scholarly journals Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study

2020 ◽  
Author(s):  
Christopher Papandreou ◽  
Mònica Bulló ◽  
Pablo Hernández-Alonso ◽  
Miguel Ruiz-Canela ◽  
Jun Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Multiple Testing ◽  
Conditional Logistic Regression ◽  
Case Control Studies ◽  
Logistic Regression Models ◽  
Liquid Chromatography Tandem Mass ◽  
Nested Case Control ◽  
Incident Cases ◽  
Predimed Study

Abstract Background Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. Methods Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. Results After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30–2.63) and 1.57 (1.09–2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99–1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03–1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57–4.03), 1.65 (1.00–2.71) and 1.65 (1.04–2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. Conclusions Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.

scholarly journals Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

2020 ◽  
Vol 113 (1) ◽  
pp. 162-171
Author(s):  
Raul Zamora-Ros ◽  
Leila Lujan-Barroso ◽  
David Achaintre ◽  
Silvia Franceschi ◽  
Cecilie Kyrø ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Conditional Logistic Regression ◽  
Differentiated Thyroid Carcinoma ◽  
Blood Concentrations ◽  
Logistic Regression Models ◽  
Not Otherwise Specified ◽  
Ferulic Acids ◽  
Nested Case Control ◽  
Control Study ◽  
Prospective Investigation

ABSTRACT Background Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods A nested case–control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

scholarly journals Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 306
Author(s):  
Nerea Becerra-Tomás ◽  
Miguel Ruiz-Canela ◽  
Pablo Hernández-Alonso ◽  
Mònica Bulló ◽  
Jun Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Conditional Logistic Regression ◽  
Negative Ion ◽  
Plasma Metabolites ◽  
Mediterranean Population ◽  
Case Control Studies ◽  
Increased Risk ◽  
Glycolysis Pathway ◽  
Negative Ion Mode

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.

scholarly journals Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 18-18
Author(s):  
Leticia Goni ◽  
Cristina Razquin ◽  
Estefania Toledo ◽  
Marta Guasch-Ferre ◽  
Clary B. Clish ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Dietary Intervention ◽  
Urea Cycle ◽  
Conditional Logistic Regression ◽  
Virgin Olive Oil ◽  
Case Control ◽  
Control Group ◽  
Ratio Test ◽  
Case Control Studies

Abstract Objectives To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. Methods We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA ratio)) were determined using liquid chromatography tandem mass spectrometry. We used conditional logistic regression models, adjusted for potential confounders, to analyze the associations between the metabolites and incident AF or HF. Potential interactions between metabolites and intervention (MD groups vs control group) were tested with the likelihood ratio test. Results The study population comprised a total of 1241 participants (509 cases) for AF case-control and 824 participants (326 cases) for HF case-control. Arginine was inversely associated with incident AF (OR per SD 0.83, 95% CI 0.73; 0.94) and HF (OR per SD 0.82, 95% CI 0.69; 0.97). Whereas ADMA/SDMA ratio was positively associated with AF (OR per SD 1.19, 95% CI 1.02; 1.41) but not with HF risk. A statistically significant interaction (P = 0.044) was found between arginine and intervention on HF risk. The lower risk of HF associated with arginine was only observed in participants of the MD groups (EVOO + nuts). Conclusions The results of the present study suggest that urea cycle metabolites, arginine and ADMA/SDMA ratio specifically, could be involved in AF and HF pathophysiology. Moreover, the dietary intervention may modify the association between arginine and HF. Funding Sources National Institutes of Health (NIH), Spanish Government Official Agency for funding biomedical research-Instituto de Salud Carlos III (ISCIII) and CIBEROBN

scholarly journals A systematic assessment of the association between frequently prescribed medicines and the risk of common cancers: a series of nested case-control studies

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
R. D. McDowell ◽  
C. Hughes ◽  
P. Murchie ◽  
C. Cardwell
Keyword(s):  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
Exposure Dose ◽  
Case Control ◽  
Case Control Studies ◽  
Systematic Assessment ◽  
Exposure Response ◽  
Prescribed Medicines ◽  
Nested Case Control ◽  
Novel Associations

Abstract Background Studies systematically screening medications have successfully identified prescription medicines associated with cancer risk. However, adjustment for confounding factors in these studies has been limited. We therefore investigated the association between frequently prescribed medicines and the risk of common cancers adjusting for a range of confounders. Methods A series of nested case-control studies were undertaken using the Primary Care Clinical Informatics Unit Research (PCCIUR) database containing general practice (GP) records from Scotland. Cancer cases at 22 cancer sites, diagnosed between 1999 and 2011, were identified from GP records and matched with up to five controls (based on age, gender, GP practice and date of registration). Odds ratios (OR) and 95% confidence intervals (CI) comparing any versus no prescriptions for each of the most commonly prescribed medicines, identified from prescription records, were calculated using conditional logistic regression, adjusting for comorbidities. Additional analyses adjusted for smoking use. An association was considered a signal based upon the magnitude of its adjusted OR, p-value and evidence of an exposure-response relationship. Supplementary analyses were undertaken comparing 6 or more prescriptions versus less than 6 for each medicine. Results Overall, 62,109 cases and 276,580 controls were included in the analyses and a total of 5622 medication-cancer associations were studied across the 22 cancer sites. After adjusting for comorbidities 2060 medicine-cancer associations for any prescription had adjusted ORs greater than 1.25 (or less than 0.8), 214 had a corresponding p-value less than or equal to 0.01 and 118 had evidence of an exposure-dose relationship hence meeting the criteria for a signal. Seventy-seven signals were identified after additionally adjusting for smoking. Based upon an exposure of 6 or more prescriptions, there were 118 signals after adjusting for comorbidities and 82 after additionally adjusting for smoking. Conclusions In this study a number of novel associations between medicine and cancer were identified which require further clinical and epidemiological investigation. The majority of medicines were not associated with an altered cancer risk and many identified signals reflected known associations between medicine and cancer.

scholarly journals Nested Case-Control Studies With Multiple Measurements: Estimating Marginal Relationships

2021 ◽  
Author(s):  
Joshua N. Sampson ◽  
Paul S. Albert ◽  
Mark P. Purdue
Keyword(s):  
Conditional Logistic Regression ◽  
Case Control ◽  
Case Control Studies ◽  
Robust Variance ◽  
Non Hodgkin Lymphoma ◽  
Multiple Measurements ◽  
Matched Case ◽  
Nested Case Control ◽  
Standard Software ◽  
Single Time Point

Abstract Background: We consider the analysis of nested, matched, case-control studies that have multiple biomarker measurements per individual. We propose a simple approach for estimating the marginal relationship between a biomarker measured at a single time point and the risk of an event. We know of no other standard software package that can perform such analyses while explicitly accounting for the matching. Results: We propose an application of conditional logistic regression (CLR) that can include all measurements and uses a robust variance estimator. We compare our approach to other methods such as performing CLR with only the first measurement, CLR with an average of all measurements, and Generalized Estimating Equations. In simulations, our approach is significantly more powerful than CLR with one measurement or an average of all measurements, and has similar to power to GEE but correctly accounts for the matching. We then apply our approach to the CLUE cohort to show that an increased level of the immune marker sCD27 is associated with non‐Hodgkin lymphoma (NHL) and, by evaluating the strength of the association as a function of time until diagnosis, that the an increased level is likely an effect of the disease as opposed to a cause of the disease. The approach can be implemented by the R function clogitRV available at https://github.com/sampsonj74/clogitRV.Conclusion: We offered an approach and software for analyzing matched case-control studies with multiple measurements. We demonstrated that these methods are accurate, precise, and statistically powerful.

scholarly journals Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Christos V Chalitsios ◽  
Dominick E Shaw ◽  
Tricia M McKeever
Keyword(s):  
Cumulative Dose ◽  
Inhaled Corticosteroids ◽  
Conditional Logistic Regression ◽  
Fragility Fractures ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Case Control Studies ◽  
Increased Risk ◽  
Nested Case Control

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

scholarly journals Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case–control study

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322308 ◽  
Author(s):  
Jonathan Blackwell ◽  
Sonia Saxena ◽  
Irene Petersen ◽  
Matthew Hotopf ◽  
Hanna Creese ◽  
...  
Keyword(s):  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Subsequent Development ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Gi Symptoms ◽  
Nested Case Control ◽  
Incident Cases ◽  
Control Study

ObjectiveDepression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD.DesignWe conducted a nested case–control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn’s disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5–5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status.ResultsWe identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38).ConclusionsDepression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.

scholarly journals Types of Carbohydrates Intake during Pregnancy and Frequency of a Small for Gestational Age Newborn: A Case-Control Study

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 523 ◽  
Author(s):  
Carmen Amezcua-Prieto ◽  
Juan Martínez-Galiano ◽  
Naomi Cano-Ibáñez ◽  
Rocío Olmedo-Requena ◽  
Aurora Bueno-Cavanillas ◽  
...  
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Inverse Association ◽  
Odds Ratios ◽  
Case Control Studies ◽  
Logistic Regression Models ◽  
Matched Case ◽  
Brown Bread

The objective of this study was to assess the relationship between consumption of different types of carbohydrates (CHO) during pregnancy and the risk of having a small for gestational age (SGA) newborn. A retrospective matched case–control design was carried out with a total of 518 mother-offspring pairs. A total of 137 validated items were included in the food frequency questionnaire (FFQ). Conditional logistic regression models were used to calculate crude odds ratios (cORs) and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Having more than 75 g/day of brown bread showed an inverse association with SGA (aOR = 0.64, CI 0.43–0.96). In contrast, an intake of industrial sweets more than once a day (aOR = 2.70, CI 1.42–5.13), or even 2–6 times a week (aOR = 1.84, CI 1.20–2.82), increased the odds of having a SGA newborn. During pregnancy, the higher the increase of wholegrain cereal and bread, the lower the possibility of having a SGA newborn, but the opposite occurred with refined sugar products—just consuming industrial bakery products or pastries twice a week increased the odds of having an SGA infant. Case–control studies cannot verify causality and only show associations, which may reflect residual confusion due to the presence of unknown factors. It is possible that a high consumption of sugary foods is a marker of a generally poor lifestyle.

scholarly journals Serum IGFBP-2 and Risk of Atypical Hyperplasia of the Breast

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chelsea Catsburg ◽  
Marc J. Gunter ◽  
Lesley Tinker ◽  
Rowan T. Chlebowski ◽  
Michael Pollak ◽  
...  
Keyword(s):  
Conditional Logistic Regression ◽  
Atypical Hyperplasia ◽  
Mammary Tissue ◽  
Inverse Association ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Nested Case Control ◽  
Nonsignificant Decrease ◽  
Control Study

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.

scholarly journals Impact of opportunistic screening on squamous cell and adenocarcinoma of the cervix in Germany: A population-based case-control study

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253801
Author(s):  
Luana F. Tanaka ◽  
Dirk Schriefer ◽  
Kathrin Radde ◽  
Gunther Schauberger ◽  
Stefanie J. Klug
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell ◽  
Case Control Study ◽  
Precancerous Lesions ◽  
Conditional Logistic Regression ◽  
Population Based ◽  
Case Control ◽  
Logistic Regression Models ◽  
Incident Cases ◽  
Control Study

Background We investigated the uptake of opportunistic cervical cancer screening (CCS) and other risk factors and their association with cervical cancer in Germany in a case-control study. Methods and findings We recruited incident cases of cervical cancer (ICD-10 C53) diagnosed between 2012 and 2016 and matched with three population-based controls, based on age and region of residence. Cases and controls reported their CCS participation during the past ten years (frequent: every three years; no or infrequent: less than every three years) and other relevant variables. We fitted conditional logistic regression models, reporting odds ratios (OR) and 95% confidence intervals (95% CI). We report overall and stratified analyses by histologic group (squamous cell–SCC, and adenocarcinoma–AC), T category (T1 and T2+), and age (<50 and ≥50 years). We analysed 217 cases and 652 matched controls. 53.0% of cases and 85.7% of controls attended CCS frequently. In the overall adjusted model, no or infrequent participation in CCS (OR 5.63; 95% CI 3.51 to 9.04), having had more than one sexual partner (OR 2.86; 95%CI 1.50 to 5.45) and obesity (OR 1.69; 95% CI 1.01 to 2.83) were associated with cervical cancer. Twelve years of schooling (OR 0.37; 95% CI 0.23 to 0.60) and a net monthly income of €3000 or more (OR 0.50; 95% CI 0.30 to 0.82) were protective factors. In the stratified analyses, no or infrequent participation was associated with T1 (OR 4.37; 95% CI 2.48 to 7.71), T2+ (OR 10.67; 95% CI 3.83 to 29.74), SCC (OR 6.88; 95% CI 4.08 to 11.59) and AC (OR 3.95; 95% CI 1.47 to 10.63). Conclusion Although women who frequently attended CCS were less likely to develop cervical cancer, especially larger tumours, the high proportion of cases who had been frequently screened prior to diagnosis underscores the need to investigate the quality of cytology and treatment of precancerous lesions in Germany.

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