk for cardiovascular disease.

In Western countries cholesterol stones account for 90% or more, but in Korea they account for 50%. Recently the incidence of cholesterol stones is increasing due to westernization, but this phenomenon occurs mainly in women with increases in obesity and age. Therefore, it was not clear whether the study by Mendez-Sanchez et al. is applicable to the middle-aged Korean male population, but the maximum value of common carotid IMT also increased in Korean men who had gallstones.

This study is meaningful from the standpoint that it reported the relationship between gallstones and carotid IMT in the Korean male population by analyzing most risk factors for gallstone disease and atherosclerosis, but there were a few limitations. First, the sample size was relatively small and the subjects were limited to males, so it is impractical to generalize to the whole population including females. Second, some data about history of hypertension, diabetes, exercise, smoking, and alcohol intake were missing, so it was difficult to conduct an accurate evaluation about them. Third, ultrasonography was conducted solely by the radiologist, but 6 different radiologists were employed for ultrasonography, hence individual technical difference and possibility of error cannot be ruled out. Fourth, the subjects were selected amongst people under medical examination who had both abdomen and carotid ultrasonographies, and those tests were optional, hence there is a possibility of selective bias. As a result, those people who could financially afford both tests, were generally interested in health, or had risk factors for cardio-cerebrovascular disease would have been included in the study subjects. Fifth, 'the sum of days × METs' was used to evaluate exercise quantity, but it was a self-designed evaluation method which had limitations in feasibility and standardization. Sixth, only the maximum value was used for the measurement of common carotid IMT, but if the evaluation included the mean values measured from both carotid arteries or several areas of a unilateral artery, more significant results could have been obtained.

In conclusion, the maximum value of common carotid IMT increased significantly with presence of gallstones and with increases in age, BMI, and fasting glucose. The presence of gallstones was independently significant to the maximum value of common carotid IMT, which means that gallstones are closely related to atherosclerosis in men.