The present study evaluated incidence and risk factors for GD in a large population from various Italian regions, thus providing a more detailed picture of the epidemiological characteristics of this disease. Incidence was higher in females than in males and increased with age. In our population, the risk factors for GD in males were increasing age, BMI, concomitant diseases such as diabetes, liver cirrhosis, peptic ulcer, coronary disease, HDL and total cholesterol, and high levels of triglycerides while, in females, only increasing age and BMI. Increasing age, pain in the right hypochondrium/epigastrium, and the presence of concomitant diseases are predictors of GD. Pain in the right hypochondrium or epigastrium was the only symptom associated with GD; symptom severity increased as a function of the natural history of the disease. Increasing age in men and aging and BMI in females were the only predictive factors for the eventual presence of symptoms.
GD is a very common gastrointestinal disorder mainly in the Western world[1,2
]; although this disease has a low mortality rate, its economic and health impact is significant due to its high morbidity. In fact, GD is one of the most common abdominal conditions for which patients are admitted to hospitals in developed countries[3
]. Knowledge of disease epidemiology is therefore crucial in managing this disorder, not only for planning preventive programs, but also for the identification of the best therapeutic strategy. Several US-based surveys have been carried out in Europe[19-23
] and in North[24,25
] and South[26
] America as well as in Asia[27,28
], indicating prevalence rates for GD ranging from 5.9%[20
] to 21.9%[22
]. However, few studies[11-14
] have been carried out to evaluate incidence and risk factors of GD, mainly due to the difficulties in following up large populations for several years. The MICOL study was designed to obtain a general overview of GD in Italy, investigating GD in terms of prevalence, incidence, risk factors, and natural history[15
]. In the present study, a large general population was evaluated with the objective of identifying gallstone incidence and risk factors as well as the morphological and clinical characteristics of newly developed gallstones. Incidence was higher than that measured in previous Italian studies[12-14
]; these differences could be related to the small population sample evaluated in the earlier studies. Furthermore, prevalence was also higher than in Denmark (4.5% and 5.8%, in males and females, respectively)[11
]. Differences in research design may justify these differences even it is not possible to exclude the role of environmental factors.
In the present study, the response rate was higher (79%) than that reported in other GD incidence surveys performed in the north (63.7)[12
] and in the centre (73.5%)[14
] of Italy and similar to that observed in Denmark (82.8%)[11
] and in southern Italy (87.7%)[13
]; this percentage indicates a high adherence of the target population to the epidemiological study.
The participation rate was also higher in the present incidence study (79%) than in the previous study evaluating GD prevalence (64.4%)[15
]; this difference could be related to a possible self-selection of patients or to an effect of dilution in the prevalence study since, in that study, 14 units participated while, in the present study, only 7 units were able to adhere to the protocol.
We documented variability between the different units in terms of incidence; this difference could be related to the role of environmental factors (life style, dietary habit, etc.) even if we were unable to identify any possible difference between the different operative units.
Gender, increasing age, and BMI were confirmed as true risk factors for GD; in males, low levels of cholesterol, high levels of triglycerides, and the presence of co-morbidities such as diabetes, peptic ulcer, angina, and liver cirrhosis represented additional risk factors. These results further confirm the importance of environmental factors in gallstone development, possibly related to an unhealthy life style. In fact, recent epidemiological studies have suggested that GD may be included in those disorders which characterize the metabolic syndrome[29,30
]. In particular, a close relationship between obesity and cardiovascular disease (two of the more characteristic features of the metabolic syndrome) and GD has been identified[31,32
We did not confirm a family history of gallstones, dieting, the number of pregnancies, and the use of contraceptive pills, which were found to be significantly associated with GD in the prevalence study as risk factors[16
]. We are unable to interpret the significance of this result; however, the data available on some risk factors for GD are frequently conflicting[8,10
]. The prospective cohort design of the present study and the use of US as the diagnostic tool have reduced the possibility of a recall and other information bias; furthermore, the high response rate makes selection bias unlikely.
An important result of the present study is related to the clinical manifestation of incident gallstones. In fact, we have confirmed the observation made in the prevalence study[15,17
] that pain in the right hypochondrium and/or epigastrium is the only symptom significantly associated with gallstones while the so-called “non-specific biliary symptoms”, i.e. dyspeptic symptoms, showed the same frequency in gallstone-free subjects and GD patients.
We have also confirmed our previous observation[17
] concerning the usefulness of splitting the subjects enrolled in the study into 4 categories reproducing the different stages of GD (absence of disease, silent disease, overt disease, severe disease); in fact, the frequency and severity of the clinical symptoms and the signs of GD increased throughout the 3 disease categories.
Furthermore, for those characteristics that are an expression of the degree of pain severity (pain forcing to rest, presence of clinical signs of gallstone complications) they progressively increased from silent gallstones to symptomatic gallstones to cholecystectomized patients for gallstones, suggesting that the natural history of GD moves from a silent to a clinically evident stage; this is also true for newly developed gallstones. This information may be useful in choosing the best therapeutic strategy in gallstone patients since surgical treatment is indicated only in true symptomatic gallstone patients[5,33
Finally, we were unable to identify any predictive factor for the presence of biliary pain in terms of gallstone characteristics (number and size), while increasing age in males and a high BMI in females were related to the presence of biliary pain. These results are in agreement with some[34
], but in disagreement with others[35,36
In conclusion, this study provides data on the gallstone incidence and risk factors for GD in a large free-living population; the incidence rate is higher in females and it increases with age. Increasing age and BMI represent true risk factors for GD; pain in the right hypochondrium and/or epigastrium is confirmed as the only symptom related to GD; pain, as well as its characteristics of disease severity, increases in severity and frequency throughout the different stages of GD (from silent to severe disease). This information may help physicians in clinical decision making.