849 resultados para Risk factor


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Multiple studies have shown an association between periodontitis and coronary heart disease due to the chronic inflammatory nature of periodontitis. Also, studies have indicated similar risk factors and patho-physiologic mechanisms for periodontitis and CHD. Among these factors, smoking has been the most discussed common risk factor and some studies suggested the periodontitis - CHD association to be largely a result of confounding due to smoking or inadequate adjustment for it. We conducted a secondary data analysis of the Dental ARIC Study, an ancillary study to the ARIC Study, to evaluate the effect of smoking on the periodontitis - CHD association using three periodontitis classifications namely, BGI, AAP-CDC, and Dental-ARIC classification (Beck et al 2001). We also compared these results with edentulous ARIC participants. Using Cox proportional hazard models, we found that the individuals with the most severe form of periodontitis in each of the three classifications (BGI: HR = 1.56, 95%CI: 1.15 – 2.13; AAP-CDC: HR = 1.42, 95%CI: 1.13 – 1.79; and Dental-ARIC: HR = 1.49, 95%CI: 1.22 – 1.83) were at a significantly higher risk of incident CHD in the unadjusted models; whereas only BGI-P3 showed statistically significant increased risk in the smoking adjusted models (HR = 1.43, 95%CI: 1.04 – 1.96). However none of the categories in any of the classifications showed significant association when a list of traditional CHD risk factors was introduced into the models. On the other hand, edentulous participants showed significant results when compared to the dentate ARIC participants in the crude (HR = 1.56, 95%CI: 1.34 – 1.82); smoking adjusted (HR = 1.39, 95%CI: 1.18 – 1.64) age, race and sex adjusted (HR = 1.52, 95%CI: 1.30 – 1.77); and ARIC traditional risk factors (except smoking) adjusted (HR = 1.27, 95%CI: 1.02 – 1.57) models. Also, the risk remained significantly higher even when smoking was introduced in the age, sex and race adjusted model (HR = 1.38, 95%CI: 1.17 – 1.63). Smoking did not reduce the hazard ratio by more than 8% when it was included in any of the Cox models. ^ This is the first study to include the three most recent case definitions of periodontitis simultaneously while looking at its association with incident coronary heart disease. We found smoking to be partially confounding the periodontitis and coronary heart disease association and edentulism to be significantly associated with incident CHD even after adjusting for smoking and the ARIC traditional risk factors. The difference in the three periodontitis classifications was not found to be statistical significant when they were tested for equality of the area under their ROC curves but this should not be confused with their clinical significance.^

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Background. Inhibition of tumor necrosis factor (TNF) is associated with progression of latent tuberculosis infection (LTBI) to active disease. LTBI screening prior to starting TNF inhibitor therapy is recommended. Blood tests, collectively known as interferon-gamma release assays (IGRAs), offer a means other than the tuberculin skin test (TST) of screening for LTBI. However, in the setting of immune compromise, anergy may limit the clinical utility of IGRAs. ^ Methods. A cross-sectional study was conducted in children and young adults ≤ 21 years of age who were cared for at Texas Children's Hospital in Houston, TX, during 2011 and who were candidates for, or were receiving, tumor necrosis factor (TNF)-inhibitor therapy. All subjects answered a risk factor questionnaire and were tested for LTBI by two commercially available IGRAs (QuantiFERON-Gold In-Tube assay and the T-SPOT.TB assay), along with the TST. T-cell phenotypes were evaluated through flow cytometry, both at baseline and after antigen stimulation. ^ Results. Twenty-eight subjects were enrolled. All were TST negative and none were IGRA positive. Results were negative for the 27 subjects who were tested with QuantiFERON-Gold In-Tube. However, 26% of subjects demonstrated anergy in the T-SPOT.T. Patients with T-SPOT. TB anergy had lower quantitative IFN-γ responses to mitogen in the QFT assay—the mean IFN-γ level to mitogen in patients without T-SPOT.TB anergy was 9.84 IU/ml compared to 6.91 IU/ml in patients with T-SPOT.TB anergy (P = 0.046). Age and use of TNF inhibitors, corticosteroids, or methotrexate use were not significantly associated with T-SPOT.TB anergy. Antigen stimulation revealed depressed expression of intracellular IFN-γ in subjects with T-SPOT. TB anergy. ^ Conclusions. The frequency of anergy in this population is higher than would be expected from studies in adults. There appears to be inappropriate IFN-γ responses to antigen in subjects with T-SPOT. TB anergy. This immune defect was detected by the T-SPOT. TB assay but not by the QuantiFERON-Gold In-Tube assay. Further data are needed to clarify the utility of IGRAs in this population.^

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Injection drug use is the third most frequent risk factor for new HIV infections in the United States. A dual mode of exposure: unsafe drug using practices and risky sexual behaviors underlies injection drug users' (IDUs) risk for HIV infection. This research study aims to characterize patterns of drug use and sexual behaviors and to examine the social contexts associated with risk behaviors among a sample of injection drug users. ^ This cross-sectional study includes 523 eligible injection drug users from Houston, Texas, recruited into the 2009 National HIV Behavioral Surveillance project. Three separate set of analyses were carried out. First, using latent class analysis (LCA) and maximum likelihood we identified classes of behavior describing levels of HIV risk, from nine drug and sexual behaviors. Second, eight separate multivariable regression models were built to examine the odds of reporting a given risk behavior. We constructed the most parsimonious multivariable model using a manual backward stepwise process. Third, we examined whether HIV serostatus knowledge (self-reported positive, negative, or unknown serostatus) is associated with drug use and sexual HIV risk behaviors. ^ Participants were mostly male, older, and non-Hispanic Black. Forty-two percent of our sample had behaviors putting them at high risk, 25% at moderate risk, and 33% at low risk for HIV infection. Individuals in the High-risk group had the highest probability of risky behaviors, categorized as almost always sharing needles (0.93), seldom using condoms (0.10), reporting recent exchange sex partners (0.90), and practicing anal sex (0.34). We observed that unsafe injecting practices were associated with high risk sexual behaviors. IDUs who shared needles had higher odds of having anal sex (OR=2.89, 95%CI: 1.69-4.92) and unprotected sex (OR=2.66, 95%CI: 1.38-5.10) at last sex. Additionally, homelessness was associated with needle sharing (OR=2.24, 95% CI: 1.34-3.76) and cocaine use was associated with multiple sex partners (OR=1.82, 95% CI: 1.07-3.11). Furthermore, twenty-one percent of the sample was unaware of their HIV serostatus. The three groups were not different from each other in terms of drug-use behaviors: always using a new sterile needle, or in sharing needles or drug preparation equipment. However, IDUs unaware of their HIV serostatus were 33% more likely to report having more than three sexual partners in the past 12 months; 45% more likely to report to have unprotected sex and 85% more likely to use drug and or alcohol during or before at last sex compared to HIV-positive IDUs. ^ This analysis underscores the merit of LCA approach to empirically categorize injection drug users into distinct classes and identify their risk pattern using multiple indicators and our results show considerable overlap of high risk sexual and drug use behaviors among the high-risk class members. The observed clustering pattern of drug and sexual risk behavior among this population confirms that injection drug users do not represent a homogeneous population in terms of HIV risk. These findings will help develop tailored prevention programs.^

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Background: Inflammatory breast cancer (IBC) is rare and accounts for 2.5% of all invasive breast cancers. The 5-year survival rates are significantly lower than for other types of breast cancer, highlighting the significance of cancer prevention in IBC. The comprehensive multi-disciplinary team Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at University of Texas MD Anderson Cancer Center treats the largest number of Inflammatory Breast patients in a single center. Because of this unique center, large patient resources, and good medical and epidemiological records, we were able to conduct the largest single center case-control and case-case study on IBC. Methods: We identified 246 patients diagnosed with IBC and 397 cancer free patients seen at the Dan L Duncan Cancer Prevention Clinic. Breast cancer reproductive risk factors and lifestyle risk factors were compared between tumor subtypes of IBC patients (Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+), Human Epidermal Growth Factor 2 positive (HER2+)), and (ER -/PR-/HER2-)) and cancer free controls. Results: Breastfeeding was the only significant risk factor (p<0.01) between tumor subtypes in IBC patients. In the case-control study that included all IBC patients and cancer free patients the descriptive statistics indicate significant difference in BMI, history of smoking, number of children, age of first pregnancy, any breastfeeding and total time breastfeeding (p<0.05). No differences were found in the frequency of other breast cancer risk factors. Conclusion: The associations determined between cancer free controls and IBC patients have identified previously unknown risk factors for IBC. The risk factors identified by the case control study suggest BMI, history of smoking, and the protective effect of breastfeeding as potential modifiable risk factors that can be used to decrease the incidence of IBC. Impact: These results highlight the importance of evaluating epidemiologic risk factors of IBC, which could lead to the identification of distinct etiologic pathways that could be targeted for prevention.^

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Background: Surgical site infections (SSIs) after abdominal surgeries account for approximately 26% of all reported SSIs. The Center for Disease Control and Prevention (CDC) defines 3 types of SSIs: superficial incisional, deep incisional, and organ/space. Preventing SSIs has become a national focus. This dissertation assesses several associations with the individual types of SSI in patients that have undergone colon surgery. ^ Methods: Data for this dissertation was obtained from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP); major colon surgeries were identified in the database that occurred between the time period of 2007 and 2009. NSQIP data includes more than 50 preoperative and 30 intraoperative factors; 40 collected postoperative occurrences are based on a follow-up period of 30 days from surgery. Initially, four individual logistic regressions were modeled to compare the associations between risk factors and each of the SSI groups: superficial, deep, organ/space and a composite of any single SSI. A second analysis used polytomous regression to assess simultaneously the associations between risk factors and the different types of SSIs, as well as, formally test the different effect estimates of 13 common risk factors for SSIs. The final analysis explored the association between venous thromboembolism (VTEs) and the different types of SSIs and risk factors. ^ Results: A total of 59,365 colon surgeries were included in the study. Overall, 13% of colon cases developed a single type of SSI; 8% of these were superficial SSIs, 1.4% was deep SSIs, and 3.8% were organ/space SSIs. The first article identifies the unique set of risk factors associated with each of the 4 SSI models. Distinct risk factors for superficial SSIs included factors, such as alcohol, chronic obstructive pulmonary disease, dyspnea and diabetes. Organ/space SSIs were uniquely associated with disseminated cancer, preoperative dialysis, preoperative radiation treatment, bleeding disorder and prior surgery. Risk factors that were significant in all models had different effect estimates. The second article assesses 13 common SSI risk factors simultaneously across the 3 different types of SSIs using polytomous regression. Then each risk factor was formally tested for the effect heterogeneity exhibited. If the test was significant the final model would allow for the effect estimations for that risk factor to vary across each type of SSI; if the test was not significant, the effect estimate would remain constant across the types of SSIs using the aggregate SSI value. The third article explored the relationship of venous thromboembolism (VTE) and the individual types of SSIs and risk factors. The overall incidence of VTEs after the 59,365 colon cases was 2.4%. All 3 types of SSIs and several risk factors were independently associated with the development of VTEs. ^ Conclusions: Risk factors associated with each type of SSI were different in patients that have undergone colon surgery. Each model had a unique cluster of risk factors. Several risk factors, including increased BMI, duration of surgery, wound class, and laparoscopic approach, were significant across all 4 models but no statistical inferences can be made about their different effect estimates. These results suggest that aggregating SSIs may misattribute and hide true associations with risk factors. Using polytomous regression to assess multiple risk factors with the multiple types of SSI, this study was able to identify several risk factors that had significant effect heterogeneity across the 3 types of SSI challenging the use of aggregate SSI outcomes. The third article recognizes the strong association between VTEs and the 3 types of SSIs. Clinicians understand the difference between superficial, deep and organ/space SSIs. Our results indicate that they should be considered individually in future studies.^

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Ultraviolet radiation plays a critical role in the induction of non-melanoma skin cancer. UV radiation is also immune suppressive. Moreover, UV-induced systemic immune suppression is a major risk factor for skin cancer induction. Previous work had shown that UV exposure in vivo activates a cytokine cascade involving PGE2, IL-4, and IL-10 that induces immune suppression. However, the earliest molecular events that occur immediately after UV-exposure, especially those upstream of PGE2, were not well defined. To determine the initial events and mediators that lead to immune suppression after a pathological dose of UV, mouse keratinocytes were analyzed after sunlamp irradiation. It is known that UV-irradiated keratinocytes secrete the phospholipid mediator of inflammation, platelet-activating factor (PAF). Since PAF stimulates the production of immunomodulatory compounds, including PGE2, the hypothesis that UV-induced PAF activates cytokine production and initiates UV-induced immune suppression was tested. Both UV and PAF activated the transcription of cyclooxygenase (COX)-2 and IL-10 reporter gene constructs. A PAF receptor antagonist blocked UV-induced IL, 10 and COX-2 transcription. PAF mimicked the effects of UV in vivo and suppressed delayed-type hypersensitivity (DTH), and immune suppression was blocked when UV-irradiated mice were injected with a PAF receptor antagonist. This work shows that UV generates PAF-like oxidized lipids, that signal through the PAF receptor, activate cytokine transcription, and induce systemic immune suppression. ^

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Mouse models show that congenital neural tube defects (NTDs) can occur as a result of mutations in the platelet-derived growth factor receptor-α gene (PDGFRα). Mice heterozygous for the PDGFRα-mutation Patch, and at the same time homozygous for the undulated mutation in the Pax1 gene, exhibit a high incidence of lumbar spina bifida occulta, suggesting a functional relation between PDGFRα and Pax1. Using the human PDGFRα promoter linked to a luciferase reporter, we show in the present paper that Pax1 acts as a transcriptional activator of the PDGFRα gene in differentiated Tera-2 human embryonal carcinoma cells. Two mutant Pax1 proteins carrying either the undulated-mutation or the Gln → His mutation previously identified by us in the PAX1 gene of a patient with spina bifida, were not or less effective, respectively. Surprisingly, Pax1 mutant proteins appear to have opposing transcriptional activities in undifferentiated Tera-2 cells as well as in the U-2 OS osteosarcoma cell line. In these cells, the mutant Pax1 proteins enhance PDGFRα-promoter activity whereas the wild-type protein does not. The apparent up-regulation of PDGFRα expression in these cells clearly demonstrates a gain-of-function phenomenon associated with mutations in Pax genes. The altered transcriptional activation properties correlate with altered protein–DNA interaction in band-shift assays. Our data provide additional evidence that mutations in Pax1 can act as a risk factor for NTDs and suggest that the PDGFRα gene is a direct target of Pax1. In addition, the results support the hypothesis that deregulated PDGFRα expression may be causally related to NTDs.

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IMPORTANCE Obesity is a risk factor for deep vein thrombosis of the leg and pulmonary embolism. To date, however, whether obesity is associated with adult cerebral venous thrombosis (CVT) has not been assessed. OBJECTIVE To assess whether obesity is a risk factor for CVT. DESIGN, SETTING, AND PARTICIPANTS A case-control study was performed in consecutive adult patients with CVT admitted from July 1, 2006 (Amsterdam), and October 1, 2009 (Berne), through December 31, 2014, to the Academic Medical Center in Amsterdam, the Netherlands, or Inselspital University Hospital in Berne, Switzerland. The control group was composed of individuals from the control population of the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study, which was a large Dutch case-control study performed from March 1, 1999, to September 31, 2004, and in which risk factors for deep vein thrombosis and pulmonary embolism were assessed. Data analysis was performed from January 2 to July 12, 2015. MAIN OUTCOMES AND MEASURES Obesity was determined by body mass index (BMI). A BMI of 30 or greater was considered to indicate obesity, and a BMI of 25 to 29.99 was considered to indicate overweight. A multiple imputation procedure was used for missing data. We adjusted for sex, age, history of cancer, ethnicity, smoking status, and oral contraceptive use. Individuals with normal weight (BMI <25) were the reference category. RESULTS The study included 186 cases and 6134 controls. Cases were younger (median age, 40 vs 48 years), more often female (133 [71.5%] vs 3220 [52.5%]), more often used oral contraceptives (97 [72.9%] vs 758 [23.5%] of women), and more frequently had a history of cancer (17 [9.1%] vs 235 [3.8%]) compared with controls. Obesity (BMI ≥30) was associated with an increased risk of CVT (adjusted odds ratio [OR], 2.63; 95% CI, 1.53-4.54). Stratification by sex revealed a strong association between CVT and obesity in women (adjusted OR, 3.50; 95% CI, 2.00-6.14) but not in men (adjusted OR, 1.16; 95% CI, 0.25-5.30). Further stratification revealed that, in women who used oral contraceptives, overweight and obesity were associated with an increased risk of CVT in a dose-dependent manner (BMI 25.0-29.9: adjusted OR, 11.87; 95% CI, 5.94-23.74; BMI ≥30: adjusted OR, 29.26; 95% CI, 13.47-63.60). No association was found in women who did not use oral contraceptives. CONCLUSIONS AND RELEVANCE Obesity is a strong risk factor for CVT in women who use oral contraceptives.

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Thesis (Ph.D.)--University of Washington, 2016-06

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Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

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Background: Metformin is commonly prescribed to treat type 2 diabetes mellitus, however it is associated with the potentially lethal condition of lactic acidosis. Prescribing guidelines have been developed to minimize the risk of lactic acidosis development, although some suggest they are inappropriate and have created confusion amongst prescribers. The aim of this study was to investigate whether metformin dose was influenced by the presence of risk factors for lactic acidosis. Methods: The study was prospective, and retrieved information from patients admitted to hospital who were prescribed metformin at their time of admission. Results: Eighty-three patients were included in the study, 60 of whom had a least one risk factor for lactic acidosis. Of those 60 patients, 78.3% had a dose adjustment, with renal impairment, hepatic impairment, surgery and use of radiological contrast media - the risk factors most likely to result in a dose adjustment. When dose adjustments did occur, metformin was withheld on 88.7% of occasions. Conclusion: Metformin dose was influenced by the presence of risk factors for lactic acidosis, although it was dependent upon the number and particular risk factor/s present.

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Associations between parenting style and depressive symptomatology in a community sample of young adolescents (N = 2596) were investigated using self-report measures including the Parental Bonding Instrument and the Center for Epidemiologic Studies Depression Scale. Specifically, the 25-item 2-factor and 3-factor models by Parker et al. (1979), Kendler's (1996) 16-item 3-factor model, and Parker's (1983) quadrant model for the Parental Bonding Instrument were compared. Data analysis included analysis of variance and logistic regression. Reanalysis of Parker's original scale indicates that overprotection is composed of separate factors: intrusiveness (at the individual level) and restrictiveness (in the social context). All models reveal significant independent contributions from paternal care, maternal care, and maternal overprotection (2-factor) or intrusiveness (3-factor) to moderate and serious depressive symptomatology, controlling for sex and family living arrangement. Additive rather than multiplicative interactions between care and overprotection were found. Regardless of the level of parental care and affection, clinicians should note that maternal intrusiveness is strongly associated with adverse psychosocial health in young adolescents.

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Objective: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. Method: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n = 9 114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. Results: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR) = 0.08, 95% CI 0.01-0.95; RR = 0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR = 0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. Conclusion: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia. (C) 2003 Elsevier B.V. All rights reserved.

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Ross River virus (RE) is a mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand human and environmental factors driving such events, 57 historical reports oil RR Outbreaks between 1896 and 1998 were examined collectively. The magnitude, regularity, seasonality, and locality of outbreaks were found to be wide ranging; however, analysis of climatic and tidal data highlighted that environmental conditions let differently ill tropical, arid, and temperate regions. Overall, rainfall seems to be the single most important risk factor, with over 90% of major outbreak locations receiving higher than average rainfall in preceding mouths. Many temperatures were close to average, particularly in tropical populations; however, in arid regions, below average maximum temperatures predominated, and ill southeast temperate regions, above average minimum temperatures predominated. High spring tides preceded coastal Outbreaks, both in the presence and absence of rainfall, and the relationship between rainfall and the Southern Oscillation Index and Lit Nina episodes suggest they may be useful predictive tools, but only ill southeast temperate regions. Such heterogeneity predisposing outbreaks supports the notion that there are different RE epidemiologies throughout Australia but also Suggests that generic parameters for the prediction and control of outbreaks are of limited use at a local level.

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Objectives To assess the associations between three measurements of socioeconomic position (SEP) - education, occupation and ability to cope on available income - and cardiovascular risk factors in three age cohorts of Australian women. Methods Cross-sectional analysis of three cohorts of Australian women aged 18-23, 45-50 and 70-75 years. Results In general, for all exposures and in all three cohorts, the odds of each adverse risk factor (smoking, obesity and physical inactivity) were lower in the most advantaged compared with the least advantaged. Within each of the three cohorts, the effects of each measurement of SEP on the outcomes were similar. There were, however, some notable between-cohort differences. The most marked differences were those with smoking. For women aged 70-75 (older), those with the highest educational attainment were more likely to have ever smoked than those with the lowest level of attainment. However, for the other two cohorts, this association was reversed, with a stronger association between low levels of education and ever smoking among those aged 18-23 (younger) than those aged 45-50 (mid-age). Similarly, for older women, those in the most skilled occupational classes were most likely to have ever smoked, with opposite findings for mid-age women. Education was also differently associated with physical inactivity across the three cohorts. Older women who were most educated were least likely to be physically inactive, whereas among the younger and mid-age cohorts there was little or no effect of education on physical inactivity. Conclusion These findings demonstrate the dynamic nature of the association between SEP and some health outcomes. Our findings do not appear to confirm previous suggestions that prestige-based measurements of SEP are more strongly associated with health-related behaviours than measurements that reflect material and psychosocial resources.