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Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study – Scientific Reports


Our large-scale, population-based retrospective cohort study showed that cholecystectomy was associated with a higher risk of developing cardiovascular disease, especially within two years of the surgery. This increased risk was more pronounced among males, those with BMI < 25 kg/m2, and those with more medical comorbidities with Charlson comorbidity index 2 or higher. Such increased risk of CVD was no longer observed when patients were followed for more than 2 years after surgery. Of note, cholecystectomy was associated with changes in systolic blood pressure, total cholesterol, and BMI following surgery.

A previous study suggested that Total bile acids (TBA) are to be biomarkers of liver injury. So monitoring of IBA has been suggested for liver injury about differentiation of variety33. In Fig. 2, when cholecystectomy is performed, the first mechanism is to reduce the risk of cardiovascular disease by improving the intermediate metabolic profile due to inhibition of fat absorption or weight loss. Another mechanism is known to have a microbiome problem3,34. There is limitation to know whether mechanism is to reduce risk when the bile is gone, but there are probably primary biliary cirrhosis or mechanisms that cause liver damage or abdominal inflammation, but no other mechanisms have been identified. It can be shown that the mechanism of this study suggested that the no association in CVD risk after cholecystectomy is due to weight loss or improvement of intermediate metabolic profile.

Figure 2

The mechanism of cholecystectomy and metabolism.

In the previous study, the cholecystectomy group had higher risk of diabetes mellitus, hypertension and dyslipidemia than in the nonsurgical group32,35. The control group had a higher proportion of non-smokers than the surgical group32. This condition shows that the people who underwent cholecystectomy were those with high CVD risk.

From this point of view, previous studies have studied cancer in digestive organs such as colon cancer with cholecystectomy, and studies on degenerative brain diseases such as the relationship between cholecystectomy and Parkinson’s disease. Based on this background, this study designed a study on whether cholecystectomy affected cardiovascular disease. In order to overcome the limitation that the conclusion of many papers so far has not found an intermediate explanatory stage between cholecystectomy and the disease of the resulting variable, we analyzed how cholecystectomy primarily affected our body’s health metabolic index in short-term and analyzed its effect.

When extracted as a cholecystectomy subject, subjects who underwent cholecystectomy in a relatively healthy state were extracted except for those with a history of cancer and cardiovascular disease related to liver and gallbladder, but subjects with cholecystectomy were already high and body mass index was basically vulnerable to cardiovascular disease. As a result, CVD showed a high risk of development in subjects with cholecystectomy during the follow-up period from immediately after cholecystectomy to 2015, especially in CVD and CHD during the short period from immediately after surgery to 2 years. In addition, the amount of change in the body’s metabolic index over a short period of time was analyzed, and as a result, most of the metabolic indicators tended to improve.

The existing hypothesis suggested that cholesterol can rise in the body by affecting cholesterol metabolism due to any effect in the metabolism of bile after undergoing cholecystectomy, and related existing studies have been conducted. Compared to previous studies, the first advantage of this study was that it looked before and after, and the limitation of the existing one-point study was that patients undergoing cholecystectomy were basically patients with poor metabolic indicators as cholesterol levels were high. In this study, basically, subjects who underwent cholecystectomy had relatively poor metabolic indicators before surgery than those who did not. However, after undergoing surgery called cholecystectomy, cholesterol dropped. Previous studies have assumed that cholecystectomy with only these mechanisms can cause abnormalities in bile metabolism and raise cholesterol levels, but when looking at this study the baseline had higher cholecystectomy subjects, but cholesterol levels or various indicators fell after surgery. Therefore, several existing papers have suggested two mechanisms related to cholesterol metabolism after cholecystectomy, but this study suggests that the part related to the hypothesis of cholesterol drop is more likely. That’s the conclusion of this study. However, the results at one point in the previous study are probably related to the metabolic high-risk group, but this study has a great advantage in that it considers the before and after comparison to accurately see the effect of cholecystectomy. Therefore, from the results of the above study, the overall beneficial effect of cholecystectomy is estimated in terms of cholesterol metabolism.

Furthermore, the risk of cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy. Although there were concerns that cholecystectomy might have harmful effects in the past in metabolic indicators, such as cholesterol12, the results of this study suggest that there are more beneficial results.

Study limitation

The limitation of this study is that it is not a total inspection DB because it is a retrospective cohort study. Since the study was not conducted with the total number of people, there is a limit to the application of the research results to the entire population due to the lack of population. Second, in the operational definition, patients who have undergone cholecystectomy may have been affected by each disease because they have underlying diseases such as gallbladder cancer, biliary tract cancer, and liver cancer, and remove them during liver transplantation. In addition, the effect of cardiovascular disease and underlying diseases related to liver and gallbladder may reflect the above analysis results. Third, it was explained that it is a bridge between cholecystectomy and disease, but the above results cannot explain whether the primary result of cholecystectomy is a change in metabolic indicators or its causality. Last, In the long-term analysis, cholecystectomy patients in our study represent an otherwise healthy sub-population with at least 2-years of survivorship, which may introduce type II error. To minimize survivor bias, however, both the case and controls were given at least 2-years of survival time. Therefore, it should be noted that it simply means association, and future studies suggest that studies should be conducted to explain the intermediate stage of cholecystectomy and disease of outcome variables.

Clinical competencies

Cholecystectomy is a surgical procedure to remove organs. There are a lot of worries because it affects the body permanently. Some of previous studies suggested negative relationship between cholecystectomy and cardiovascular disease, Parkinson’s disease, and digestive cancer. However, the above study can relieve the worries of the previous research results. It can be interpreted that the short-term effect of cardiovascular disease due to cholecystectomy was affected by the patient’s preoperative health condition. In patients 2 years after cholecystectomy, unlike concerns caused by existing studies, the effect was improved in metabolic health after surgery. And after 2 years, the association between cholecystectomy and cardiovascular disease decreased.

Translational outlook

Patients who have undergone cholecystectomy due to relatively non-critical diseases do not increase the risk of cardiovascular disease from a long-term perspective because metabolic indicators become healthy in the short term due to surgery.



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