Search

The aim of this study was to examine patterns of 10-year survival after elective repair of unruptured abdominal aortic aneurysms (AAAs) in different patient groups.Patients having open repair or endovascular aneurysm repair (EVAR) in the English National Health Service between January 2006 and December 2015 were identified from Hospital Episode Statistics data. Postoperative survival among patients of different age and Royal College of Surgeons of England (RCS) modified Charlson co-morbidity score profiles were analysed using flexible parametric survival models. The relationship between patient characteristics and risk of rupture after repair was also analysed.Some 37 138 patients underwent elective AAA repair, of which 15 523 were open and 21 615 were endovascular. The 10-year mortality rate was 38·1 per cent for patients aged under 70 years, and the survival trajectories for open repair and EVAR were similar when patients had no RCS-modified Charlson co-morbidity. Among older patients or those with co-morbidity, the 10-year mortality rate rose, exceeding 70 per cent for patients aged 80 years. Mean survival times over 10 years for open repair and EVAR were often similar in subgroups of older and more co-morbid patients, but their survival trajectories became increasingly dissimilar, with open repair showing greater short-term risk within 6 months but lower 10-year mortality rates. The risk of rupture over 9 years was 3·4 per cent for EVAR and 0·9 per cent for open repair, and was weakly associated with patient factors.Long-term survival patterns after elective open repair and EVAR for unruptured AAA vary markedly across patients with different age and co-morbidity profiles.El objetivo de este artículo fue examinar los patrones de supervivencia a 10 aáos tras reparación electiva de aneurismas de la aorta abdominal sin rotura (abdominal aortic aneurysms, AAA) en diferentes grupos de pacientes. MÉTODOS: Se identificaron pacientes sometidos a reparación abierta (open repair, OR) o reparación endovascular (endovascular aneurysm repair, EVAR) del aneurisma en el Sistema Nacional de Salud Inglés entre enero de 2006 y diciembre de 2015, a partir de los datos del Hospital Episode Statistics. Se analizaron la supervivencia postoperatoria entre los pacientes de diferentes edades y los perfiles de comorbilidad con la puntuación de Charlson modificada del Royal College of Surgeons of England (RCS) utilizando modelos de supervivencia paramétricos flexibles. También se analizó la relación entre las características de los pacientes y el riesgo de rotura tras la reparación.Un total de 37.138 pacientes fueron sometidos a reparaciones electivas de AAA, de las cuales 15.523 fueron reparaciones abiertas y 21.615 endovasculares. La mortalidad a los 10 aáos fue del 38% para los pacientes de edad inferior a los 70 aáos, y las curvas de supervivencia de la OR y EVAR fueron similares cuando los pacientes no tenían comorbilidad con el Charlson modificado del RCS. Entre los pacientes de edad avanzada y aquellos pacientes con comorbilidad, la mortalidad a los 10 aáos aumentó, excediendo el 70% para los pacientes de más de 80 aáos de edad. La media de los tiempos de supervivencia superior a 10 aáos para OR y EVAR fueron similares dentro de los subgrupos de pacientes de edad avanzada y más comorbilidad, pero las curvas de supervivencia se hicieron cada vez más diferentes, con la OR mostrando un mayor riesgo a corto plazo en los primeros 6 meses pero tasas de mortalidad a los 10 aáos más bajas. El riesgo de rotura mas allá de los 9 aáos fue 3,4% para EVAR y 0,9% para la reparación abierta, con una débil asociación con los factores inherentes a los pacientes. CONCLUSIÓN: Los patrones de supervivencia a largo plazo tras OR y EVAR electivas para AAA sin rotura varían notablemente entre pacientes con perfiles de edad y comorbilidad diferentes.

Background and Purpose— Carotid endarterectomy (CEA) reduces the risk of stroke in recently symptomatic patients and less so in asymptomatic patients. Recent evidence suggests that the number of CEAs may be declining. The aim of this study was to investigate annual patterns of CEA in asymptomatic and symptomatic patients in England from 2011 to 2017. Methods— Data from the National Vascular Registry were used to describe (1) the number of CEA procedures in England and its 9 geographic regions from 2011 to 2017, (2) the characteristics of patients undergoing CEA, and (3) whether rates of CEA correlated with the number of vascular arterial units within each region. Annual stroke incidence for each region was derived from official population figures and the number of index stroke admissions per year. Results— The overall number of CEAs performed in England fell from 4992 in 2011 to 3482 in 2017, a 30% decline. Among symptomatic patients, there was a 25% decline, the number of CEAs falling from 4270 to 3217. In asymptomatic patients, there were 722 CEAs performed in 2011 and 265 in 2017, a 63% decline. CEAs per 100 000 adults within all regions declined over time but the size of change varied across the regions (range, 1.7–5.5 per 100 000). The regional numbers of CEAs per year were associated with changes in the regional stroke incidence, the proportion of CEAs performed in asymptomatic patients, and the number of hospitals performing CEA. Conclusions— This population-based study revealed a 63% decline in CEAs among asymptomatic patients between 2011 and 2017, possibly because of changing attitudes in the role of CEA. Reasons for the 25% decline in CEAs among symptomatic patients are unclear as UK guidelines on CEA have not changed for these patients. Whether the proportion of symptomatic patients with 50% to 99% ipsilateral stenosis has changed requires investigation.

Background and aims Individual-level socioeconomic deprivation is associated with an increased risk of adverse patient outcomes following cardiovascular disease interventions, but the role of area-level socioeconomic circumstances as a predictor for treatment outcomes is unclear. We have examined the association of neighbourhood socioeconomic deprivation with risks of major lower limb amputation and death following surgical and endovascular lower limb revascularisation due to peripheral artery disease (PAD). Methods Patients aged 50+ years who underwent surgical or endovascular lower limb revascularisation for PAD were identified from Hospital Episode Statistics, a nationwide hospital data warehouse in England. Major amputations and deaths within a year of revascularisation were ascertained from HES and national mortality register, respectively. Index of Multiple Deprivation (IMD) was used to measure neighbourhood deprivation. Flexible parametric competing risks models were used to estimate sub-distribution hazard ratios (SHRs) for amputation and death. Results In all, 65,806 patients underwent endovascular and 20,072 underwent surgical revascularisation. The covariate-adjusted 1-year risk of major amputation was higher among patients from the most deprived compared to least deprived neighbourhoods following endovascular revascularisation (SHR: 1.24, 95% confidence interval, CI:1.10 to 1.38) and surgical revascularisation (SHR:1.28, 95% CI: 1.09 to 1.51). The risk of death was higher in most deprived compared to the least deprived neighbourhoods following both procedures. Conclusions We found a consistent association between neighbourhood deprivation and amputation and death outcomes following lower limb revascularisation for PAD. These findings suggest there may be opportunities for targeted interventions to improve care of PAD patients in deprived neighbourhoods.

This cohort study examines disease-free life-years in participants with varying combinations of lifestyle risk factors. Question Are different combinations of lifestyle factors associated with years lived without chronic diseases? Findings In a multicohort study of 116 & x202f;043 participants, a statistically significant association between overall healthy lifestyle score and an increased number of disease-free life-years was noted. Of 16 different lifestyle profiles studied, the 4 that were associated with the greatest disease-free life years included body mass index lower than 25 and at least 2 of 3 factors: never smoking, physical activity, and moderate alcohol consumption. Meaning Various healthy lifestyle profiles appear to be associated with extended gains in life lived without type 2 diabetes, cardiovascular and respiratory diseases, and cancer. Importance It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 & x202f;043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results Of the 116 & x202f;043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 & x202f;911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 & x202f;383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P

Background Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease ( PAD ) is unclear. We investigated the association of job strain with hospital records of PAD , using individual‐level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom. Methods and Results Job strain (high demands and low control at work) was self‐reported at baseline (1985–2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study‐specific estimates in random effects meta‐analyses. We used τ 2 , I 2 , and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD , 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person‐years at risk (mean follow‐up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person‐years). Job strain was associated with a 1.41‐fold (95% CI, 1.11–1.80) increased average risk of hospitalization with PAD . The study‐specific estimates were moderately heterogeneous (τ 2 =0.0427, I 2 : 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations. Conclusions Job strain was associated with small but consistent increase in the risk of hospitalization with PAD , with the relative risks on par with those for coronary heart disease and ischemic stroke.

Background: The availability and diversity of lower limb revascularization procedures have increased in England in the past decade. We investigated whether these developments in care have translated to improvements in patient pathways and outcomes. Methods: Individual-patient records from Hospital Episode Statistics were used to identify 103 934 patients who underwent endovascular (angioplasty) or surgical (endarterectomy, profundaplasty, or bypass) lower limb revascularization for infrainguinal peripheral artery disease in England between January 2006 and December 2015. Major lower limb amputations and deaths within 1 year after revascularization were ascertained from Hospital Episode Statistics and Office for National Statistics mortality records. Competing risks regression was used to estimate the cumulative incidence of major amputation and death, adjusted for patient age, sex, comorbidity score, indication for the intervention (intermittent claudication, severe limb ischemia without record of tissue loss, severe limb ischemia with a record of ulceration, severe limb ischemia with a record of gangrene/osteomyelitis), and comorbid diabetes mellitus. Results: The estimated 1-year risk of major amputation decreased from 5.7% (in 2006–2007) to 3.9% (in 2014–2015) following endovascular revascularization, and from 11.2% (2006–2007) to 6.6% (2014–2015) following surgical procedures. The risk of death after both types of revascularization also decreased. These trends were observed for all indication categories, with the largest reductions found in patients with severe limb ischemia with ulceration or gangrene. Overall, morbidity increased over the study period, and a larger proportion of patients was treated for the severe end of the peripheral artery disease spectrum using less invasive procedures. Conclusions: Our findings show that from 2006 to 2015, the overall survival increased and the risk of major lower limb amputation decreased following revascularization. These observations suggest that patient outcomes after lower limb revascularization have improved during a period of centralization and specialization of vascular services in the United Kingdom.

Background The aim of this study was to estimate separate risks of major lower limb amputation and death following revascularization for peripheral artery disease (PAD) using competing risks analysis. Methods Routinely collected data from Hospital Episode Statistics (HES) were used to identify patients who underwent endovascular or open lower limb revascularization for PAD in England from 2005 to 2015. The primary outcomes were major lower limb amputation and death within 5 years of revascularization. Cox proportional hazards and Fine–Gray competing risks regression were used to examine the competing risks of these outcomes. Results Some 164 845 patients underwent their first lower limb revascularization for PAD during the study interval. Most were men (64·6 per cent) and the median age was 71 (i.q.r. 62–78) years. Following endovascular revascularization, the 5-year cumulative incidence of amputation was 4·2 per cent in patients with intermittent claudication and 18·0 per cent in those with a record of tissue loss. The corresponding rates were 10·8 and 25·3 per cent respectively after open revascularization, and 8·1 and 25·0 per cent after combined procedures. The 5-year cumulative incidence of death varied from 24·5 to 39·8 per cent, depending on procedure type. Competing risks methods consistently produced lower estimates than standard methods. Conclusion The 5-year risk of major amputation following lower limb revascularization for PAD appears lower than estimated previously. Patients undergoing revascularization for tissue loss and those who require an open procedure are at highest risk of limb loss.

Background and aims Clinical experience and observational studies suggest that individuals with coeliac disease are at increased risk of coronary heart disease (CHD), but the precise mechanism for this is unclear. Laboratory studies suggest that it may relate to tissue transglutaminase antibodies (tTGAs). Our aim was to examine whether seropositivity for tTGA and endomysial antibodies (EMAs) are associated with incident CHD in humans. Methods and results We used data from Mini-Finland Health Survey, a prospective cohort study of Finnish men and women aged 35–80 at study baseline 1978–80. TTGA and EMA seropositivities were ascertained from baseline blood samples and incident CHD events were identified from national hospitalisation and death registers. Cox regression was used to examine the associations between antibody seropositivity and incident CHD. Of 6887 men and women, 562 were seropositive for tTGAs and 72 for EMAs. During a median follow-up of 26 years, 2367 individuals experienced a CHD event. We found no clear evidence for an association between tTGA positivity (hazard ratio, HR: 1.04, 95% confidence interval, CI: 0.83, 1.30) or EMA positivity (HR: 1.16, 95% CI: 0.77, 1.74) and incident CHD, once pre-existing CVD and known CHD risk factors had been adjusted for. Conclusion We found no clear evidence for an association of tTGA or EMA seropositivity with incident CHD outcomes, suggesting that tTG autoimmunity is unlikely to be the biological link between coeliac disease and CHD.

BackgroundAdverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.MethodWe identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.ResultsWe included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).ConclusionsJob strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

Aims Clinical experience suggests that atherosclerotic disease is common in individuals with coeliac disease, but epidemiological studies have had contradicting findings. To summarise the currently available evidence, we systematically reviewed and analysed observational studies of the association of coeliac disease or dermatitis herpetiformis with coronary heart disease (CHD) or stroke. Data synthesis We searched for studies comparing CHD or stroke outcomes with individuals with and without coeliac disease or dermatitis herpetiformis. Three investigators independently searched electronic databases, identified relevant studies and extracted data. Study-specific results were combined in random-effects meta-analyses, and heterogeneity was quantified using the I 2 statistic and meta-regression. Twenty-one studies were included in our systematic review and 18 in the meta-analyses. For CHD, the pooled hazard ratio for incident disease was 1.05 (95% confidence interval (CI): 0.93, 1.19) and the overall standardised mortality ratio was 1.21 (0.99, 1.49). For stroke and brain haemorrhage, the corresponding estimates were 1.10 (95% CI: 1.00, 1.21) and 1.43 (0.97, 2.10), respectively. There was moderate to considerable heterogeneity among the study-specific estimates. In addition, many estimates were based on small numbers of outcomes and they had limitations in terms of adjustment for potential confounders. Conclusion Our meta-analyses lend some support to an association between coeliac disease and CHD or cerebrovascular disease, but the evidence base was heterogeneous and had limitations. Our systematic review highlighted a need in this area for adequately powered prospective studies with appropriate adjustment for potentially confounding factors.

The impact of celiac disease autoimmunity on bone health is unclear. We investigated the associations of seropositivity for tissue transglutaminase antibodies (tTGA) and endomysial antibodies (EMA) with incident hip fractures using data from a prospective cohort study, Mini-Finland Health Survey. Baseline serum samples, taken in 1978-80, were tested for tTGA and EMA. Incident hip fractures up to the year 2011 were ascertained from a national hospitalization register. Associations between seropositivity and hip fractures were modeled using Cox proportional hazards regression adjusted for age, sex, body mass index, vitamin D, gamma-glutamyl transferase, smoking, and self-rated health. Our analyses were based on 6919 men and women who had no record of celiac disease or hip fracture before the study baseline. A total of 382 individuals had a hip fracture during a median follow-up of 30 years. Compared with the tTGA-negative individuals (n = 6350), tTGA-positive participants (n = 569; with hip fracture, n = 51) had a higher risk of hip fractures (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.17, 2.14). The findings were similar for another tTGA test (n 200; with hip fracture, n = 26; HR = 2.23, 95% CI 1.49, 3.34). We found no evidence for an association between EMA positivity and hip fracture risk (HR = 0.92, 95% CI 0.34, 2.47; n = 74; with hip fracture, n = 4). In our prospective population-based study of Finnish adults, seropositivity for tTGA was associated with an increased hip fracture risk.

Background Availability and diversity of lower limb revascularisation procedures have increased in in the past decade, co-inciding with the reconfiguration of vascular services in the United Kingdom. The aim of our study was to investigate whether these developments in care have translated to improvements in patient outcomes. Methods We used data from Hospital Episode Statistics (HES) to identify patients who underwent endovascular or surgical (endarterectomy, profundaplasty or bypass) lower limb revascularisation for infrainguinal peripheral arterial disease (PAD) in England in 2006–2013. Major lower limb amputations and deaths were ascertained from HES and Office for National Statistics mortality register. Associations of revascularisation procedures with amputation and death outcomes were investigated using Fine-Grey competing risks regression, with adjustment for patient age, sex and comorbidity score. We examined the possible impact of patient selection by stratifying our analyses by indication for revascularisation (intermittent claudication only; severe limb ischaemia without tissue loss; severe limb ischaemia with ulceration; severe limb ischaemia with gangrene). Results Over the 8 year study period the overall number of endovascular revascularisations increased and the number of surgical procedures decreased: the evidence for this trend was the clearest among patients with the most severe underlying disease (severe limb ischaemia with ulceration or gangrene). The 1 year risk of major amputation reduced from 5.9% (in 2006–07) to 5.5% (in 2012–13) following endovascular evascularization and from 10.8% (2006–07) to 7.4% (2012–13) following surgical procedures (p Discussion Our findings suggest that patient outcomes following lower limb revascularisation have improved during a period of centralisation and specialisation of vascular services in the United Kingdom, despite higher morbidity and an increasing proportion of patients treated for the severe end of the PAD spectrum.

Overtime work and long working hours are associated with an increased risk of many adverse health outcomes, such as coronary heart disease and stroke. However, the relationship of excess working hours with incident cancer is unclear. To address this gap in the knowledge, we examined the association between weekly working hours and cancer risk using individual-participant data from 12 prospective studies from Denmark, Finland, Germany, Sweden, the Netherlands and the UK.Our analyses were based on data from 116 462 working men and women, who were free of cancer at study baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers. Weekly working hours were self-reported. During a follow-up ranging from 4 to 22 years, 4 371 participants were diagnosed with cancer (n colorectal cancer: 393, n lung cancer: 247, n breast cancer: 833, n prostate cancer: 534). Compared to standard working time (35–40 hours/week), working >55 hours/week was not associated with the overall cancer incidence (multivariable-adjusted HR (95% CI): 1.00 (0.85, 1.16). Similarly, working hours were unrelated to incident colorectal, lung and prostate cancers. Compared to standard hours, working >55 hours/week was associated with 1.60-fold (95% CI: 1.12–2.29) risk of female breast cancer. This association was independent of age, socioeconomic position, shift- and night-time work and lifestyle factors, but it may have been influenced by residual confounding from parity. To our knowledge, ours is the largest investigation of this topic to-date and the first to examine the association of working hours with the overall cancer risk and the risk of specific cancers. Our findings suggest that working long hours is not a risk factor for cancer in general, or lung, colorectal or prostate cancers in particular. The observed association with breast cancer would warrant further research.

Objective Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. Method The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. Results In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10–56) in 2009 to 12 days (IQR 7–26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0–2 days) compared with 2.0% (3–7 days); adjusted odds ratio 1.64 (95% CI 1.04–2.59) but not with longer delays. Conclusions The delay from symptom to CEA in symptomatic patients with ipsilateral 50–99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms.

Background Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk. Methods We pooled data from three population-based prospective Finnish studies: FINRISK 1992 ( n = 5289), FINRISK 1997 ( n = 7160) and Health 2000 ( n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models. Results Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses. Conclusions We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.

We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk. We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women’s Heart and Health Study (4,286 women aged 60–80) and the Caerphilly Cohort (2,398 men aged 45–59) using Cox regression and pooled our findings with previous prospective studies’ in fixed and random effects meta-analyses. CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk. Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.

Our aim was to systematically review the epidemiologic evidence for an association of circulating interleukin-6 (IL-6), an inflammatory cytokine and cancer. We systematically searched electronic databases Embase, Medline and Web of Science for the studies of circulating IL-6 and any form of cancer. We identified and reviewed 189 discrete studies, consisting of 177 prevalent studies and three prospective studies. Cancer patients' IL-6 concentrations were higher than healthy controls' in most studies, but the results of investigations comparing IL-6 in cancer patients and individuals with benign diseases were less consistent. Due to the small number of prospective studies it is impossible to determine whether IL-6 is causally related to cancer. Large prospective studies of circulating IL-6 or studies using the functional variants of the IL-6 gene as instruments for circulating IL-6 concentrations would provide information on possible aetiological links between IL-6 and malignancy.

The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case–control or cross‐sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene–cancer association studies would be valuable in investigating the role of CRP in cancer.

Background: Inflammation is associated with worse prognosis and survival in many cancers. Our aim was to investigate the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations with all-cause mortality in cancer patients and to determine whether any associations were specific to malignancy. Method: We used data from the British Women's Heart and Health Study, a cohort of 4,286 women aged 60 to 79 years. We investigated the associations between CRP, IL-6, and survival in women with and without cancer using Cox regression and assessed the interaction between cancer status and these inflammatory markers to determine whether these associations differed according to cancer status. Results: Elevated CRP and IL-6 were associated with decreased survival in women with cancer [unadjusted hazard ratio per doubling of CRP, 1.22, 95% confidence interval (95% CI), 1.03, 1.46; and per doubling of IL-6, 1.52, 95% CI, 1.25, 1.86] and in women without cancer [CRP: 1.24 (1.12, 1.37); IL-6: 1.53 (1.35, 1.75)]. Adjustment for age, body mass index, physical activity level, socioeconomic position, HRT use, and tobacco smoking did not change these associations. After mutual adjustment, IL-6 but not CRP was independently associated with survival. We found no strong evidence that these associations differed between cancer patients and cancer-free women. Conclusions: Elevated CRP and IL-6 concentrations were similarly associated with an increased risk of death in elderly women with and without cancer. Thus, in this group, these markers are likely to be indicators of non-cancer comorbidities rather than related to the malignancy itself. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1155–9)

Background and Purpose— Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain. Methods— We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke. Results— In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status. Conclusion— Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.

Celiac disease, an autoimmune disease induced by dietary gluten, is associated with metabolic bone disorders, such as low bone mineral density. However, it is unclear whether this translates into an association between celiac disease and such hard clinical outcomes as bone fractures.To systematically review and pool the evidence for the relationship of celiac disease with prevalence and incidence of bone fractures.We systematically searched Pubmed, Scopus, Web of Science, and Cochrane Library in January 2014 for studies of celiac disease and bone fractures.Observational studies of any design, in which bone fracture outcomes were compared in individuals with and without celiac disease were included.Two investigators independently extracted results from eligible studies.In the meta-analyses of case-control and cross-sectional studies, bone fractures were almost twice as common in individuals with a clinically diagnosed celiac disease as in those without the disease. In the meta-analyses of prospective studies, celiac disease at baseline was associated with a 30% increase (95% confidence interval [CI]: 1.14, 1.50) in the risk of any fracture and a 69% increase in the risk of hip fracture (95% CI: 1.10, 2.59). The two studies of unrecognized celiac disease (elevated circulating concentrations of celiac disease-specific autoantibodies but no celiac disease diagnosis) had contradicting findings.Our findings suggest that clinically diagnosed celiac disease and bone fractures co-occur and that celiac disease was associated with an increased risk of hip fractures as well as fractures in general. Further research would be needed to determine whether unrecognized celiac disease is associated with the risk of bone fractures.

Background: It is unclear whether a healthy lifestyle mitigates the adverse effects of job strain on coronary artery disease. We examined the associations of job strain and lifestyle risk factors with the risk of coronary artery disease. Methods: We pooled individual-level data from 7 cohort studies comprising 102 128 men and women who were free of existing coronary artery disease at baseline (1985-2000). Questionnaires were used to measure job strain (yes v. no) and 4 lifestyle risk factors: current smoking, physical inactivity, heavy drinking and obesity. We grouped participants into 3 lifestyle categories: healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2-4 risk factors). The primary outcome was incident coronary artery disease (defined as first nonfatal myocardial infarction or cardiac-related death). Results: There were 1086 incident events in 743 948 person-years at risk during a mean follow-up of 7.3 years. The risk of coronary artery disease among people who had an unhealthy lifestyle compared with those who had a healthy lifestyle (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.18-2.98; population attributable risk 26.4%) was higher than the risk among participants who had job strain compared with those who had no job strain (HR 1.25, 95% CI 1.06-1.47; population attributable risk 3.8%). The 10-year incidence of coronary artery disease among participants with job strain and a healthy lifestyle (14.7 per 1000) was 53% lower than the incidence among those with job strain and an unhealthy lifestyle (31.2 per 1000). Interpretation: The risk of coronary artery disease was highest among participants who reported job strain and an unhealthy lifestyle; those with job strain and a healthy lifestyle had half the rate of disease. A healthy life style may substantially reduce disease risk among people with job strain.

Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers.Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intakeResults A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer.Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.

Job strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain - heart disease association., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives. We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. Methods. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118 701; longitudinal data: n = 43 971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Results. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Conclusions. Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between work-related stress and lifestyle. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e8. doi:10.2105/AJPH.2012.301090). AuthorCount: 32:Other Funders:Finnish Work Environment Fund; German Social Accident Insurance; Academy of Finland 132944; BUPA Foundation 22094477; Heinz Nixdorf Foundation (Germany;) German Ministry of Education and Science ; German Research Foundation; Medical Research Council (United Kingdom); Economic and Social Research Council professorial fellowship . IPD-Work Consortium

Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. : The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. : In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10-56) in 2009 to 12 days (IQR 7-26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0-2 days) compared with 2.0% (3-7 days); adjusted odds ratio 1.64 (95% CI 1.04-2.59) but not with longer delays. : The delay from symptom to CEA in symptomatic patients with ipsilateral 50-99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms.

The authors aggregated the results of observational studies examining the association between long working hours and coronary heart disease (CHD). Data sources used were MEDLINE (through January 19, 2011) and Web of Science (through March 14, 2011). Two investigators independently extracted results from eligible studies. Heterogeneity between the studies was assessed using the I(2) statistic, and the possibility of publication bias was assessed using the funnel plot and Egger's test for small-study effects. Twelve studies were identified (7 case-control, 4 prospective, and 1 cross-sectional). For a total of 22,518 participants (2,313 CHD cases), the minimally adjusted relative risk of CHD for long working hours was 1.80 (95% confidence interval (CI): 1.42, 2.29), and in the maximally (multivariate-) adjusted analysis the relative risk was 1.59 (95% CI: 1.23, 2.07). The 4 prospective studies produced a relative risk of 1.39 (95% CI: 1.12, 1.72), while the corresponding relative risk in the 7 case-control studies was 2.43 (95% CI: 1.81, 3.26). Little evidence of publication bias but relatively large heterogeneity was observed. Studies varied in size, design, measurement of exposure and outcome, and adjustments. In conclusion, results from prospective observational studies suggest an approximately 40% excess risk of CHD in employees working long hours.

Objective To examine whether breast feeding is associated with behavioural development in children aged 5 years. Design The authors used data from a large, prospective, nationally representative UK cohort, the Millennium Cohort Study. Participants 10 037 mother–child pairs from white ethnic background (9525 term and 512 preterm children) were included in the analyses. Methods Duration of breast feeding (at all or exclusively) was ascertained from parental interview at study baseline, when the children were aged 9 months. Child behaviour was assessed using a parent-completed questionnaire, the Strengths and Difficulties Questionnaire (SDQ). The authors used logistic regression to investigate the associations of breastfeeding duration with abnormal parent-rated SDQ total and subscores at age 5 in term and preterm children separately. Results Abnormal SDQ scores were less common in term children (n=1129/9525, 12%) than pre-term (n=78/512, 15%) children. Term children breast fed for 4 months or longer (n=2741/9525, 29%) had lower odds of an abnormal total SDQ score (multivariable-adjusted OR compared with never breastfed children (n=3292/9525, 35%) 0.67, 95% CI: 0.54 to 0.83). This effect was similar for all the SDQ subscores. In preterm children, longer duration of breast feeding was generally associated with lower odds of abnormal SDQ total and subscores but the effect estimates were imprecise. The associations between exclusive breast feeding and abnormal SDQ scores were similar to those of any breast feeding and abnormal SDQ scores. Conclusions The findings suggest that, at least in term children, longer duration of breast feeding is associated with fewer parent-rated behavioural problems in children aged 5 years.

Aim Our aim was to examine whether breast feeding is associated with behavioural development in children aged 5 years. Methods We used data from a large, prospective, nationally representative UK cohort, the Millennium Cohort Study. Breast feeding was ascertained from parent-interviews at baseline and child behaviour from parent-rated outcome, the Strengths and Difficulties Questionnaire (SDQ). Our analyses included 10 037 mother-child pairs with data on breast feeding, SDQ and potential confounders. 9525 of the children were born at term and 512 were preterm. We used logistic regression models to investigate the associations of breast feeding duration with abnormal parent-rated SDQ total and sub-scores at age five in term and preterm children separately. Results Overall, abnormal SDQ scores were less common in breast fed than formula-fed children. Term children breast fed for four months or longer had lower odds of an abnormal total SDQ score (multivariable-adjusted OR compared to never breast fed children: 0.65, 95% CI 0.52 to 0.82). This effect was similar for all the SDQ sub-scores. In preterm children prolonged breast feeding was generally associated with lower odds of abnormal SDQ total and sub-scores but the effect estimates were imprecise. The associations between exclusive breast feeding and abnormal SDQ scores were similar to those of any breast feeding and abnormal SDQ scores. Conclusions Our findings suggest that, at least in term children, prolonged breast feeding is associated with having fewer parent-rated behavioural problems at the age of 5 years.