scholarly journals Prediction of coronary disease incidence in the general population by circulating RNY(YRNA)-derived small RNA

Author(s):  
Vera L. Costa ◽  
Jean-Bernard Ruidavet ◽  
Vanina Bongard ◽  
Bertrand Perret ◽  
Emanuela Repetto ◽  
...  

ABSTRACTDuring the development of atherosclerotic lesion, s-RNYs (small RNAs of about 24/34 nucleotides) are derived by the processing of long Ro-associated non-coding RNAs (RNYs) in macrophages. The levels of serum s-RNYs have been found significantly upregulated in patients with coronary heart disease (CHD) compared to age-matched healthy individuals. The present study aimed to examine the predictive value of serum s-RNYs for CHD events in the general population.Within the frame of nested-case-control study, the GENES study, we measured the absolute expression of a RNY-derived small RNA, the s-RNY1-5p, in the serum of healthy individuals who encountered a CHD event within 12 years of follow-up (n = 31) (Cases) and compared them to individuals who remained event-free (Controls) (n = 30).The expression of s-RNY1-5p in serum was significantly upregulated in Cases compared to Controls (p = 0.027). The proportion of CHD event-free was significantly higher among individuals with serum s-RNY1-5p below the median value (631 molecule / mL). In a multivariate model adjusted for age, smoking and treatment for hypertension, diabetes and dyslipidemia, the risk of CHD events increased more than 4-fold in individuals with serum s-RNY1-5p above the median value (HR, 4.36; 95%CI, 1.22-15.60). Significant association with CHD events was also observed when considering s-RNY1-5p as a continuous variable (p = 0.022). Serum s-RNY1-5p is an independent predictor of CHD in healthy individuals and could be considered as a biomarker in primary prevention of cardiovascular diseases.TRANSLATIONAL PERSPECTIVESHere, we reported that s-RNY1-5p was significantly upregulated in the serum of individuals who underwent CHD and was positively associated with CHD events. Those results argue in favor of s-RNY1-5p being a novel predictive molecular biomarker for cardiovascular events. In the future, measurement of s-RNY1-5p expression levels and other 5’ s-RNYs, such as s-RNY4-5p, could be used in clinical practice in addition to classical risk factors to identify those high-risk individuals who might benefit from prevention medicine.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vera L. Costa ◽  
Jean-Bernard Ruidavets ◽  
Vanina Bongard ◽  
Bertrand Perret ◽  
Emanuela Repetto ◽  
...  

AbstractDuring the development of atherosclerotic lesion, s-RNYs (small RNAs of about 24/34 nucleotides) are derived by the processing of long Ro-associated non-coding RNAs (RNYs) in macrophages. The levels of serum s-RNYs have been found significantly upregulated in patients with coronary heart disease (CHD) compared to age-matched CHD-free individuals. The present study aimed to examine the predictive value of serum s-RNYs for CHD events in the general male population. Within the frame of nested-case–control study, the GENES study, we measured the absolute expression of a RNY-derived small RNA, the s-RNY1-5p, in the serum of individuals (without CHD at baseline) who encountered a CHD event within 12 years of follow-up (n = 30) (Cases) and compared them to individuals who remained event-free (Controls) (n = 30). The expression of s-RNY1-5p in serum was significantly upregulated in Cases compared to Controls (p = 0.027). The proportion of CHD event-free was significantly higher among individuals with serum s-RNY1-5p below the median value (631 molecules/mL). In a multivariable model adjusted for age, smoking, hypertension, diabetes and dyslipidemia, the risk of CHD events increased more than fourfold in individuals with serum s-RNY1-5p above the median value (HR, 4.36; 95% CI 1.22–15.60). A positive association with CHD events was also observed when considering s-RNY1-5p as a continuous variable (p = 0.022). Based on our results, we conclude that serum s-RNY1-5p is an independent predictor of CHD events in a general male population and might be a relevant biomarker for early detection of cardiovascular diseases.


2020 ◽  
pp. 159-180
Author(s):  
Bendix Carstensen

This chapter addresses Case-control and case-cohort studies. In a Case-control study, one samples persons based on their disease outcome, so the fraction of diseased persons in a Case-control study is usually known (at least approximately) before data collection. In a cohort (follow-up) study, the relationship between some exposure and disease incidence is investigated by following the entire cohort and measuring the rate of occurrence of new cases in the different exposure groups. The follow-up records all persons who develop the disease during the study period. Implicit in this is that the relevant exposure information is available at all times for all persons under follow-up. The chapter then looks at the statistical model for the odds ratio, before differentiating between odds ratio and rate ratio. It also considers confounding and stratified sampling; individually matched studies; and nested Case-control studies.


Author(s):  
Kavindhran Velen ◽  
Nguyen Viet Nhung ◽  
Nguyen Thu Anh ◽  
Pham Duc Cuong ◽  
Nguyen Binh Hoa ◽  
...  

Abstract Background Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention and control interventions. We aimed to identify risk factors associated with developing TB among HHCs. Methods We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs. Results We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.03–2.0), residing in an urban setting (aOR, 1.8; 1.3–2.5), prior TB (aOR, 4.6; 2.5–8.7), history of diabetes (aOR, 3.1; 1.7–5.8), current smoking (aOR, 3.1; 2.2–4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1–2.3). Conclusions Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chelsea Catsburg ◽  
Marc J. Gunter ◽  
Lesley Tinker ◽  
Rowan T. Chlebowski ◽  
Michael Pollak ◽  
...  

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86,ptrend= 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03,ptrend= 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.


BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e052841
Author(s):  
Gabriella Wojewodka ◽  
Martin C Gulliford ◽  
Mark Ashworth ◽  
Mark P Richardson ◽  
Leone Ridsdale

ObjectivesPeople with epilepsy (PWE) have a higher mortality rate than the general population. Epilepsy-related deaths have increased despite all-cause mortality decreasing in the general population pre-COVID-19. We hypothesised that clinical and lifestyle factors may identify people more at risk.DesignWe used a retrospective cohort study to explore cause of death and a nested case–control study to identify risk factors.SettingWe explored factors associated with mortality using primary care population data from 1 April 2004 to 31 March 2014. Data were obtained from the Clinical Practice Research Datalink which compiles anonymised patient data from primary care in the UK. Cause of death data was supplemented from the Office of National Statistics when available.ParticipantsThe analysis included 70 431 PWE, with 11 241 registered deaths.ResultsThe number of deaths within the database increased by 69% between the first and last year of the study. Epilepsy was considered as a contributing cause in approximately 45% of deaths of PWE under 35. Factors associated with increased risk of death included attendance at emergency departments and/or emergency admissions (OR 3.48, 95% CI 3.19 to 3.80), antiepileptic drug (AED) polytherapy (2 AEDs: OR 1.60, 95% CI 1.51 to 1.71; 3 AEDs: OR 2.06, 95% CI 1.86 to 2.29; 4+AEDs: OR 2.62, 95% CI 2.23 to 3.08), status epilepticus (OR 2.78, 95% CI 1.64 to 4.71), depression (OR 1.67, 95% CI 1.57 to 1.76) and injuries (OR 1.54, 95% CI 1.43 to 1.67). No seizures in the prior year (OR 0.52, 95% CI 0.41 to 0.65).ConclusionOur results add to existing evidence that deaths in epilepsy are increasing. Future studies could focus on identifying PWE at high risk and addressing them with clinical interventions or better self-management. Identifying specific risk factors for younger people should be a priority as epilepsy may be a factor in close to half of deaths of PWE under 35 years of age.


Author(s):  
Christina Santella ◽  
Alain Bitton ◽  
Christopher Filliter ◽  
Talat Bessissow ◽  
Maria Vutcovici ◽  
...  

Abstract Background The specific contribution of anti-TNF therapy to the onset of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD) remains uncertain. Thus, the purpose of this nested case-control study was to explore whether the use of anti-TNF therapy is associated with an increased risk of HZ. Methods Using the Regie de l’Assurance Maladie du Québec, we identified incident cases of IBD between 1998 and 2015. We matched IBD cases of HZ with up to 10 IBD HZ-free controls on year of cohort entry and follow-up. Current use was defined as a prescription for anti-TNF therapy 60 days before the index date, with nonuse as the comparator. We conducted conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for potential confounders. Results The cohort consisted of 15,454 incident IBD patients. Over an average follow-up of 5.0 years, 824 patients were diagnosed with HZ (incidence of 9.3 per 1000 person-years). Relative to nonuse, current use of anti-TNF therapy was associated with an overall increased risk of HZ (OR, 1.5; 95% CI, 1.1–2.1). The risk was increased among those older than 50 years (OR, 2.1; 95% CI, 1.2–3.6) and those additionally using steroids and immunosuppressants (OR, 4.1; 95% CI, 2.3–7.2). Conclusions Use of anti-TNF therapy was associated with an increased risk of HZ among patients with IBD, particularly among those older than 50 years and those on combination therapy. Prevention strategies for HZ ought to be considered for younger IBD patients commencing treatment.


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