Assessment Of Smoke Exposure Research Articles

Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility.

Pack-year smoking history is an imperfect and biased measure of cumulative tobacco exposure. The use of pack-year smoking history to determine lung cancer screening eligibility in the current US Preventive Services Task Force (USPSTF) guideline may unintentionally exclude many high-risk individuals, especially those from racial and ethnic minority groups. It is unclear whether using a smoking duration cutoff instead of a smoking pack-year cutoff would improve the selection of individuals for screening. We analyzed 49,703 individuals with a smoking history from the Southern Community Cohort Study (SCCS) and 22,126 individuals with a smoking history from the Black Women's Health Study (BWHS) to assess eligibility for screening under the USPSTF guideline versus a proposed guideline that replaces the ≥20-pack-year criterion with a ≥20-year smoking duration criterion. Under the USPSTF guideline, only 57.6% of Black patients with lung cancer in the SCCS would have qualified for screening, whereas a significantly higher percentage of White patients with lung cancer (74.0%) would have qualified (P < .001). Under the proposed guideline, the percentage of Black and White patients with lung cancer who would have qualified for screening increased to 85.3% and 82.0%, respectively, eradicating the disparity in screening eligibility between the groups. In the BWHS, using a 20-year smoking duration cutoff instead of a 20-pack-year cutoff increased the percentage of Black women with lung cancer who would have qualified for screening from 42.5% to 63.8%. Use of a 20-year smoking duration cutoff instead of a 20-pack-year cutoff greatly increases the proportion of patients with lung cancer who would qualify for screening and eliminates the racial disparity in screening eligibility between Black versus White individuals; smoking duration has the added benefit of being easier to calculate and being a more precise assessment of smoking exposure compared with pack-year smoking history.

The Relationship Between Personal Factors, Smoke Exposure at Home, and Respiratory Problems in Early Childhood in Nakhon Si Thammarat Province, Thailand.

The purpose of this study was to examine the relationship between personal factors, smoke exposure at home, and respiratory problems in early childhood in Nakhon Si Thammarat Province, Thailand. This study was retrospective. There was a total of 414 samples in the study. The instruments included the questionnaire about the personal data of early childhood and their caregivers, the smoke exposure assessment form, and the early childhood respiratory problem assessment form. The relationship between personal factors, smoke exposure at home, and respiratory problems in early childhood was analyzed by the Chi-squared test and binary logistic regression. The results revealed that smoke exposure at home in early childhood was moderate (52.2%). There 68.8% had respiratory problems. The relationship between birth weight, and smoke exposure at home in early childhood was found to be significantly related to respiratory problems (X2 =5.014 p< 0.05 and X2 = 85.711 p< 0.001, respectively). It was found that children with a birth weight ≤2500g had respiratory problems at 2.55 times of the samples with birth weight >2500g (AOR = 2.55, 95% CI: 1.10-5.96), and moderate-high smoke exposure had respiratory problems at 8.86 times of the samples with low smoke exposure (AOR = 8.86, 95% CI: 5.39-14.60). Nutritional status and breastfeeding were not significantly related to respiratory problems in early childhood p > 0.05. The birth weight and smoke exposure at home factors were found to be related to their respiratory problems in early childhood. Thus, it is necessary to reduce stimuli, especially smoking at home. Moreover, the standard birth weight of their early childhood will reduce the rate of respiratory problems.

Serum cotinine cut-points for secondhand smoke exposure assessment in children under 5 years: A systemic review.

BackgroundSerum cotinine has become the most widely used biomarker of secondhand smoke exposure (SHS) over time in all ages. The aim of this study was to review the serum cotinine cut-points used to classify children under 5 years as exposed to SHS.MethodsA systematic review performed in the Pubmed (MEDLINE) and EMBASE databases up to April 2021 was conducted using as key words "serum cotinine", “tobacco smoke pollution” (MeSH), "secondhand smoke", "environmental tobacco smoke" and “tobacco smoke exposure”. Papers which assessed SHS exposure among children younger than 5 years old were included. The PRISMA 2020 guidelines were followed. Analysis was pre-registered in PROSPERO (registration number: CRD42021251263).Results247 articles were identified and 51 fulfilled inclusion criteria. The selected studies were published between 1985–2020. Most of them included adolescents and adults. Only three assessed postnatal exposure exclusively among children under 5 years. None of the selected studies proposed age-specific cut-points for children < 5 years old. Cut-point values to assess SHS exposure ranged from 0.015 to 100 ng/ml. The most commonly used cut-point was 0.05 ng/ml, derived from the assay limit of detection used by the National Health and Nutrition Examination Survey (NHANES).ConclusionsNo studies have calculated serum cotinine age-specific cut-points to ascertained SHS exposure among children under 5 years old. Children’s age-specific cut-points are warranted for health research and public health purposes aimed at accurately estimating the prevalence of SHS exposure and attributable burden of disease to such exposure, and at reinforcing 100% smoke-free policies worldwide, both in homes, private vehicles and public places.

Secondhand smoke exposure assessment in outdoor hospitality venues across 11 European countries

ObjectiveDue to partial or poorly enforced restrictions secondhand tobacco smoke (SHS) is still present in outdoor hospitality venues in many European countries. This study aimed to assess SHS concentrations in outdoor hospitality venues across Europe and identify contextual exposure determinants. MethodsCross-sectional study. We measured airborne nicotine and evidence of tobacco use in terraces of bars, cafeterias, and pubs from 11 European countries in 2017–2018. Sites were selected considering area-level socioeconomic indicators and half were visited during nighttime. We noted the smell of smoke, presence of smokers, cigarette butts, ashtrays, and number of physical covers. Contextual determinants included national smoke-free policies for the hospitality sector, the Tobacco Control Scale score (2016), and the national smoking prevalence (2017–2018). We computed medians and interquartile ranges (IQR) of nicotine concentrations and used multivariate analyses to characterize the exposure determinants. ResultsNicotine was present in 93.6% of the 220 sites explored. Overall concentrations were 0.85 (IQR:0.30–3.74) μg/m3 and increased during nighttime (1.45 IQR:0.65–4.79 μg/m3), in enclosed venues (2.97 IQR:0.80–5.80 μg/m3), in venues with more than two smokers (2.79 IQR:1.03–6.30 μg/m3), in venues in countries with total indoor smoking bans (1.20 IQR:0.47–4.85 μg/m3), and in venues in countries with higher smoking prevalence (1.32 IQR:0.49–5.34 μg/m3). In multivariate analyses, nicotine concentrations were also positively associated with the observed number of cigarette butts. In venues with more than two smokers, SHS levels did not significantly vary with the venues’ degree of enclosure. ConclusionsOur results suggest that current restrictions in outdoor hospitality venues across Europe have a limited protective effect and justify the adoption of total smoking bans in outdoor areas of hospitality venues.

Fall 2020 Proceedings of the Cannabis Chemistry Subdivision

The cannabis industry is unique in many facets, most of them products of history. Cannabis has been prevalent in society for millennia, but for the period between 1937 and 1997 prohibition was imposed in the United States stifling research and creating an unregulated market. From 1997 to present, starting with California, there has been a wave of state-by-state legalizations. Each of these states has individual regulations that operators must comply with. For those working with hemp (cannabis containing less than 0.3% THC by dry weight), there is an entirely different framework of federal regulations. As an unfortunate consequence of this history, the science of cannabis along with the safety culture are relatively unevolved compared with other modern industries. In 2015, the Cannabis Chemistry Subdivision (CANN) of the division of Chemical Health and Safety (CHAS) was recognized by the America Chemical Society (ACS). Since its inception, CANN symposia at ACS National Meetings have served as the premiere venue for cannabis chemists and scientists to share their research, much of it related to improving the health and safety culture in the industry. This proceedings publication highlights 16 presentations that were given at CANN symposia during the Fall 2020 ACS National Meeting. Topics covered include analytical testing methods, consumer education and protection, formulation science, intellectual property considerations, best practices for pharmacokinetics and dosing studies, assessment of smoke exposure, and more.

Accuracy of the Smoking Questionnaire

Summary The smoking questionnaire (SQ), a multidimensional questionnaire covering the major dimensions of cigarette smoking, was developed to address the heterogeneity in the assessment of smoking exposure. It consists of eight questions and can be completed within a few minutes. Test-retest reliability of the SQ and concurrent validity with the Behavior Risk Factor Surveillance System (BRFSS) 2011 questionnaire were examined in a clinical study conducted in adult US current menthol cigarette smokers. The SQ and the BRFSS were self-administrated twice before and after randomization with a 6-day interval. The inter-temporal analyses included current smokers aged 22 to 66 years who completed the SQ at both timepoints. The percent agreement of items and 95% confidence intervals were calculated for the comparisons between the two timepoints and between the SQ and the BRFSS questionnaire. To evaluate the feasibility of the SQ and to capture subjects’ opinions about the SQ, a meta-questionnaire was administrated. High test-retest reliability levels (percent agreement of &gt; 70 to 100% between the two timepoints) were found for SQ smoking behavior items, in particular for items related to current smoking status, 100-cigarettes lifetime, regular smoking, age of initiation and preferred brand. Moderate (55% agreement) to high test-retest reliability (84% agreement) was found for daily consumption of manufactured cigarettes. The comparison between the SQ and the BRFSS 2011 showed a high concurrent validity (98 to 100% agreement). The SQ was completed on average in 3 to 4 min and was assessed as easy to use. The findings demonstrate that the SQ is reliable in smokers and a practical tool to assess smoking exposure in clinical studies.

Secondhand smoke exposure assessment and counseling in the Chinese pediatric setting: a qualitative study.

BackgroundAssisting smoking parents to quit smoking and eliminating the secondhand smoke (SHS) exposure of their children is a global health priority. Engaging healthcare workers in developing countries to address this priority has been a challenge. This study intends to explore issues around current practice related to SHS exposure assessment and counseling and identify barriers to SHS exposure reduction counseling in the Chinese pediatric setting.MethodsWe conducted qualitative interviews (11 focus groups discussions (FGDs) with pediatricians, 6 FGDs with pediatric nurses and 11 in-depth interviews (IDIs) with hospital administrators) among 101 health-care professionals (HCP) from 5 hospitals in four major cities of Guangxi Province, China. All FGDs/ IDIs were audio recorded and analysed thematically.ResultsThe findings suggest that few Chinese pediatricians routinely address the SHS exposure of children in their usual practice. All HCPs felt the need for clinical interventions to promote SHS exposure reduction for children. Primary barriers to SHS exposure reduction counseling in the Chinese pediatric setting included: lack of skills and training in tobacco use reduction and cessation counseling; time constraints and heavy workloads, uncertainty about the usefulness of smoking cessation interventions and lack of hospital-wide systems requiring pediatricians to record tobacco use or SHS exposure information. Ideas for overcoming these barriers were building capacity of pediatricians, collaboration with international organization to initiate training, engaging top level leaders in the effort and ensuring financial resources to support the program.ConclusionsThis study among hospital administrators and service providers in China demonstrated a high level of interest in delivering SHS exposure reduction interventions in the pediatric setting. The findings can inform the creation and delivery of clinical interventions in China to promote SHS exposure reduction to children in the pediatric setting.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2431-14-266) contains supplementary material, which is available to authorized users.

Determination of serum cotinine by isotope dilution liquid chromatography tandem mass spectrometry

Objective To establish a method for measuring serum cotinine by isotope dilution liquid chromatography tandem mass spectrometry （ID-LC/MS/MS）and provide an assay that can be applied to the evaluation of the level of smoke exposure and to the risk analysis of smoking related diseases. Methods Blood samples were collected from 94 apparently healthy subjects from October to December in 2010 and centrifuged, and the sera were separated.Serum samples were mixed with ［D3］-cotinine (as the internal standard) and treated with acetonitriles to precipitate protein.After centrifugation, the supernatants were transferred and evaporated under a stream of nitrogen until dryness and reconstituted with mobile phase.Then the residuals were analyzed by LC/MS/MS system with multiple reaction monitor model; the concentration of cotinine were quantified by the isotope internal standard method and the stand curve was employed with a series of calibration.To estimate the precision of the method, five frozen serum pools were repeatedly analyzed in five runs, and every pool was analyzed in triplicate.In addition, the recovery rates were analyzed with the serum sample added with different levels of standard.The stability of cotinine in serum preserved at room temperature, 4 ℃ and -80 ℃, respectively.Finally, the levels of cotinine of94 healthy subjects were measured to evaluate the distribution of cotinine with different smoke statuses. Results Serum cotinine measured by ID-LC/MS/MS was separated well with few interferences.The correlation coefficients between the peak area ratios and cotinine concentrations were higher than 0.9993.The values of within-run coefficients of variation （CV） of five frozen serum pools (0.68, 48.42, 94.34, 250.95 and 287.04 μg/L) were 2.19%，0.78%，0.75%，0.65% and 0.67％, respectively.The values of total CV were 4.71%，1.40%，1.98%，1.10% and 1.03％, respectively.The limit of detection （LOD） and limit of quantitation （LOQ） were 0.013 and 0.050 μg/L, respectively.The analytical recoveries ranged from 99.22% to 102.67%.The samples could maintain stability within 2 d at room temperature, 7 d at 4 ℃ and 3 months at -80 ℃ resulting the accuracy of measurements from 99.28% to 100.87% and the CV<5%.The levels of cotinine of 94 healthy subjects were measured and shown skewed and leptokurtic distribution.The concentrations of twenty smokers, fourteen former smokers and sixty non-smokers were 116.40 (63.17-241.12), 0.67 (0.15-0.95) and 0.22 (0.15-0.42) μg/L, respectively. Furthermore, the level of cotinine of former smokers (Z=-2.12, P＜0.05) and smokers (Z=-6.67, P<0.001) were statistically higher than non-smokers. Conclusions An ID-LC/MS/MS method for serum cotinine detection has been established.It is hoped that the method will be applied to the assessment of smoke exposure and its association with the risks of smoking related diseases since it is simple, specific, precise, sensitive and accurate.（Chin J Lab Med, 2012, 35:333-338） Key words: Smoke; Cotinine; Isotope dilution mass spectrometry; Liquid chromatography tandem mass spectrometry

Domestic smoke exposure is associated with alveolar macrophage particulate load

Indoor air pollution is associated with impaired respiratory health. The pre-dominant indoor air pollutant to which two billion of the world's population is exposed is biomass fuel smoke. We tested the hypothesis that reported smoke exposure in men and women is associated with increased alveolar macrophage uptake of biomass smoke particulates. Healthy volunteers attending for research bronchoscopy in Malawi completed a questionnaire assessment of smoke exposure. Particulate matter visible in alveolar macrophages (AM) was quantified using digital image analysis. The geometric mean of the percentage area of the cytoplasm occupied by particulates in 50 cover-slip adherent AM was calculated and termed particulate load. In 57 subjects (40 men and 17 women) there was a significant difference between the particulate load in groups divided according to pre-dominant lighting form used at home (ANOVA P = 0.0009) and type of cooking fuel (P = 0.0078). Particulate load observed in macrophages is associated with the reported type of biomass fuel exposure. Macrophage function in relation to respiratory health should now be investigated in biomass smoke exposed subjects.

Exposición involuntaria al humo de tabaco en lugares públicos de la Ciudad de México

Mexican legislation considers many public places as smoke-free spaces. However, no environmental tobacco smoke exposure assessment studies exist to evaluate compliance with governmental regulations and to identify opportunities for tobacco control. The main objective of this study is to quantify airborne nicotine concentrations in public places in Mexico City. During March 2004, nicotine passive monitors were allocated in a hospital, two schools, a public office building, an airport, seven restaurants, and three bars following a common protocol applied in other Latin American countries. Monitors were analyzed at the Johns Hopkins University, extracting the nicotine and quantifying it using nitrogen selective gas chromatography. Median concentrations of environmental nicotine were estimated by type of place and smoking restriction. Airborne nicotine was detected in all public places. The highest concentrations were observed in bars (6.01 microg/m3), restaurants (0.69 microg/m3), airport (0.21 microg/m3), and public offices (0.10 microg/m3). Nicotine exposure concentrations are similar to those previously observed in other capital cities of Latin America. Nicotine levels in the airport and public offices reflect the lack of compliance with mandatory non-smoking official regulations in Mexico. High nicotine concentrations in bars and restaurants provide evidence for the need to advance smoke-free legislative action in these public and work places.

Forest Fire Smoke Exposure Assessment: Use of Remote Sensing Data in a Pollution Dispersion Model

TM3-O-09 Introduction: Climate change analysts predict that wildfires will become more frequent and intense worldwide over the next 50 years. The health effects of smoke from these events are not well understood, largely due to lack of exposure data. Because most fires burn in areas with sparse air quality monitoring, novel exposure assessment methods are needed to facilitate epidemiologic studies on affected populations. Here we use physically based numerical models in combination with remote sensing data to estimate smoke-related elevations in 24-hour average PM10 concentrations across a 325,000 km2 region of Canada over a 92-day period in 2003. Methods: We initialized the CALMET meteorologic model with data from 99 surface weather stations and output from a numerical weather prediction model. Resulting fields were used as input for the CALPUFF dispersion model. Fire locations were remotely detected by 2 satellite-borne Moderate Resolution Imaging Spectroradiometers (MODIS). Three methods for estimating particle emissions were compared: 1) the U.S. Forest Service's Emissions Production Model (EPM), 2) Forestry Canada's Fire Behavior Prediction (FBP) System, and 3) calculations based on the radiative power of MODIS-detected fires (MRP). The spatial validity of model output was assessed by the horizontal overlap between CALPUFF-predicted and MODIS-imaged plumes. The 24-hour average concentration estimates were evaluated by comparison to surface PM10 (TEOM) measurements. Results: Test results for a 12,500 km2 area over a 14-day period indicate that CALMET/CALPUFF captured 65% of plume footprints on average; 2 examples are shown below. Surface concentrations at the only monitoring site in the test area were underestimated by the EPM emission rates and overestimated by the FBP and MRP methods. Regressions between modeled and measured 24-hour averages had slopes (R2) of 0.20 (0.70), 1.80 (0.70), and 6.93 (0.68), respectively. The high R2 values suggest that CALPUFF captures the temporal trend in all cases. Although MRP particle emission rates are unrealistic for highly radiative fires, these arithmetic estimates are more easily scaled than those from the EPM and FBP models. Techniques for further optimization and final results for the entire domain will be discussed. Discussion: Most simulations of wildfire plume dispersion require cumbersome models for estimating fire spread and particle emission rates. Here we demonstrate that readily available remote sensing data have the potential to produce results of equivalent quality. This will simplify and expedite smoke exposure estimates for future epidemiologic analyses.FIGURE.: Dark areas depict plume footprints as imaged by MODIS and gray lines depict CALPUFF plume contours at the surface. Location of the air quality monitoring site is shown as a white dot.

Is residual confounding a reasonable explanation for the apparent protective effects of beta-carotene found in epidemiologic studies of lung cancer in smokers?

The results of three randomized trials of beta-carotene supplementation for the prevention of lung cancer among smokers are in contradiction to a large body of epidemiologic evidence for the reduction of risk of lung cancer among smokers with higher intake and/or higher serum levels of beta-carotene. Complicating this issue are widely noted negative associations between tobacco use and intake or serum levels of beta-carotene. Although observational studies attempt to control for reported smoking histories, the accuracy of self-reported smoking is uncertain; correlations as low as 0.5 between reported and true smoking exposure are not inconsistent with studies of biomarkers of cigarette exposure. The authors developed a simple statistical model for random errors in reported smoking (relative to true tobacco exposure) and assumed a modest (inverse) relation between true tobacco exposure and serum beta-carotene. Calculations from this model, combined with a model for lung cancer contemplated by Doll and Peto (J Epidemiol Community Health 1978;78:303-13), suggest that biases in assessment of smoking exposure between smokers with low versus high beta-carotene intake may plausibly explain much or all of the observed protective effect of high beta-carotene levels. Appropriate cohort studies of lung cancer in smokers, utilizing biomarkers of smoking, are needed and are presently ongoing.

Measurement of nicotine in hair by reversed-phase high-performance liquid chromatography with electrochemical detection

We have developed an assay for nicotine in hair based on reversed-phase HPLC with electrochemical detection. The method uses a low-metal, high-purity silica reversed-phase column. We have investigated the washing, digestion and extraction procedures and discuss the important points in the HPLC method development. The assay is presented as an application in a population of exposed and non-exposed children. Analytical parameters are satisfactory with linearity, recoveries, limit of quantitation and precision all suitable for epidemiological studies involving environmental tobacco smoke exposure assessment.

Rationale and design of the LURIC study--a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease.

Coronary artery disease (CAD), arterial hypertension and Type 2 diabetes mellitus are common polygenetic disorders which have a major impact on public health. Disease prevalence and progression to cardiovascular complications, such as myocardial infarction (MI), stroke or heart failure, are the product of environment and gene interaction. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study aims to provide a well-defined resource for the study of environmental and genetic risk factors, and their interactions, and the study of functional relationships between gene variation and biochemical phenotype (functional genomics) or response to medication (pharmacogenomics). Long-term follow-up on clinical events will allow us to study the prognostic importance of common genetic variants (polymorphisms) and plasma biomarkers. Cardiology unit in tertiary care medical centre in south-west Germany. Prospective cohort study of individuals with and without cardiovascular disease at baseline. LURIC is an ongoing prospective study of currently > 3300 individuals in whom the cardiovascular and metabolic phenotypes CAD, MI, dyslipidaemia, hypertension, metabolic syndrome and diabetes mellitus have been defined or ruled out using standardised methodologies in all study participants. Inclusion criteria for LURIC were: German ancestry (limitation of genetic heterogeneity) clinical stability (except for acute coronary syndromes [ACSs]) availability of a coronary angiogram (this inclusion criterium was waived for family members provided that they met all other inclusion and exclusion criteria) Exclusion criteria were: any acute illness other than ACSs any chronic disease where non-cardiac disease predominated a history of malignancy within the past five years. Exclusion criteria were pre-specified in order to minimise the impact of concomitant non-cardiovascular disease on intermediate biochemical phenotypes or on clinical prognosis (limitation of clinical heterogeneity). A standardised personal and family history questionnaire and an extensive laboratory work-up (including glucose tolerance testing in non-diabetics and objective assessment of smoking exposure by determination of cotinine plasma levels) was obtained from all individuals after informed consent. A total of 115 ml of fasting venous blood was sampled for the determination of a pre-specified wide range of intermediate biochemical phenotypes in serum, plasma or whole blood, for leukocyte DNA extraction and immortalisation of B-lymphocytes. Biochemical phenotypes measured included markers of endothelial dysfunction, inflammation, oxidative status, coagulation, lipid metabolism and flow cytometric surface receptor expression of lympho-, mono- and thrombocytes. In addition, multiple aliquots of blood samples were stored for future analyses. A total of 3500 LURIC baseline measurements were performed in 3316 individuals between July 1997 and January 2000. The baseline examination was repeated within a median of 35 days in 5% of study participants (n = 166, including a third examination in 18 after a median of 69 days) for pharmacogenomic assessment of lipid-lowering therapy and for quality control purposes. A five-year follow-up on major clinical events (death, any cardiovascular event including MI, stroke and revascularisation, malignancy and any hospitalisation) is ongoing. The clinical phenotypes prevalent at baseline in the cohort of 2309 men (70%) with a mean age of 62 +/- 11 years and 1007 women (30%), mean age 65 +/- 10 years, were angiographically-documented CAD in 2567 (79%), MI in 1368 (41%), dyslipidaemia in 2050 (62%) with hypercholesterolaemia > or = 240 mg/dl (27%), hypertriglyceridaemia > or = 150 mg/dl (44%) and HDL-cholesterol < or = 35 mg/dl (38%) in individuals not treated with lipid-lowering agents, systemic hypertension in 1921 (58%), metabolic syndrome in 1591 (48%), Type 2 diabetes in 1063 (32%) and obesity defined by body mass index > or = 30 kg/m2 in 770 (23%). Control patients in whom CAD had been ruled out angiographically were five years younger than those with CAD (59 +/- 12 and 64 +/- 10 years, respectively; p < 0.001), twice as often females (48% compared to 25% females in the CAD group, p < 0.001) and had significantly less cardiovascular risk factors than individuals with CAD. The prevalence of specific cardiovascular risk subsets in LURIC, such as the elderly (> or = 75 years), was 375 (11%), while 213 (6%) were young adults (< 45 years) and 904 (27%) were postmenopausal women (90% of all females). A low risk status (< or = 1 out of the four traditional risk factors: dyslipidaemia, smoking, hypertension and diabetes mellitus) was identified in 314 (9%) individuals of the entire cohort (5% in CAD and 26% in controls, p < 0.001) and 97 (3%) carried none of the four risk factors (1% in CAD and 9% in controls, p < 0.001). (ABSTRACT TRUNCATED)