Reviewer #1
1. The methods used for treatment of the large material is difficult to follow, certain data have
been omitted in the flanks, and the figures provided are impossible to understand.
The symbols should be included in the figure so that the significance is more easy to understand.
To address the difficulty in understanding so many figures and to reduce redundancy in Results
as suggested by another reviewer, we have included only two figures in the revised manuscript to
illustrate the influence of potential biases on the shape of the relation between BMI and mortality.
We have added symbols to the figures as suggested.
2. Expressions like reverse causation bias and potential bias should be explained.
We have provided an explanation of ‘reverse causation bias’ and ‘potential bias’ in the
Introduction.
“The most serious concern in studies of body weight and mortality is that low body weight may
be the result rather than the cause of a preexisting illness that leads ultimately to death, a
phenomenon referred to as reverse causation.1-4 This phenomenon could underlie, at least in part,
the elevated risk of death associated with leanness observed in many epidemiologic studies.”
(page 2)
Potential biases include bias related to preexisting illness (reverse causation) and confounding by
cigarette smoking.
3. Table 1 and 2 How could the various factors be adjusted for age, education, occupation etc.
Which figures are used for such corrections?
We used Cox models to adjust for potential confounding variables including age, education, etc.
Reviewer #2
1. The term usual BMI is not clear, so please specify it in the abstract
Usual adult BMI refers to average adult BMI. We have clarified this term as suggested.
2. "Few previous studies, however, have evaluated the association of body weight and total
mortality by simultaneously taking into account the potential biases discussed above"
There are studies, which address the relation between BMI and mortality taking into account the
potential biases of reverse causation and smoking.
We agree with the reviewer and have removed this statement in the revised manuscript.
3. "Weight loss due to clinical or subclinical illness and differential loss of lean body mass often
occur in old age, posing a particular methodological challenge for studies of older people"
The term differential is not clear here. Do you mean preferential, or differential according to
what?
We have changed the term “differential” to “preferential” as suggested.
4. Could you briefly describe the selection procedure, is it random sample?
We have added information regarding the selection procedure as suggested.
“All women 40 to 70 years of age living in seven typical urban communities of Shanghai were
invited to participate in the study. Between December 1996 and May 2000, a total of 74,942
women were recruited, with a participation rate of 92.7%.” (page 4)
Our study population is representative of the general population of women in urban Shanghai.
The details of the study have been published previously.
Zheng W, Chow WH, Yang G, et al. The Shanghai Women's Health Study: rationale, study
design, and baseline characteristics. Am J Epidemiol. 2005;162:1123-1131.
5. How was the death certificates coded, did you do it yourself? Have you any impression of the
quality/validity of the certificates, the causes of death and so on. Please clarify this issue in the
method section, and mention it briefly in the discussion in relation to the impact on your results.
We have clarified and added discussion about death certification and coding as suggested.
“The underlying cause of death was determined on the basis of death certificates, which were
coded uniformly according to the codes of the International Classification of Diseases, Ninth
Revision (ICD-9) by trained health professionals at the Shanghai Vital Statistics Unit.” (page 5)
“Another limitation of the study is the possibility of misclassification of the cause of death based
solely on death certificates. However, a study evaluating the validity of cause-of-death statistics
in urban China, including Shanghai, has shown that information on death certificates was
reasonably accurate with regard to major causes of death such as CVD and cancer, suggesting
that our results on cause-specific mortality were unlikely to be seriously biased.” (page 12)
Rao C, Yang G, Hu J, Ma J, Xia W, Lopez AD. Validation of cause-of-death statistics in urban
China. Int J Epidemiol. 2007;36(3):642-651.
6. "The objectives of the present analysis were to examine the associations of BMI at various
ages and usual adult BMI with mortality and to address the influence of potential
methodological biases on the associations."
Please avoid redundancy.
We have removed this sentence as suggested.
7. "to estimate relative risks (RRs) of death associated with each BMI category and their 95%
confidence intervals (CIs)"
I believe it is Hazard Ratios? Please correct this throughout the manuscript. You must
investigate the proportional hazard assumption in your models, and mention that you obtain
proportional hazards
We have made the correction as suggested.
We evaluated the proportional hazards assumption by including interaction terms between
exposure variables and follow-up time and found no evidence of violating the assumption. (page
6)
8. "Tests for linear trend in risk across BMI categories were performed by using the median
value for each BMI category and modeling them as continuous variables".
This is ok, but I am just wondering why you don't use the splines for this purpose?
As with many previous epidemiologic studies, this approach was used when exposure was
treated as categorical variables and the trend across categories of exposure was evaluated.
9. "The median value of BMI was treated as the reference point, with knots placed at the 5th,
50th, and 95th percentiles of the BMI distribution."
Why did you choose these knots? If you used quartiles, the analyses would be more comparable
with the categorical analyses.
Restricted cubic spline regression was used to evaluate the shape of the dose-response relation
between mortality and BMI on a continuous basis.
The 5th, 50th, and 95th percentiles are the most recommended (the default) locations when 3
knots are chosen.
10. "Of the total participants, 2,111 had ever smoked"
Do you mean smokers and past smokers?
We have rephrased the sentence to avoid confusion:
"Of the total participants, 2,111 were ever smokers, including current and former smokers"
(page 6)
11. Since you provide both tables and figures, you have some redundancy it the results. Please
try to minimize this.
We have reduced the number of figures as suggested.
12. The study of changes in BMI is different to the study of BMI assessed at one point in time.
The results are interesting, but you need to clarify adjustments, how you handle the baseline
level and so on in the methods, and also discuss the findings according to other studies of BMI
changes.
We have deleted the figure on weight change and focused only on BMI and mortality in the
revised manuscript.
13. You discuss the impact of age on your results, by comparing the measured data with the selfreported data. In order to eliminate a putative impact on the results from the measurement
method, it would strengthen the results if you also analyzed the measured baseline BMI in subsamples of different ages and found the same results.
We agree with the reviewer that it would be desirable to stratify the analyses of measured
baseline BMI by age; however, our study does not have sufficient statistical power to conduct
such analyses.
14. As far as I know, most well conducted studies on BMI and mortality are from cohorts in USA
and Europe. Please emphasize that you have data from China and comment on this in relation to
your findings, since it is a strength that make the study different from previous studies.
We appreciate reviewer’s comment and have emphasized the uniqueness of the study population
in revised manuscript.
“It is worth noting that unlike previous studies, most of which were conducted in Western
populations, our study was conducted in a generally lean population of Chinese women.”
(page 8)
15. Please provide a small descriptive table of your cohort.
We have added the table as suggested.
16. Is it possible to make the legends a bit shorter?
You have several figures, is it possible to combine some of them?
Please provide the number of subjects included in the analyses/figures.
We have made the changes as suggested.