Omayma Alshaarawy

Polycyclic aromatic hydrocarbon biomarkers and serum markers of inflammation. A positive association that is more evident in men

BACKGROUND Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants, occurring from anthropogenic and natural sources. Several animal studies have reported a positive association of PAHs with inflammation. However, it is not clear if lower background exposure to PAHs is associated with inflammation in humans, independent of smoking, a major source of PAHs. METHODS We examined participants from the National Health and Nutrition Examination Survey 2001-2002, 2003-2004, and 2005-2006. Our exposures of interest were eight urinary monohydroxy polycyclic aromatic hydrocarbon biomarkers. Our outcomes were serum markers of inflammation; C-reactive protein (CRP) (≤10 mg/L) and total white blood cell (WBC) count (4000-12,000 cells/μL). RESULTS Compared to participants with summed biomarkers of low-molecular weight (LMW) PAHs in the lowest quartile, the multivariable odds ratios (95% confidence interval) of high serum CRP (≥3 mg/L) and high total WBC count (defined as at or above the 95 percentile of total WBC distribution) among participants in the highest exposure quartile were 1.77 (1.13, 2.76) and 1.34 (1.12, 1.60) respectively. Urinary 1-hydroxypyrene, the biomarker of the higher molecular weight pyrene, was positively associated with total WBC count, and to lesser extent with serum CRP. In subsequent analyses, the positive association between LMW PAHs and serum CRP and total WBC count was found to be present within the stratified subgroups, independent of smoking and other potential confounders. The positive association was more evident among adult males when compared to females. CONCLUSIONS Urinary PAH biomarkers were found to be positively associated with serum CRP and total WBC count independent of smoking and other potential confounders. The association was more evident in men.

Urinary polycyclic aromatic hydrocarbon biomarkers and diabetes mellitus

Objective The aim of the current study is to investigate the association of polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants, with diabetes mellitus. Animal studies link PAHs to inflammation and subsequent development of diabetes mellitus. In addition, occupational studies suggest that exposure to other aromatic hydrocarbons such as dioxins may be associated with diabetes risk in humans. Design We examined participants from the merged National Health and Nutrition Examination Survey 2001–2002, 2003–2004 and 2005–2006. Exposures of interest were eight urinary monohydroxy-PAHs. Our outcome was diabetes mellitus defined as a glycohemoglobin level (HbA1c) ≥6.5%, a self-reported physician diagnosis of diabetes or use of oral hypoglycaemic medication or insulin. Analyses were adjusted for age, sex, body mass index, race, alcohol consumption, poverty–income ratio, total cholesterol and serum cotinine. Results We observed a positive association between urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed low molecular weight (LMW) PAH biomarkers, and diabetes mellitus. Compared with participants with summed LMW PAH biomarkers in the lowest quartile, the multivariable-adjusted OR of diabetes mellitus among those in the highest quartile was 3.1 (95% CI 1.6 to 5.8). Conclusions Urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed LMW PAH biomarkers are associated with diabetes mellitus in US adults 20–65 years of age. The association of a one-time biomarker of PAH exposure has limitations commonly associated with cross-sectional studies, yet is consistent with experimental animal data and is worthy of additional consideration.

The association of urinary polycyclic aromatic hydrocarbon biomarkers and cardiovascular disease in the US population

BACKGROUND Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants produced by incomplete combustion of organic materials. Pre-clinical and occupational studies have reported a positive association of PAHs with oxidative stress, inflammation and subsequent development of atherosclerosis, a major underlying risk factor for cardiovascular disease (CVD). The aim of the current study is to estimate the association between levels of PAH biomarkers and CVD in a national representative sample of United States (US) adults. METHODS We examined adult participants (≥20years of age) from the merged US National Health and Nutrition Examination Survey 2001-2010. Logistic regression models were used to estimate the associations of each urinary PAH biomarker and CVD. Post-exploratory structural equation modeling was then used to address the interdependent response variables (angina, heart attack, stroke and coronary heart disease) as well as the interdependencies of PAH biomarkers. RESULTS PAH biomarkers were positively associated with cardiovascular disease in multiple logistic regression models, although some associations were not statistically robust. Using structural equation modeling, latent PAH exposure variable was positively associated with latent CVD level variable in the multivariable adjusted model (β=0.12; 95% CI: 0.03, 0.20). CONCLUSION A modest association between levels of PAH biomarkers and CVD was detected in US adults. Further prospective studies with adequate sample size are needed to replicate or refute our findings.

Association of Serum Cotinine Levels and Hypertension in Never Smokers

Hypertension is a major public health problem. Identifying novel risk factors for hypertension, including widely prevalent environmental exposures, is therefore important. Active smoking is a well-known risk factor for hypertension and cardiovascular diseases. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine, and high blood pressure among never smokers. We examined 2889 never smokers from the National Health and Nutrition Examination Survey 2005–2008. Our exposure of interest was secondhand smoke exposure among never smokers, estimated by serum cotinine level, and our main outcome was hypertension (n=1004). We found that in never smokers, higher serum cotinine levels were positively associated with hypertension. In comparison with those with serum cotinine levels ⩽0.025 ng/mL, the multivariable odds ratio (95% confidence interval) of hypertension among those with serum cotinine levels ≥0.218 ng/mL was 1.44 (1.01–2.04). In addition, higher serum cotinine was positively associated with mean change in systolic blood pressure (odds ratio [95% confidence interval], 3.24 [0.86–5.63]; P=0.0061). However, no association was present with diastolic blood pressure. In conclusion, in never smokers, higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with systolic blood pressure and hypertension independent of age, sex, ethnicity, education, alcohol drinking, body mass index, glycohemoglobin, total cholesterol, and other confounders.

Markers of Sleep-Disordered Breathing and Prediabetes in US Adults

Background. Prediabetes is a preclinical stage in the hyperglycemia continuum where subjects are at increased risk of developing diabetes. Several studies reported a positive association between markers of sleep-disordered breathing (SDB) and diabetes. However, few studies investigated the relationship between SDB markers and prediabetes. Methods. We examined 5,685 participants ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2008. The exposure of interest was SDB markers including sleep duration, snoring, snorting, and daytime sleepiness. The outcome was prediabetes (n = 2058), among subjects free of diabetes. Results. SDB markers were associated with prediabetes. Compared to those without any sleep disturbance, the multivariable odds ratio (OR) (95% confidence interval (CI)) of prediabetes among those with three or more SDB markers was 1.69 (1.28–2.22). In subgroup analyses, the association between SDB markers and prediabetes was stronger among women (OR (95% CI) = 2.09 (1.36–3.23) when compared to men (1.52 (1.00–2.35)) and was present among non-Hispanic whites (2.66 (1.92–3.69)) and Mexican Americans (1.99 (1.13–3.48)), but not among non-Hispanic blacks (1.10 (0.70–1.73)). Conclusion. SDB markers were associated with prediabetes. This association was stronger in women and was present mainly in non-Hispanic whites and Mexican Americans.

Cannabis Smoking and Diabetes Mellitus: Results from Meta-analysis with Eight Independent Replication Samples.

Background: In preclinical animal studies, evidence links cannabis with hyperphagia, obesity, and insulin resistance. Epidemiologic data, however, suggest an inverse cannabis smoking–diabetes mellitus association. Here, we offer epidemiologic estimates from eight independent replications from (1) the National Health and Nutrition Examination Surveys, and (2) the National Surveys on Drug Use and Health (2005–2012). Methods: For each national survey participant, computer-assisted self-interviews assess cannabis smoking and physician-diagnosed diabetes mellitus; the National Health and Nutrition Examination Surveys provide additional biomarker values and a composite diabetes diagnosis. Regression analyses produce estimates of cannabis smoking–diabetes associations. Meta-analyses summarize the replication estimates. Results: Recently active cannabis smoking and diabetes mellitus are inversely associated. The meta-analytic summary odds ratio is 0.7 (95% confidence interval = 0.6, 0.8). Conclusions: Current evidence is too weak for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective (or spurious) cannabis smoking–diabetes mellitus association suggested in prior research.

Cannabis smoking and serum C-reactive protein: A quantile regressions approach based on NHANES 2005–2010

BACKGROUND Pre-clinical studies link cannabinoid-1 receptor activation to inflammation and atherosclerotic effects; anti-inflammation and immunosuppression seem to be mediated by cannabinoid-2 receptor activation. In this epidemiological study, we aim to present estimates on suspected cannabis-attributable immunomodulation as manifest in serum C-reactive protein (CRP) levels as non-specific inflammatory markers with interpretable clinical values. With strength of data from recent large nationally representative community sample surveys, the research approach illustrates value of a quantile regressions approach in lieu of the commonly used but relatively arbitrary cutpoints for CRP values. METHODS The study population encompasses 20-59 year old participants from the National Health and Nutrition Examination Surveys, 2005-2010 (n=1115 recently active cannabis smokers and 8041 non-smokers, identified via confidential Audio Computer Assisted Self-Interviews). Age, sex, race, education, income-poverty ratio, alcohol consumption, and tobacco smoking also were measured, together with body mass index (BMI), which actually might be on a mediational path. Quantile regressions, with bootstrapping for variance estimation, made it possible to hold these covariates constant while estimating cannabis-CRP associations. RESULTS Evidence suggesting possible cannabis-attributable immunomodulation emerges at CRP levels below the median (p<0.05). Whereas BMI might help explain a cannabis link with serum CRP, but BMI-stratified analyses disclosed no appreciable variation of the cannabis-CRP relationship across BMI subgroups. CONCLUSIONS Extending pre-clinical research on cannabis-attributable immunomodulation, this studys CRP evidence points toward possible anti-inflammatory effects of cannabis smoking. More definitive evidence can be derived by combining pre-clinical research, studies of patients, and epidemiological research approaches.

Cannabis use and blood pressure levels: United States National Health and Nutrition Examination Survey, 2005-2012.

Objective: Preclinical studies have reported acute cardiovascular effects of cannabis, including a dose-dependent increase in blood pressure (BP), whereas orthostatic hypotension may follow as a result of decreased vascular resistance. In case reports, evidence links cannabis with acute cardiovascular events in young and middle-aged adults. Here, we offer epidemiologic estimates on cannabis use and BP levels association from the US National Health and Nutrition Examination Surveys 2005–2012 (n = 12 426). Methods: Computer-assisted self-interviews assessed cannabis use. BP was determined by an average of up to four measurements taken during a single examination. Regression modeling was used to examine cannabis use and BP association. Results: Recently active cannabis use was associated with increase in SBP (&bgr; = 1.6; 95% confidence interval: 0.6, 2.7) in the age–sex-adjusted model. Additional covariate adjustment did not affect the positive association. No association between cannabis use and DBP was detected. Conclusion: A modest association between recent cannabis use and SBP was detected among a relatively large nationally representative sample of US adults. With the legalization of cannabis, there is a need for preclinical, clinical and prospective population-based research on the cardiovascular effects of cannabis use.

Serum Cotinine Levels and Prehypertension in Never Smokers

Background. Few studies have shown that self-reported secondhand smoke exposure in never smokers is associated with high blood pressure. However, there are no studies investigating the relationship between secondhand smoke exposure, measured objectively by serum cotinine levels, and high blood pressure in never smokers. Methods. We examined never smokers (n = 2027) from the National Health and Nutrition Examination Survey 2005–2008. Our exposure of interest was the secondhand smoke exposure estimated by serum cotinine level and our outcome was prehypertension (n = 734), defined as a systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. Results. We found that, in never smokers, serum cotinine levels were positively associated with prehypertension. Compared to those with cotinine levels in the lowest quartile (≤0.024 ng/mL), the multivariable odds ratio (95% confidence interval) of prehypertension among those with cotinine levels in the highest quartile (≥0.224 ng/mL) was 1.45(1.00, 2.11); P trend = 0.0451. In subsequent subgroup analyses, the positive association was found to be stronger among men, non-Whites, and non-obese subjects. Conclusion. Higher secondhand smoke exposure measured objectively by serum cotinine levels was found to be associated with prehypertension in certain subgroups of a representative sample of the US population.

Inverse association linking serum levels of potential antioxidant vitamins with C-reactive protein levels using a novel analytical approach.

Exposures to antioxidants (AO) are associated with levels of C-reactive protein (CRP), but the pattern of evidence is mixed, due in part to studying each potential AO, one at a time, when multiple AO exposures might affect CRP levels. By studying multiple AO via a composite indicator approach, we estimate the degree to which serum CRP level is associated with serum AO level. Standardised field survey protocols for the US National Health and Nutrition Examination Survey (NHANES) 2003-2006 yielded nationally representative cross-sectional samples of adults aged 20 years and older (n 8841). NHANES latex-enhanced nephelometry quantified serum CRP levels. Liquid chromatography quantified serum concentrations of vitamins A, E and C and carotenoids. Using structural equations, we regressed CRP level on AO levels, and derived a summary estimate for a composite of these potential antioxidants (CPA), with covariates held constant. The association linking CPA with CRP was inverse, stronger for slightly elevated CRP (1·8≤CRP<10 mg/l; slope= -1·08; 95 % CI -1·39, -0·77) and weaker for highly elevated CRP (≥10 mg/l; slope= -0·52; 95 % CI -0·68, -0·35), with little change when covariates were added. Vitamins A and C, as well as lutein+zeaxanthin, were prominent contributors to the composite. In these cross-sectional data studied via a composite indicator approach, the CPA level and the CRP level were inversely related. The stage is set for more confirmatory longitudinal or intervention research on multiple vitamins. The composite indicator approach might be most useful in epidemiology when several exposure constructs are too weakly inter-correlated to be studied via formal measurement models for underlying latent dimensions.