Risk factors in central retinal vein occlusion: A multi-center case-control study conducted on the Italian population

Purpose To explore the risk factors for central retinal vein occlusion (CRVO) by comparing a large sample of patients with healthy controls. Materials and Methods Multi-center case-control study. The study group includes patients affected by central retinal vein occlusion, confirmed angiographically, aged 50 years old or above (Group A). The control group includes healthy subjects without an history of retinal vein occlusion (Group B). Outcome measures: age, gender, active smoking, presence of uncontrolled arterial hypertension (uHTN), presence of the following comorbidities: diabetes mellitus type II (DMII), chronic liver disease (CLD), chronic kidney disease (CKD), thyroid disease (TD), systemic lupus erythematosus (SLE), hyperhomocystenemia (HHcy), dyslipidemia (DLip), carotid artery disease (CAD), glaucoma, atrial fibrillation (AF), migraine headache (MH), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea syndrome (OSAS), history of myocardial infarction (MI). Odds-ratios were calculated with logistic regression analysis. Results A total of 203 patients (Group A) and 339 controls (Group B). Statistically-significant differences were found for the following variables: age (OR: 1.109 [1.081–1.138], p < .001), active smoking (OR: 2.048 [1.210- 3.466], p < .008), DMII (OR: 4.533 [2.097–9.803], p < .001), HHcy (OR: 4.507 [2.477–10.001 ], p < .001), DLip (OR: 2.255 [1.352–3.762], p = .002), CAD (OR: 6.632 [2.944- 14.942], p < .001), glaucoma (OR: 4.656 [2.031–10.673], < .001), OSAS (OR: 1.744 [1.023–2.975], < .041), uHTN (OR: 3.656 [2.247–5.949], < .001). No statistically-significant differences were found for the other variables. Conclusions Older age, active smoking, as well as presence of DMII, HHcy, DLip, CAD, glaucoma, OSAS, and uHTN, all increase the risk for CRVO. A comprehensive assessment of patients with CRVO is paramount. Adequate control of all the aforementioned risk factors is likely of great significance in reducing the incidence of CRVO among the general population, and it likely plays an important role in improving the prognosis following the occlusive event.

Active Smoking Induces Aberrations in Digestive Tract Microbiota of Rats

Cigarette smoking could have certain effects on gut microbiota. Some pioneering studies have investigated effects of active smoking on the microbiome in local segments of the digestive tract, while active smoking-induced microbiome alterations in the whole digestive tract have not been fully investigated. Here, we developed a rat model of active smoking and characterized the effects of active smoking on the microbiota within multiple regions along the digestive tract. Blood glucose and some metabolic factors levels, the microbial diversity and composition, relative abundances of taxa, bacterial network correlations and predictive functional profiles were compared between the control group and active smoking group. We found that active smoking induced hyperglycemia and significant reductions in serum insulin and leptin levels. Active smoking induced region-specific shifts in microbiota structure, composition, network correlation and metabolism function along the digestive tract. Our results demonstrated that active smoking resulted in a reduced abundance of some potentially beneficial genera (i.e. Clostridium, Turicibacter) and increased abundance of potentially harmful genera (i.e. Desulfovibrio, Bilophila). Functional prediction suggested that amino acid, lipid, propanoate metabolism function could be impaired and antioxidant activity may be triggered. Active smoking may be an overlooked risk to health through its potential effects on the digestive tract microbiota, which is involved in the cause and severity of an array of chronic diseases.

Change in exposure of children to second-hand smoke with impact on children’s health and change in parental smoking habits after smoking ban in Bavaria – a multiple cross-sectional study

Background Concerns about smoking displacement from public places to private amenities aroused following smoking ban implementation in Bavaria in 2008. We analysed children’s exposure to second-hand smoke (SHS) before and after the ban, its effect on children’s health and prevalence of active smoking in adults. Methods Six cross-sectional surveys (n = 32,443) on pre-school children in Bavaria were analysed, two surveys before the smoking ban in years 2004 and 2005 (S1 and S2) and four after the ban in 2008, 2012, 2014 and 2016 (S4, S6, S7 and S8). Using multivariable logistic regression, we analysed change in children’s intra- and extrauterine SHS exposure and its adverse health effects (Asthma, wheezing, bronchitis and neurodermatitis) as well as change in parental active smoking. Results The response rates were 78% for S1, 73% for S2, 61% for S4, 62% for S6, 56% for S7 and 54% for S8. Odds of parents never smoked at home in presence of children increased significantly from before to after the ban with odds ratios (OR) 1.17 (CI95% 1.01–1.35), 1.65 (CI95% 1.39–1.95), 2.85 (CI95% 2.32–3.51), 2.24 (CI95% 1.84–2.72) and 3.66 (CI95% 2.89–4.63) for S2, S4, S6, S7 and S8, respectively with S1 as reference. Compared to S4, odds of parents who were not actively smoking is significantly higher in S7 (OR = 1.13 (CI95% 1.03–1.24)) and S8 (OR = 1.24 (CI95% 1.13–1.36)). The odds of mothers who never smoked during pregnancy increased over time with OR = 1.22 (CI95% 1.06–1.40) for S2 and 1.57 (CI95% 1.33–1.86) for S8 compared to S1. Adverse health effects related to children’s exposure to SHS are significantly less in S8 compared to S1. Conclusion After 11 years of smoking ban in Bavaria, smoking displacement to homes was disproved. Exposure of children to SHS intrauterine and at home is decreasing. Number of parents who are not actively smoking is increasing over time. Prevalence of health problems in children related to exposure to SHS is decreasing.

Renal Function and Risk of Arterial Thrombotic Events in Patients Positive for Lupus Anticoagulant

Background: Patients with lupus anticoagulant (LA) are at risk for arterial and venous thromboembolic events. Recent work suggests that LA positive patients who experience thrombotic events in different vascular beds constitute distinct subgroups. To risk stratify patients, further work is needed to better characterize predictors for thromboembolic events in these subgroups. Aims: The aim of this study was to identify baseline characteristics and laboratory parameters associated with the development of arterial or venous thrombotic events. Methods: Patients with at least 2 previous positive LA tests were serially monitored for thrombotic events within the prospective Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Patients without clinical follow-up were excluded from this analysis. Statistical analysis was performed with RStudio (Version 1.1.442). Results: One-hundred-eighty-seven patients were followed (Table 1) for a median of 11.4 years and 1865 follow-up visits (median visit/patient=9). Fifty-seven prospective thrombotic events (TE), including 27 arterial thrombotic events (ATE) and 30 venous thrombotic events (VTE), were observed. This corresponded to 10-year prospective ATE, VTE and overall thrombosis incidences of 13.9% [95%CI: 8.3, 19.6], 18.8% [12.2, 25.4], and 32.0% [24.1, 39.8], respectively. (Figure 1). Thirty-seven of the 57 events occurred in patients with a prior history of thrombosis ("recurrent thrombosis"). In univariable competing risk analysis, age (subdistribution hazard ratio (SHR) = 1.02, 95% CI: 1.00-1.05, p=0.019), body mass index (BMI, 1.05, 1.00-1.11, p=0.042), history of ATE (3.14, 1.45-6.81, p=0.0038), active smoking (2.16, 1.00-4.62, p=0.049), diabetes (4.16, 1.47-11.8, p=0.0073), VKA use at baseline (0.42, 0.18-0.97, p=0.042), aCL IgM positivity (2.48, 1.05-5.83, p=0.038), aβ 2GPI IgM positivity (2.86, 1.18-6.93, p=0.020), mean platelet volume (1.17, 1.06- 1.30, p=0.0024), creatinine (3.76, 1.32- 10.7, p=0.013), and estimate glomerular filtration rate (eGFR, 0.98, 0.96-0.99, p=0.0011) were associated with prospective risk of ATE (Table 2). Conversely, the prospective risk of VTE was univariably associated only with prior history of VTE (3.26, 1.40-7.68, p=0.0061). After adjusting for traditional arterial thrombotic risk factors (age, sex, BMI, active smoking, diabetes,), history of ATE (SHR = 3.97, 95% CI: 1.71-9.025, p=0.0014), prior history of both ATE and VTE (3.87, 1.06-14.16, p=0.041), creatinine (3.93, 1.22-12.66, p=0.022), and eGFR (CKD-EPI, 0.96, 0.96-0.99, p=0.0037) remained independently associated with prospective risk of ATE (Table 2). In detail, the 10-year cumulative risk of ATE was 24.9% [95%CI: 8.8, 41.0], 15.0% [5.8, 24.2], and 6.7% [2.2, 13.8] in patients with a baseline eGFR less than 60 mL/min/1.73m 2, between 60 and 89 mL/min/1.73m 2, and greater than or equal to 90 mL/min/1.73m 2, respectively (Gray's test, p=0.019, Figure 2). Conclusion: Approximately 14% of patients persistently positive for LA experienced an ATE over 10 years. After adjusting for traditional arterial risk factors, decreased renal function was associated with an increased prospective risk of ATE. Notably, decreased renal function was not associated with development of VTE and the association with ATE was also independent of underlying SLE, LLD, or rheumatic disease (data not shown). Clinically, LA positive patients with decreased renal function may represent a subgroup that might benefit from more aggressive anti-thrombotic therapy or anti-thrombotic prophylaxis. Figure 1 Figure 1. Disclosures Pabinger: Bayer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

Risk factors in young patients with myocardial infarction: what is different from the general population?

Introduction Patients that suffer from myocardial infarction (MI) at a younger age are of special medical and socioeconomic interest. Data on risk factors for MI in this patient group are however scarce. Methods In this case–control study, clinical characteristics of consecutive patients admitted to hospital with MI at age of ≤45 years were compared to a randomly selected cohort from the general population in the same geographic region in Germany. After 3:1 matching on age and gender and multivariable analyses, independent risk factors for the occurrence of MI at a younger age were analyzed. Results 522 patients with MI ≤45 years were compared to 1191 matched controls from the general population. The proportion of active smokers was more than 3-fold higher in younger MI-patients compared to the general population (82.4% vs. 24.1%, p&lt;0.01), while the proportion of persons consuming alcohol at least 2 times a week was higher in the general population (19.9% vs. 36.6%, p&lt;0.01). Younger patients with MI were more often obese (median body mass index 28.4 vs. 25.5 kg/m2, p&lt;0.01), had a higher proportion of hypertension (25.1% vs. 0.5%, p&lt;0.01) or diabetes mellitus (11.7% vs. 1.7%, p&lt;0.01) and had more often a family history of the father (22.4% vs. 7.1%, p&lt;0.01) or the mother (7.5% vs. 1.3%, p&lt;0.01) for premature coronary artery disease. In multivariable analysis, hypertension or diabetes, active smoking, family history and body mass index ≥30 kg/m2 were strong predictors for the occurrence of MI at a younger age, while alcohol consumption was a protective factor (Figure). Conclusions This case-control study demonstrates a very strong association of active smoking, metabolic syndrome and family history with the occurrence of MI at a younger age. The contrary is found regarding alcohol consumption. These data suggest that the risk of young-onset MI goes beyond family history and underline the importance of primary prevention efforts to reduce smoking and metabolic syndrome in children, adolescents and young adults in order to reduce the burden of cardiovascular diseases. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Bremen Heart FoundationLeibniz Institute for Prevention Research and Epidemiology

Smoking induces sex-specific changes in the small airway proteome

Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. Conclusions The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.

National Trends in Tobacco Smoke Exposure and its Disruption on Vitamin D Levels Among U.S. Population, 2001-2014

Background: Persuasive evidence suggests that tobacco smoking is endocrine-disrupting and may interfere with vitamin D (VD) endocrine systems, but supporting research is limited and results vary greatly.Methods: Data from the National Health and Nutrition Examination Survey, 2001-2014, was used to evaluate the trends in tobacco smoke exposure among U.S. general participants aged ≥3 yr (n=49338). We examined the linear association between serum cotinine and 25(OH)D concentrations, as well as relationship between tobacco smoke exposure categories (active, passive, non-smoking) with VD status (deficiency, inadequacy, sufficiency, intoxication), and assessed whether specific gender, age (3-11, 12-19, 20-59, ≥60 yr) or ethnicity/race groups were disproportionately impacted.Results: During 2001-2004, the trends of active smoking rates stabilized between 17.2% to 19.6%. Serum cotinine was significantly and inversely associated with 25(OH)D in adult participants (≥ 20 yr). Tobacco smoke exposure, including both active and passive smoking exposure, was associated with increased risk of VD deficiency in adults. Moreover, active smoking of adults was additionally related to enhanced risk of VD inadequacy. These associations showed somewhat gender difference, with consistent and stronger associations observed in female adults. In contrast, effects of tobacco smoke exposure on VD levels were mostly protective or non-significant among children and adolescents aged 3-19 yr.Conclusion: The percentage of U.S. general population with active smoking exposure stabilized over the 14-yr period and was still high. Tobacco smoke exposure may disrupt vitamin D levels. Our results also provided initial evidence of active smoking exposure on VD intoxication, which needs to be further verified.Implication: Convincing studies have linked tobacco use exposure, including active and passive smoking exposure, to dysfunctional VDES accompanied with declined serum levels of VD metabolites. However, evidence on the association between tobacco smoke exposure and VD status was rather limited, and there were no researches to date that estimated their relationship in children and adolescents. This study analyzed national survey data, to evaluate the national trends in tobacco smoke exposure over a decade, and to comprehensively assess the impacts of tobacco smoke exposure on VD levels across specific gender-, age- and ethnicity/race- groups. The evidence suggests that the prevalence of active smoking exposure stabilized over the 14-yr period and was still high. Moreover, tobacco smoke exposure may disrupt vitamin D levels among general population, with age- and gender- differences observed.