Author's response to reviews

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1 Author's response to reviews Title: Diverse risks of incident cardiovascular disease and all-cause mortality in men and women with low cash margins living alone: cohort data from 60-year-olds Authors: Axel C Carlsson (axelcefam@hotmail.com) Bengt Starrin (bengt.starrin@kau.se) Bruna Gigante (Bruna.Gigante@ki.se) Karin Leander (karin.leander@ki.se) Mai-Lis Hellenius (Mai-Lis.Hellenius@ki.se) Ulf de Faire (ulf.defaire@ki.se) Version: 2 Date: 3 October 2013 Author's response to reviews: see over

2 Dear Editor of BMC Public Health: We are grateful for the opportunity to submit a revision of our manuscript entitled Diverse risks of incident cardiovascular disease and all-cause mortality in men and women with low cash margins living alone: cohort data from 60-year-olds. The manuscript has undergone additional revisions based on the relevant suggestions from the Reviewers. Please see the revised manuscript and our specific replies to the comments of the Reviewers below. We feel that the review process has substantially improved our manuscript and hope that it now is suitable for publication in BMC Public Health. Sincerely, Axel C Carlsson # 1 Reviewer's report Title: Diverse hazards in men and women with low cash margins living alone: cohort data from 60-year-olds Version:1 Date:10 August 2013 Reviewer: Mikaela von Bonsdorff Reviewer's report: Major compulsory revision The paper investigates the association between having a cash margin and CVD and all-cause mortality in a population which was 60-years of age at baseline. The topic is current and investigates the health effects of socioeconomic status in a way that has been less reported. However, there are several things that need to be addressed. Title - The title does not describe the whole paper. - The outcome is not evident, what hazards? Author response: We agree with the Reviewer that the title could describe the topic of the paper better. We have changed the title to: Diverse risks of incident cardiovascular disease and all-cause mortality in men and women with low cash margins living alone: cohort data from 60-year-olds Abstract - In the abstract you do not include marital status/cohabiting into the aim, but at the end of the Introduction you do include it. Author response: We thank the Reviewer for the careful reading of our manuscript. The aim in the abstract of the revised version of our manuscript now reads:

3 The aim of this study was to investigate whether having a cash margin and living alone or cohabiting is associated with incident cardiovascular disease (CVD) and all-cause mortality. - Regarding the outcomes it would be clearer to use incident CVD to set it apart from mortality, so that one would not read CVD mortality and all-cause mortality. Author response: Good suggestion, we have changed to incident CVD and allcause mortality throughout the revised version of the manuscript. - What was the starting year (or range) of the study, it is important to know this because of the worldwide changes in the financial situation. Author response: We agree that these are important issues to clarify. We state in the (second sentence) of the methods section that: From August 1997 to March 1999, every third individual (male or female) was invited to participate in a thorough cardiovascular and metabolic health screening. And in the abstract and the outcomes section of the methods, we state that the median follow-up was 11 years. We added the following to the outcomes section of the methods: The mean follow-up time was 11 years and ended December 31, 2010 (range ). - Since you do not state that you formed the four groups and do not write anything about the living arrangements, it is not easy to read the results. Author response: The formation of the four groups has been added to the statistics section. - The results part in the Abstract is confusing, please make this clearer (e.g. in the first sentence you write women and men but present HR s for women only). - Present the fully adjusted HR s. Author response: We are sorry about this unfortunate error and have corrected accordingly. Moreover, we agree that fully adjusted HR s are better to present in the abstact and have replaced them. The results section of the abstract now reads: Compared with cohabiting women with a cash margin, the risk of all-cause mortality was higher among cohabiting women without a cash margin, with hazard ratios (HRs) of 1.97 (95% confidence interval (CI) ). Single men without a cash margin were at an increased risk of both incident CVD and all-cause mortality: HR 2.84 (95% CI ) and 2.78 (95% CI ), respectively. Single men with cash margins still had an increased risk of all-cause mortality: HR 1.67 (95% CI ). - The Introduction is narrow and needs to be more detailed so that it will be

4 easier to place this piece of work into the bigger picture. Author response: We have rewritten the introduction in the revised version of our paper. If there are additional studies that the Reviewer suggests that we should cite, we will be happy to add them. - You cite some of the literature but there are several important papers that should be cited. Author response: In addition to the papers we cited previously, we cite several other important papers in the revised version of our manuscript. - The first sentence does not really seem to be suitable for this paper or it needs to be explained. The second sentence needs to be placed at the end of the Intro. - Use cohabiting throughout the text not marital status/cohabiting. Author response: We thank the Reviewer for these thoughtful suggestions. The introduction has been rewritten. Methods - Page 4 first paragraph state the duration of the follow-up. Author response: We added the following sentence to that section: Identification number of the participants enabled follow-up for an average of 11 years in national Swedish registers. - You do not adjust for alcohol consumption, in case you have that data please adjust for it. Author response: We have data from a frequency questionnaire of consumption of beer, wine and hard liquor. The sensitivity to detect high consumers of alcohol with self-reported questions has been estimated to be 69% using a thorough psychiatric interview as the gold standard,[3] with a specificity of around 90% (Theobald H, Bygren LO, Carstensen J, Engfeldt P: Validity of two questions on alcohol use in a health survey questionnaire. Scand J Public Health 1999, 27(1):73-77).). Based on this fact, we adjusted all models presented in table 4 of the revised manuscript for high alcohol consumption in addition to all variables in the previous version of our manuscript. The essential findings of the present study remained. Please see table 4. - Page 5 first paragraph revise the list concerning education into text form. Author response: It now reads: Education level was defined as: Lower level education, i.e. compulsory school, year education, i.e. high school, and >12-year education, i.e. university.

5 - Page 5 you have marital status in the title when you should be referring to living arrangements. Author response: We rephrased the title using living alone which we believe is easy to understand. It now reads: Diverse risks of incident cardiovascular disease and all-cause mortality in men and women with low cash margins living alone: cohort data from 60-year-olds - Can you say something more about the validity of the cash margin question? Do you have information on their occupation? Author response: Very good suggestion. We added a validation of cash margin / cohabiting using logistic regression (to study the association between employment and the four cash margin/cohabiting groups). The association was strong as shown in Reviewer table 1

6 Reviewer table 1. Validation of cash margin cohabiting using logistic regression. Employment Women Odds Ratio (95% Confidence Interval) Employment Men Odds Ratio (95% Confidence Interval) Cohabiting with cash margin Reference Reference Single with cash margin 0.98 ( ) Cohabiting without cash margin 0.29*** ( ) Single without cash margin 0.34*** ( ) 0.56 ( ) 0.27*** ( ) 0.27*** ( ) *** p<0.001 We decided to add this interesting new table to our manuscript as table 2 and add this validation to all parts of the revised version of our manuscript. - Page 5 third paragraph move the explanation on formation of the four groups into the statistical analyses part. Please show the interaction term for cash margin and cohabiting on CVD and also for mortality. Author response: We have moved this section to the statistical methods in the revised version of our manuscript. The interaction terms for cash margin and cohabiting are also shown under the sub-headline incident CVD and all-cause mortality of the results section of the revised manuscript. It reads: There was no significant interaction between cash margin and cohabiting in women, p=0.22 for incident cardiovascular diasease and p=0.32 for mortality. The interaction was of potential importance in men, p=0.11 for incident cardiovascular diasease and p=0.081 for mortality. The hazard ratio for being single was 0.81 (95% CI ) for incident cardiovascular disease and 1.32 (95% CI ) for mortality in women. The corresponding HRs for being single in men were 1.47 (95% CI ) for incident cardiovascular disease and 1.98 (95% CI ) for mortality. The hazard ratio for not having a cash margin was 1.23 (95% CI )in women and 2.11 (95% CI ) in men for incident cardiovascular disease, and ~2 (p<0.001) for mortality in both men and women. - Page 6 third paragraph add numbers for those excluded from the CVD

7 analyses. Author response: We consider these data as results and have accordingly included them in detail in the first section of the results section- - Explain the formation of the time variable used in the Cox regression. Author response: The following sentence has been added to the statistics section of our revised version of the manuscript: We retrieved data on the time (in days from the baseline examination) to incident cardiovascular disease and all-cause mortality from the national hospital discharge register and the national cause of death register. - Why did you decide to analyze men and women separately? What were the interaction terms for gender and cash margin/cohabiting on the outcomes? Or did you do gender-specific analyses based on the literature? Author response: The p-value for the interaction terms are presented above and in the revised version of our manuscript. More detail on gender differences from the literature are given in the revised version of our introduction. A combination of literature and diverse hazards for men and for women for cohabiting was the reason. - Page 7 second paragraph it would be more logical to first present the pooled analyses and after that for men and women separately. Author response: We have rearranged the manuscript and present sex-adjusted models after the models in women and in men. - Page 7 second paragraph the sentence Sex-adjusted models... is confusing because you report risk for men and women, please revise this. Author response: Thank you. We have deleted as suggested. - It would be clearer to first present all results for incident CVD and then separately for mortality. Author response: We respectfully disagree with the Reviewer. We would prefer to first present all crude model results and then present the educational level and lifestyle-adjusted models. We thus decided not to further divide the results section into two additional sub-sections. However, we are willing to reconsider if the Reviewer feels strongly that the present way to present data is unclear. Discussion - Page 9 second paragraph you bring up an important aspect which is related to the cash margin question which is that the person might be able to loan the money and thus we do not really know about their own financial situation. Please verify this in the existing data, e.g. do you have data on their income level?

8 Author response: We do not have good reliable data on income, but we have self-reported employment level and have included such an analysis. It is described as follows in the results: The cash margin /cohabiting variable was highly associated with employment status as shown in table 2. Both men and women without cash margin had low odds of being employed halftime or more. Single women with cash margin were employed as often as cohabiting women with cash margin. In contrast, single men with cash margin had lower odds of being employed. Correlation between educational level and cash margin? Author response: Excellent suggestion. We added a logistic regression model of educational level as an explanatory variable of cash margin. Please see statistics section, and the results which read: We also studied the association between lack of cash margin and educational level using logistic regression (data not shown in tables). University education was highly inversely associated with (p<001) cash margin, in both men and women using lower education as referent. High school was (compared with lower education) only significantly associated with cash margin in men (p<0.01). - What are the implications for public health? Author response: We added a section of public health implications where we emphasize that it is important to identify single men without cash margin and thus lower status and increased risks. Level of interest: An article of importance in its field Quality of written English: Acceptable Statistical review: Yes, and I have assessed the statistics in my report. Declaration of competing interests: I have no competing interests Author response: Confirmed. #2 Reviewer's report Title:Diverse hazards in men and women with low cash margins living alone: cohort data from 60-year-olds Version:1 Date:21 August 2013 Reviewer:Masuma Novak Reviewer's report: COMMENTS FOR THE AUTHOR: 'Diverse hazards in men and women with low cash margins living alone: cohort data from 60-year-olds. This is a very interesting study but following issues which need to be addressed

9 before publication: 1) In the introduction section, authors could give more insight into previous studies which showed different types of health effect of this particular variable cash margin, not just mentioning the variable, and whether the effects are similar between gender or not. Author response: We have rewritten the introduction as this point was made by all Reviewers. 2) Method section, definition of education needs further explanation. The term compulsory school may not be obvious for the international readers, particularly in Asia, where education system is very different. The 2nd definition is high school 9-12 years, is it really? Or is it 10-12, not very clear, because compulsory schooling is up to 9 years. Please define clearly. Author response: This section has been rewritten as well. 3) Method section, under Cash margin (CM) and marital status para the authors have mentioned that CM and its association with socioeconomic status (SES) and health this part should be moved to introduction and elaborate further if these effects are shown to be different/similar between men and women (see comment # 1). Author response: Good suggestion. This whole section is a part of the present and entirely rewritten introduction. 4) Discussion section, last para - Although participation rate of 78% is very high in a population-based setting, it is clear that 22% of them declined participation. Selection bias is likely as people with lower SES tend to participate less frequently. I therefore doubt the statement that this cohort is highly representative of the Swedish population. The authors should really comment on this and this statement needs to be rephrased. Author response: Very good point. We have rephrased this section. It now reads: We were able to reach the target population (60-year-old residents of Stockholm County) with a high response rate (78%); however, the response rate was likely lower in individuals with a low cash margin, possibly making the real effects of our findings in the population even greater. 5) The authors should discuss on quality of case ascertainment using death certificates by means of CVD events identification. The authors should at least include one or two sentences on this topic in the discussion. Author response: We added a section about our follow-up to the discussion. It reads:

10 Finally, the In Hospital Care Register and the Cause of Death Register in Sweden are nearly complete (99.8%) [36], enabling long-term evaluation without any significant loss to follow-up [7, 17]. Level of interest:an article whose findings are important to those with closely related research interests Quality of written English:Needs some language corrections before being published Statistical review:yes, but I do not feel adequately qualified to assess the statistics. Declaration of competing interests: #3 Reviewer's report Title:Diverse hazards in men and women with low cash margins living alone: cohort data from 60-year-olds Version:1 Date:22 August 2013 Reviewer: Johanna Eronen Reviewer's report Major compulsory revisions 1. In the introduction, you give some examples on the harmful causes of financial stress on health. What about living status (single/cohabiting) and its role on health? I d suggest you expand the introduction and include living status in it also. Author response: As this was also suggested by Reviewer #1, we decided to rewrite the introduction taking these issues into account. 2. I would also like to see a justification for using cash margin as an indicator of financial stress in the introduction. Author response: Good suggestion. The cash margin as an indicator of financial stress is motivated in the introduction of the revised version of our manuscript. 3. In your discussion you state that cohabiting seems to protect men but not women. Why is it so? Could you discuss the role of living status more extensively? Author response: Good suggestion. We added a final explanation to our findings in the discussion. It reads: Finally, besides the fact that men are less prone to seek healthcare and to follow their doctors recommendations as mentioned above, we can only speculate why single men

11 and women have different risks. Stressful events in early life have been shown to have a greater effect on psychosocial function late life in men than in women [35], and it is possible that these effects contribute to and propagate the divergent risks associated with cash margin/cohabiting in men and women. It is also possible that men are more affected socially and thus have more financial stress, than women are when they lack cash margin. 4. In the second paragraph of the discussion, you write that Individuals without a cash margin -- are likely to have answered high/severe. How do you validate this argument? For example, can cohabiting women without cash margin rely on their husbands and thus not have high/severe level of financial stress? Author response: Excellent suggestion. As suggested by Reviewer # 1 we added a validation using employment, please see table 2. We have also revised this sentence with this new data. Minor Essential Revisions 1. In the abstract, you do not mention cohabiting until in the results-section. Could you add it into the background-section? Author response: The introduction has been entirely rewritten and we agree with the Reviewer that this is good, to explain the cohabiting variable as married and living with a partner and then just refer to cohabiting. 2. In the end of the Introduction where you state the aim of the study you write marital status/cohabiting and the Results-section under the heading Incident CVD and all-cause mortality, you write married/cohabiting while elsewhere in the text you use only cohabiting. Could you give the definition of cohabiting in your study already in the introduction and use the same term through the text? Author response: Good suggestion, we have changed accordingly throughout the manuscript. 3. I would also suggest you to decide whether you use the term cash margin or cash margins and use it consistently throughout the text. Author response: We have made an effort to use cash margin in throughout the revised manuscript. 4. In the Data collection section you describe how the presence of diabetes was defined. Could you also add the definition of CVD? Author response: Good suggestion. We have added a definition of CVD at baseline to the revised methods section. It reads: The presence of CVD and diabetes at the baseline investigation were determined using the questionnaire. CVD at baseline was identified by prior CVD events in the national hospital discharge register or as having reported one or more of the following: myocardial infarction, stroke, heart failure angina (heart or legs) in the questionnaire. We also excluded individuals with missing data on any these questions in the questionnaire.

12 5. How was physical activity measured, and what was the definition of moderate or intensive physical activity? Author response: We used a questionnaire to determine different levels of physical activity. From these a dichotomous variable were created. We have clarified this in the following way: Physical activity was defined as moderate or intensive leisure time physical activity more than once a week and determined by questionnaire. Daily intake of fruit and vegetables were also determined from the questionnaire. The answers of these questions were transformed into dichotomous variables. 6. In the paragraph entitled Cash margin and marital status, you cite a report of the Swedish FHI. Please add this into the references and add a proper citation in the text. Author response: This section has been moved to the introduction as suggested above. The data comes from the National Swedish Institute of Public Health and we have clarified this reference accordingly. (The National Swedish Institute of Public Health, report A 2009:11) 7. When you present the outcomes you write that they are either or. Shouldn t it be and? Author response: Thank you, we have changed as suggested. 8. The figures in the abstract and in the Results-section are not exactly the same as in tables 1a and 1b. Have you excluded some of the participants and if yes, on what basis? Author response: We have double-checked all number and tables in the revised manuscript. They should be correct in the revised manuscript. Level of interest: An article whose findings are important to those with closely related research interests Quality of written English: Acceptable Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: I declare that I have no competing interests