Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects.

BACKGROUND: Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. METHOD: A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). RESULTS: Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. CONCLUSION: This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.

Cadmium exposure is associated with reduced grip strength in US adults.

BACKGROUND: Muscle strength is a strong predictor of all-cause mortality in the general population. Recent studies have shown an association between environmental pollution and declined grip strength. No previous research has evaluated the specific association between cadmium exposure, a well-known risk factor of several chronic diseases, and muscle strength. METHODS: Cross-sectional study among 4,197 individuals aged ≥40 years, who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014, provided data on grip strength, and had either blood or urine cadmium determinations. Grip strength was measured using a Takei digital handgrip dynamometer, and combined grip strength was calculated as the sum of the largest reading from each hand. RESULTS: Median (interquartile range) concentrations of blood (BCd) and creatinine-corrected urine cadmium (Cr-UCd) were 0.32 µg/L (0.20-4.56) and 0.27 µg/g (0.15-0.46), respectively. After adjusting for sociodemographic, anthropometric, health-related behavioral, and clinical risk factors, and serum creatine phosphokinase concentrations, the highest (vs lowest) quartile of BCd was associated with a reduction in combined grip strength of 1.93 kg (95% confidence interval [CI]: -3.51, -0.34), p-trend <0.001. The corresponding values comparing Cr-UCd quartiles 4 vs 1 were -3.24 kg (95% CI: -5.68, -0.79), p-trend <0.001. These results were consistent across socio-demographic and clinical subgroups. CONCLUSIONS: In the US adult population, higher cadmium exposure was associated with decreased grip strength. These results may have important public health implications given the widespread cadmium exposure.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study.

Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48 µg g-1 creatinine (geometric mean=0.94 µg g-1) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 µg g-1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (ß)=1.64, P=0.002). These associations were present among light- and never-smokers (ß=2.03, P=0.002, n=2627), although not significant among never-smokers (ß=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (ß=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.

Association of selenium and copper with lipids in umbilical cord blood.

Altered levels of selenium and copper have been linked with altered cardiovascular disease risk factors including changes in blood triglyceride and cholesterol levels. However, it is unclear whether this can be observed prenatally. This cross-sectional study includes 274 singleton births from 2004 to 2005 in Baltimore, Maryland. We measured umbilical cord serum selenium and copper using inductively coupled plasma mass spectrometry. We evaluated exposure levels vis-à-vis umbilical cord serum triglyceride and total cholesterol concentrations in multivariable regression models adjusted for gestational age, birth weight, maternal age, race, parity, smoking, prepregnancy body mass index, n-3 fatty acids and methyl mercury. The percent difference in triglycerides comparing those in the highest v. lowest quartile of selenium was 22.3% (95% confidence interval (CI): 7.1, 39.7). For copper this was 43.8% (95% CI: 25.9, 64.3). In multivariable models including both copper and selenium as covariates, copper, but not selenium, maintained a statistically significant association with increased triglycerides (percent difference: 40.7%, 95% CI: 22.1, 62.1). There was limited evidence of a relationship of increasing selenium with increasing total cholesterol. Our findings provide evidence that higher serum copper levels are associated with higher serum triglycerides in newborns, but should be confirmed in larger studies.

Selenium status and cardiometabolic health: state of the evidence.

Use of selenium enriched foods, supplements and fertilizers has increased markedly in recent years in the US and other Western countries because of the perception that the anti-oxidant properties of selenium could potentially reduce the risk of cancer and other chronic diseases. However, concern has been raised recently about possible adverse cardiometabolic effects of high selenium exposure, including an increased risk of diabetes and hyperlipidemia with high selenium intake. Hence, from a public health perspective, the relationship between selenium status and cardiometabolic health should be clarified in order to help guide consumers in their choices of nutritional supplements and enriched food products. Additional experimental evidence is needed to provide new insights into the role of selenium and of specific selenoproteins in human biology, especially to clarify the underlying mechanisms linking selenium to chronic disease endpoints. Further epidemiological studies and randomized clinical trials across populations with different selenium status should be conducted to determine the causal effect of selenium on cardiovascular disease and risk factors. Nevertheless, at the present time the widespread use of selenium supplements or other strategies that artificially increase selenium status above the level required for optimal selenoprotein activity is not justified and should not be encouraged.

Secondhand tobacco smoke concentrations in motor vehicles: a pilot study.

CONTEXT: Motor vehicles represent important microenvironments for exposure to secondhand smoke (SHS). While some countries and cities have banned smoking in cars with children present, more data are needed to develop the evidence base on SHS exposure levels in motor vehicles to inform policy and education practices aimed at supporting smoke-free motor vehicles when passengers are present. OBJECTIVE: To assess exposure to secondhand tobacco smoke in motor vehicles using passive airborne nicotine samplers. METHODS: 17 smokers and five non-smokers who commute to and from work in their own vehicle participated. Two passive airborne nicotine samplers were placed in each vehicle for a 24-hour period, one at the front passenger seat headrest and the other in the back seat behind the driver. At the end of the sampling period, airborne nicotine was analysed by gas chromatography. RESULTS: Median (IQR) air nicotine concentrations in smokers' vehicles were 9.6 mug/m(3) (5.3-25.5) compared to non-detectable concentrations in non-smokers' vehicles. After adjustment for vehicle size, window opening, air conditioning and sampling time, there was a 1.96-fold increase (95% CI 1.43 to 2.67) in air nicotine concentrations per cigarette smoked. CONCLUSIONS: Air nicotine concentrations in motor vehicles were much higher than air nicotine concentrations generally measured in public or private indoor places, and even higher than concentrations measured in restaurants and bars. These high levels of exposure to SHS support the need for education measures and legislation that regulate smoking in motor vehicles when passengers, especially children, are present.

Ultrasonographic and magnetic resonance images of rotator cuff lesions compared with arthroscopy or open surgery findings.

Our purpose was to compare the accuracy of ultrasonography (US) and magnetic resonance (MR) in the diagnosis of rotator cuff injuries (focusing on supraspinatus tears) using arthroscopy or open surgery findings. Using US and MR, we studied all painful shoulders seen during 1998 in our orthopaedic unit. Diagnosis was confirmed in 61 cases. The diagnosis of full thickness rotator cuff tear was highly specific on both imaging techniques (100% for US and 97.1% for MR) but was not as sensitive on US (57.7%) as on MR (80.8%). The diagnosis of partial tear was acceptably specific (67.9% for US and 75.5% for MR) but was not sensitive (overall, 12.5% for US vs 50% for MR). The specificity of a US diagnosis of a tear allows us to recommend surgery, thus making it a good imaging technique for the initial study of painful shoulders. The low sensitivity makes it necessary to undertake an additional MR study. If the MR also discovers no pathology, the sensitivity based on the US and MR images (92.7%) can be sufficient to avoid a false-negative diagnosis.