The PhenX Toolkit: Recommended Measurement Protocols for Social Determinants of Health Research.

Health disparities are driven by unequal conditions in the environments in which people are born, live, learn, work, play, worship, and age, commonly termed the Social Determinants of Health (SDoH). The availability of recommended measurement protocols for SDoH will enable investigators to consistently collect data for SDoH constructs. The PhenX (consensus measures for Phenotypes and eXposures) Toolkit is a web-based catalog of recommended measurement protocols for use in research studies with human participants. Using standard protocols from the PhenX Toolkit makes it easier to compare and combine studies, potentially increasing the impact of individual studies, and aids in comparability across literature. In 2018, the National Institute on Minority Health and Health Disparities provided support for an initial expert Working Group to identify and recommend established SDoH protocols for inclusion in the PhenX Toolkit. In 2022, a second expert Working Group was convened to build on the work of the first SDoH Working Group and address gaps in the SDoH Toolkit Collections. The SDoH Collections consist of a Core Collection and Individual and Structural Specialty Collections. This article describes a Basic Protocol for using the PhenX Toolkit to select and implement SDoH measurement protocols for use in research studies. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Basic Protocol: Using the PhenX Toolkit to select and implement SDoH protocols.

Mental health, chronic and infectious conditions among pregnant persons in US state prisons and local jails 2016-2017.

BACKGROUND: Pregnant individuals in incarcerated settings have unique healthcare needs. Rates of mental health, infectious diseases, and chronic disease are higher among nonpregnant incarcerated women compared with those who are not, but the prevalence of these conditions among pregnant people in custody has not been documented. OBJECTIVES: The objective of this study is to describe the prevalence of metabolic, infectious, and mental health conditions in pregnant people to identify the medical needs of high-risk pregnancies in US state prisons and local jails. STUDY DESIGN: This was a prospective epidemiologic surveillance of a convenience sample of state prisons (n = 20) and local jails (n = 3). METHODS: We used purposive and snowball sampling to recruit a national sample of prisons and jails of a range of sizes and geographies. Reporters submitted to our study database monthly data on selected pregnancy comorbidities for 6 months between 2016 and 2017. Screening, diagnosis, and tracking of these conditions are derived from each facility's medical record and health care delivery systems. RESULTS: Of the 445 newly admitted pregnant people in prisons and 243 in jails, the most prevalent conditions were mental health conditions and hepatitis C. Specifically, 34.1% (n = 152) in prison and 23.5% (n = 57) in jail had a substance use disorder, and 27.4% (n = 122) of those in prison and 17.7% (n = 43) in jail had a psychiatric diagnosis. Finally, 20.2% (n = 91) in prison and 6.6% (n = 16) in jail had hepatitis C. CONCLUSIONS: This study demonstrates that chronic medical and mental health conditions are prevalent among pregnant people in US prisons and jails. However, significant variability in the reported number of cases of these conditions from state to state and between facility types implies a lack of or inadequate screening practices. These data indicate the need for comprehensive screening and appropriate care for the complex needs of pregnant incarcerated people.

OBJECTIVES: The objective of this study is to describe the prevalence of these conditions in pregnant people to identify the medical needs of high-risk pregnancies in US state prisons and local jails. STUDY DESIGN: The study involved ongoing systematic data collection, analysis and interpretation of pregnancy data from a convenience sample of state prisons (n = 20) and local jails (n = 3). METHODS: We intentionally recruited a national sample of prisons and jails of a range of sizes and geographies that house pregnant individuals. Some study facilities were referred from others. Reporters submitted to our study database monthly data on selected pregnancy comorbidities for 6 months between 2016 and 2017. Screening, diagnosis, and tracking of these conditions derived from each facility's medical record and health care delivery systems. RESULTS: Of the 445 newly admitted pregnant people in prisons and 243 in jails, the most prevalent conditions were mental health conditions and hepatitis C. Specifically, 34.1% (n = 152) in prison and 23.5% (n = 57) in jail had a substance use disorder and 27.4% (n = 122) of those in prison and 17.7% (n = 43) in jail had a psychiatric diagnosis. Finally, 20.2% (n = 91) in prison and 6.6% (n = 16) in jail had hepatitisc. CONCLUSIONS: This study demonstrates that chronic medical and mental health conditions are prevalent among pregnant people in US prisons and jails. However, significant variability in the reported number of cases of these conditions from state to state and between facility types implies a lack of or inadequate screening practices. These data indicate the need for comprehensive screening and appropriate care for the complex needs of pregnant incarcerated people.

Health care conditions among pregnant persons in US state prisons and local jails 2016­2017Background: Pregnant individuals in incarcerated settings have unique health care needs. Rates of mental health, infectious diseases, and chronic disease are higher among nonpregnant incarcerated women compared with those who are not, but the prevalence of these conditions among pregnant people in custody has not been documented.

Conditions of Confinement in U.S. Carceral Facilities During COVID-19: Individuals Speak-Incarcerated During the COVID-19 Epidemic.

Objectives: We aimed to describe conditions of confinement among people incarcerated in the United States during the coronavirus disease 2019 (COVID-19) pandemic using a community-science data collection approach. Methods: We developed a web-based survey with community partners to collect information on confinement conditions (COVID-19 safety, basic needs, support). Formerly incarcerated adults released after March 1, 2020, or nonincarcerated adults in communication with an incarcerated person (proxy) were recruited through social media from July 25, 2020 to March 27, 2021. Descriptive statistics were estimated in aggregate and separately by proxy or formerly incarcerated status. Responses between proxy and formerly incarcerated respondents were compared using Chi-square or Fisher's exact tests based on α=0.05. Results: Of 378 responses, 94% were by proxy, and 76% reflected state prison conditions. Participants reported inability to physically distance (≥6 ft at all times; 92%), inadequate access to soap (89%), water (46%), toilet paper (49%), and showers (68%) for incarcerated people. Among those receiving prepandemic mental health care, 75% reported reduced care for incarcerated people. Responses were consistent between formerly incarcerated and proxy respondents, although responses by formerly incarcerated people were limited. Conclusions: Our findings suggest that a web-based community-science data collection approach through nonincarcerated community members is feasible; however, recruitment of recently released individuals may require additional resources. Our data obtained primarily through individuals in communication with an incarcerated person suggest COVID-19 safety and basic needs were not sufficiently addressed within some carceral settings in 2020-2021. The perspectives of incarcerated individuals should be leveraged in assessing crisis-response strategies.

Economic burden related to fistulas or strictures among commercially insured patients with Crohn's disease in the United States.

BACKGROUND: Crohn's disease (CD) is a chronic, progressive, immune-mediated gastrointestinal condition that can lead to fistulizing or stricturing complications. OBJECTIVE: To quantify the burden of illness related to fistulas and/or strictures in patients with CD. METHODS: Using the Optum Research Database from October 2015 to December 2019, patients with CD were classified according to 1 of 3 condition cohorts: CD with fistula (CD-F), CD with stricture (CD-S), or CD with fistula and stricture (CD-FS). Each cohort was matched to a nonfistula, nonstricture CD cohort. Postdiagnosis per patient per year (PPPY) costs and health care resource utilization were assessed, accounting for variable lengths of follow-up periods. Multivariable generalized linear models were used to estimate the adjusted mean costs in each cohort. RESULTS: The CD-F, CD-S, and CD-FS cohorts included 1,317; 4,650; and 894 patients, respectively. The mean age of patients within the CD-S and their comparator cohorts was higher than in the CD-F or CD-FS cohorts (59.9 vs 49.5 vs 49.6 years). At baseline, cardiovascular disease was the most common comorbidity across all condition and comparator cohorts. Condition cohorts had 2-4 times more inpatient visits, 5-8 times more surgical visits, and 2-3 times more endoscopies PPPY than comparator cohorts. Compared with their respective comparator cohort, patients in the 3 condition cohorts had higher medication, medical, and total health care costs. CONCLUSIONS: This study demonstrates a significant economic burden related to fistulas and/or strictures among patients with CD, highlighting the importance of prevention, early recognition, and appropriate management of CD-related complications. DISCLOSURES: Yanni Fan, Ling Zhang, Jennifer S Thompson, and Kimberly G Brodovicz are employees of Boehringer Ingelheim. Rhonda L Bohn, Monik C Jiménez, and Stephani Gray (Bohn Epidemiology, LLC) are paid consultants to Boehringer Ingelheim. Gil Y Melmed reports receiving grants from Pfizer; consulting fees from Boehringer Ingelheim, AbbVie, Arena, BMS, Celgene, Entasis, Ferring Lilly, Fresenius Kabi, Medtronic, Samsung Bioepis, Janssen, Takeda, Pfizer, Prometheus Labs, and TechLab. We conducted a retrospective study using administrative claims data from the Optum Research Database, a database of a commercially insured population in the United States. All patient data were anonymized and deidentified; therefore, informed consent was not necessary. Restrictions apply to the availability of these data because of a contract between Optum and Boehringer Ingelheim, and data are thus unavailable to the public. For enquiries on the dataset analyzed in this study, please contact Optum (https://www.optum.com).

Examining COVID-19 mortality rates by race and ethnicity among incarcerated people in 11 U.S. state prisons (March-October 2021).

Background: Populations who are incarcerated have experienced disproportionately high coronavirus disease 2019 (COVID-2019) mortality rates compared to the general population. However, mortality rates by race/ethnicity from federal, state, and local carceral settings are largely unavailable due to unregulated reporting; therefore, racial/ethnic inequities have yet to be examined. We aimed to estimate coronavirus disease 2019 (COVID-19) mortality rates among individuals incarcerated in U.S. state prisons by race and ethnicity (RE). Methods: Public records requests to state Departments of Corrections were used to identify deaths from COVID-19 among incarcerated adults occurring from March 1-October 1, 2020. We requested race, ethnicity, and age specific data on deaths and custody populations; sufficient data to calculate age-adjusted rates were obtained for 11 state systems. Race and ethnic specific unadjusted deaths rates per 100,000 persons were calculated overall and by state, based on March 1, 2020 custody populations. Rate ratios (RR) and 95% confidence intervals (95%CI) compared aggregated age-adjusted death rates by race and ethnicity, with White individuals as the reference group. Results: Of all COVID-related deaths in U.S. prisons through October 2020, 23.35% (272 of 1165) were captured in our analyses. The average age at COVID-19 death was 63 years (SD = 10 years) and was significantly lower among Black (60 years, SD = 11 years) compared to White adults (66 years, SD = 10 years; p < 0.001). In age-standardized analysis, COVID-19 death rates were significantly higher among Black (RR = 1.93, 95% CI: 1.25-2.99), Hispanic (RR = 1.81, 95% CI: 1.10-2.96) and those of Other racial and ethnic groups (RR = 2.60, 95% CI: 1.01-6.67) when compared to White individuals. Conclusions: Age-standardized death rates were higher among incarcerated Black, Hispanic and those of Other racial and ethnic groups compared to their White counterparts. Greater data transparency from all carceral systems is needed to better understand populations at disproportionate risk of COVID-19 morbidity and mortality.

Differences in Metabolomic Profiles Between Black and White Women and Risk of Coronary Heart Disease: an Observational Study of Women From Four US Cohorts.

BACKGROUND: Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk. METHODS: Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS. RESULTS: Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate <0.05); similar trends were observed in MESA. The RDMP, composed of 152 metabolites, was identified in the WHI-OS and showed significantly different distributions between Black and White women in the WHI-HT and MESA. Higher RDMP quartiles were associated with an increased risk of incident CHD (odds ratio=1.51 [0.97-2.37] for the highest quartile comparing to the lowest; Ptrend=0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS. CONCLUSIONS: Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.

Effects of Objective and Perceived Social Isolation on Cardiovascular and Brain Health: A Scientific Statement From the American Heart Association.

Background Social isolation, the relative absence of or infrequency of contact with different types of social relationships, and loneliness (perceived isolation) are associated with adverse health outcomes. Objective To review observational and intervention research that examines the impact of social isolation and loneliness on cardiovascular and brain health and discuss proposed mechanisms for observed associations. Methods We conducted a systematic scoping review of available research. We searched 4 databases, PubMed, PsycInfo, Cumulative Index of Nursing and Allied Health, and Scopus. Findings Evidence is most consistent for a direct association between social isolation, loneliness, and coronary heart disease and stroke mortality. However, data on the association between social isolation and loneliness with heart failure, dementia, and cognitive impairment are sparse and less robust. Few studies have empirically tested mediating pathways between social isolation, loneliness, and cardiovascular and brain health outcomes using appropriate methods for explanatory analyses. Notably, the effect estimates are small, and there may be unmeasured confounders of the associations. Research in groups that may be at higher risk or more vulnerable to the effects of social isolation is limited. We did not find any intervention studies that sought to reduce the adverse impact of social isolation or loneliness on cardiovascular or brain health outcomes. Conclusions Social isolation and loneliness are common and appear to be independent risk factors for worse cardiovascular and brain health; however, consistency of the associations varies by outcome. There is a need to develop, implement, and test interventions to improve cardiovascular and brain health for individuals who are socially isolated or lonely.

Association of Individual and Familial History of Correctional Control With Health Outcomes of Patients in a Primary Care Center.

Importance: Research has shown that experiences of incarceration, probation, and parole are associated with worse health outcomes for incarcerated individuals and their families. Objectives: To quantify the proportion of patients in an urban primary care clinic with an individual or family history of incarceration, probation, and/or parole and to evaluate how correctional control is associated with subjective and objective health outcomes. Design, Setting, and Participants: This cross-sectional, mixed-methods study used patient surveys and retrospective medical record review to assess the experience of correctional control among 200 English-speaking adult patients presenting for care at the Rhode Island Hospital Center for Primary Care between July 9, 2019, and January 10, 2020. Main Outcomes and Measures: Patient surveys included closed and open-ended questions pertaining to personal or familial experiences of incarceration, probation, and parole, as well as health outcomes associated with these experiences. Medical record review abstracted key health indicators and health care use data. Results: In this cross-sectional study of 200 adult patients (1 participant was removed from the full analytic sample owing to missing ethnicity data; 113 of 199 men [56.8%]; mean [SD] age, 51.2 [14.0] years) presenting for primary care, 78 of 199 (39.2%) had a history of incarceration, 32 of 199 (16.1%) were on probation or parole at the time of the study, and 92 of 199 (46.2%) reported having a family member with a history of incarceration. Of the 199 patients, 62 (31.2%) identified as non-Hispanic Black, 93 (46.7%) identified as non-Hispanic White, and 44 (22.1%) identified as belonging to another race (American Indian and Alaska Native, Asian, Native Hawaiian and Other Pacific Islander, or other nonspecified). Compared with participants without a history of correctional control, those with a personal history of incarceration were at greater odds of having an emergency department visit that did not result in hospitalization in models adjusted for age, sex, and race and ethnicity (odds ratio, 2.87; 95% CI, 1.47-5.75). Conclusions and Relevance: This cross-sectional study suggests that primary care clinicians should screen for correctional control as a prevalent social determinant of health.

Pregnancy Prevalence and Outcomes in 3 United States Juvenile Residential Systems.

STUDY OBJECTIVE: To describe the number of admissions of pregnant adolescents to US juvenile residential systems (JRS) and the outcomes of pregnancies that ended while in custody. DESIGN: Prospective study. SETTING: Three nonrandomly selected JRS in 3 US states. PARTICIPANTS: Designated reporter at each JRS reporting aggregate data on various pregnant admissions, outcomes, and systems' policies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Monthly number of pregnant people admitted, pregnant people at the end of the month, births, preterm births, cesarean deliveries, miscarriages, induced abortions, ectopic pregnancies, maternal and newborn deaths, and administrative policies. RESULTS: There were 71 admissions of pregnant adolescents reported over 12 months from participating JRS. At the time of the census, 6 of the 183 female adolescents (3.3%) were pregnant. Eight pregnancies ended while in custody. Of these, 1 pregnancy was a live full-term birth, 4 were miscarriages, and 3 were induced abortions. There were no newborn deaths or maternal deaths. Administrative policies and services varied among the JRS. For example, all JRS had a prenatal care provider on-site, whereas 2 JRS helped cover the costs of abortions. CONCLUSION: To our knowledge, this study is the first to report the estimates of pregnancy and pregnancy outcomes among justice-involved youth in JRS. Our findings indicate that there are pregnant adolescents in JRS and most return to their communities while pregnant, highlighting the importance of continuity of care. More work is needed to understand the complexities of health care needs of justice-involved pregnant youth during and after their incarceration.

Ten-Year Differences in Women's Awareness Related to Coronary Heart Disease: Results of the 2019 American Heart Association National Survey: A Special Report From the American Heart Association.

BACKGROUND: High awareness that cardiovascular disease is the leading cause of death (LCOD) among women is critical to prevention. This study evaluated longitudinal trends in this awareness among women. METHODS AND RESULTS: Online surveys of US women (≥25 years of age) were conducted in January 2009 and January 2019. Data were weighted to the US population distribution of sociodemographic characteristics. Multivariable logistic regression was used to evaluate knowledge of the LCOD. In 2009, awareness of heart disease as the LCOD was 65%, decreasing to 44% in 2019. In 2019, awareness was greater with older age and increasing education and lower among non-White women and women with hypertension. The 10-year awareness decline was observed in all races/ethnicities and ages except women ≥65 years of age. The greatest declines were among Hispanic women (odds ratio of awareness comparing 2019 to 2009, 0.14 [95% CI, 0.07-0.28]), non-Hispanic Black women (odds ratio, 0.31 [95% CI, 0.19-0.49]), and 25- to 34-year-olds (odds ratio, 0.19 [95% CI, 0.10-0.34]). In 2019, women were more likely than in 2009 to incorrectly identify breast cancer as the LCOD (odds ratio, 2.59 [95% CI, 1.86-3.67]), an association that was greater in younger women. Awareness of heart attack symptoms also declined. CONCLUSIONS: Awareness that heart disease is the LCOD among women declined from 2009 to 2019, particularly among Hispanic and non-Hispanic Black women and in younger women (in whom primordial/primary prevention may be most effective). An urgent redoubling of efforts by organizations interested in women's health is required to reverse these trends.

Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women.

Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Racial Variation in Stroke Risk Among Women by Stroke Risk Factors.

Background and Purpose- In the United States, black Americans exhibit a greater risk of stroke and burden of stroke risk factors than whites; however, it is unclear whether these stroke risk factors influence stroke risk differently across racial groups. Methods- In total, 126 018 participants of the Women's Health Initiative (11 389 black and 114 629 white women), free of stroke and coronary heart disease at baseline (1994-1998), were followed through 2010. Participants completed baseline clinical exams with standardized measurements of blood pressure and anthropometrics, medication inventory and self-reported questionnaires on sociodemographics, behaviors/lifestyle, and medical history. Incident total, ischemic and hemorrhagic strokes were updated annually through questionnaires with medical record confirmation. Rate differences (per 100 000 person-years) and hazard ratios (HR) based on multivariable Cox models and were estimated. Results- Over a median of 13 years, 4344 stroke events were observed. Absolute incidence rates were higher in black than white women in each age group. In age-adjusted analyses, the risk of stroke was significantly higher among black compared with white women (HR=1.47, 95% CI, 1.33-1.63); adjustment for stroke risk factors, which may be on the causal pathway, attenuated the estimate. Racial disparities were greatest among women 50 to <60 years (HR=3.48; 95% CI, 2.31-5.26; rate difference =99) and diminished with increasing age (60 to <70 HR=1.80; 95% CI, 1.50-2.16; rate difference =107; ≥70 years: HR=1.26; 95% CI, 1.10-1.43; rate difference =87; Pinteraction <0.001). Black women 50 to <60 years remained at significantly higher risk than white women after adjustment for stroke risk factors (HR=1.76; 95% CI, 1.09-2.83). Conclusions- There was a moderately greater risk of total stroke among black compared with white women; however, racial disparities were greatest among women aged 50 to <60 years. Interventions targeted at younger black women may provide the greatest benefit in reducing disparities.

Cardiovascular Risk Factors and Dehydroepiandrosterone Sulfate Among Latinos in the Boston Puerto Rican Health Study.

Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (µg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (ß = -12.4; 95% CI: -15.2, -9.7; per 5 years), being female (vs. male) (ß = -46; 95% CI: -55.3, -36.6), and plasma triglyceride concentration (ß = -0.2; 95% CI: -0.3, -0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (ß = 1.8; 95% CI: 0.6, 3 and ß = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (P interaction < 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology.

Sex differences in stroke: Challenges and opportunities.

Biologic sex influences many variables that are important to brain health in general, and to stroke or cerebral ischemia in particular, such as general health status, cerebrovascular anatomy and function, unique risk factors such as pregnancy and preeclampsia, symptomatology, and therapeutic response. A more complete understanding of the scale and depth of sexual dimorphism in the brain and the role of more general sex-based factors is crucial to reducing the burden of stroke in women and men. This focused review highlights recent findings in stroke, including sex differences in epidemiology, risk factor reduction, comparative use of stroke therapeutics in both sexes, the importance of frailty in women, and the biologic basis for sex differences in stroke. Such findings show tremendous promise for the future of personalized medicine in stroke prevention and treatment.

Association between sex hormones and ambulatory blood pressure.

INTRODUCTION: Higher levels of total testosterone and lower levels of sex hormone-binding globulin (SHBG) have been associated with increased blood pressure (BP) in women with an inverse association between total testosterone and BP among men. Fewer studies have examined associations with 24-h ambulatory blood pressure (ABP), blunted nocturnal BP decline or the role of dehydroepiandrosterone sulfate (DHEAS), a precursor to androgens. METHODS: Baseline blood samples were assayed for 229 normotensive men (≥50 years) and women (≥55 years) participating in the VITamin D and OmegA-3 TriaL. Standardized seated BP (SBP and DBP) and 24-h ABP were measured by trained technicians. Self-reported cardiovascular risk factors and sociodemographic variables were reported on baseline questionnaires. Sex stratified linear regression models adjusted for age, race/ethnicity, BMI, smoking and alcohol estimated the association between each sex hormone and measures of BP and 24-h ABP. Logistic regression used to estimate associations with blunted nocturnal decline (>10% reduction in SBP or DBP during sleeping hours). RESULTS: Total testosterone and SHBG demonstrated significant inverse correlations with SBP whereas DHEAS was not significantly associated with BP. Among men, in multivariable analyses, each 10% increase in DHEAS was associated with a 0.41 mmHg higher seated DBP (ß = 4.29, 95% CI 0.84-7.73) and each 10% increase in total testosterone and SHBG was associated with a 0.54 mmHg (ß = -5.65, 95% CI -10.45 to -0.84) and 0.60 mmHg (ß = -6.30, 95% CI -11.38 to -1.21) decrease in seated DBP, respectively. No significant associations were observed among women. CONCLUSION: Among men only, we observed statistically significant inverse cross-sectional associations between total testosterone and SHBG with seated DBP, and a significant positive association with DHEAS levels.

Plasma Retinol-Binding Protein 4 Levels and the Risk of Ischemic Stroke among Women.

BACKGROUND: Plasma retinol-binding protein 4 (RBP4) levels have been associated with cardiovascular risk factors and risk of coronary heart disease, but little is known about the association between RBP4 and the risk of ischemic stroke. We hypothesized that elevated RBP4 levels would be associated with an increased risk of ischemic stroke among women. METHODS: We performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. We measured prediagnostic RBP4 levels in 471 ischemic stroke cases who were confirmed by medical record review and in 471 controls who were matched 1:1 to the cases on age, race, blood collection date, menopausal status, postmenopausal hormone use, and smoking status. We analyzed the association between RBP4 levels and ischemic stroke using multivariable conditional logistic regression conditional on the matching factors and adjusted for physical activity, body mass index, aspirin use, alcohol consumption, diet, history of diabetes, high cholesterol, high blood pressure, or heart disease, and cholesterol and hemoglobin A1C levels. RESULTS: Median levels of RBP4 were similar in cases (31.1 µg/mL) and controls (31.0 µg/mL; P value from the Wilcoxon rank-sum test = .82). Quartiles of RBP4 were not associated with an increased risk of ischemic stroke (highest quartile compared to lowest quartile: multivariate-adjusted odds ratio, .75; 95% confidence interval, .48, 1.17). We also did not observe associations between RBP4 and ischemic stroke of thrombotic or embolic origin. CONCLUSIONS: Elevated levels of RBP4 were not associated with an increased risk of ischemic stroke.

Prospective association between ß2-microglobulin levels and ischemic stroke risk among women.

OBJECTIVE: To determine whether elevated ß2-microglobulin (B2M) levels were associated with an increased risk of incident ischemic stroke events among women. METHODS: We performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. We measured B2M levels in 473 ischemic strokes cases confirmed by medical record review and in 473 controls matched 1:1 to the cases on age, race, date of blood collection, menopausal status, postmenopausal hormone use, and smoking status. We analyzed the association between B2M and ischemic stroke using multivariable conditional logistic regression to adjust for traditional stroke risk factors. RESULTS: Median levels of B2M were higher among cases (1.86 mg/L) than controls (1.80 mg/L, p = 0.009, Wilcoxon rank-sum test). Women in the highest B2M quartile had a multivariable-adjusted increased risk of ischemic stroke compared to those in the lowest quartile (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.02-2.39). Results were similar when restricted to those without evidence of chronic kidney disease (estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2) (OR 1.49, 95% CI 1.08-2.06). In an exploratory analysis, the association between B2M and thrombotic stroke was similar to the overall ischemic stroke results, but no association was observed for embolic stroke risk. CONCLUSION: High levels of B2M were associated with an increased risk of ischemic stroke among women.