Alcohol consumption and its association with long-term prognosis among cardiovascular disease patients

Moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals, but it remains unclear if this association is also present in those with cardiovascular disease (CVD). Inconsistency exists across guidelines regarding the recommended drinking limits for CVD patients. This thesis consists of three studies aiming to better understand alcohol consumption in this patient population and its association with long-term prognosis. By pooling the results from de novo analyses of three cohorts and 12 published studies identified through a systematic review, meta-analyses of 48423 CVD patients (Study 1) found lower risk of mortality and subsequent cardiovascular events for an alcohol consumption up to 105 grams per week compared to current non-drinking. These effects, however, were significantly attenuated or absent after distinguishing former drinkers from non-drinkers. Meanwhile, little is known about the longitudinal dynamics of alcohol consumption in CVD patients and the associated health risks. With repeated-measures data from two cohorts (n=12502), Study 2 plotted CVD patients’ mean trajectory of weekly alcohol consumption as a function of time, centred on the date of diagnosis and spanning up to 30 years before and after the diagnosis. For male patients, mean consumption increased over time, peaked at eight years before diagnosis at 95 grams per week, and declined afterwards. A flatter trajectory was seen in female patients, which remained stable at around 30 grams per week and started to decline after diagnosis. In Study 3, alcohol consumption trajectory was further differentiated into six distinct groups in an inception cohort of 1306 patients with incident CVD and related to their subsequent mortality risk from all causes. Patients who consistently drank moderately (within 112 grams per week) had a similar risk of mortality as those who were continuous non-drinkers. While increases in risk were found among patients who stopped drinking compared to continuous moderate drinkers, former drinkers also had the worst self-rated health. Temporal variability in alcohol consumption highlights the importance of taking a longitudinal approach to examine alcohol health relations. Findings indicating protective effects of baseline moderate drinking in CVD patients may be largely explained by a referent group contaminated by less healthy former drinkers and are not seen when considering long-term drinking trajectories. This thesis provides novel knowledge about alcohol’s relation to cardiovascular health, which could be used to inform CVD patient care and low-risk drinking guidelines

Association of alcohol consumption with morbidity and mortality in patients with cardiovascular disease: original data and meta-analysis of 48,423 men and women.

BackgroundLight-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is also present in those with disease. To examine the association between alcohol consumption and prognosis in individuals with pre-existing cardiovascular disease (CVD), we conducted a series of meta-analyses of new findings from three large-scale cohorts and existing published studies.MethodsWe assessed alcohol consumption in relation to all-cause mortality, cardiovascular mortality, and subsequent cardiovascular events via de novo analyses of 14,386 patients with a previous myocardial infarction, angina, or stroke in the UK Biobank Study (median follow-up 8.7 years, interquartile range [IQR] 8.0-9.5), involving 1640 deaths and 2950 subsequent events, and 2802 patients and 1257 deaths in 15 waves of the Health Survey for England 1994-2008 and three waves of the Scottish Health Survey 1995, 1998, and 2003 (median follow-up 9.5 years, IQR 5.7-13.0). This was augmented with findings from 12 published studies identified through a systematic review, providing data on 31,235 patients, 5095 deaths, and 1414 subsequent events. To determine the best-fitting dose-response association between alcohol and each outcome in the combined sample of 48,423 patients, models were constructed using fractional polynomial regression, adjusting at least for age, sex, and smoking status.ResultsAlcohol consumption was associated with all assessed outcomes in a J-shaped manner relative to current non-drinkers, with a risk reduction that peaked at 7 g/day (relative risk 0.79, 95% confidence interval 0.73-0.85) for all-cause mortality, 8 g/day (0.73, 0.64-0.83) for cardiovascular mortality and 6 g/day (0.50, 0.26-0.96) for cardiovascular events, and remained significant up to 62, 50, and 15 g/day, respectively. No statistically significant elevated risks were found at higher levels of drinking. In the few studies that excluded former drinkers from the non-drinking reference group, reductions in risk among light-to-moderate drinkers were attenuated.ConclusionsFor secondary prevention of CVD, current drinkers may not need to stop drinking. However, they should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g (or equivalent to 13 UK units, with one unit equal to half a pint of beer/lager/cider, half a glass of wine, or one measure of spirits) a week

Association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis.

BACKGROUND: Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. METHODS: MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10-1.58, n = 15 studies, I2 = 0%) and 1.23 (95%CI 0.99-1.54, n = 14, I2 = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47-8.76, n = 2, I2 = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09-6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83-8.62, n = 3, I2 = 77.9%) and 3.34 (95%CI 0.79-14.1, n = 4, I2 = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65-1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I2 = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. CONCLUSION: Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required

PiggyBac transgenic strategies in the developing chicken spinal cord

The chicken spinal cord is an excellent model for the study of early neural development in vertebrates. However, the lack of robust, stable and versatile transgenic methods has limited the usefulness of chick embryos for the study of later neurodevelopmental events. Here we describe a new transgenic approach utilizing the PiggyBac (PB) transposon to facilitate analysis of late-stage neural development such as axon targeting and synaptic connection in the chicken embryo. Using PB transgenic approaches we achieved temporal and spatial regulation of transgene expression and performed stable RNA interference (RNAi). With these new capabilities, we mapped axon projection patterns of V2b subset of spinal interneurons and visualized maturation of the neuromuscular junction (NMJ). Furthermore, PB-mediated RNAi in the chick recapitulated the phenotype of loss of agrin function in the mouse NMJ. The simplicity and versatility of PB-mediated transgenic strategies hold great promise for large-scale genetic analysis of neuronal connectivity in the chick

Two ultraviolet radiation datasets that cover China

Ultraviolet (UV) radiation has significant effects on ecosystems, environments, and human health, as well as atmospheric processes and climate change. Two ultraviolet radiation datasets are described in this paper. One contains hourly observations of UV radiation measured at 40 Chinese Ecosystem Research Network stations from 2005 to 2015. CUV3 broadband radiometers were used to observe the UV radiation, with an accuracy of 5%, which meets the World Meteorology Organization's measurement standards. The extremum method was used to control the quality of the measured datasets. The other dataset contains daily cumulative UV radiation estimates that were calculated using an all-sky estimation model combined with a hybrid model. The reconstructed daily UV radiation data span from 1961 to 2014. The mean absolute bias error and root-mean-square error are smaller than 30% at most stations, and most of the mean bias error values are negative, which indicates underestimation of the UV radiation intensity. These datasets can improve our basic knowledge of the spatial and temporal variations in UV radiation. Additionally, these datasets can be used in studies of potential ozone formation and atmospheric oxidation, as well as simulations of ecological processes

Trajectories of alcohol consumption in relation to all-cause mortality in patients with cardiovascular disease: a 35-year prospective cohort study.

BACKGROUND AND AIMS: Research into alcohol consumption and cardiovascular disease (CVD) patients' prognosis has largely ignored the longitudinal dynamics in drinking behaviour. This study measured the association between alcohol consumption trajectories and mortality risk in CVD patients. DESIGN: Prospective cohort study. Setting was the UK-based Whitehall II Study. Participants were a total of 1306 participants with incident non-fatal CVD (coronary heart disease/stroke) events. MEASUREMENTS: Up to eight repeated measures of alcohol intake were available for each patient from the most recent assessment phase pre-incident CVD and all subsequent phases post-incident CVD, spanning up to three decades. Six trajectory groups of alcohol consumption were identified using group-based trajectory modelling and related to the risk of all-cause mortality, adjusting for demographics and changes in life-style and health status. FINDINGS: Three hundred and eighty deaths were recorded during a median follow-up of 5 years after patients' last alcohol assessment. Compared with patients who consistently drank moderately (≤ 14 units/week), former drinkers had a greater risk of mortality (hazard ratio = 1.74, 95% confidence interval = 1.19-2.54) after adjustment for covariates. There was no significantly increased risk of mortality in long-term abstainers, reduced moderate drinkers, stable or unstable heavy drinkers. Cross-sectional analyses based only on drinking information at patients' last assessment found no significant differences in mortality risk for abstainers, former or heavy drinkers versus moderate drinkers. CONCLUSIONS: Cardiovascular disease patients who consistently drink ≤ 14 units/week appear to have a similar risk of mortality to those who are long-term abstainers, which does not support a protective effect of moderate drinking on total mortality. Cardiovascular disease patients who stop drinking appear to have increased mortality risk compared with continuous moderate drinkers, but this may be linked to poor self-rated health before cardiovascular disease onset

Binge-Pattern Alcohol Consumption and Genetic Risk as2 Determinants of Alcohol-Related Liver Disease

Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions

Prediction model of sintering bed temperature based on lognormal distribution function: construction and application

The monitoring of sintering bed temperature is crucial for controlling physical and chemical reactions during the sintering process and achieving low carbonization trends. However, accurately monitoring this temperature is challenging due to the ''black box'' nature of the sintering bed, which includes the sintering trolley and cup. As a result, a theoretical model needs to be developed urgently to predict the sintering bed's temperature profile. In this investigation, we propose a mathematical model that utilizes the characteristic value of the lognormal distribution to estimate indirectly the temperature of the sintering bed based on the measured temperature of the sintering exhaust gas. The sintering exhaust gas temperature and sintering bed temperature conform to the function: T=T0+A2πw⋅te−(ln(t−tc))2w22. To further enhance the accuracy of the sintering bed temperature prediction, the longitudinal positions of the sintering bed were expanded from three points to multiple points, enabling the construction of a temperature prediction function for the entire sinter bed and obtaining a cloud map of the sintering bed temperature. By determining the sintering terminal point and controlling the sintering machine's speed according to the location of the high-temperature region on the cloud map, the performance of the temperature prediction model was optimized. Through an analysis of the mathematical model and construction of the sintering temperature profile, a predictive route of exhaust gas temperature → three-point sintering bed → total sintering bed was established. This predictive method can significantly enhance the understanding of the sintering process and can be employed in industrial plants