We found that the presence of GB polyps alone was associated with a 42.5 % increase in the risk of developing IHD compared with a non-polyp control group. To our knowledge, only one other report has described a relationship between GB polyps and CVD . However, in this latter study, the authors did not fully assess IHD-related risk factors to sufficiently show a causal relationship between GB polyps and IHD. In our study, we evaluated multiple risk factors that influence the development of IHD, including blood glucose levels, lipid profiles, blood pressure, liver function, alcohol intake, smoking status, and self-reported diseases, such as T2DM and hypertension. By including these factors, we discovered that when patients with GB polyps and impaired FPG presented with hypertension or dyslipidaemia, these comorbidities increased the risk of IHD by approximately 2-fold.
It is generally believed that GB disease is positively correlated with metabolic syndrome, obesity, and T2DM because these conditions share common risk factors, such as sedentary life styles, dyslipidaemia, and fat rich diets [11, 15]. Our results imply that GB polyps are closely related to the development of IHD, although this association may be an epiphenomenon and not a causal effect. However, our findings suggest that GB polyps may be a risk factor for IHD that is independent of traditional risk factors.
In the present study, patients who presented with GB polyps and the comorbidity hypertension or dyslipidaemia developed an increased risk of IHD that was greater than patients with GB polyps alone. This interaction was observed in patients with impaired FPG, but not in those with T2DM. Epidemiological studies have reported that the development of IHD is enhanced when CVD risk factors are combined with obesity and metabolic syndrome, but not T2DM, in the general population [16–19]. This finding may be explained in part by the medications used (e.g. metformin) and life style modifications that may occur after a diagnosis of T2DM. Metformin has been shown to protect the heart from fibrosis and remodelling after myocardial infarction and decrease inflammation and oxidative stress . As a result, patients with T2DM taking metformin may have a weakened risk of developing IHD .
Recent epidemiological and experimental studies have reported possible mechanisms by which GB polyps influence the development of IHD. GB polyps are tumour or tumour-like protrusions arising from the GB mucosa and are divided into true polyps and pseudopolyps . True polyps are classified as adenomas or adenocarcinomas, and pseudopolyps, which represent over 90 % of GB polyps, consist mainly of cholesterol and inflammatory polyps [23, 24]. As the names suggest, the growth and development of the majority of GB polyps are closely related with cholesterol metabolism and inflammation . Acetyl-CoA acetyltransferase 2 (ACAT2) is a key enzyme in the biogenesis of lipid bodies, which may facilitate the pinocytosis of cholesterol and papillary hyperplasia in the GB mucosa . Additionally, this enzyme decreases GB contractility leading to cholesterol deposition in the GB wall . ACAT2 is also responsible for incorporation of cholesteryl ester in apoprotein B-containing lipoproteins that leads to increased very low-density lipoprotein (VLDL) secretion and coronary artery atherosclerosis . It has been reported that inflammation is closely related to ACAT2 activity and downregulating ACAT2 is associated with lowering cholesterol and preventing atherosclerosis . Collectively, the interactive linkage between ACAT activity, inflammation, and dyslipidaemia may lead to the development of both GB polyps and IHD .
Previous cross-sectional studies have consistently found that patients with metabolic syndrome have a high prevalence of GB polyps, suggesting that insulin resistance may be a potential cause [15, 30]. An epidemiological study reported that hyperinsulinemia increased the incidence of GB polyp in Korean men . Therefore, we propose that screening patients with GB polyps for metabolic disturbances will be important for early detection and prevention of IHD.
The present study had several strengths. First, potential IHD-related confounding factors were assessed by blood tests along with traditional risk factors. Second, the identification of GB polyps occurred during the process of screening the general population rather than relying on the diagnosis by doctors based on symptoms of GB disease. Therefore, we minimised the mis-classification of asymptomatic patients into the control group in our study and decreased cohort bias. Third, this study was carried out using data from a large scale, prospective cohort study to ascertain IHD risk factors and included analyses of multiple physiological tests.
Nevertheless, this study also has some limitations. Cholesterol polyps and adenomas may indicate underlying pathogenesis . For the majority of patients with GB polyps, there was no information regarding a pathological condition because the data were obtained from asymptomatic patients who underwent health check-ups. Additionally, this study was a retrospective cohort study and USG was performed only at baseline. Therefore, we were unable to discover new-onset GB polyps during the follow-up period, which may have led to a selection bias and underestimation of the association between GB polyps and IHD incidence. Despite these limitations, this is the first study to assess a role for conventional IHD risk factors in the association between GB polyps and development of IHD.