Research Article: Assessing Sex Differences in the Risk of Cardiovascular Disease and Mortality per Increment in Systolic Blood Pressure: A Systematic Review and Meta-Analysis of Follow-Up Studies in the United States

Date Published: January 25, 2017

Publisher: Public Library of Science

Author(s): Yu-Chung Wei, Nysia I. George, Ching-Wei Chang, Karen A. Hicks, C. Mary Schooling.


In the United States (US), cardiovascular (CV) disease accounts for nearly 20% of national health care expenses. Since costs are expected to increase with the aging population, informative research is necessary to address the growing burden of CV disease and sex-related differences in diagnosis, treatment, and outcomes. Hypertension is a major risk factor for CV disease and mortality. To evaluate whether there are sex-related differences in the effect of systolic blood pressure (SBP) on the risk of CV disease and mortality, we performed a systematic review and meta-analysis. We conducted a comprehensive search using PubMed and Google Scholar to identify US-based studies published prior to 31 December, 2015. We identified eight publications for CV disease risk, which provided 9 female and 8 male effect size (ES) observations. We also identified twelve publications for CV mortality, which provided 10 female and 18 male ES estimates. Our meta-analysis estimated that the pooled ES for increased risk of CV disease per 10 mmHg increment in SBP was 25% for women (95% Confidence Interval (CI): 1.18, 1.32) and 15% for men (95% CI: 1.11, 1.19). The pooled increase in CV mortality per 10 mm Hg SBP increment was similar for both women and men (Women: 1.16; 95% CI: 1.10, 1.23; Men: 1.17; 95% CI: 1.12, 1.22). After adjusting for age and baseline SBP, the results demonstrated that the risk of CV disease per 10 mm Hg SBP increment for women was 1.1-fold higher than men (P<0.01; 95% CI: 1.04, 1.17). Heterogeneity was moderate but significant. There was no significant sex difference in CV mortality.

Partial Text

Cardiovascular (CV) disease is a worldwide health problem. However, compared to other high-income countries, the United States (US) spends significantly more on healthcare yet ranks lower in many outcome measures of health, including average life expectancy [1]. In the US, CV disease is the leading cause of death [2], and treatment of CV disease accounts for approximately 1/6th of the healthcare budget [3]. Approximately one in every five CV deaths is attributed to hypertension [4, 5]. Projections show that by 2030, the prevalence of CV disease and hypertension in the US will be 43.9% and 41.4%, respectively [4]. Compared to other populations, the US population has unique healthcare challenges given the epidemic of overweight and obesity, which predisposes adults and children to hypertension and other cardiovascular risk factors [6]. In addition, data from self-report surveys indicated that the age-adjusted prevalence of heart disease and stroke for both men and women was highest in the US in comparison to 12 European countries [7]. Thus, understanding the relationship between hypertension and the risk of CV disease and mortality in the US population is critical in directing efforts to improve public health.

Eighteen publications met the selection and inclusion criteria. Two of the 18 publications discussed the risk of both CV disease and CV mortality. The resulting data for the risk of CV disease included 9 female and 8 male ES observations (totaling 95,772 female and 30,555 male subjects, respectively) [11, 14, 32, 40–44]. Likewise, the CV mortality data consisted of 10 female and 18 male ES estimates (totaling 65,806 female and 92,515 male subjects, respectively) [13, 14, 43, 45–53]. A flowchart of the data search and selection process is provided in Fig 1. A summary of the studies for the risk of CV disease is presented in Table 1 and S3 Table; the studies for CV mortality are presented in Table 2 and S4 Table.

The association between BP and the risk of CV disease and CV mortality has been demonstrated previously, but the influence of moderators is still unclear. In particular, research regarding the significance of sex in evaluating the risk of CV disease and CV mortality has been inconclusive. Some studies indicated that the risk of CV disease was higher in women than men for the same unit change in SBP or within the same BP category [10, 11] while other studies reported no significant findings [32, 56]. Inconsistent results were also observed in the analysis of CV mortality [13, 48, 55]. Furthermore, a meta-analysis of individual data from 9,357 European, Asian, and South American subjects from 11 populations demonstrated that while the hazard ratios associated with nighttime SBP were significantly higher in women than in men, the hazard ratios associated with conventional BP measurements showed no sex differences [57]. Similar conclusions were reached in a separate meta-analysis. Roush et al. [58] conducted a meta-analysis of 10 cohorts consisting of patients from Europe, Brazil, and Japan to assess the interaction between sex and SBP. They concluded that a 1 SD (and generally, a 10 mm Hg) increase in ambulatory SBP (but not clinic SBP) demonstrated significantly higher risks for cardiovascular events in women than in men.




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