Evaluating Sex Differences in the Effect of Increased Systolic Blood Pressure on the Risk of Cardiovascular Disease in Asian Populations: A Systematic Review and Meta-Analysis

Background: Cardiovascular disease (CVD) is a serious health concern worldwide, and half of the cases of CVD occur in Asia. Because hypertension or high blood pressure has been confirmed to be an important risk factor for CVD, controlling blood pressure is helpful for CVD prevention. Although many studies have shown a sex difference in the impact of blood pressure on the risk of CVD, the risk threshold of blood pressure remained the same for both sexes in the latest global guidelines. Objective: The study aimed to evaluate sex differences in the effect of increased blood pressure on the risk of CVD in Asian populations. Methods: In this study, we performed a systematic review via PubMed, Embase, and MEDLINE to select studies conducted with Asian populations published before 30 June 2021. Results: Six female and eleven male effect sizes for CVD risk from six articles were identified. The unadjusted pooled effect size for CVD risk per 10-mmHg increase in systolic blood pressure was estimated to be 1.20 for females (95% confidence interval: [1.10, 1.32]) and 1.19 for males (95% confidence interval: [1.11, 1.27]). Furthermore, using meta-regression to adjust for the significant effect of smoking, we showed that the impact of a 10-mmHg systolic blood pressure increase on CVD risk among females was 1.232 times that among males, corresponding to a significant sex difference (95% confidence interval: [1.065, 1.426]; P = 0.02). In summary, the effect of an increased systolic blood pressure on the risk of CVD in females was significantly higher than that in males in the Asian population.


INTRODUCTION
Describe the rationale for the review in the context of what is already known. 2

Objectives 4
Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

Protocol and registration 5
Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
9 Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

2-3
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.
2 Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. Table 3 Study selection 9

3, Supplementary
State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).
3 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. 3

Data items 11
List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. 3

12
Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

3-4
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

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Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

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Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. Figure 1 Study characteristics 18

4,
For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.
4, Table 1, Supplementary Table 5 Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

Summary of evidence 24
Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

7-8
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

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Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research. 9

Funding 27
Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.  Table 5 13 List of citations located and those excluded, including justification 2-3, Figure 1  Description of statistical methods (e.g., complete description of fixed or random effects models, justification of whether the chosen models account for predictors of study results, doseresponse models, or cumulative meta-analysis) in sufficient detail to be replicated

3-4 24
Provision of appropriate tables and graphics  Table giving descriptive information for each study included  Table 1, Supplementary Table 5 27 Results of sensitivity testing (e.g., subgroup analysis) 5-7, Figure Table 4 Reporting of conclusions should include