Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). RESULTS.: The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). CONCLUSIONS.: In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Stressors and Impact of the COVID-19 Pandemic on Vulnerable Hispanic Caregivers and Children.

Psychological sequelae are important elements of the burden of disease among caregivers. Recognition of the impact of adversity and stress biomarkers is important to prevent mental health problems that affect rearing practices and child well-being. This cross-sectional study explored social determinants of health (SDoH)-mediated stressors during COVID-19 and risks for mental health problems among caregivers of children with prenatal Zika virus exposure. Twenty-five Hispanic caregivers completed surveys assessing SDoH vulnerabilities, COVID-exposures and impact, post-traumatic stress disorder (PTSD) symptomatology, and provided a hair sample for cortisol concentration (HCC). Most caregivers had low education, household income < $15,000/year, and were unemployed. Stressors included disrupted child education and specialized services, and food insecurity. While most reported PTSD symptomatology, multivariate linear regression models adjusted for the caregiver's age, education, and the child's sex, revealed that caregivers with high symptomatology had significantly lower HCC than those with low symptomatology and those with food insecurity had significantly higher HCC than participants without food insecurity. The impact of COVID-19 on daily life was characterized on average between worse and better, suggesting variability in susceptibility and coping mechanisms, with the most resilient identifying community support and spirituality resources. SDoH-mediators provide opportunities to prevent adverse mental health outcomes for caregivers and their children.

Preconception Cardiometabolic Markers and Birth Outcomes Among Women in the Hispanic Community Health Study/Study of Latinos.

Background: Associations between preconception cardiometabolic markers and birth outcomes have been noted, but data are scarce for Hispanics/Latinos. We examined the association between preconception cardiometabolic markers, birthweight and preterm birth among U.S. Hispanic/Latina women. Materials and Methods: The Hispanic Community Health Study/Study of Latinos is a cohort study of U.S. adults 18-74 years of age, including 3,798 women of reproductive age (18-44 years) from four field centers representing Hispanic/Latino backgrounds of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American. A baseline clinic examination (2008-2011) and a second clinic examination (2014-2017), including ascertainment of birth outcomes, allowed for identification of 517 singleton live births between the exams. Preconception cardiometabolic markers included abdominal obesity (waist circumference ≥88 cm), body mass index >30 kg/m2, high blood pressure (systolic ≥120 mmHg and diastolic ≥80 mmHg), elevated triglycerides (≥150 mg/dL), low high-density lipoprotein cholesterol (<50 mg/dL), elevated fasting glucose (≥100 mg/dL), and insulin. Complex survey linear regression modeled the association between cardiometabolic markers and birthweight-for-gestational age z-score; complex survey logistic regression modeled the association with preterm birth. Analyses adjusted for Hispanic/Latina background, field center, years between baseline and birth, age, and nulliparity. Results: In adjusted linear regression models, elevated fasting glucose was associated with higher birthweight z-scores (ß = 0.56, 95% confidence interval [95% CI] 0.14 to 0.99), even after further adjustment for maternal percent body fat (ß = 0.53, 95% CI 0.10 to 0.95). In adjusted logistic regression models, high blood pressure (odds ratio [OR] = 2.57, 95% CI 1.13 to 5.88) and increased insulin (OR = 1.50, 95% CI 1.06 to 2.14, for a 10 mU/L increase) were associated with higher odds for preterm birth. Conclusions: Infant birthweight and preterm birth may be influenced by selected cardiometabolic risk factors before pregnancy among Hispanic/Latina women.

Diabetes Incidence Among Hispanic/Latino Adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: To examine diabetes incidence in a diverse cohort of U.S. Hispanic/Latinos. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study of Latinos is a prospective cohort study with participants aged 18-74 years from four U.S. metropolitan areas. Participants were assessed for diabetes at the baseline examination (2008-2011), annually via telephone interview, and at a second examination (2014-2017). RESULTS: A total of 11,619 participants returned for the second examination. The overall age-adjusted diabetes incidence rate was 22.1 cases/1,000 person-years. The incidence was high among those with Puerto Rican and Mexican backgrounds as well as those aged ≥45 years and with a BMI ≥30 kg/m2. Significant differences in diabetes awareness, treatment, and health insurance coverage, but not glycemic control, were observed across Hispanic/Latino background groups, age groups, and BMI categories. CONCLUSIONS: Differences in diabetes incidence by Hispanic/Latino background, age, and BMI suggest the susceptibility of these factors.

Neighborhood segregation and cancer prevention guideline adherence in US Hispanic/Latino adults: Results from the HCHS/SOL.

Background: Adherence to the American Cancer Society (ACS) guidelines for cancer prevention is associated with a lower risk of cancer and mortality. The role of neighborhood segregation on adherence to the guidelines among Hispanic/Latino adults is relatively unexplored. Materials and methods: The Hispanic Community Health Study/Study of Latinos is a community-based prospective cohort of 16,462 Hispanic/Latino adults, ages 18-74 years enrolled in 2008-2011 from the Bronx, Chicago, Miami and San Diego. Dimensions of neighborhood segregation were measured using 2010 United States' census tracts:-evenness (the physical separation of a group), exposure (the propensity for contact between groups), and their joint effect (hypersegregation). ACS guideline adherence levels - low, moderate, high - were created from accelerometry-measured physical activity, dietary intake, alcohol intake, and body mass index. Weighted multinominal logistic regressions estimated relative risk ratios (RRR) and 95% confidence intervals (CI) for guideline adherence levels and its components. Results: Hispanic/Latino adults were classified as low (13.7%), moderate (58.8%) or highly (27.5%) adherent to ACS guidelines. We found no evidence of an association between segregation and overall guideline adherence. Exposure segregation associated with lower likelihood of moderate adherence to alcohol recommendations (RRRmoderate vs. low:0.86, 95%CI:0.75-0.98) but higher likelihood for diet recommendations (RRRmoderate vs. low:1.07, 95%CI:1.01-1.14). Evenness segregation associated with lower likelihood of high adherence to the physical activity recommendations (RRRhigh vs. low:0.73, 95%CI:0.57-0.94). Hypersegregation was associated with individual guideline components. Conclusion: We found evidence of a cross-sectional relationship between neighborhood segregation and ACS cancer prevention guideline components, but not with overall ACS guideline adherence.

Associations of Sleep-disordered Breathing and Insomnia with Incident Hypertension and Diabetes. The Hispanic Community Health Study/Study of Latinos.

Rationale: Sleep disorders are associated with hypertension and diabetes, which are primary risk factors for cardiovascular diseases and mortality. It is important to understand these associations in Hispanic/Latino individuals, in whom cardiovascular death is the leading cause of mortality.Objectives: To investigate the prospective associations of sleep-disordered breathing (SDB) and insomnia with incident hypertension and diabetes among U.S. Hispanic/Latino people over 6 years of follow-up and to assess potential sex differences in these associations.Methods: Data from 11,623 Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos (visit 1, 2008-2011; visit 2, 2014-2017) were analyzed using survey logistic regression models, adjusting for potential confounders.Measurements and Main Results: SDB (apnea-hypopnea index of 5 or more) and insomnia (Women's Health Initiative Insomnia Rating Scale of 9 or more) were measured at baseline. Incident hypertension (stage 2 or greater) and diabetes were defined according to national guidelines. In the target population, 52.6% were women, with a mean age of 41.1 ± 14.9 years at baseline. SDB was associated with 1.54 higher adjusted odds of incident hypertension (95% confidence interval [CI], 1.18-2.00) and 1.33 higher odds of incident diabetes (95% CI, 1.05-1.67) compared with no SDB. Insomnia was associated with incident hypertension (odds ratio, 1.37; 95% CI, 1.11-1.69) but not with diabetes. The association between insomnia and incident hypertension was stronger among men than among women.Conclusions: SDB was associated with incident hypertension and diabetes. Insomnia was associated with incident hypertension. These findings support the importance of sleep disorders as modifiable targets for disease prevention and reduction.

Emerging Concepts in Precision Medicine and Cardiovascular Diseases in Racial and Ethnic Minority Populations.

Cardiovascular diseases remain the leading cause of mortality and a major contributor to preventable deaths worldwide. The dominant modifiable risk factors and the social and environmental determinants that increase cardiovascular risk are known, and collectively, are as important in racial and ethnic minority populations as they are in majority populations. Their prevention and treatment remain the foundation for cardiovascular health promotion and disease prevention. Genetic and epigenetic factors are increasingly recognized as important contributors to cardiovascular risk and provide an opportunity for advancing precision cardiovascular medicine. In this review, we explore emerging concepts at the interface of precision medicine and cardiovascular disease in racial and ethnic minority populations. Important among these are the lack of racial and ethnic diversity in genomics studies and biorepositories; the resulting misclassification of benign variants as pathogenic in minorities; and the importance of ensuring ancestry-matched controls in variant interpretation. We address the relevance of epigenetics, pharmacogenomics, genetic testing and counseling, and their social and cultural implications. We also examine the potential impact of precision medicine on racial and ethnic disparities. The National Institutes of Health's All of Us Research Program and the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Initiative are presented as examples of research programs at the forefront of precision medicine and diversity to explore research implications in minorities. We conclude with an overview of implementation research challenges in precision medicine and the ethical implications in minority populations. Successful implementation of precision medicine in cardiovascular disease in minority populations will benefit from strategies that directly address diversity and inclusion in genomics research and go beyond race and ethnicity to explore ancestry-matched controls, as well as geographic, cultural, social, and environmental determinants of health.

Factors associated with undiagnosed diabetes among adults with diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

AIMS: To investigate sociodemographic and health factors associated with undiagnosed diabetes among adults with diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). METHODS: Among 3384 adults with self-reported diabetes or undiagnosed diabetes in the baseline HCHS/SOL, we estimated odds ratios (OR) of being undiagnosed for demographic, cultural, access to care, and health factors. RESULTS: Among individuals with diabetes, 37.0% were undiagnosed. After adjustment and compared to people of Mexican heritage, people of Cuban and South American heritage had 60% (OR = 1.60, 95% CI = 1.02-2.50) and 91% (OR = 1.91, 1.16-3.14) higher odds of being undiagnosed, respectively. Individuals with a higher odds of being undiagnosed were women (OR = 1.64, 1.26-2.13), those with no health insurance (OR = 1.31, 1.00-1.71), individuals who received no healthcare in the past year (OR = 3.59, 2.49-5.16), those who were overweight (vs. normal weight) (OR = 1.60, 1.02-2.50), and those with dyslipidemia (OR = 1.38, 1.10-1.74). Individuals with lower odds of being undiagnosed were those with a family history of diabetes (OR = 0.54, 0.43-0.68), and those with hypertension (OR = 0.46, 0.36-0.58). CONCLUSIONS: Variation by Hispanic heritage group, sex, and access to medical care highlight where concentrated efforts are need to improve diabetes awareness. Our findings will inform clinical and public health practices to improve diabetes awareness among vulnerable populations.

Thyroid hormones and breast cancer association according to menopausal status and body mass index.

BACKGROUND: Thyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women. METHODS: To assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models. RESULTS: Higher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01-11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17-3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed. CONCLUSIONS: There is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.

Variations of dietary intake by glycemic status and Hispanic/Latino heritage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: A healthy diet is important for diabetes prevention and control; however, few studies have assessed dietary intake among US Hispanics/Latinos, a diverse population with a significant burden of diabetes. To address this gap in the literature, we determined intake of energy, macro/micronutrients, and vitamin supplements among Hispanics/Latinos by glycemic status and heritage. RESEARCH DESIGN AND METHODS: Cross-sectional study of adults aged 18-74 years from the Hispanic Community Health Study/Study of Latinos (2008-2011) with complete baseline data on glycemic status and two 24-hour dietary recalls (n=13 089). Age-adjusted and sex-adjusted and multivariable-adjusted measures of intake were determined by glycemic status and heritage. RESULTS: Mean age-adjusted and sex-adjusted energy intake was significantly lower among Hispanics/Latinos with diagnosed diabetes compared with those with normal glycemic status (1665 vs 1873 kcal, P<0.001). Fiber intake was higher among those with diagnosed diabetes versus normal glycemic status (P<0.01). Among those with diagnosed diabetes, energy intake was highest among those with Cuban heritage compared with most other heritage groups (P<0.01 for all, except Mexicans), but there was no difference after additional adjustment. Fiber intake was significantly lower for those of Cuban heritage (vs Dominican, Central American, and Mexican), and sodium intake was significantly higher (vs all other heritage groups) (P<0.01 for all); findings were null after additional adjustment. There was no difference in supplemental intake of vitamin D, calcium, magnesium, or potassium by glycemic status. CONCLUSIONS: As part of the care of Hispanics/Latinos with diabetes, attention should be made to fiber and sodium consumption.

Correction to: Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium.

The authors regret that Yinchang Lu's name incorrectly included a middle initial in the author list. The details given in this erratum are correct.

Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium.

AIMS/HYPOTHESIS: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies. METHODS: A multiethnic study of up to 26,760 unrelated individuals without diabetes, of predominantly Hispanic/Latino and African ancestries, were genotyped using the Metabochip. Transethnic meta-analysis of racial/ethnic-specific linear regression analyses were performed for fasting glucose and fasting insulin. We attempted to replicate 39 fasting glucose and 17 fasting insulin loci. Genetic fine-mapping was performed through sequential conditional analyses in 15 regions that included both the initially reported SNP association(s) and denser coverage of SNP markers. In addition, Metabochip-wide analyses were performed to discover novel fasting glucose and fasting insulin loci. The most significant SNP associations were further examined using bioinformatic functional annotation. RESULTS: Previously reported SNP associations were significantly replicated (p ≤ 0.05) in 31/39 fasting glucose loci and 14/17 fasting insulin loci. Eleven glycaemic trait loci were refined to a smaller list of potentially causal variants through transethnic meta-analysis. Stepwise conditional analysis identified two loci with independent secondary signals (G6PC2-rs477224 and GCK-rs2908290), which had not previously been reported. Population-specific conditional analyses identified an independent signal in G6PC2 tagged by the rare variant rs77719485 in African ancestry. Further Metabochip-wide analysis uncovered one novel fasting insulin locus at SLC17A2-rs75862513. CONCLUSIONS/INTERPRETATION: These findings suggest that while glycaemic trait loci often have generalisable effects across the studied populations, transethnic genetic studies help to prioritise likely functional SNPs, identify novel associations that may be population-specific and in turn have the potential to influence screening efforts or therapeutic discoveries. DATA AVAILABILITY: The summary statistics from each of the ancestry-specific and transethnic (combined ancestry) results can be found under the PAGE study on dbGaP here: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1.

HEMOGLOBIN A1C, BLOOD PRESSURE, AND LDL-CHOLESTEROL CONTROL AMONG HISPANIC/LATINO ADULTS WITH DIABETES: RESULTS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS (HCHS/SOL).

OBJECTIVE: To determine the prevalence of Hispanic/Latino adults with diabetes who meet target hemoglobin A1c, blood pressure (BP), and low-density-lipoprotein cholesterol (LDL-C) recommendations, and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) and statin medication use by heritage and sociodemographic and diabetes-related characteristics. METHODS: Data were cross-sectional, collected between 2008 and 2011, and included adults age 18 to 74 years who reported a physician diagnosis of diabetes in the Hispanic Community Health Study/Study of Latinos (N = 2,148). Chi-square tests compared the prevalence of hemoglobin A1c, BP, and LDL-C targets and ACE/ARB and statin use across participant characteristics. Predictive margins regression was used to determine the prevalence adjusted for sociodemographic characteristics. RESULTS: The overall prevalence of A1c <7.0% (53 mmol/mol), BP <130/80 mm Hg, and LDL-C <100 mg/dL was 43.0, 48.7, and 36.6%, respectively, with 8.4% meeting all three targets. Younger adults aged 18 to 39 years with diabetes were less likely to have A1c <7.0% (53 mmol/mol) or LDL-C <100 mg/dL compared to those aged 65 to 74 years; younger adults were more likely to have BP <130/80 mm Hg (P<.05 for all). Individuals of Mexican heritage were significantly less likely to have A1c <7.0% (53 mmol/mol) compared to those with Cuban heritage, but they were more likely to have BP <130/80 mm Hg compared to those with Dominican, Cuban, or Puerto Rican heritage (P<.05 for all); there was no difference in LDL-C by heritage. Overall, 38.2% of adults with diabetes were taking a statin, and 50.5% were taking ACE/ARB medications. CONCLUSION: Hemoglobin A1c, BP, and LDL-C control are suboptimal among Hispanic/Latinos with diabetes living in the U.S. With 8.4% meeting all three recommendations, substantial opportunity exists to improve diabetes control in this population. ABBREVIATIONS: A1c = hemoglobin A1c; ABC = hemoglobin A1c, blood pressure, low-density-lipoprotein cholesterol; ACE = angiotensin-converting enzyme; ADA = American Diabetes Association; ARB = angiotensin receptor blocker; BMI = body mass index; BP = blood pressure; CHD = coronary heart disease; CVD = cardiovascular disease; HCHS/SOL = Hispanic Community Health Study/Study of Latinos; LDL-C = low-density-lipoprotein cholesterol; NHANES = National Health and Nutrition Examination Survey; PAD = peripheral artery disease.

Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci.

Most body mass index (BMI) genetic loci have been identified in studies of primarily European ancestries. The effect of these loci in other racial/ethnic groups is less clear. Thus, we aimed to characterize the generalizability of 170 established BMI variants, or their proxies, to diverse US populations and trans-ethnically fine-map 36 BMI loci using a sample of >102,000 adults of African, Hispanic/Latino, Asian, European and American Indian/Alaskan Native descent from the Population Architecture using Genomics and Epidemiology Study. We performed linear regression of the natural log of BMI (18.5-70 kg/m2) on the additive single nucleotide polymorphisms (SNPs) at BMI loci on the MetaboChip (Illumina, Inc.), adjusting for age, sex, population stratification, study site, or relatedness. We then performed fixed-effect meta-analyses and a Bayesian trans-ethnic meta-analysis to empirically cluster by allele frequency differences. Finally, we approximated conditional and joint associations to test for the presence of secondary signals. We noted directional consistency with the previously reported risk alleles beyond what would have been expected by chance (binomial p < 0.05). Nearly, a quarter of the previously described BMI index SNPs and 29 of 36 densely-genotyped BMI loci on the MetaboChip replicated/generalized in trans-ethnic analyses. We observed multiple signals at nine loci, including the description of seven loci with novel multiple signals. This study supports the generalization of most common genetic loci to diverse ancestral populations and emphasizes the importance of dense multiethnic genomic data in refining the functional variation at genetic loci of interest and describing several loci with multiple underlying genetic variants.

Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?

Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (>12 000 participants) and also assessed the generalization of previously known loci to this population. We then evaluated whether iron-associated variants were associated with diabetes and glycemic traits. We found evidence for a novel association between TIBC and a variant near the gene for protein phosphatase 1, regulatory subunit 3B (PPP1R3B; rs4841132, ß = -0.116, P = 7.44 × 10-8). The effect strengthened when iron deficient individuals were excluded (ß = -0.121, P = 4.78 × 10-9). Ten of sixteen variants previously associated with iron traits generalized to HCHS/SOL, including variants at the transferrin (TF), hemochromatosis (HFE), fatty acid desaturase 2 (FADS2)/myelin regulatory factor (MYRF), transmembrane protease, serine 6 (TMPRSS6), transferrin receptor (TFR2), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ABO blood group (ABO), and GRB2 associated binding protein 3 (GAB3) loci. In examining iron variant associations with glucose homeostasis, an iron-raising variant of TMPRSS6 was associated with lower HbA1c levels (P = 8.66 × 10-10). This association was attenuated upon adjustment for iron measures. In contrast, the iron-raising allele of PPP1R3B was associated with higher levels of fasting glucose (P = 7.70 × 10-7) and fasting insulin (P = 4.79 × 10-6), but these associations were not attenuated upon adjustment for TIBC-so iron is not likely a mediator. These results provide new genetic information on iron traits and their connection with glucose homeostasis.

Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18-74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses. RESULTS: Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81 [3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P < 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P < 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease. CONCLUSIONS: Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further.

Prevalence of Low Cardiovascular Risk Profile Among Diverse Hispanic/Latino Adults in the United States by Age, Sex, and Level of Acculturation: The Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Favorable levels of all readily measurable major cardiovascular disease risk factors (ie, low risk [LR]) are associated with lower risks of cardiovascular disease morbidity and mortality. Data are not available on LR prevalence among Hispanic/Latino adults of diverse ethnic backgrounds. This study aimed to describe the prevalence of a low cardiovascular disease risk profile among Hispanic/Latino adults in the United States and to examine cross-sectional associations of LR with measures of acculturation. METHODS AND RESULTS: The multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos examined 16 415 men and women aged 18 to 74 years at baseline (2008-2011) with diverse Hispanic/Latino backgrounds. Analyses involved 14 757 adults (mean age 41.3 years; 60.6% women). LR was defined using national guidelines for favorable levels of serum cholesterol, blood pressure, and body mass index and by not having diabetes mellitus and not currently smoking. Age-adjusted LR prevalence was low (8.4% overall; 5.1% for men, 11.2% for women) and varied by background (4.2% in men of Mexican heritage versus 15.0% in women of Cuban heritage). Lower acculturation (assessed using proxy measures) was significantly associated with higher odds of a LR profile among women only: Age-adjusted odds ratios of having LR were 1.64 (95% CI 1.24-2.17) for foreign-born versus US-born women and 1.96 (95% CI 1.49-2.58) for women residing in the United States <10 versus ≥10 years. CONCLUSIONS: Among diverse US Hispanic/Latino adults, the prevalence of a LR profile is low. Lower acculturation is associated with higher odds of a LR profile among women but not men. Comprehensive public health strategies are needed to improve the cardiovascular health of US Hispanic/Latino adults.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Comparing measures of overall and central obesity in relation to cardiometabolic risk factors among US Hispanic/Latino adults.

OBJECTIVE: US Hispanics/Latinos have high prevalence of obesity and related comorbidities. We compared overall and central obesity measures in associations with cardiometabolic outcomes among US Hispanics/Latinos. METHODS: Multivariable regression assessed cross-sectional relationships of six obesity measures with cardiometabolic outcomes among 16,415 Hispanics/Latinos aged 18-74 years. RESULTS: BMI was moderately correlated with waist-to-hip ratio (WHR; women, r = 0.37; men, r = 0.58) and highly correlated with other obesity measures (r ≥ 0.87) (P < 0.0001). All measures of obesity were correlated with unfavorable levels of glycemic traits, blood pressure, and lipids, with similar r-estimates for each obesity measure (P < 0.05). Multivariable-adjusted prevalence ratios (PRs) for diabetes (women, 6.7 [3.9, 11.5]; men, 3.9 [2.2, 6.9]), hypertension (women, 2.4 [1.9, 3.1]; men, 2.5 [1.9, 3.4]), and dyslipidemia (women, 2.1 [1.8, 2.4]; men, 2.2 [1.9, 2.6]) were highest for individuals characterized as overweight/obese (BMI ≥ 25 kg/m(2)) and with abnormal WHR (women ≥0.85; men, ≥0.90), compared with those with normal BMI and WHR (P < 0.0001). Among normal-weight individuals, abnormal WHR was associated with increased cardiometabolic condition prevalence (P < 0.05), particularly diabetes (women, PR = 4.0 [2.2, 7.1]; men, PR = 3.0 [1.6, 5.7]). CONCLUSIONS: Obesity measures were associated with cardiometabolic risk factors to a similar degree in US Hispanics/Latinos. WHR is useful to identify individuals with normal BMI at increased cardiometabolic risk.