Impact of cholecystectomy on acute coronary syndrome according to … – Nature.com

Previous studies have reported that the presence of GS is associated with an increased risk of ACS. Our results verified this and additionally showed that patients without cholecystectomy for GS are associated with an increased risk of ACS compared to the control group. Interestingly, the effects of cholecystectomy for GS on the risk of ACS differed depending on the underlying metabolic disease. When cholecystectomy was performed on patients with GS with an underlying metabolic disease, such as hypertension, diabetes, or hyperlipidemia, the risk of ACS was not significantly different compared to those without GS, but this trend was reversed in the GS group without underlying metabolic disease. In patients without all three diseases (diabetes, hypertension, and dyslipidemia), cholecystectomy was still associated with an increased risk of ACS than the control group. However, when the diseases were considered individually, the presence or absence of diabetes alone was not associated with an increased risk of ACS after cholecystectomy. These findings imply that when cholecystectomy is planned for GS, underlying metabolic diseases should be considered to reduce the risk of ACS.

Previous studies and our results have shown a significantly increased risk of ACS among patients with GS4,5,7,12. Patients with GS frequently have risk factors for ACS, which could explain the increased risk of ACS. Our subgroup analysis showed that GS was associated with an even higher risk of ACS in patients with diabetes, hyperlipidemia, and hypertension. Therefore, patients with gallstones were at increased risk of developing ACS not simply because they already had other risk factors, but because the presence of GS itself posed a risk.

Age, obesity, body mass index, low serum high-density lipoprotein cholesterol levels, diabetes mellitus, inadequate physical inactivity, and excessive alcohol use have all been identified as ACS risk factors7. These are also shared risk factors for GS, which could explain the increased risk of ACS in the GS group13. The formation of gallstones is thought to be caused primarily by biliary cholesterol supersaturation caused by metabolic abnormalities in the liver and the subsequent physico-chemical imbalance of cholesterol solubility in bile4,14,15. The term ACS refers to a group of conditions characterized by a sudden decrease in blood flow to the heart, such as unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction.

The association between GS and ACS is easily understood but is unpredictable with cholecystectomy. The previous studies have reported varied effects of cholecystectomy on the risk of ACS. Chen et al. investigated the effect of cholecystectomy on the subsequent risk of ACS in patients with GS10. The cumulative incidence of ACS was lower in patients with GS who underwent cholecystectomy than in those who did not. In contrast, Norberto et al. analyzed the relationship between cholecystectomy for GS and risk factors for ACS. Multivariate analysis revealed that the cholecystectomy group had a higher incidence of metabolic risk variables for ACS than the control group. Patients who underwent cholecystectomy exhibited a higher incidence of risk factors for ACS regardless of age, sex, or body mass index9. In terms of patients baseline characteristics, the study by Chen et al. had a higher proportion of patients with metabolic illnesses than the study by Norberto et al. This suggests that the effect of cholecystectomy on the risk of ACS may differ depending on the underlying presence of metabolic diseases. Our results prove that the above-mentioned hypothesis is most likely to be true. In patients with metabolic diseases, not undergoing cholecystectomy was associated with a higher risk of ACS than the control group, but the risk did not significantly differ after cholecystectomy compared to the control group. Among patients without metabolic disorders, cholecystectomy was still associated with increased ACS risk in the GS group compared to the control group. These findings should be verified in future studies.

Although the treatment of asymptomatic gallstone patients is not generally recommended, current treatment strategies for symptomatic gallstone patients require surgical treatment. Following cholecystectomy, the gallbladder reservoir decreases, resulting in the continuous release of hepatic bile into the duodenum lumen16. As a result, the bile acid pool circulates more quickly, exposing enterohepatic organs and, eventually, peripheral tissues to a larger flow of bile acids during the diurnal cycle fasting periods17. Few studies have investigated the serum lipid profiles of individuals who underwent laparoscopic cholecystectomy. They showed that lipid and bile acid metabolisms are functionally linked18. There have been several hypotheses suggesting that cholecystectomy affects the lipid profile, which in turn affects the risk of ACS19,20. However, the results of previous studies cannot fully explain our findings, therefore, more research on the mechanism is required.

On the other hand, we also regard the mechanistic link between gallstones and cardiovascular disease that is associated with the gut microbiome. Patients with gallstones exhibit a distorted secretion of bile acids that play a crucial role in regulating gut microbiota21. Dysbiosis of gut microbiota may influence various host functions associated with cardiovascular risk22,23,24. Previous studies have reported that metabolites produced by gut microbiota, such as trimethylamine N-oxide and L-carnitine, inhibit bile acid transporters and promote atherosclerosis and cardiovascular risk25,26. Proteobacteria has been found to be linked to a wide range of metabolic disturbances, including an increased risk of obesity and cardiovascular disease27,28. Cholecystectomy alters bile flow to the intestine and can, therefore, modify the bidirectional interactions between bile acids and the intestinal microbiota29.

This study had several limitations First, the analysis was based on health insurance claim data reported with ICD-10 diagnostic codes; therefore, potential covariates, such as health behavior factors, drug prescription or laboratory test results were not included in this study. Due to a lack of clinical and laboratory data, there are still problems with diagnosis accuracy and failure to account for risk variables for gallstone disease. We adjusted all data for CCI, which provides information on the severity of an individuals health conditions. In the future, we plan to investigate the relationship between metabolic disease and cholecystectomy using the same data from the Korea National Health and Nutrition Examination Survey. Second, the characteristics, including the number and size of gallstones, which are important factors related to gallstone surgery and prognosis, could not be investigated in this study. This aspect should be recognized as a limitation of epidemiological studies based on health insurance claims data. This study aimed to provide comprehensive information using a large-scale epidemiological study, and it was the largest large-scale study to examine the effect of cholecystectomy on ACS in patients with gallstones to date.

In conclusion, GS was associated with an increased risk of ACS. When cholecystectomy was performed for GS in patients with underlying metabolic diseases, the risk of ACS was not significantly different from that in patients without GS. When cholecystectomy is planned, its effect on the risk of ACS should be considered. Further validation in a large prospective cohort study and elucidation of the underlying mechanisms are needed.

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Impact of cholecystectomy on acute coronary syndrome according to ... - Nature.com