Blood pressure and renal function responses in workers exposed to lead for up to six years.

The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the blood pressure (BP) and renal function (RF) responses for up to 6 years in the workers without previous occupational lead exposure. BP was the average of five consecutive readings and the estimated glomerular filtration rate was derived from serum creatinine (eGFRcrt) and cystatin C (eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis. The 234 workers analyzed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 µg/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p ≥ .51 and p ≥ .18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or -2 hypertension was not associated with the BL change (p ≥ .063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 3-fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2 (CI: -1.70 to 0.30 mL/min/1.73 m2 ) and -1.06 mL/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2 ). In conclusion, the BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.

Mortality and Major Adverse Cardiac Events in Patients With Breast Cancer Receiving Radiotherapy: The First Decade.

Background Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for this interval is unclear. Methods and Results We aimed to study cardiovascular event rates in the first decade following curative radiotherapy for BC. We compared mortality and cardiovascular event rates with an age- and risk factor-matched control population. We included 1095 patients with BC (mean age 56±12 years). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality caused 107 (49.1%) and 22 (10.1%) deaths, respectively. A total of 904 cases were matched to female FLEMENGHO (Flemish Study on Environment, Genes and Health Outcomes) participants. Coronary artery disease incidence was similar (risk ratio [RR], 0.75 [95% CI, 0.48-1.18]), yet heart failure (RR, 1.97 [95% CI, 1.19-3.25]) and atrial fibrillation/flutter (RR, 1.82 [95% CI, 1.07-3.08]) occurred more often in patients with BC. Age (hazard ratio [HR], 1.033 [95% CI, 1.006-1.061], P=0.016), tumor grade (HR, 1.739 [95% CI, 1.166-2.591], P=0.007), and neoadjuvant treatment setting (HR, 2.782 [95% CI, 1.304-5.936], P=0.008) were risk factors for mortality. Risk factors for major adverse cardiac events were age (HR, 1.053 [95% CI, 1.013-1.093]; P=0.008), mean heart dose (HR, 1.093 [95% CI, 1.025-1.167]; P=0.007), history of cardiovascular disease (HR, 2.386 [95% CI, 1.096-6.197]; P=0.029) and Mayo Clinic Cardiotoxicity Risk Score (HR, 2.664 [95% CI, 1.625-4.367]; P<0.001). Conclusions Ten-year mortality following curative treatment for unilateral BC was mainly cancer related, but heart failure and atrial fibrillation/flutter were already common in the first decade following irradiation. Mean heart dose, pre-existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for cardiac adverse events. These results suggest a need for early dedicated cardio-oncological follow-up after radiotherapy.

Public and occupational health risks related to lead exposure updated according to present-day blood lead levels.

Lead is an environmental hazard that should be addressed worldwide. Over time, human lead exposure in the western world has decreased drastically to levels comparable to those among humans living in the preindustrial era, who were mainly exposed to natural sources of lead. To re-evaluate the potential health risks associated with present-day lead exposure, a two-pronged approach was applied. First, recently published population metrics describing the adverse health effects associated with lead exposure at the population level were critically assessed. Next, the key results of the Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) were summarized and put in perspective with those of the published population metrics. To our knowledge, SPHERL is the first prospective study that accounted for interindividual variability between people with respect to their vulnerability to the toxic effects of lead exposure by assessing the participants' health status before and after occupational lead exposure. The overall conclusion of this comprehensive review is that mainstream ideas about the public and occupational health risks related to lead exposure urgently need to be updated because a large portion of the available literature became obsolete given the sharp decrease in exposure levels over the past 40 years.

Two-Year Responses of Renal Function to First Occupational Lead Exposure.

Introduction: Whether in advanced countries lead exposure still contributes to renal impairment is debated, because blood lead (BL) level is declining toward preindustrial levels and because longitudinal studies correlating renal function and BL changes over time are scarce. Methods: The Study for Promotion of Health in Recycling Lead (SPHERL) evaluated the 2-year renal function responses in 251 workers (mean age, 29.7 years) transiting from environmental to occupational exposure. Main study end point was the estimated glomerular filtration rate (eGFR) derived from serum creatinine (eGFRcrt), cystatin C (eGFRcys), or both (eGFRcc). BL level was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dl). Results: In the follow-up, mean baseline BL level of 4.13 µg/dl increased 3.30-fold. In fully adjusted mixed models, additionally accounting for the within-participant clustering of the 1- and 2-year follow-up data, a 3-fold BL level increment was not significantly correlated with changes in eGFR with estimates amounting to -0.86 (95% CI: -2.39 to 0.67), -1.58 (-3.34 to 0.18), and -1.32 (-2.66 to 0.03) ml/min per 1.73 m2 for eGFRcrt, eGFRcys, or eGFRcc, respectively. Baseline BL level and the cumulative lead burden did not materially modify these estimates, but baseline eGFR was a major determinant of eGFR changes showing regression to the mean during follow-up. Responses of serum osmolarity, urinary gravity, or the urinary albumin-to-creatinine ratio (ACR) were also unrelated to the BL level increment. The age-related decreases in eGFRcrt, eGFRcys, and eGFRcc were -1.41, -0.96, and -1.10 ml/min per 1.73 m2, respectively. Conclusion: In the current study, the 2-year changes in renal function were unrelated to the increase in BL level. However, given the CIs around the point estimates of the changes in eGFRcc and eGFRcys, a larger study with longer follow-up is being planned.

Incidence of Cardiovascular Events in Patients Treated With Immune Checkpoint Inhibitors.

PURPOSE: In rare cases, immune checkpoint inhibitors (ICIs) cause immune-mediated myocarditis. However, true incidence of other major adverse cardiovascular events (MACEs) after ICI treatment remains unknown, mainly because late occurring side effects are rarely reported in prospective clinical trials. The aims of this study were (1) to identify incidence and risk factors of MACE in a real-life ICI-treated cancer cohort and (2) to compare incidence rates with patients with cancer who are not treated with ICIs and population controls. METHODS: In total, 672 patients treated with ICIs were included. The primary end point was MACE, a composite of acute coronary syndrome, heart failure (HF), stroke, and transient ischemic attack. Secondary outcomes were acute coronary syndrome and HF separately. Incidence rates were compared between groups after matching according to age, sex, cardiovascular history, and cancer type. RESULTS: The incidence of MACE was 10.3% during a median follow-up of 13 (interquartile range, 6-22) months. In multivariable analysis, a history of HF (hazard ratio 2.27; 95% CI, 1.03 to 5.04; P = .043) and valvular heart disease (hazard ratio 3.01; 95% CI, 1.05 to 8.66; P = .041) remained significantly associated with MACE. Cumulative incidence rates were significantly higher in the ICI group compared with the cancer cohort not exposed to ICI and the population controls, mainly driven by a higher risk of HF events. CONCLUSION: Cardiovascular events during and after ICI treatment are more common than currently appreciated. Patients at risk are those with a history of cardiovascular disease. Compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect of ICI treatment besides the underlying risk.

A nonlinear association of total cholesterol with all-cause and cause-specific mortality.

BACKGROUND: The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality. METHODS: All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999-2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan-Meier survival curve and subgroup analyses were conducted. RESULTS: The sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18-65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group. CONCLUSIONS: A nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.

Two-Year Responses of Heart Rate and Heart Rate Variability to First Occupational Lead Exposure.

[Figure: see text].

The relationship between famine exposure during early life and carotid plaque in adulthood.

BACKGROUND: Famine exposure is a potential risk factor for adverse cardiometabolic health. However, the relationship between famine exposure during early life and carotid plaque in adulthood remains unclear. Therefore, the aim was to investigate the relationship between famine exposure during early life and the risks for carotid plaque in adulthood. METHODS: This was a cross-sectional study. Data were collected between 2017 and 2018 in Guangdong, China. Subjects who were born between 1 October 1952 and 30 September 1964, and had the carotid ultrasound measurement were enrolled. All included participants were divided into five groups: no exposure, fetal exposure, early-childhood exposure, mid-childhood exposure, and late-childhood exposure. Carotid plaque was assessed by carotid ultrasound examination. Multivariate logistic regression was used to estimate the odds ratio (OR) and confidence interval (CI) between famine exposure and carotid plaque. RESULTS: There were 2652 subjects enrolled, 973 (36.7%) of them were males, and the mean age was 59.1 ± 3.6 years. The prevalence of carotid plaque in unexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed groups were 40.2%, 40.8%, 55.3%, 56.8%, and 62.1%, respectively. When compared with the unexposed group, the fully adjusted ORs for carotid plaque from fetal-exposed, early-childhood, mid-childhood to late-childhood exposed were 1.023 (95% CI: 0.771, 1.357, P = 0.872), 1.755 (95% CI: 1.356, 2.275, P < 0.001), 1.780 (95% CI: 1.391, 2.280, P < 0.001), and 2.119 (95% CI: 1.643, 2.739, P < 0.001), respectively. Subgroup analyses showed that the famine effect on carotid plaque did not interact with body mass index, gender, smoking status, hypertension, and diabetes history (all P for interaction > 0.500). CONCLUSIONS: Famine exposure during early life was significantly associated with an increased risk of carotid plaque in adulthood.

Association between pulse pressure and ischaemic stroke in elderly patients with hypertension.

BACKGROUND: The association between pulse pressure (PP) and the risk of first ischaemic stroke (IS) is inconsistent. Therefore, we evaluated the association between PP and the risk of first IS among elderly hypertensive population in China. METHODS: This was a retrospective cohort study. Patients with hypertension and aged ≥60 years were recruited. Multivariate Cox regression was performed to evaluate the association between PP and the risk of IS. We further stratified the regression models into subgroups and test for interaction to assess whether the associations were modified by other covariates. RESULTS: A total of 3315 patients with hypertension (44.49% male; mean age 71.41±7.20 years) were included, and 206 cases of IS occurred with a median follow-up of 5.5 years. The results showed that per SD mm Hg increment in PP was associated with a 17% (95% CI 1.05 to 1.40, p=0.0172) increased risk of IS. Moreover, the HR of IS for the highest quartile of PP was 1.46 (95% CI 1.18 to 1.73, p=0.0011, p for trend <0.001) comparing with the lowest quartile of PP. Subgroup analysis showed that population aged ≥70 years, male, patients with smoking or drinking habit, diabetes at baseline, being overweight, with uncontrolled blood pressure or did not take antihypertensive drugs have a higher risk for IS. CONCLUSIONS: We found that PP was significantly associated with IS and was an independent risk factor for IS.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality.

BACKGROUND: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR). OBJECTIVE: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults. METHODS: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality. RESULTS: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79). CONCLUSIONS: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.

Two-year neurocognitive responses to first occupational lead exposure.

Objectives Lead exposure causes neurocognitive dysfunction in children, but its association with neurocognition in adults at current occupational exposure levels is uncertain mainly due to the lack of longitudinal studies. In the Study for Promotion of Health in Recycling Lead (NCT02243904), we assessed the two-year responses of neurocognitive function among workers without previous known occupational exposure newly hired at lead recycling plants. Methods Workers completed the digit-symbol test (DST) and Stroop test (ST) at baseline and annual follow-up visits. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Statistical methods included multivariable-adjusted mixed models with participants modelled as random effect. Results DST was administered to 260 participants (11.9% women; 46.9%/45.0% whites/Hispanics; mean age 29.4 years) and ST to 168 participants. Geometric means were 3.97 and 4.13 µg/dL for baseline BL, and 3.30 and 3.44 for the last-follow-up-to-baseline BL ratio in DST and ST cohorts, respectively. In partially adjusted models, a doubling of the BL ratio was associated with a 0.66% [95% confidence interval (CI) 0.03-1.30; P=0.040] increase in latency time (DST) and a 0.35% (95% CI ­1.63-1.63; P=0.59) decrease in the inference effect (ST). In fully adjusted models, none of the associations of the changes in the DST and ST test results with the blood lead changes reached statistical significance (P≥0.12). Conclusions An over 3-fold increase in blood lead over two years of occupational exposure was not associated with a relevant decline in cognitive performance.

The U Shaped Relationship Between High-Density Lipoprotein Cholesterol and All-Cause or Cause-Specific Mortality in Adult Population.

PURPOSE: The associations of high-density lipoprotein cholesterol (HDL-C) with mortality are still unclear. We explored the associations of HDL-C with all-cause and cause-specific mortality in an adult population. METHODS: Deaths were classified into all-cause, cardiovascular, and cancer mortality. Survival curve, multivariate Cox regression, and subgroup analyses were conducted, and hazard ratio (HR) and 95% confidence interval (CI) were performed. We fitted Cox regression models for all-cause, cardiovascular, and cancer mortality to evaluate their associations with categories of HDL-C (≤30, 31-40, 41-50, 51-60 [reference], 61-70, >70 mg/dL). RESULTS: A total of 42,145 (20,415 (48.44%) males, mean age 47.12±19.40 years) subjects were enrolled. At an average follow-up of 97.52±54.03 months, all-cause, cardiovascular, and cancer mortality numbers were 5,061 (12.01), 1,081 (2.56%), and 1,061 (2.52%), respectively. When compared with the reference group (HDL-C: 51-60 mg/dL), a U-shaped association was apparent for all-cause mortality, with elevated risk in participants with the lowest (≤30 mg/dL) (HR=1.33; 95% CI=1.14- 1.56) and highest (>70 mg/dL) (HR=1.14; 95% CI=1.02-1.27) HDL-C concentration. Associations for cardiovascular and cancer mortality were non-linear. An elevated risk for cancer mortality was observed in those with the highest HDL-C concentration (HR=1.06; 95% CI-0.84-1.34) compared with the reference group, although it was not statistically significant. The effect of HDL-C on mortality was adjusted by some traditional risk factors including age, gender, race, or comorbidities. CONCLUSION: A U-shaped association was observed between HDL-C and all-cause mortality among an adult population.

Two-Year Responses of Office and Ambulatory Blood Pressure to First Occupational Lead Exposure.

Lead exposure causing hypertension is the mechanism commonly assumed to set off premature death and cardiovascular complications. However, at current exposure levels in the developed world, the link between hypertension and lead remains unproven. In the Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of office blood pressure (average of 5 consecutive readings) and 24-hour ambulatory blood pressure to first occupational lead exposure in workers newly employed at lead recycling plants. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Hypertension was defined according to the 2017 American College of Cardiology/American Heart Association guideline. Statistical methods included multivariable-adjusted mixed models with participants modeled as a random effect and interval-censored Cox regression. Office blood pressure was measured in 267 participants (11.6% women, mean age at enrollment, 28.6 years) and ambulatory blood pressure in 137 at 2 follow-up visits. Geometric means were 4.09 µg/dL for baseline BL and 3.30 for the last-follow-up-to-baseline BL ratio. Fully adjusted changes in systolic/diastolic blood pressure associated with a doubling of the BL ratio were 0.36/0.28 mm Hg (95% CI, -0.55 to 1.27/-0.48 to 1.04 mm Hg) for office blood pressure and -0.18/0.11 mm Hg (-2.09 to 1.74/-1.05 to 1.27 mm Hg) for 24-hour ambulatory blood pressure. The adjusted hazard ratios of moving up across hypertension categories for a doubling in BL were 1.13 (0.93-1.38) and 0.84 (0.57-1.22) for office blood pressure and ambulatory blood pressure, respectively. In conclusion, the 2-year blood pressure responses and incident hypertension were not associated with the BL increase on first occupational exposure.

Insight into the transplacental transport mechanism of methoxylated polybrominated diphenyl ethers using a BeWo cell monolayer model.

Methoxylated polybrominated diphenyl ethers (MeO-PBDEs), a type of emerging environmental contaminants, can accumulate through the food chain and eventually enter the human body. For pregnant women, these chemicals may be transplacentally transported to their fetuses, causing early intrauterine exposure. This study was designed to explore the transport process and characteristics of MeO-PBDEs using a BeWo cell monolayer model to simulate the placental barrier effect. Concentration-dependent transplacental transport indicates that the transport of MeO-PBDEs may be dominated by passive diffusion within the studied concentration range. According to the apparent permeability coefficients, MeO-BDE congeners investigated can be classified as poorly transported compounds, with the exception of MeO-BDE28. Time-dependent transplacental transport was observed (R2 = 0.97-0.99), which showed that the intracellular accumulation of MeO-PBDEs followed pseudo-first-order kinetics process. The transport process of MeO-PBDEs in the BeWo cell assay was not found to be sensitive to the pH of 6.5-7.4. An efflux transporter, breast cancer resistance protein, may be involved in the transport process of some MeO-PBDE congeners, and influx transporters, including organic anion transporters and organic cation transporters, may also be involved in the transport process. Although the present results indicated the possible transplacental transport mechanism, more molecular biological studies should be conducted to advance the understanding of the transport mechanisms.

[Study on a breast-disease screening program and related factors among rural married women at reproductive age in Anhui province].

OBJECTIVE: To study the prevalence and its related factors on breast-diseases among women at reproductive age in the rural areas of Anhui province, and to provide data for the development of prevention and healthcare on breast-diseases. METHODS: 54 400 rural fertile women aged 15 - 49 were surveyed by a stratified-cluster-random sampling method. Breast examination was conducted in two steps: converging at the clinics, and later visiting their households. Clinical examination and X-ray scanning check up were performed. RESULTS: The rate of the breast-disease among the rural fertile women was 10.69%, and the first three breast-diseases were galactophore hyperplasia, fibroadenoma and intracanalicular papilloma, their prevalence were 9.39%, 0.65% and 0.50% respectively. The results of logistic regression showed in comparison with women and their husbands who were under 29, low education, husbands being farmers, medium menstrual flow, no dysmenorrheal, the total number of deliveries was 0 while no history of abortion, those who aged 30 to 44, high education, husbands were doing other jobs (they were mainly businessmen or teachers), more menstrual flow, dysmenorrheal, the total number of deliveries was 1, they were more likely to got breast diseases. However in comparison with women who earned less than 5000 Yuan per year, those who had 5001 to 8000 Yuan per year were less likely to get breast diseases. CONCLUSION: Breast diseases were prevalent among rural fertile women and were affected by multi-factors. We suggested that screening program on breast cancer should be carried out at regular intervals and at the same time, to intensify second-class prevention of breast cancer, together with actively treating patients with galactophore hyperplasia, to reduce the prevalence of precancerous pathological changes.