Miranda R. Jones

Migraine Headache and Ischemic Stroke Risk: An Updated Meta-analysis

BACKGROUND Observational studies, including recent large cohort studies that were unavailable for prior meta-analysis, have suggested an association between migraine headache and ischemic stroke. We performed an updated meta-analysis to quantitatively summarize the strength of association between migraine and ischemic stroke risk. METHODS We systematically searched electronic databases, including MEDLINE and EMBASE, through February 2009 for studies of human subjects in the English language. Study selection using a priori selection criteria, data extraction, and assessment of study quality were conducted independently by reviewer pairs using standardized forms. RESULTS Twenty-one (60%) of 35 studies met the selection criteria, for a total of 622,381 participants (13 case-control, 8 cohort studies) included in the meta-analysis. The pooled adjusted odds ratio of ischemic stroke comparing migraineurs with nonmigraineurs using a random effects model was 2.30 (95% confidence interval [CI], 1.91-2.76). The pooled adjusted effect estimates for studies that reported relative risks and hazard ratios, respectively, were 2.41 (95% CI, 1.81-3.20) and 1.52 (95% CI, 0.99-2.35). The overall pooled effect estimate was 2.04 (95% CI, 1.72-2.43). Results were robust to sensitivity analyses excluding lower quality studies. CONCLUSIONS Migraine is associated with increased ischemic stroke risk. These findings underscore the importance of identifying high-risk migraineurs with other modifiable stroke risk factors. Future studies of the effect of migraine treatment and modifiable risk factor reduction on stroke risk in migraineurs are warranted.

Arsenic Exposure and Hypertension: A Systematic Review

Background: Environmental exposure to arsenic has been linked to hypertension in persons living in arsenic-endemic areas. Objective: We summarized published epidemiologic studies concerning arsenic exposure and hypertension or blood pressure (BP) measurements to evaluate the potential relationship. Data sources and extraction: We searched PubMed, Embase, and TOXLINE and applied predetermined exclusion criteria. We identified 11 cross-sectional studies from which we abstracted or derived measures of association and calculated pooled odds ratios (ORs) using inverse-variance weighted random-effects models. Data synthesis: The pooled OR for hypertension comparing the highest and lowest arsenic exposure categories was 1.27 [95% confidence interval (CI): 1.09, 1.47; p-value for heterogeneity = 0.001; I2 = 70.2%]. In populations with moderate to high arsenic concentrations in drinking water, the pooled OR was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I2 = 76.6%) and 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I2 = 46.6%) before and after excluding an influential study, respectively. The corresponding pooled OR in populations with low arsenic concentrations in drinking water was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I2 = 24.6%). A dose–response assessment including six studies with available data showed an increasing trend in the odds of hypertension with increasing arsenic exposure. Few studies have evaluated changes in systolic and diastolic BP (SBP and DBP, respectively) measurements by arsenic exposure levels, and those studies reported inconclusive findings. Conclusion: In this systematic review we identified an association between arsenic and the prevalence of hypertension. Interpreting a causal effect of environmental arsenic on hypertension is limited by the small number of studies, the presence of influential studies, and the absence of prospective evidence. Additional evidence is needed to evaluate the dose–response relationship between environmental arsenic exposure and hypertension.

Reduction of secondhand tobacco smoke in public places following national smoke-free legislation in Uruguay

Background Smoke-free legislation eliminating tobacco smoke in all indoor public places and workplaces is the international standard to protect all people from exposure to secondhand smoke. Uruguay was the first country in the Americas and the first middle-income country in the world to enact a comprehensive smoke-free national legislation in March 2006. Objective To compare air nicotine concentrations measured in indoor public places and workplaces in Montevideo, Uruguay before (November 2002) and after (July 2007) the implementation of the national legislation. Methods Air nicotine concentrations were measured for 7–14 days using the same protocol in schools, a hospital, a local government building, an airport and restaurants and bars. A total of 100 and 103 nicotine samples were available in 2002 and 2007, respectively. Results Median (IQR) air nicotine concentrations in the study samples were 0.75 (0.2–1.54) μg/m3 in 2002 compared to 0.07 (0.0–0.20) μg/m3 in 2007. The overall nicotine reduction comparing locations sampled in 2007 to those sampled in 2002 was 91% (95% CI 85% to 94%) after adjustment for differences in room volume and ventilation. The greatest nicotine reduction was observed in schools (97% reduction), followed by the airport (94% reduction), the hospital (89% reduction), the local government building (86% reduction) and restaurants/bars (81% reduction). Conclusion Exposure to secondhand smoke has decreased greatly in indoor public places and workplaces in Montevideo, Uruguay, after the implementation of a comprehensive national smoke-free legislation. These findings suggest that it is possible to successfully implement smoke-free legislations in low and middle-income countries.

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 μg/m3 (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.

Urine arsenic and hypertension in US adults: the 2003-2008 National Health and Nutrition Examination Survey.

Background: High chronic exposure to inorganic arsenic may contribute to the development of hypertension. Limited information is available, however, on the association of low to moderate exposure to inorganic arsenic with blood pressure levels and hypertension. We investigated the association of exposure to inorganic arsenic (as measured in urine) with systolic and diastolic blood pressure levels and the prevalence of hypertension in US adults. Methods: We studied 4167 adults 20 years of age or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 through 2008 and for whom total arsenic, dimethylarsinate (DMA), and arsenobetaine had been assessed in urine. Results: The median (interquartile range) urine concentrations were 8.3 &mgr;g/L (4.2–17.1) for total arsenic, 3.6 &mgr;g/L (2.0–6.0) for DMA, and 1.4 &mgr;g/L (0.3–6.3) for arsenobetaine. The weighted prevalence of hypertension in the study population was 36%. After multivariable adjustment, a 2-fold increase in total arsenic was associated with a hypertension odds ratio of 0.98 (95% confidence interval = 0.86–1.11). A doubling of total arsenic minus arsenobetaine was associated with a hypertension OR of 1.03 (0.94–1.14) and a doubling of DMA concentrations was associated with a hypertension OR of 1.11 (0.99–1.24). Total arsenic, total arsenic minus arsenobetaine, or DMA levels were not associated with systolic or diastolic blood pressure. Conclusions: At the low to moderate levels, typical of the US population, total arsenic, total arsenic minus arsenobetaine, and DMA concentrations in urine were not associated with the prevalence of hypertension or with systolic or diastolic blood pressure levels. A weak association of DMA with hypertension could not be ruled out.

Race/ethnicity, residential segregation, and exposure to ambient air pollution: The Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVES We described the associations of ambient air pollution exposure with race/ethnicity and racial residential segregation. METHODS We studied 5921 White, Black, Hispanic, and Chinese adults across 6 US cities between 2000 and 2002. Household-level fine particulate matter (PM2.5) and nitrogen oxides (NOX) were estimated for 2000. Neighborhood racial composition and residential segregation were estimated using US census tract data for 2000. RESULTS Participants in neighborhoods with more than 60% Hispanic populations were exposed to 8% higher PM2.5 and 31% higher NOX concentrations compared with those in neighborhoods with less than 25% Hispanic populations. Participants in neighborhoods with more than 60% White populations were exposed to 5% lower PM2.5 and 18% lower NOX concentrations compared with those in neighborhoods with less than 25% of the population identifying as White. Neighborhoods with Whites underrepresented or with Hispanics overrepresented were exposed to higher PM2.5 and NOX concentrations. No differences were observed for other racial/ethnic groups. CONCLUSIONS Living in majority White neighborhoods was associated with lower air pollution exposures, and living in majority Hispanic neighborhoods was associated with higher air pollution exposures. This new information highlighted the importance of measuring neighborhood-level segregation in the environmental justice literature.

Menthol Cigarettes, Race/Ethnicity, and Biomarkers of Tobacco Use in U.S. Adults: The 1999–2010 National Health and Nutrition Examination Survey (NHANES)

Background: In the United States, cigarette flavorings are banned, with the exception of menthol. The cooling effects of menthol could facilitate the absorption of tobacco toxicants. We examined levels of biomarkers of tobacco exposure among U.S. smokers of menthol and nonmenthol cigarettes. Methods: We studied 4,603 White, African-American, and Mexican-American current smokers 20 years of age or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2010 and had data on cigarette type and serum cotinine, blood cadmium, and blood lead concentrations. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) was studied in 1,607 participants with available measures. Results: A total of 3,210 (74.3%) participants smoked nonmenthol cigarettes compared with 1,393 (25.7%) participants who smoked menthol cigarettes. The geometric mean concentrations comparing smokers of nonmenthol with menthol cigarettes were 163.1 versus 175.9 ng/mL for serum cotinine; 0.95 versus 1.02 μg/L for blood cadmium; 1.87 versus 1.75 μg/dL for blood lead; and 0.27 versus 0.23 ng/mL for urine NNAL. After multivariable adjustment, the ratios [95% confidence interval (CI)] comparing smokers of menthol with nonmenthol cigarettes were 1.03 (0.95–1.11) for cotinine, 1.10 (1.04–1.16) for cadmium, 0.95 (0.90–1.01) for lead, and 0.81 (0.65–1.01) for NNAL. Conclusions: In a representative sample of U.S. adult smokers, current menthol cigarette use was associated with increased concentration of blood cadmium, an established carcinogen and highly toxic metal, but not with other biomarkers. Impact: These findings provide information regarding possible differences in exposure to toxic constituents among menthol cigarette smokers compared with nonmenthol cigarette smokers. Cancer Epidemiol Biomarkers Prev; 22(2); 224–32. ©2012 AACR.

Secondhand Tobacco Smoke: An Occupational Hazard for Smoking and Non-Smoking Bar and Nightclub Employees

Background In the absence of comprehensive smoking bans in public places, bars and nightclubs have the highest concentrations of secondhand tobacco smoke, posing a serious health risk for workers in these venues. Objective To assess exposure of bar and nightclub employees to secondhand smoke, including non-smoking and smoking employees. Methods Between 2007 and 2009, the authors recruited approximately 10 venues per city and up to five employees per venue in 24 cities in the Americas, Eastern Europe, Asia and Africa. Air nicotine concentrations were measured for 7 days in 238 venues. To evaluate personal exposure to secondhand smoke, hair nicotine concentrations were also measured for 625 non-smoking and 311 smoking employees (N=936). Results Median (IQR) air nicotine concentrations were 3.5 (1.5–8.5) μg/m3 and 0.2 (0.1–0.7) μg/m3 in smoking and smoke-free venues, respectively. Median (IQR) hair nicotine concentrations were 6.0 (1.6–16.0) ng/mg and 1.7 (0.5–5.5) ng/mg in smoking and non-smoking employees, respectively. After adjustment for age, sex, education, living with a smoker, hair treatment and region, a twofold increase in air nicotine concentrations was associated with a 30% (95% CI 23% to 38%) increase in hair nicotine concentrations in non-smoking employees and with a 10% (2% to 19%) increase in smoking employees. Conclusions Occupational exposure to secondhand smoke, assessed by air nicotine, resulted in elevated concentrations of hair nicotine among non-smoking and smoking bar and nightclub employees. The high levels of airborne nicotine found in bars and nightclubs and the contribution of this exposure to employee hair nicotine concentrations support the need for legislation measures that ensure complete protection from secondhand smoke in these venues.

Smoking, Menthol Cigarettes and All-Cause, Cancer and Cardiovascular Mortality: Evidence from the National Health and Nutrition Examination Survey (NHANES) and a Meta-Analysis

Background The U.S. Food and Drug Administration has the authority to regulate tobacco product constituents, including menthol, if the scientific evidence indicates harm. Few studies, however, have evaluated the health effects of menthol cigarette use. Objective To investigate associations of cigarette smoking and menthol cigarette use with all-cause, cancer and cardiovascular risk in U.S. adults. Methods We studied 10,289 adults ≥ 20 years of age who participated in the National Health and Nutrition Examination Survey from 1999-2004 and were followed through December 2006. We also identified studies comparing risk of all-cause mortality, cardiovascular disease and cancer for menthol and nonmenthol cigarette smokers and estimates were pooled using random-effects models. Results Fifty-five percent of participants were never smokers compared to 23%, 17% and 5% of former, current nonmenthol and current menthol cigarette smokers, respectively. The adjusted hazard ratios (95% CI) for former, current nonmenthol and current menthol cigarette smokers compared to never smokers were 1.24 (0.96, 1.62), 2.40 (1.56, 3.71) and 2.07 (1.20, 3.58), respectively, for all-cause mortality; 0.92 (0.62, 1.37), 2.10 (1.02, 4.31) and 3.48 (1.52, 7.99) for cardiovascular mortality; and 1.91 (1.21, 3.00), 3.82 (2.19, 6.68) and 2.03 (1.00, 4.13) for cancer mortality. Using data from 3 studies of all-cause mortality, 5 of cardiovascular disease and 13 of cancer, the pooled relative risks (95% CI) comparing menthol cigarette smokers to nonmenthol cigarette smokers was 0.94 (0.85, 1.05) for all-cause mortality, 1.28 (0.91, 1.80) for cardiovascular disease and 0.84 (0.76, 0.92) for any cancer. Conclusions In a representative sample of U.S. adults, menthol cigarette smoking was associated with increased all-cause, cardiovascular and cancer mortality with no differences compared to nonmenthol cigarettes. In the systematic review, menthol cigarette use was associated with inverse risk of cancer compared to nonmenthol cigarette use with some evidence of an increased risk for cardiovascular disease.

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study

BACKGROUND Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). METHODS We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). RESULTS All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. CONCLUSIONS In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US.