Ten-Year Trends in Enrollment of Women and Minorities in Pivotal Trials Supporting Recent US Food and Drug Administration Approval of Novel Cardiometabolic Drugs.

Background In 1993, the US Food and Drug Administration established guidelines to increase diversity by sex and race/ethnicity of participants in clinical trials supporting novel drug approvals. In this study we investigated the 10-year trends of participation of women and minorities in pivotal trials supporting approval of new molecular entities in cardiometabolic drugs from January 2008 to December 2017. Methods and Results A list of new molecular entities was abstracted from publicly available data at Drugs@Fda. Sex and race/ethnicity data were collected from trial publications. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled. Thirty-five novel cardiovascular (n=24) and diabetes mellitus (n=11) drugs were approved by the US Food and Drug Administration during the study period. The median number of participants supporting each drug was 5930 (interquartile range, 3175-10 942). Women represented 36% (n=108 052) of trial participants (n=296 163). Women were underrepresented compared with their proportion of the disease population in trials of coronary heart disease (participation-to-prevalence ratio, 0.52), heart failure (participation-to-prevalence ratio, 0.58), and acute coronary syndrome (participation-to-prevalence ratio, 0.68). Among trial participants, 81% were white, 4% black, 12% Asian, and 11% Hispanic/Latino. There was no significant association between enrollment of women (P=0.29) or underrepresented minorities (P=0.45) with the drug approval year. Conclusions Over the past decade (2008-2017), women and minorities, particularly blacks, have continued to be inadequately represented in pivotal cardiometabolic clinical trials that support US Food and Drug Administration approval of new molecular entities. This may have major implications in determining efficacy of such therapies in these groups, and may impair generalizability of trial results to routine clinical practice.

Death by a Thousand Cuts: Stress Exposure and Black-White Disparities in Physiological Functioning in Late Life.

OBJECTIVES: This paper investigates Black-White differences in stress-including diverse measures of chronic, acute, discrimination-related, and cumulative stress exposure-and examines whether race differences in these stress measures mediate Black-White disparities in C-reactive protein (CRP) and metabolic dysregulation in later life. METHODS: Using data from the Health and Retirement Study (HRS) (2004-2012), this study uses stepwise ordinary least squares (OLS) regression models to examine the prospective associations between multiple stressors-including traumatic and stressful life events, financial strain, chronic stress, everyday and major life discrimination, and measures of cumulative stress burden-and CRP and metabolic dysregulation. Mediation analyses assessed the contribution of stress exposure to Black-White disparities in the outcomes. RESULTS: Blacks experienced more stress than Whites across domains of stress, and stress exposure was strongly associated with CRP and metabolic dysregulation. Race differences in financial strain, everyday and major life discrimination, and cumulative stress burden mediated Black-White gaps in the outcomes, with measures of cumulative stress burden mediating the greatest proportion of the racial disparities. DISCUSSION: The "thousand cuts" that Blacks experience from their cumulative stress exposure across domains of social life throughout the life course accelerate their physiological deterioration relative to Whites and play a critical role in racial health disparities at older ages.

Sleep influences on cardio-metabolic health in Indigenous populations.

Indigenous populations continue to be among the world's most marginalized population groups. Studies in Indigenous populations from high income countries (including the United States, Canada, Australia, and New Zealand) indicate increased risk of sleep disorders compared to non-Indigenous populations. Poor sleep, whether it be short sleep duration or fragmented sleep, is a well-established risk factor for cardio-metabolic diseases. Given the implications, targeted improvement of poor sleep may be beneficial for the health and well-being of Indigenous people. In this narrative review, we will: (1) discuss the effects of sleep on the cardio-metabolic processes; (2) examine sleep in Indigenous populations; (3) review the association between sleep and cardio-metabolic risk in Indigenous populations; and (4) review the potential role of sleep in cardiovascular disease risk detection and interventions to improve sleep and cardio-metabolic health in Indigenous people. In particular, this review highlights that the assessment of sleep quality and quantity may be a beneficial step toward identifying Indigenous people at risk of cardio-metabolic diseases and may represent a key intervention target to improve cardio-metabolic outcomes.

Sleep and cardiometabolic health by government-assisted rental housing status among Black and White men and women in the United States.

OBJECTIVES: To investigate Black-White disparities in suboptimal sleep and cardiometabolic health by government-assisted rental housing status. DESIGN: National Health Interview Survey (NHIS) pooled cross-sectional data (2004-2016). SETTING: United States. PARTICIPANTS: Black and White adult participants (n = 80,880). MEASUREMENTS: Poisson regression with robust variance was used to estimate prevalence ratios (PRs) and 95% confidence intervals for self-reported unrecommended (<6 hours), short (≤6-<7 hours), and long (>9 hours) sleep duration (each separately vs recommended (≤7-9 hours)) and sleep difficulties (eg, trouble falling/staying asleep ≥3 days/week) (yes vs no) among Blacks compared to Whites within rental housing categories (government-assisted vs unassisted), separately, for men and women. Within sex/housing categories, we applied the same approach to compare cardiometabolic health outcomes (ie, overweight/obesity, hypertension, diabetes, heart disease, stroke) between Blacks with worse sleep and Whites with recommended sleep. Models were adjusted for age and other potential confounders. RESULTS: Participants' mean age was 42 ±â€¯18 years, 57% were female, and 30% Black. Blacks in unassisted housing had a higher prevalence of unrecommended and short sleep (PR = 1.22 [1.15-1.30] -men, PR = 1.14 [1.08-1.21] -women) compared to their White counterparts (phousing⁎race = 0.001 -men, phousing⁎race = 0.008 -women), but no Black-White differences (PR = 0.88 [0.73-1.07] -men, PR = 0.98 [0.89-1.09] -women) were observed among government-assisted renters. Generally, Blacks were less likely to report sleep difficulties than Whites. Cardiometabolic health disparities between Blacks with worse sleep and Whites with recommended sleep were generally smaller among government-assisted renters, but relationships varied by sex. CONCLUSIONS: There were no racial disparities in short sleep duration, and cardiometabolic health disparities were generally attenuated when Blacks and Whites resided in government-assisted rental housing.

Racial/Ethnic and County-level Disparity in Inpatient Utilization among Hawai'i Medicaid Population.

We investigated racial/ethnic and county-level disparities in inpatient utilization for 15 clinical conditions among Hawaii's Medicaid population. The study was conducted using inpatient claims data from more than 200,000 Hawai'i Medicaid beneficiaries, reported in the year 2010. The analysis was performed by stratifying the Medicaid population into three age groups: children and adolescent group (1-20 years), adult group (21-64 years), and elderly group (65 years and above). Among the differences found, Asians had a low probability of inpatient admissions compared to Whites for many disease categories, while Native Hawaiian/Pacific Islanders had higher probabilities than Whites, across all age groups. Pediatric and adult groups from Hawai'i County (Big Island) had lower probabilities for inpatient admissions compared to Honolulu County (O'ahu) for most disease conditions, but higher probabilities were observed for several conditions in the elderly group. Notably, the elderly population residing on Kaua'i County (Kaua'i and Ni'ihau islands) had substantially increased odds of hospital admissions for several disease conditions, compared to Honolulu.

At the intersection of place, race, and health in Brazil: Residential segregation and cardio-metabolic risk factors in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Residential segregation is the spatial manifestation of entrenched socioeconomic and racial inequities and is considered a fundamental cause of racial inequalities in health. Despite the well-documented racialized spatial inequalities that exist in urban areas throughout Brazil, few empirical investigations have examined the link between residential segregation and health and considered its implications for racial health inequalities in this setting. In the present study, we used data from the Brazilian Longitudinal Study of Adult Health (2008-2010) to examine the association between economic residential segregation and two major cardio-metabolic risk factors-hypertension and diabetes. We also examined whether associations were stronger for historically marginalized racial groups in Brazil. Residential segregation was calculated for study-defined neighborhoods using the Getis-Ord Local Gi* statistic and was based on household income data from the 2010 IBGE demographic census. Multivariable logistic regression models were used to examine associations. In our sample, Blacks and Browns were more likely to live in economically segregated neighborhoods. After taking into account income, education, and other demographic characteristics we found that individuals living in the most economically segregated neighborhoods were 26% more likely to have hypertension and 50% more likely to have diabetes than individuals living in more affluent areas. Although Blacks and Browns living in highly segregated neighborhoods had higher prevalence of hypertension and diabetes compared to Whites, we observed no statistically significant racial differences in the associations with residential segregation. Our findings suggest that residential segregation may be an important structural determinant of cardio-metabolic risk factors in Brazil. Moreover, the systematic and disproportionate exposure of Blacks and Browns to highly segregated neighborhoods may implicate these settings as potential drivers of racial inequalities in cardio-metabolic risk factors in urban settings in Brazil.

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults.

RATIONALE: Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. OBJECTIVE: To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. METHODS: Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. RESULTS: Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (ß -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (ß -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (ß -111 ml (-22 ml, -201 ml) and FEV1 (ß -100 ml (-12 ml, -188 ml)). Results were similar in men and women. CONCLUSIONS: Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Indicators of abdominal size relative to height associated with sex, age, socioeconomic position and ancestry among US adults.

BACKGROUND/OBJECTIVES: The supine sagittal abdominal diameter (SAD) and standing waist circumference (WC) describe abdominal size. The SAD/height ratio (SADHtR) or WC/height ratio (WHtR) may better identify cardiometabolic disorders than BMI (weight/height2), but population-based distributions of SADHtR and WHtR are not widely available. Abdominal adiposity may differ by sociodemographic characteristics. SUBJECTS/METHODS: Anthropometry, including SAD by sliding-beam caliper, was performed on 9894 non-pregnant adults ≥20 years in the US National Health and Nutrition Examination Surveys of 2011-2014. Applying survey design factors and sampling weights, we estimated nationally representative SADHtR and WHtR distributions by sex, age, educational attainment, and four ancestral groups. RESULTS: The median (10th percentile, 90th percentile) for men's SADHtR was 0.130 (0.103, 0.165) and WHtR 0.569 (0.467, 0.690). For women, median SADHtR was 0.132 (0.102, 0.175) and WHtR 0.586 (0.473, 0.738). Medians for SADHtR and WHtR increased steadily through age 79. The median BMI, however, reached maximum values at ages 40-49 (men) or 60-69 (women) and then declined. Low educational attainment, adjusted for age and ancestry, was associated with elevated SADHtR more strongly than elevated BMI. While non-Hispanic Asians had substantially lower BMI compared to all other ancestral groups (adjusted for sex, age and education), their relative reductions in SADHtR and WHtR, were less marked. CONCLUSIONS: These cross-sectional data are consistent with monotonically increasing abdominal adipose tissue through the years of adulthood but decreasing mass in non-abdominal regions beyond middle age. They suggest also that visceral adipose tissue, estimated by SADHtR, expands differentially in association with low socioeconomic position. Insofar as Asians have lower BMIs than other populations, employing abdominal indicators may attenuate the adiposity differences reported between ancestral groups. Documenting the distribution and sociodemographic features of SADHtR and WHtR supports the clinical and epidemiologic adoption of these adiposity indicators.

Delivery of cardio-metabolic preventive services to Hungarian Roma of different socio-economic strata.

BACKGROUND: Because the cardiovascular mortality in Hungary is high, particularly among the socio-economically deprived and the Roma, it is implied that primary health care (PHC) has a limited ability to exploit the opportunities of evidence-based preventions, and it may contribute to social health inequalities. OBJECTIVES: Our study investigated the underuse of PHC preventive services. METHODS: Random samples of adults aged 21-64 years free of hypertension and diabetes mellitus were surveyed with participation rate of 97.7% in a cross-sectional study. Data from 2199 adults were collected on socio-demographic status, ethnicity, lifestyle and history of cardio-metabolic preventive service use. Delivery rates were calculated for those aged 21-44 years and those aged 45-64 years, and the influence of socio-demographic variables was determined using multivariate logistic regression. RESULTS: Delivery rates varied between 12.79% and 99.06%, and the majority was far from 100%. Although most preventive service use was independent of education, younger participants with vocational educations underutilized problematic drinking (P = 0.011) and smoking (P = 0.027) assessments, and primary or less educated underutilized blood glucose (P = 0.001) and serum cholesterol (P = 0.005) checks. Health care measures of each lifestyle assessment (P nutrition = 0.032; P smoking = 0.021; P alcohol = 0.029) and waist circumference measurement (P = 0.047) were much less frequently used among older Roma. The blood glucose check (P = 0.001) and family history assessment (P = 0.043) were less utilized among Roma. CONCLUSIONS: The Hungarian PHC underutilizes the cardio-metabolic prevention contributing to the avoidable mortality, not generating considerably health inequalities by level of education, but contributing to the bad health status among the Roma.

Response and participation of underserved populations after a three-step invitation strategy for a cardiometabolic health check.

BACKGROUND: Ethnic minority and native Dutch groups with a low socioeconomic status (SES) are underrepresented in cardiometabolic health checks, despite being at higher risk. We investigated response and participation rates using three consecutive inexpensive-to-costly culturally adapted invitation steps for a health risk assessment (HRA) and further testing of high-risk individuals during prevention consultations (PC). METHODS: A total of 1690 non-Western immigrants and native Dutch with a low SES (35-70 years) from six GP practices were eligible for participation. We used a 'funnelled' invitation design comprising three increasingly cost-intensive steps: (1) all patients received a postal invitation; (2) postal non-responders were approached by telephone; (3) final non-responders were approached face-to-face by their GP. The effect of ethnicity, ethnic mix of GP practice, and patient characteristics (gender, age, SES) on response and participation were assessed by means of logistic regression analyses. RESULTS: Overall response was 70% (n = 1152), of whom 62% (n = 712) participated in the HRA. This was primarily accomplished through the postal and telephone invitations. Participants from GP practices in the most deprived neighbourhoods had the lowest response and HRA participation rates. Of the HRA participants, 29% (n = 207) were considered high-risk, of whom 59% (n = 123) participated in the PC. PC participation was lowest among native Dutch with a low SES. CONCLUSIONS: Underserved populations can be reached by a low-cost culturally adapted postal approach with a reminder and follow-up telephone calls. The added value of the more expensive face-to-face invitation was negligible. PC participation rates were acceptable. Efforts should be particularly targeted at practices in the most deprived areas.

East is east and West is west: perspectives on the menopause in Asia and The West.

There is a school of thought that believes that menopausal symptoms are a peculiarly 'Western' phenomenon, not experienced by women from other regions and particularly not from Asia where, it has been claimed, dietary, social and cultural factors afforded protection for women living in that region. More recently, studies conducted in multi-ethnic communities living in Western countries as well as in Asian communities have found that the menopause and its consequences are similar world-wide. Ethnic differences within Asia account for small differences in endogenous hormone levels and age at menopause between Asian and Western women, and the type of menopause symptoms and their prevalence also differ between those two communities. However, like in the West and perhaps because of a Western influence, the long-term health problems of postmenopausal women including cardiovascular disease, osteoporosis and breast cancer are of major importance to Asian women and health services in the 21st century.

Fetuin-A does not explain ethnic disparity in cardiometabolic risk factors and subclinical atherosclerosis between Hispanics and non-Hispanic whites.

BACKGROUND: Fetuin-A has been associated with insulin resistance and inversely related with vascular calcification. The present study evaluated whether serum fetuin-A explains the ethnic disparity in the subclinical atherosclerosis and risk for diabetes between healthy Hispanic and non-Hispanic white (NHW) subjects. METHODS: Fetuin-A was measured in serum of 76 age-matched healthy males (41 NHW, 35 Hispanics). Body mass index, blood pressure, serum lipoprotein cholesterol and triglyceride levels, coronary artery calcium (CAC), fasting glucose and insulin concentrations, and plasma glucose levels 2 h after a 75-g oral glucose tolerance test were measured in all participants. Insulin resistance was estimated using the homeostasis model assessment (HOMA). RESULTS: Fasting insulin, fasting and 2-h serum glucose, and HOMA values were all significantly higher in Hispanics (p < 0.05 for all), yet CAC trended lower and the prevalence of very high CAC (>400 Agatston score) was lower (P = 0.03). There was no statistically significant difference in serum fetuin-A when comparing Hispanics and NHW (P = 0.12). Furthermore, there was no correlation between fetuin-A levels and CAC (P = 0.9). CONCLUSIONS: Serum fetuin-A concentration was not associated with measures of insulin resistance or with preclinical atherosclerosis in Hispanics and NHW. These data indicate that the disparity in prevalence of insulin resistance, type 2 diabetes, and subclinical atherosclerosis between Hispanics and NHW does not appear attributable to differences in fetuin-A concentrations.