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Pirie K.,Cancer Epidemiology Unit | Peto R.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Green J.,Cancer Epidemiology Unit | Reeves G.K.,Cancer Epidemiology Unit | Beral V.,Cancer Epidemiology Unit
International Journal of Cancer | Year: 2016

To assess directly the effects of various risk factors on lung cancer incidence among never smokers, large prospective studies are needed. In a cohort of 1.2 million UK women without prior cancer, half (634,039) reported that they had never smoked. Mean age at recruitment was 55 (SD5) years, and during 14 (SD3) years of follow-up, 0.2% (1,469) of these never smokers developed lung cancer. Cox regression was used to estimate relative risks (RRs) of lung cancer for 34 potential risk factors, of which 31 were nonsignificant (p>0.05). The remaining three risk factors were associated with a significantly increased incidence of lung cancer in never smokers: non-white vs. white ethnicity (RR=2.34, 95% CI 1.55-3.52, p<0.001), asthma requiring treatment vs. not (RR=1.32, 1.10-1.58, p=0.003) and taller stature (height≥165 cm vs. <160 cm: RR=1.16, 1.03-1.32, p=0.02). There was little association with other sociodemographic, anthropometric or hormonal factors, or with dietary intakes of meat, fish, fruit, vegetables and fiber. The findings were not materially affected by restricting the analyses to adenocarcinomas, the most common histological type among never smokers. © 2016 UICC. Source


Baigent C.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU
The Lancet | Year: 2013

Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 personyears) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, ob struction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefl y due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), nonsignificantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional eff ects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p<0·0001; and naproxen 4·22, 2·71-6·56, p<0·0001). Interpretation The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making. Funding UK Medical Research Council and British Heart Foundation. Source


Reith C.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Armitage J.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU
Atherosclerosis | Year: 2016

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Observational data indicate that low-density lipoprotein cholesterol (LDL-C) levels are strongly positively associated with the risk of coronary heart disease (CHD) whilst the level of high-density lipoprotein cholesterol (HDL-C) is strongly inversely associated, with additional associations being observed for other lipid parameters such as triglycerides, apolipoproteins and lipoprotein(a) (Lp(a)). This has led to an interest in the development of a range of lipid intervention therapies. The most widely used of these interventions are statins, but even with intensive statin therapy some groups of patients remain at significant residual cardiovascular (CV) risk. In addition, some people are intolerant of statin therapy. In these circumstances, additional therapeutic agents may be needed. This review considers the evidence behind and the pros and cons of such additional agents. © 2015 Elsevier Ireland Ltd. Source


De Lemos J.,AFCAPS TEXCAPS AirForce Texas Coronary Atherosclerosis Prevention Study | Braunwald E.,AFCAPS TEXCAPS AirForce Texas Coronary Atherosclerosis Prevention Study | Blazing M.,AFCAPS TEXCAPS AirForce Texas Coronary Atherosclerosis Prevention Study | Murphy S.,AFCAPS TEXCAPS AirForce Texas Coronary Atherosclerosis Prevention Study | And 78 more authors.
PLoS ONE | Year: 2012

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer). © 2012 CTT Collaboration. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Herrington W.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Lacey B.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Sherliker P.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Armitage J.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU | Lewington S.,Clinical Trial Service Unit and Epidemiological Studies Unit CTSU
Circulation Research | Year: 2016

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low-and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic. © 2016 The Authors. Source

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