Review for 10.1186/s12876-022-02149-5 (2022)

Reviewer’s report
Title: 
The Association Between Hypertension and The Risk Of Gallstone
disease: A Cross-sectional Study
Version: 
2 
Date: 
20 Dec 2021
Reviewer: 
Gabriel Sandblom
Reviewer's report:
The paper describes a large register study on the association between
hypertension and gallstone formation. They found a statistically significant,
albeit very small, association. The authors should be congratulated for being able
to present results from such a large study group. However, I have some
comments:
1. "Identification and early intervention against risk factors for gallstone disease"
is suggested to be an important issue and an aim of conducting the study. I do
not agree with this statement that seems to suggest that primary and secondary
prevention of gallstone disease are effective ways of improving public health.
Most efforts to avoid gallstone formation, including treatment of hypertension,
are futile and gallstones are in most cases asymptomatic and rarely associated
with severe morbidity. On the contrary, the low odds ratios shown in the present
study should be interpreted as a negative result, i.e., other strategies should be
sought if the aim is to prevent gallstone disease.
2. The statistical significance is probably to a greater extent explained by the
large number of patients than a strong association. The odds ratio was not larger
than what would be expected considering the numerous potential confounders,
e.g., dietary factors, drinking habits, liver cirrhosis and participation bias. Do the
authors have any data on these background factors?
3. How many were invited to the screening and how many participated? Was
there a complete overlap between those who underwent the ultrasound
examination and had their blood pressure measure? If there were dropouts in the
data assembling for any of the variables, this could cause a bias. 
4. Do the authors have a reasonable explanation for the reduced prevalence of
gallstones in patients aged >90 years? The only reasonable explanation I could
think of would be detection bias or participation bias. As mentioned above, more
data about the number of patients and participation rate is needed.
5. In the abstract it is stated that hypertension increases the risk of gallstone
disease. As a study such as the present one cannot prove any causal relationship,
this should be corrected to "significant association". The same verb also occurs a
couple of times in the manuscript text.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No