Per- and polyfluoroalkyl substances exposure and bone mineral density in the U.S. population from NHANES 2005-2014.

BACKGROUND: Environmental exposures such as perfluoroalkyl substances (PFASs) were considered potential risks for bone mineral density (BMD). OBJECTIVE: To examine the associations between PFASs and BMD among the U.S. population. METHODS: This study included a total of 6416 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2014). Multiple linear regression models were used to analyze the associations between serum PFASs and BMD and the coefficient ß with 95% confidence intervals (95% CI) was calculated as the effect estimate. Covariates such as age, race, BMI, smoking, alcohol intake, milk intake, and physical activity were adjusted in these models. Additionally, gender and menopausal period were considered in further subgroup analyses. RESULTS: Based on the combined data of NHANES 2005-2014, the effects from exposure to PFASs on BMD were found with gender and menopausal status differences. Positive associations were found in PFOA (ß = 0.010; 95% CI: 0.003, 0.016), PFHxS (ß = 0.007; 95% CI: 0.003, 0.012), and PFNA (ß = 0.001; 95% CI: 0.001, 0.017) in total population. Negative associations for PFOA (ß = -0.020; 95% CI: -0.029, -0.012), PFOS (ß = -0.011; 95% CI: -0.028, -0.011), PFHxS (ß = -0.019; 95% CI: -0.025, -0.013), PFDE (ß = -0.010; 95% CI: -0.016, -0.005), and PFNA (ß = -0.011; 95% CI: -0.021, -0.002) were found in women, while no significant association was found in men. In further subgroup analyses, women in pre-menopause status showed consistent negative associations. SIGNIFICANCE: PFASs exposure may be associated with BMD and gender and menopausal status confound the associations.

HDL-C, longitudinal change and risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. METHODS: We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. CONCLUSIONS: Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association between visit-to-visit variability in HbA1c and cognitive function decline in the elderly population. METHODS: We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA1c variability and cognitive function decline with adjustment for demographics, mean HbA1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol. RESULTS: The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA1c variability, participants in the highest quartile of HbA1c variability had a significantly worse memory decline rate (-0.094 SD/year, 95% CI -0.185, -0.003) and executive function decline rate (-0.083 SD/year, 95% CI -0.125, -0.041), irrespective of mean HbA1c values over time. Among individuals without diabetes, each 1-SD increment in HbA1c CV was associated with a significantly higher rate of memory z score decline (-0.029, 95% CI -0.052, -0.005) and executive function z score decline (-0.049, 95% CI -0.079, -0.018) in the fully adjusted model. CONCLUSIONS/INTERPRETATION: We observed a significant association between long-term HbA1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.

Association between CPR-related genetic variants and risk of ischemic stroke: a nested case-control study.

Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.