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BackgroundEpigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.MethodsBlood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE-/-) mouse model of atherosclerosis.ResultsA total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women's Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic.ConclusionsDifferential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.

OBJECTIVE We examined the association of arsenic in federally regulated community water systems (CWS) and unregulated private wells with type 2 diabetes (T2D) incidence in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially and ethnically diverse urban U.S. communities. RESEARCH DESIGN AND METHODS We evaluated 1,791 participants from SHFS and 5,777 participants from MESA who had water arsenic estimates available and were free of T2D at baseline (2001-2003 and 2000-2002, respectively). Participants were followed for incident T2D until 2010 (SHFS cohort) or 2019 (MESA cohort). We used Cox proportional hazards mixed-effects models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, BMI, smoking status, and education. RESULTS T2D incidence was 24.4 cases per 1,000 person-years (mean follow-up, 5.6 years) in SHFS and 11.2 per 1,000 person-years (mean follow-up, 14.0 years) in MESA. In a meta-analysis across the SHFS and MESA cohorts, the hazard ratio (95% CI) per doubling in CWS arsenic was 1.10 (1.02, 1.18). The corresponding hazard ratio was 1.09 (0.95, 1.26) in the SHFS group and 1.10 (1.01, 1.20) in the MESA group. The corresponding hazard ratio (95% CI) for arsenic in private wells and incident T2D in SHFS was 1.05 (0.95, 1.16). We observed statistical interaction and larger magnitude hazard ratios for participants with BMI <25 kg/m² and female participants. CONCLUSIONS Low to moderate water arsenic levels (<10 µg/L) were associated with T2D incidence in the SHFS and MESA cohorts. [ABSTRACT FROM AUTHOR]

Background and objectives: Systemic lupus erythematosus (SLE) is an autoimmune condition that can highly impact patients' quality of life (QoL). However, there is a lack of knowledge about SLE, affecting the general population and health care professionals (HCPs) alike. This lack of knowledge has negative implications for patients and the healthcare system, worsening prognosis, negatively impacting QoL, and increasing healthcare utilization. The aim of this paper is to draw attention, according to the perspective of the participants of this study, to the lack of awareness of SLE and its consequences in Spain, and to suggest improvements. Patients and methods: This qualitative, descriptive, observational, multicenter, and cross-sectional study included 40 patients with moderate or severe SLE, recruited during their routine visits in six university hospitals in Spain. The study also included 11 caregivers and 9 HCPs. All participants were individually interviewed. Data from the interviews were coded and analyzed thematically by two anthropologists following a phenomenological perspective. Results: Our study identified a lack of disease awareness among primary care physicians, emergency medicine doctors, and other specialists treating SLE symptomatology. This led to diagnostic delays, which had a clinical and emotional impact on patients. Furthermore, symptom awareness was found to be context dependent. Differences in symptom awareness between HCPs and patients led to a mismatch between the severity evaluation made by doctors and patients. Some HCPs did not consider the limitations of the current severity evaluation of SLE, and therefore attributed symptoms potentially caused by SLE to the unfavorable socioeconomic conditions patients lived in. Finally, a lack of social awareness among friends, family members, and romantic partners led to lower social support, increased isolation, and negative physical and emotional impact for patients. Gender differences in the provision of support were identified. Conclusion: This study highlights the need to increase SLE awareness among patients, HCPs, and the broader public in order to improve patient QoL. Being aware of the clinical and emotional impact of such lack of awareness, as well as the role played by context on the patient experience of SLE, is a crucial step towards achieving this goal. [ABSTRACT FROM AUTHOR]

Objective: Hyperglycemia can increase urinary zinc excretion. We evaluated the association of higher urinary zinc level with new diagnosis of incident type 2 diabetes mellitus (T2DM) in adult populations with a high burden of T2DM from AZ, OK, and ND and SD. We also assessed the cross-sectional association of urinary zinc levels with prevalent prediabetes.Research Design and Methods: We included 1,339 adults free of T2DM at baseline (1989-1991) followed through 1998-1999 in the Strong Heart Study (SHS) and 1,905 family members of SHS participants followed as part of the Strong Heart Family Study (SHFS) through 2006-2009.Results: T2DM incidence was 14.7% (mean follow-up 6.6 years) in the SHS and 13.5% (mean follow-up 5.6 years) in the SHFS. After adjustment for sex, site, education, smoking status, BMI, and estimated glomerular filtration rate, the hazard ratio of T2DM in comparing 75th vs. 25th percentiles of urinary zinc distribution was 1.21 (95% CI 1.08, 1.36) in the SHS and 1.12 (0.96, 1.31) in the SHFS. These associations were attenuated but significant in the SHS after adjustment for HOMA of insulin resistance (HOMA-IR) score. With exclusion of participants with prediabetes at baseline, urinary zinc remained significantly associated with T2DM in the SHS. In cross-sectional analyses, prediabetes was associated with higher urinary zinc levels.Conclusions: Urinary zinc levels were associated with T2DM incidence and prediabetes prevalence even after adjustment for HOMA-IR in populations with a high burden of T2DM. These results highlight the importance of zinc metabolism in diabetes development. [ABSTRACT FROM AUTHOR]