Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Muscle density is inversely associated with all-cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women. METHODS AND RESULTS: Adult participants (N=1869) in the Multi-Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2-L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm2. Sex-stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex-specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow-up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (P trend=0.15). However, there was an inverse association between density and CHD (P trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (P trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile; P trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile; P trend<0.001), and null for stroke (P trend=0.67). Associations for women were mostly null. CONCLUSIONS: For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.

Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: The Multi-Ethnic Study of Atherosclerosis.

Information on the associations of testosterone levels with abdominal muscle volume and quality in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. After adjustment, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.79, 0.1-3.4, & 1.79, 0.4-3.2, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, & -0.34, -0.6 - -0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.

Integrating community voices in the research continuum: Perspectives on a consultation service.

The Community Research Advisory Council (C-RAC) of the Johns Hopkins Institute for Clinical and Translational Research was established in 2009 to provide community-engaged research consultation services. In 2016-2017, C-RAC members and researchers were surveyed on their consultation experiences. Survey results and a 2019 stakeholder meeting proceeding helped redesign the consultation services. Transitioning to virtual consultations during COVID-19, the redesigning involved increasing visibility, providing consultation materials in advance, expanding member training, and effective communications. An increase in consultations from 28 (2009-2017) to 114 (2020-2022) was observed. Implementing stakeholder-researcher inputs is critical to holistic and sustained community-engaged research.

Community-academic partnerships to embrace and ensure diversity, equity, and inclusion in translational science: Evidence of successful community engagement.

Community-Research Advisory Councils (C-RAC) provide a unique mechanism for building sustainable community-academic partnership, fostering bidirectional understanding of complex research issues, disseminating timely research findings, and thereby improving public trust in science. Created in 2009, the Johns Hopkins C-RAC has a mission to achieve diversity, equity, and inclusion (DEI) of stakeholders across the entire research continuum. It has nurtured over a decade of partnership among community and academic stakeholders toward addressing health disparity, health equity, structural racism, and discrimination. Evidence of successful strategies to ensure DEI in partnership and lessons learned are illustrated in this special communication.

Reproductive Experiences and Cardiovascular Disease Care in Pregnancy-Capable and Postmenopausal Individuals: Insights From the American Heart Association Research Goes Red Registry.

To evaluate preconception health and adverse pregnancy outcome (APO) awareness in a large population-based registry. We examined data from the Fertility and Pregnancy Survey of the American Heart Association Research Goes Red Registry to questions regarding prenatal health care experiences, postpartum health, and awareness of the association of APOs with cardiovascular disease (CVD) risk. Among postmenopausal individuals, 37% were unaware that APOs were associated with long-term CVD risk, significantly varying by race-ethnicity. Fifty-nine percent of participants were not educated regarding this association by their providers, and 37% reported providers not assessing pregnancy history during current visits, significantly varying by race-ethnicity, income, and access to care. Only 37.1% of respondents were aware that CVD was the leading cause of maternal mortality. There is an urgent, ongoing need for more education on APOs and CVD risk, to improve the health-care experiences and postpartum health outcomes of pregnant individuals.

Cardiovascular Interactions of Renin-Angiotensin-Aldosterone System Assessed by Cardiac Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The effects of the renin-angiotensin-aldosterone system in cardiovascular system have been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity (PRA) and cardiovascular structure and function. METHODS: We studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and PRA blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded. RESULTS: The aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m2 higher left ventricle (LV) mass index (P = 0.04) and 0.11 ml/m2 higher left atrium (LA) minimal volume index (P < 0.01). Additionally, higher log-transformed aldosterone was associated with lower LA maximum strain and LA emptying fraction (P < 0.01). Aldosterone levels were not significantly associated with aortic measures. Log-transformed PRA was associated with lower LV end diastolic volume index (ß standardized = 0.08, P = 0.05). PRA levels were not significantly associated with LA and aortic structural or functional differences. CONCLUSIONS: Higher levels of aldosterone and PRA are associated with concentric LV remodeling changes. Moreover, aldosterone was related to deleterious LA remodeling changes.

Blood Levels of Angiotensinogen and Hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Angiotensinogen is the proximal precursor of the angiotensin peptide hormones of the renin-angiotensin-aldosterone system (RAAS). Clinical trials are ongoing targeting angiotensinogen for the treatment of hypertension and heart failure. The epidemiology of angiotensinogen is not well defined, particularly its relationship to ethnicity, sex, and blood pressure (BP)/hypertension. OBJECTIVES: The authors sought to determine the relationship of circulating angiotensinogen levels to ethnicity, sex, BP, incident hypertension, and prevalent hypertension in a modern sex-balanced ethnically diverse cohort. METHODS: Plasma angiotensinogen levels were measured in 5,786 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Linear, logistic, and Cox proportional hazards models were utilized to examine the associations of angiotensinogen with BP, prevalent hypertension, and incident hypertension, respectively. RESULTS: Angiotensinogen levels were significantly higher in females than males and differed across self-reported ethnicities with the ordering (from highest to lowest): White, Black, Hispanic, and Chinese adults. Higher levels were associated with higher BP and odds of prevalent hypertension, after adjusting for other risk factors. Equivalent relative differences in angiotensinogen were associated with greater differences in BP in males vs females. In males not taking RAAS-blocking medications, a standard deviation increment in log-angiotensinogen was associated with 2.61 mm Hg higher systolic BP (95% CI: 1.49-3.80), while in females the same increment in angiotensinogen was associated with 0.97 mm Hg higher systolic BP (95% CI: 0.30-1.65). CONCLUSIONS: Significant differences in angiotensinogen levels are present between sexes and ethnicities. A positive association is present between levels and prevalent hypertension and BP, which differs between sexes.

Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Introduction-Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods-Oxidative stress was measured in 475 women and 266 men, aged 48-55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results-Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions-Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.

Reproductive Experiences and Cardiovascular Disease Care in Pregnancy Capable and Post-Menopausal Individuals: Insights from the American Heart Association Research Goes Red Registry.

Background: Information on reproductive experiences and awareness of adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD) risk among pregnancy-capable and post-menopausal individuals has not been well described. We sought to evaluate preconception health and APO awareness in a large population-based registry. Methods: Data from the Fertility and Pregnancy Survey of the American Heart Association Research Goes Red Registry (AHA-RGR) were used. Responses to questions pertaining to prenatal health care experiences, postpartum health, and awareness of the association of APOs with CVD risk were used. We summarized responses using proportions for the overall sample and by stratifications, and we tested differences using the Chi-squared test. Results: Of 4,651individuals in the AHA-RGR registry, 3,176 were of reproductive age, and 1,475 were postmenopausal. Among postmenopausal individuals, 37% were unaware that APOs were associated with long-term CVD risk. This varied by different racial/ethnic groups (non-Hispanic White: 38%, non-Hispanic Black: 29%, Asian: 18%, Hispanic: 41%, Other: 46%; P = 0.03). Fifty-nine percent of the participants were not educated regarding the association of APOs with long-term CVD risk by their providers. Thirty percent of the participants reported that their providers did not assess pregnancy history during current visits; this varied by race-ethnicity ( P = 0.02), income ( P = 0.01), and access to care ( P = 0.02). Only 37.1% of the respondents were aware that CVD was the leading cause of maternal mortality. Conclusions: Considerable knowledge gaps exist in the association of APOs with CVD risk, with disparities by race/ethnicity, and most patients are not educated on this association by their health care professionals. There is an urgent and ongoing need for more education on APOs and CVD risk, to improve the health-care experiences and postpartum health outcomes of pregnant individuals.

Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results: In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions: Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

The association of multidimensional sleep health with adiposity in heart failure with preserved ejection fraction.

BACKGROUND: There are bi-directional relationships between sleep disturbances and obesity, both of which are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). However, little is known about the sleep-obesity association in HFpEF. OBJECTIVES: To determine associations of multidimensional sleep health, night movement, sleep fragmentation, and sleep-disordered breathing (SDB) risk with overall and regional adiposity in HFpEF patients. METHODS: Men and women with HFpEF (n = 49) were assessed via 14-day actigraphy, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale to derive multidimensional sleep health. SDB risk was assessed via Berlin Questionnaire. Body composition was measured using anthropometry; MRI quantification of epicardial, abdominal, liver, and thigh adipose tissue was performed in a subsample (n = 22). Spearman correlation (rs) and linear regression analyses (ß coefficient) were used to estimate bivariate and age-adjusted associations. RESULTS: Multidimensional sleep health was inversely associated with BMI (rs = -0.50, p < .001; unadjusted: ß = -4.00, 95%CI: -5.87, -2.13; age-adjusted: ß = -2.48, 95%CI: -4.65, -0.30), thigh subcutaneous adipose tissue (rs = -0.50, p = .018; unadjusted: ß = -36.95, 95%CI: -67.31, -6.59), and thigh intermuscular fat (age-adjusted: ß = -0.24, 95%CI: -0.48, -0.01). Night movement and sleep fragmentation were associated with greater intermuscular thigh and lower liver fat. High SDB risk was associated with a higher visceral-to-subcutaneous ratio of abdominal adiposity and lower thigh adiposity. CONCLUSIONS: Adverse multidimensional sleep health is associated with higher adiposity measures in HFpEF patients. Further studies are needed to determine whether intervening on sleep could ameliorate excess adiposity or whether weight loss could improve sleep quality in HFpEF.

Digital and virtual strategies to advance community stakeholder engagement in research during COVID-19 pandemic.

Despite the adversity presented by COVID-19 pandemic, it also pushed for experimenting with innovative strategies for community engagement. The Community Research Advisory Council (C-RAC) at Johns Hopkins University (JHU), is an initiative to promote community engagement in research. COVID-19 rendered it impossible for C-RAC to conduct its meetings all of which have historically been in person. We describe the experience of advancing the work of the C-RAC during COVID-19 using digital and virtual strategies. Since March 2020, C-RAC transitioned from in person to virtual meetings. The needs assessment was conducted among C-RAC members, and individualized solutions provided for a successful virtual engagement. The usual working schedule was altered to respond to COVID-19 and promote community engaged research. Attendance to C-RAC meetings before and after the transition to virtual operation increased from 69% to 76% among C-RAC members from the community. In addition, the C-RAC launched new initiatives and in eighteen months since January 2020, it conducted 50 highly rated research reviews for 20 research teams. The experience of the C-RAC demonstrates that when community needs are assessed and addressed, and technical support is provided, digital strategies can lead to greater community collaborations.

Parity History and Later Life Sex Hormone Levels in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Multiparity is a risk factor for cardiovascular disease (CVD). A more androgenic sex hormone profile, with a higher testosterone (T)/estradiol (E2) ratio, is associated with worse CVD outcomes in women and might be one mechanism linking multiparity to increased CVD risk. We investigated the relationship between parity and sex hormones at mid-to-older age. METHODS: We performed a cross-sectional analysis of 2979 women with data on parity and endogenous sex hormone levels from the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort. Parity and gravidity (our exposures) were categorized as 0 (reference), 1-2, 3-4, or ≥ 5. Our outcome measures were T, E2, sex hormone binding globulin, dehydroepiandrosterone, and T/E2 ratio. Progressively adjusted linear regression was used to evaluate the association of parity/gravidity with sex hormones. RESULTS: In multivariable adjusted models, there were no significant associations of parity with E2, dehydroepiandrosterone, and sex hormone binding globulin. Compared with nulliparity, after adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher T, but this was not significant for grand multiparity (≥ 5 live births). However, grand multigravidity (≥ 5 pregnancies) was associated with 10% (95% confidence interval [CI], 1%-20%) higher T and 14% (95% CI, 1%-29%) higher T/E2, compared with null gravidity. Grand multiparity was associated with an 18% (95% CI, 4%-34%) higher T/E2 ratio compared with nulliparity, after adjustment for CVD risk factors. CONCLUSIONS: In this multiethnic cohort, women with grand multigravidity and grand multiparity had higher T/E2 levels, reflecting a more androgenic sex hormone profile. Longitudinal studies on sex hormones' influence on the relationship between multiparity and CVD are warranted.

Oxidative Stress and Menopausal Status: The Coronary Artery Risk Development in Young Adults Cohort Study.

Background: Low endogenous estrogen concentrations after menopause may contribute to higher oxidative stress and greater cardiovascular disease (CVD) risk. However, differences in oxidative stress between similarly aged premenopausal and postmenopausal women are not well-characterized on a population level. We hypothesized that urinary isoprostane concentrations, a standard measure of systemic oxidative stress, are higher in women who have undergone menopause compared to premenopausal women. Methods and Results: We examined differences in urinary 8-isoprostane (iPF2α-III) and 2,3-dinor-8-isoprostane (iPF2α-III-M) indexed to urinary creatinine between 279 postmenopausal and 196 premenopausal women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, using linear regression with progressive adjustment for sociodemographic factors and traditional CVD risk factors. Unadjusted iPF2α-III-M concentrations were higher among postmenopausal compared to premenopausal women (Median [25th, 75th percentile]: 1762 [1178, 2974] vs. 1535 [1067, 2462] ng/g creatinine; p = 0.01). Menopause was associated with 25.5% higher iPF2α-III-M (95% confidence interval [6.5-47.9]) adjusted for age, race, college education, and field center. Further adjustments for tobacco use (21.2% [2.9-42.6]) and then CVD risk factors (18.8% [0.1-39.6]) led to additional partial attenuation. Menopause was associated with higher iPF2α-III in Black but not White women. Conclusions: We conclude that postmenopausal women had higher oxidative stress, which may contribute to greater CVD risk. ClinicalTrials.gov Identifier: NCT00005130.

Coronary artery calcium and atherosclerotic cardiovascular disease risk in women with early menopause: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background and Aims: We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM). Methods: To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at <45 years of age. Results: The cohort was 64.1 ± 9.1 years old and 28.0% experienced EM. There were 291 ASCVD events over 12.5 ± 3.6 year follow-up with a higher event rate among those with EM compared to those without EM of 13.6 vs. 9.0 per 1,000 year follow-up (p < 0.01). Women with EM had a slightly lower prevalence of CAC = 0 (55.1%) than women without EM (59.7%) (p = 0.04) despite no difference in mean age. Among women with CAC = 0, the cumulative incidence of ASCVD at 10 years was low-to-borderline for women with (5.4%) and without EM (3.2%) (p = 0.06). However, women with EM had a significantly higher 15-year risk with an adjusted HR of 1.96 (95% CI: 1.26-3.04). In multivariable Cox models, women with CAC ≥ 1 had progressively increased ASCVD risk that did not significantly differ by EM status. Conclusion: In MESA, >50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM. Condensed abstract: This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.

Polycystic ovary syndrome: a "risk-enhancing" factor for cardiovascular disease.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is hallmarked by hyperandrogenism, oligo-ovulation, and polycystic ovarian morphology. Polycystic ovary syndrome, particularly the hyperandrogenism phenotype, is associated with several cardiometabolic abnormalities, including obesity, dyslipidemia, elevated blood pressure, and prediabetes or type 2 diabetes. Many, but not all, studies have suggested that PCOS is associated with increased risk of cardiovascular disease (CVD), including coronary heart disease and stroke, independent of body mass index and traditional risk factors. Interpretation of the data from these observational studies is limited by the varying definitions and ascertainment of PCOS and CVD across studies. Recent Mendelian randomization studies have challenged the causality of PCOS with coronary heart disease and stroke. Future longitudinal studies with clearly defined PCOS criteria and newer genetic methodologies may help to determine association and causality. Nevertheless, CVD risk screening remains critical in this patient population, as improvements in metabolic profile and reduction in CVD risk are achievable with a combination of lifestyle management and pharmacotherapy. Statin therapy should be implemented in women with PCOS who have elevated atherosclerotic CVD risk. If CVD risk is uncertain, measurement of subclinical atherosclerosis (carotid plaque or coronary artery calcium) may be a useful tool to guide shared decision-making about initiation of statin therapy. Other medications, such as metformin and glucagon-like peptide-1 receptor agonists, also may be useful in reducing CVD risk in insulin-resistant populations. Additional research is needed to determine the best pathways to mitigate PCOS-associated CVD risk.

Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis.

Elevated levels of testosterone and fibroblast growth factor 23 (FGF-23) are both independently associated with a higher risk of cardiovascular disease (CVD). However, the relationship between sex hormones and FGF-23 is not well established. We explored the association between sex hormones and FGF-23 among middle-aged to older men and women in MESA. We studied 3,052 men and 2,868 postmenopausal women free of CVD at the time of enrollment with baseline serum sex hormones [total testosterone (T), free T, estradiol (E2) and sex hormone binding globulin (SHBG)] and intact FGF-23. In sex-stratified analyses, we examined the cross-sectional associations between log-transformed sex hormones (per 1 SD) and log-transformed FGF-23 using multiple linear regression adjusted for socio-demographics, CVD risk factors, estimated glomerular filtration rate and mineral metabolites (25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone). The mean (SD) age of study participants was 64 (10) years. The median (IQR) of FGF-23 was similar in women and men [38 (30-46) vs 38 (31-47) pg/mL]. In adjusted analyses, among women, 1 SD increment in free T was associated with 3% higher FGF-23 while SHBG was associated with 2% lower FGF-23. In men, 1 SD increment in E2 was associated with 6% higher FGF-23 whereas total T/E2 ratio was associated with 7% lower FGF-23. In conclusion, this exploratory analysis found that a more androgenic sex hormone profile was directly associated with FGF-23 in women and inversely associated with FGF-23 in men. Longitudinal studies are required to determine whether FGF-23 mediates the relationship between sex hormones and CVD risk.

A novel operator-independent noninvasive device for assessing arterial reactivity.

Background: Endothelial dysfunction is associated with increased risk of cardiovascular disease (CVD). Currently available noninvasive methods of measuring endothelial function have limitations. We tested a novel device that provides an automated measurement of the difference between baseline and post-ischemic, hyperemia-induced, brachial arterial compliance, a phenomenon known to be endothelium-dependent. The association between the calculated index, Flow-mediated Compliance Response (FCR), and established CVD risk indices was determined. Methods: Adults with CVD risk factors or known coronary artery disease (CAD) were enrolled. Framingham Risk Score (FRS) was calculated and presence of metabolic syndrome (MetSyn) was assessed. Carotid artery plaques were identified by ultrasound. Cardiorespiratory fitness was assessed by 6-minute walk test (6MWT). FCR was measured using the device. Results: Among 135 participants, mean age 49.3 +/- 17.9 years, characteristics included: 48% female, 7% smokers, 7% CAD, 10% type 2 diabetes, 34% MetSyn, and 38% with carotid plaque. Those with MetSyn had 24% lower FCR than those without (p < 0.001). Lower FCR was associated with higher FRS percentile (r = -0.29, p < 0.001), more MetSyn factors (r = -0.30, p < 0.001), more carotid plaques (r = -0.22, p = 0.01), and lower 6MWT (r = 0.34, p < 0.0001). Conclusion: FCR, an index of arterial reactivity obtained automatically using a novel, operator-independent device, was inversely associated with established CVD risk indices, increased number of carotid plaques, and lower cardiorespiratory fitness. Whether measuring FCR could play a role in screening for CVD risk and assessing whether endothelial function changes in response to treatments aimed at CVD risk reduction, warrants further study.

Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Sex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants. METHODS: We studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately. RESULTS: The mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors. CONCLUSIONS: In this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.