| 31. |
- Tschiderer, Lena, et al.
(författare)
-
Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque : Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
-
Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development.Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques).Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
|
|
| 32. |
- Atabaki-Pasdar, Naeimeh, et al.
(författare)
-
Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
- 2021
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.Competing Interest StatementHR is an employee and shareholder of Sanofi. MIM: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MIM has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MIM is an employee of Genentech, and a holder of Roche stock. AM is a consultant for Lilly and has received research grants from several diabetes drug companies. PWF has received research grants from numerous diabetes drug companies and fess as consultant from Novo Nordisk, Lilly, and Zoe Global Ltd. He is currently the Scientific Director in Patient Care at the Novo Nordisk Foundation. Other authors declare non competing interests.Funding StatementThe work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT) resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. NAP is supported in part by Henning och Johan Throne-Holsts Foundation, Hans Werthen Foundation, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. HPM is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). RK is funded by the Novo Nordisk Foundation (NNF18OC0031650) as part of a postdoctoral fellowship, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AK, PM, HF, JF and GNG are supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. TJM is funded by an NIHR clinical senior lecturer fellowship. S.Bru acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). ATH is a Wellcome Trust Senior Investigator and is also supported by the NIHR Exeter Clinical Research Facility. JMS acknowledges support from Science for Life Laboratory (Plasma Profiling Facility), Knut and Alice Wallenberg Foundation (Human Protein Atlas) and Erling-Persson Foundation (KTH Centre for Precision Medicine). MIM is supported by the following grants; Wellcome (090532, 098381, 106130, 203141, 212259); NIH (U01-DK105535). PWF is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study protocol was obtained from each of the regional research ethics review boards separately (Lund, Sweden: 20130312105459927, Copenhagen, Denmark: H-1-2012-166 and H-1-2012-100, Amsterdam, Netherlands: NL40099.029.12, Newcastle, Dundee and Exeter, UK: 12/NE/0132), and all participants provided written informed consent at enrolment. The research conformed to the ethical principles for medical research involving human participants outlined in the Declaration of Helsinki.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAuthors agree to make data and materials supporting the results or analyses presented in their paper available upon reasonable request
|
|
| 33. |
- Gunter, Marc J, et al.
(författare)
-
Coffee drinking and mortality in 10 European countries : A multinational cohort study
- 2017
-
Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 167:4, s. 236-247
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. Design: Prospective cohort study. Setting: 10 European countries. Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; 7-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.
|
|
| 34. |
|
|
| 35. |
- Noethlings, Ute, et al.
(författare)
-
Intake of vegetables, legumes, and fruit, and risk for all-cause, cardiovascular, and cancer mortality in a European diabetic population
- 2008
-
Ingår i: Journal of Nutrition. - 1541-6100. ; 138:4, s. 775-781
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of intake of vegetables, legumes and fruit with all-cause and cause-specific mortality in a population with prevalent diabetes in Europe. A cohort of 10,449 participants with self-reported diabetes within the European Prospective Investigation into Cancer and Nutrition study was followed for a mean of 9 y. Intakes of vegetables, legumes, and fruit were assessed at baseline between 1992 and 2000 using validated country-specific questionnaires. A total of 1346 deaths occurred. Multivariate relative risks (RR) for all-cause mortality were estimated in Cox regression models and FIR for cause-specific mortality were derived in a competing risk model. An increment in intake of total vegetables, legumes, and fruit of 80 g/d was associated with a RR of death from all causes of 0.94 [95% CI 0.90-0.98]. Analyzed separately, vegetables and legumes were associated with a significantly reduced risk, whereas nonsignificant inverse associations for fruit intake were observed. Cardiovascular disease (CVD) mortality and mortality due to non-CVD/non-cancer causes were significantly inversely associated with intake of total vegetables, legumes, and fruit (RR 0.88 [95% CI 0.81-0.95] and 0.90 [0.82-0.99], respectively) but not cancer mortality 0.08 [0.99-1.17]). Intake of vegetables, legumes, and fruit was associated with reduced risks of all-cause and CVD mortality in a diabetic population. The findings support the current state of evidence from general population studies that the protective potential of vegetable and fruit intake is larger for CVD than for cancer and suggest that diabetes patients may benefit from a diet high in vegetables and fruits.
|
|
| 36. |
|
|
| 37. |
- Oort, Sabine van, et al.
(författare)
-
Modifiable lifestyle factors and heart failure : A Mendelian randomization study
- 2020
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 227, s. 64-73
-
Tidskriftsartikel (refereegranskat)abstract
- Background Lifestyle factors may be important targets in the prevention of heart failure. The current knowledge on the relationship between lifestyle factors and heart failure originates mostly from observational studies. The objective of this study was to investigate causal associations of multiple lifestyle factors with heart failure risk by using Mendelian randomization. Methods We obtained summary statistics data for single nucleotide polymorphisms associated with the following 5 lifestyle factors at genome-wide significance in genome-wide association studies of European-descent individuals: smoking, alcohol consumption, coffee consumption, physical activity, and sleep duration. The corresponding data for heart failure were acquired from a genome-wide association study comprising 47,309 cases and 930,014 controls of European ancestry. For the primary analyses, we used the inverse-variance weighted method. Results Genetic predisposition to smoking initiation (ever smoked regularly) was robustly associated with a higher odds of heart failure (odds ratio: 1.28; 99% CI: 1.21-1.35). Genetically predicted longer sleep duration was associated with a lower odds of heart failure (odds ratio per hour/day: 0.73; 99% CI: 0.60-0.89). We found no associations of alcohol consumption, coffee consumption, and physical activity with heart failure. Conclusions This Mendelian randomization study showed that smoking initiation increases heart failure risk, whereas longer sleep duration decreases the risk of heart failure. Sleep duration should be regarded as novel risk factor in heart failure prevention guidelines. The potential causal role of alcohol and coffee consumption and physical activity for heart failure warrants further investigation in future larger Mendelian randomization analyses.
|
|
| 38. |
- Slieker, Roderick C, et al.
(författare)
-
Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study
- 2021
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:11, s. 2683-2693
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
|
|
| 39. |
- Sluijs, Ivonne, et al.
(författare)
-
The amount and type of dairy product intake and incident type 2 diabetes : results from the EPIC-InterAct Study
- 2012
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:2, s. 382-390
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products.Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups.Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis.Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles.Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. Ant J Clin Nutr 2012;96:382-90.
|
|
| 40. |
- van Oort, Sabine, et al.
(författare)
-
Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension : A Mendelian Randomization Study
- 2020
-
Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 76:6, s. 1971-1979
-
Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants (P<5×10−8) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts: the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio [OR] per 1 SD, 1.17 [1.10–1.25]), body mass index (OR per 1 SD, 1.42 [1.37–1.48]), alcohol dependence (OR, 1.10 [1.06–1.13]), and insomnia (OR, 1.17 [1.13–1.20]) were associated with a higher odds of hypertension. Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 [0.83–0.94]) and educational level (OR per 1 SD, 0.56 [0.54–0.59]) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.
|
|
