What Drives the Contemporary Black–White Racial Disparities in Gout in the US? Impact of Social Determinants of Health
Round 1
Reviewer 1 Report
This is well written review paper for the community to demonstrate the health disparity in Black, especially for women.
1. Author need to describe the different portion of CKD between men and women. How can authors explain that BMI is the biggest risk factor in black women? In Black men, BMI only explains 12 %.
2. Genetic risk of APOL1 is underestimated in this review. Authors need to add the role in Black.
Author Response
Thank you for your consideration and favourable review of our review paper. We appreciate the Reviewers’ feedback and have addressed their queries to the fullest extent possible. Please find below our detailed point-by-point responses to each comment and the corresponding manuscript revisions.
Reviewer 1:
This is well written review paper for the community to demonstrate the health disparity in Black, especially for women.
- Author need to describe the different portion of CKD between men and women. How can authors explain that BMI is the biggest risk factor in black women? In Black men, BMI only explains 12 %.
Reply) BMI itself was the strongest risk factor for both Black men and women. However, BMI levels were similar between Black and White men, whereas BMI was higher in Black women than White women (by 3.2 kg/m2), which led to the discrepant contributions for the observed gout risk disparity (56% vs 12%, respectively). It is important to note that, in order to be a strong contributor for the disparity, the factor distribution has to be different between the compared groups. This is now mentioned in the manuscript:
“To mediate the racial disparity, a factor needed to be both associated with gout (or hyperuricaemia) and differ in levels or frequency between Black and White individuals.” Lines 140-142
- Genetic risk of APOL1 is underestimated in this review. Authors need to add the role in Black.
Reply) We discussed APOL1’s role in Section 4.5 based on Refs 70, 71, 72, 73, and 74. While we acknowledged the role of the APOL1 risk alleles for the higher prevalence of CKD in Black adults (compared to White), these studies suggest that racial differences in social determinants and clinical factors play a greater role.72 Sociodemographic and environmental factors together explained 44%73 of the racial difference in CKD incidence in one study and 64% of the racial difference in another,74 where poorer access to healthcare among Black participants also contributed.74
If the reviewer could point to some specific literature that we might have missed, we would be happy to consider.
Reviewer 2 Report
Thank you for the opportunity to review your paper. This is a well-crafted review article, addressing a major gap in literature. There is a paucity of research on health disparities of gout in the United States, and this article is one of the few published papers to stimulate this discussion. While genetics could play a significant role in developing gout in some populations, Blacks and African Americans are more likely to develop gout due to non-genetic factors. This paper does a great job of interrogating the role of social factors and disease mediators in developing gout. Nonetheless, I have some suggestions to strengthen the article.
1- Lines 50-53: I understand the preamble of discussing health disparities in Black and White. However, I believe bringing Māori and Pacific Islanders to this discussion is a distraction. I strongly suggest a general statement on health disparities in other populations and my preference is to remove it altogether.
2- Table 1: Although the author diseases the publication in the paper, it was not mentioned in Table 1. Please include this publication PMID: 30618180 in your assessment of gout between Black and White
3- Lines 116-118: I suggest adding a citation. Given the nature of the topic and purpose of the paper, I may recommend this paper PMID: 36079846
4- Lines 124: Race is controversial. I suggest that the authors may reword this. For example, "race is less of a biological framework and more of a social construct."
5- Line 128: Please avoid the word must. I would suggest “Race should be considered….”
6- Lines 130-132. I suggest adding a citation. Given the nature of the topic and purpose of the paper, I may recommend this paper PMID: 36079846
7- Section 4.2: It's understandable that diet and alcohol can have a dose-response relationship with uric acid levels. Also, certain diet and lifestyle factors may have a urate-lowering effect PMID: 36079846. Therefore, an emphasis on food quality and certain dietary patterns should be well described. Another lifestyle factor could be smoking which may lower uric acid levels. Therefore, recognizing the totality of the effect should be addressed or at least mentioned.
8- Lines: 206-208: I think the authors are correct, but they also need to recognize that occasional drinking is not the primary driver of developing hyperuricemia or gout, but rather chronic consumption of alcohol. Indeed, once alcohol dependence occurs, Blacks and Hispanics experience higher rates than Whites of recurrent or persistent alcohol dependence.
9- Section 4.4: Diuretic medications could greatly influence the risk of hyperuricemia and gout. However, with the excess cardiovascular disease burden among Black, such as heart failure and MI, the occurrence of other drugs to manage those conditions could worsen the urate-raising effect or could lower uric acid. Beta-blockers losartan are widely used in HF and MI patients of whom a majority is Black Therefore, it's the excess of co-morbidities that could drive the overall effect of medications used. Also, differential response to therapy could vary between populations rendering some groups to be good or poor responders to pharmacotherapy, including diuretics. https://www.mdpi.com/2673-9879/2/2/11#
10- Section 5.1: It's important to report the evidence that patients treated for their gout in a nationally representative sample could garner added benefits above and beyond lower uric acid levels. https://www.mdpi.com/2674-0621/3/1/6
11- Lines 276-279: Please use this reference PMID: 36881837
12- Section 6: I completely conquer with the recommendations the authors provided. However, I believe another recommendation should also include building strong gout competency management and clinical cultural competency among providers who work with diverse populations. I strongly recommend reviewing this article https://www.mdpi.com/2072-6643/14/17/3590
Author Response
Thank you for your consideration and favourable review of our review paper. We appreciate the Reviewers’ feedback and have addressed their queries to the fullest extent possible. Please find below our detailed point-by-point responses to each comment and the corresponding manuscript revisions.
Reviewer 2:
Thank you for the opportunity to review your paper. This is a well-crafted review article, addressing a major gap in literature. There is a paucity of research on health disparities of gout in the United States, and this article is one of the few published papers to stimulate this discussion. While genetics could play a significant role in developing gout in some populations, Blacks and African Americans are more likely to develop gout due to non-genetic factors. This paper does a great job of interrogating the role of social factors and disease mediators in developing gout. Nonetheless, I have some suggestions to strengthen the article.
1- Lines 50-53: I understand the preamble of discussing health disparities in Black and White. However, I believe bringing Māori and Pacific Islanders to this discussion is a distraction. I strongly suggest a general statement on health disparities in other populations and my preference is to remove it altogether.
Reply) We very much appreciate the reviewer’s comment; however, we are somewhat unsure why a well-documented example of differential disease burden of gout from New Zealand, with higher health care utilization and suboptimal pharmacologic management, is a distraction for our topic. To the best of our knowledge, those are probably the best characterized, most studied populations, also thanks to world-renowned gout researchers in New Zealand. Furthermore, similar to Black Americans, Māori and Pacific Islanders were affected by the Western lifestyle environmental hit, as suggested by landmark epidemiologic studies (e.g., Prior et al. Migration and gout: Tokelau Island migrant study BMJ 1987). Finally, the social and environmental reasons for disparity in gout care are likely shared with common themes among underserviced minorities in developed countries. As such, if allowed, we would like to keep this example in introducing our main topic about racial disparities in the US.
2- Table 1: Although the author diseases the publication in the paper, it was not mentioned in Table 1. Please include this publication PMID: 30618180 in your assessment of gout between Black and White
Reply) We did not include PMID: 30618180 because that paper’s NHANES data overlap entirely with the NHANES data in with Ref #23 (McCormick et al JAMA Net Open 2022) and the paper did not report OR or RR.
3- Lines 116-118: I suggest adding a citation. Given the nature of the topic and purpose of the paper, I may recommend this paper PMID: 36079846
Reply) We agree and have added the suggested citation.
4- Lines 124: Race is controversial. I suggest that the authors may reword this. For example, "race is less of a biological framework and more of a social construct."
Reply) We have made the suggested change:
“Furthermore, race is less of a biological framework and more of a social construct, and many individuals self-reporting Black race will have African and non-African genetic admixture.” Lines 124-126
5- Line 128: Please avoid the word must. I would suggest “Race should be considered….”
Reply) We have made the suggested change:
“As such, race should be considered as a social construct,…” Line 129
6- Lines 130-132. I suggest adding a citation. Given the nature of the topic and purpose of the paper, I may recommend this paper PMID: 36079846
Reply) We agree and have added the suggested citation.
7- Section 4.2: It's understandable that diet and alcohol can have a dose-response relationship with uric acid levels. Also, certain diet and lifestyle factors may have a urate-lowering effect PMID: 36079846. Therefore, an emphasis on food quality and certain dietary patterns should be well described. Another lifestyle factor could be smoking which may lower uric acid levels. Therefore, recognizing the totality of the effect should be addressed or at least mentioned.
Reply) We have added PMID: 36079846 to our reference in Section 4.2 (#30), which describes about the most studied dietary pattern of DASH diet, which is associated with lower serum urate and gout risk, as well as the barriers to adherence and higher financial burden among Black adults in the US, as contributing causes for the gout disease burden. Similarly, half of the section discussed the role of alcohol. Smoking is not replicated consistently in studies with unclear underlying biologic mechanisms (Fanning et al. Semin Arthritis Rheum 2018 Jun;47(6):825-842). As such, we are reluctant to acknowledge that risk factor in our review.
“Interventions aimed at promoting healthier eating patterns like the DASH or others described in the Dietary Guidelines for Americans,46 ensuring fresh produce and other appealing foods with documented benefits for serum urate levels and gout30 are available for purchase in local neighbourhoods, and reducing financial barriers to adherence, could reduce racial disparities in the prevalence of gout and hyperuricemia.” Lines 199-204
8- Lines: 206-208: I think the authors are correct, but they also need to recognize that occasional drinking is not the primary driver of developing hyperuricemia or gout, but rather chronic consumption of alcohol. Indeed, once alcohol dependence occurs, Blacks and Hispanics experience higher rates than Whites of recurrent or persistent alcohol dependence.
Reply) We have revised this sentence to convey that habitual alcohol consumption, rather than occasional drinking, is the primary driver of hyperuricemia and gout risk, and that the frequency of alcohol consumption is lower among Black Americans than White Americans.
“Habitual consumption of alcoholic beverages, principally beer and spirits, has also been associated with increased serum urate levels56 and risk of incident57,58 and recurrent59, 60 gout… However, data show the frequency of alcohol consumption is lower among Black Americans than White,23, 61 on average, indicating this risk factor does not contribute to the excess prevalence of gout and hyperuricemia among Black Americans at the population level.”
9- Section 4.4: Diuretic medications could greatly influence the risk of hyperuricemia and gout. However, with the excess cardiovascular disease burden among Black, such as heart failure and MI, the occurrence of other drugs to manage those conditions could worsen the urate-raising effect or could lower uric acid. Beta-blockers losartan are widely used in HF and MI patients of whom a majority is Black Therefore, it's the excess of co-morbidities that could drive the overall effect of medications used. Also, differential response to therapy could vary between populations rendering some groups to be good or poor responders to pharmacotherapy, including diuretics. https://www.mdpi.com/2673-9879/2/2/11#
Reply) We agree and have additionally cited the suggested paper (https://www.mdpi.com/2673-9879/2/2/11#). We feel the current Section 4.4 reflect the reviewer’s comments sufficiently.
“Furthermore, while again acknowledging the incongruity between self-reported race/ethnicity and genetic ancestry, genetic research to-date has focussed heavily on European ancestry populations, and there is a critical need for genetic studies of gout and its comorbidities and treatments, including gene-environmental interactions, and pharmacogenetic research to guide personalised gout medication choices and doses,95 with more diverse populations and multi-ethnic genotyping arrays.” Lines 353-358
10- Section 5.1: It's important to report the evidence that patients treated for their gout in a nationally representative sample could garner added benefits above and beyond lower uric acid levels. https://www.mdpi.com/2674-0621/3/1/6
Reply) We appreciate the Reviewer’s suggestion, but don’t feel this reference fits into this discussion, as it does not report on racial disparities in gout treatment. As well, that study reported only on cross-sectional associations (i.e., between ULT use and lower levels of hsCRP, LDL, and total cholesterol), while prospective studies are needed to provide better evidence on the potential benefits of ULT.
11- Lines 276-279: Please use this reference PMID: 36881837
Reply) Thank you for suggesting this new publication. As below, we have added this citation and revised the text:
“While gout has been associated with a higher risk of myocardial infarction, stroke, and premature death among White individuals,1, 86-90 almost no data on these critical outcomes exist specifically for Black adults. In a recent study of a predominantly Black urban population, gout was cross-sectionally associated with increased prevalence of cardiovascular disease and heart failure,91 although they did not compare Black and White gout patients, and a worse impact is suspected among Black gout patients given their higher background risk.”
12- Section 6: I completely conquer with the recommendations the authors provided. However, I believe another recommendation should also include building strong gout competency management and clinical cultural competency among providers who work with diverse populations. I strongly recommend reviewing this article https://www.mdpi.com/2072-6643/14/17/3590
Reply) We agree and now emphasise the need for greater cultural competency among gout care providers:
“Implementation strategies of improved gout care delivery models for this underserved group, including enhanced cultural competency among gout providers who work with diverse populations, would be vital to help close the care gap.30” Lines 349-352
