Age at quitting smoking as a predictor of risk of cardiovascular disease incidence independent of smoking status, time since quitting and pack-years

BACKGROUND Risk prediction for CVD events has been shown to vary according to current smoking status, pack-years smoked over a lifetime, time since quitting and age at quitting. The latter two are closely and inversely related. It is not known whether the age at which one quits smoking is an additional important predictor of CVD events. The aim of this study was to determine whether the risk of CVD events varied according to age at quitting after taking into account current smoking status, lifetime pack-years smoked and time since quitting. FINDINGS We used the Cox proportional hazards model to evaluate the risk of developing a first CVD event for a cohort of participants in the Framingham Offspring Heart Study who attended the fourth examination between ages 30 and 74 years and were free of CVD. Those who quit before the median age of 37 years had a risk of CVD incidence similar to those who were never smokers. The incorporation of age at quitting in the smoking variable resulted in better prediction than the model which had a simple current smoker/non-smoker measure and the one that incorporated both time since quitting and pack-years. These models demonstrated good discrimination, calibration and global fit. The risk among those quitting more than 5 years prior to the baseline exam and those whose age at quitting was prior to 44 years was similar to the risk among never smokers. However, the risk among those quitting less than 5 years prior to the baseline exam and those who continued to smoke until 44 years of age (or beyond) was two and a half times higher than that of never smokers. CONCLUSIONS Age at quitting improves the prediction of risk of CVD incidence even after other smoking measures are taken into account. The clinical benefit of adding age at quitting to the model with other smoking measures may be greater than the associated costs. Thus, age at quitting should be considered in addition to smoking status, time since quitting and pack-years when counselling individuals about their cardiovascular risk.This research was supported by an NHMRC health services research grant (no. 465130), an NHMRC/NHF PhD scholarship and a Vichealth Fellowship

Age-specific trends in cardiovascular mortality rates in Australia between 1980 and 2005

Aim: Recent analyses suggest the decline in coronary heart disease (CHD) mortality rates is slowing in younger age groups in countries such as the UK and US. We aimed to assess recent mortality rate trends in all circulatory disease and its subtypes in Australia. Methods: Annual all circulatory, CHD, and cerebrovascular disease mortality rates between 1980 and 2005 for Australia were analysed. Data were stratified by sex and ten-year age group (age 35 to 85+). The annual rate of change and significant changes in trends were identified using joinpoint Poisson regression. Results: Age standardised all circulatory disease mortality rates continue to decline in Australia, falling from 441 per 100,000 in 1980 to 145 per 100,000 in 2005 for males and from 264 per 100,000 to 96 per 100,000 for females. The rate of decline from both CHD and cerebrovascular disease appears to be stable or accelerating for individuals aged 55 years and over. However, the decline in young men and women aged 35-54 years is slowing for CHD and cerebrovascular disease mortality alike (except cerebrovascular disease mortality in males aged 35-44). For females aged 35-44 and 45-54 there has been no change in the cerebrovascular mortality rate since 1993 and 1999, respectively. Conclusions: In Australia, whilst in older adults the decline in cardiovascular mortality rates is generally accelerating, in younger adults it appears to be slowing. It will be important to identify the causes of these trends

Comparing trends in BMI and waist circumference

The nature of excess body weight may be changing over time to one of greater central adiposity. The aim of this study is to determine whether BMI and waist circumference (WC) are increasing proportionately among population subgroups and the range of bodyweight, and to examine the public health implications of the findings. Our data are from two cross-sectional surveys (the US National Health and Nutrition Examination Studies (NHANES) in 1988-1994 (NHANES III) and 2005-2006), from which we have used samples of 15,349 and 4,176 participants aged ≥20 years. Between 1988-1994 and 2005-2006 BMI increased by an average of 1.8kg/m2 and WC by 4.7cm (adjusted for sex, age, race-ethnicity, and education). The increase in WC was more than could be attributed simply to increases in BMI. This independent increase in WC (of on average, 0.9cm) was consistent across the different BMI categories, sexes, education levels, and race-ethnicity groups. It occurred in younger but not older age groups. Overall in each BMI category, the prevalence of low-risk WC decreased and the prevalence of increased-risk or substantially increased-risk WC increased. These results suggest that the adverse health consequences associated with obesity may be increasingly underestimated by trends in BMI alone. Since WC is closely linked to adverse cardiovascular outcomes, it is important to know the prevailing trends in both of these parameters

TFG Promotes Organization of Transitional ER and Efficient Collagen Secretion

Collagen is the most abundant protein in the animal kingdom. It is of fundamental importance during development for cell differentiation and tissue morphogenesis as well as in pathological processes such as fibrosis and cancer cell migration. However, our understanding of the mechanisms of procollagen secretion remains limited. Here, we show that TFG organizes transitional ER (tER) and ER exit sites (ERESs) into larger structures. Depletion of TFG results in dispersion of tER elements that remain associated with individual ER-Golgi intermediate compartments (ERGICs) as largely functional ERESs. We show that TFG is not required for the transport and packaging of small soluble cargoes but is necessary for the export of procollagen from the ER. Our work therefore suggests a key relationship between the structure and function of ERESs and a central role for TFG in optimizing COPII assembly for procollagen export.Medical Research Council UK/MR/J000604/1Medical Research Council UK/MR/K018019/1Medical Research Council UK/MR/G080184

Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers

Background: Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. Methods: The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. Findings: Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. Interpretation: The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. Funding: Funding was through an Innovate UK Biomedical Catalyst grant (ID# 92138-556187), a Chief Scientist Office grant (TCS/19/11) and core support from Medical Research Council (MC_ UU_12014) core funding for the MRC-University of Glasgow Centre for Virus Research

Translational neuroscience: the state of the nation (a PhD student perspective)

Many brain disorders are currently untreatable. It has been suggested that taking a ‘translational’ approach to neuroscientific research might change this. We discuss what ‘translational neuroscience’ is and argue for the need to expand the traditional translational model if we are to make further advances in treating brain disorders

Methodological problem with comparing increases in different measures of body weight

<p>Abstract</p> <p>Background</p> <p>A number of studies have compared proportional increases over time in waist circumference (WC) and body mass index (BMI). However this method is flawed. Here, we explain why comparisons of WC and BMI must take into account the relationship between them. We used data from two cross-sectional US surveys (NHANES 1988-94 and 2005-06), and calculated the percentage change in the average BMI and the average WC between the two surveys, comparing the results with a regression analysis of changes in WC relative to BMI.</p> <p>Findings</p> <p>The crude percentage change in BMI (5.8%) was marginally greater than for WC (5.1%). But these percentages cannot be directly compared, as the relationship between the measures is described by a regression equation with an intercept term that does not equal zero. The coefficient of time from the regression equation will determine whether or not WC is on average larger for a given BMI at the second compared with the first time point.</p> <p>Conclusion</p> <p>Differences in the percentage change in WC and the percentage change in BMI cannot be usefully directly compared. Comparisons of increases in the two measures must account for the relationship between them as described by the regression equation.</p

Age-specific trends in cardiovascular mortality rates in the Netherlands between 1980 and 2009

Recent analyses suggest the decline in coronary heart disease mortality rates is slowing in younger age groups in countries such as the US and the UK. This work aimed to analyse recent trends in cardiovascular mortality rates in the Netherlands. Analysis was of annual all circulatory, ischaemic heart disease (IHD), and cerebrovascular disease mortality rates between 1980 and 2009 for the Netherlands. Data were stratified by sex and 10-year age group (age 35–85+). The annual rate of change and significant changes in the trend were identified using joinpoint Poisson regression. For almost all age and sex groups examined the rate of IHD and cerebrovascular disease mortality in the Netherlands has more than halved between 1980 and 2009. The decline in mortality from both IHD and cerebrovascular disease is continuing for all ages and sex groups, with anacceleration in the decline apparent from the late 1990s/early 2000s. The decline in age-specific all circulatory, coronary heart disease and cerebrovascular disease mortality rates continues for all age and sex groups in the Netherlands