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GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer
Type: article, Author: W Zhou and et al, Date: 2020-08-11
Gluten intake and metabolic health: conflicting findings from the UK Biobank
Type: article, Author: I Behrendt and et al, Date: 2020-08-06
Kidney Disease Biomarkers Improve Heart Failure Risk Prediction in the General Population
Type: article, Author: C Nowak and et al , Date: 2020-08-06
Last updated May 3, 2020
2019 |
J Lee; et al Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease Journal Article In: Nature Medicine, 2019. Links | BibTeX | Tags: 9310, cardiovascular disease @article{Lee2019b, title = {Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease}, author = {J Lee and et al }, url = {https://www.ncbi.nlm.nih.gov/pubmed/31700174 }, year = {2019}, date = {2019-11-07}, journal = {Nature Medicine}, keywords = {9310, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } |
E Di Angelantonio; et al World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions Journal Article In: The Lancet Global Health, 2019. Abstract | Links | BibTeX | Tags: 26865, cardiovascular disease @article{Angelantonio2019, title = {World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions}, author = {E Di Angelantonio and et al}, url = {https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30318-3/fulltext}, year = {2019}, date = {2019-09-02}, journal = {The Lancet Global Health}, abstract = {To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Funding World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.}, keywords = {26865, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Funding World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research. |
RE Farmer; R Mathur; AF Schmidt; K Bhaskaran; G Fatemifar; SV Eastwood; C Finan; S Denaxas; L Smeeth; N Chaturvedi In: Journal of the American Heart Association, 2019. Abstract | Links | BibTeX | Tags: 21893, cardiovascular disease, obesity @article{Farmer2019, title = {Associations Between Measures of Sarcopenic Obesity and Risk of Cardiovascular Disease and Mortality: A Cohort Study and Mendelian Randomization Analysis Using the UK Biobank}, author = {RE Farmer and R Mathur and AF Schmidt and K Bhaskaran and G Fatemifar and SV Eastwood and C Finan and S Denaxas and L Smeeth and N Chaturvedi }, url = {https://www.ncbi.nlm.nih.gov/pubmed/31221000}, year = {2019}, date = {2019-07-02}, journal = {Journal of the American Heart Association}, abstract = {Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio [ HR ] range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation.}, keywords = {21893, cardiovascular disease, obesity}, pubstate = {published}, tppubtype = {article} } Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio [ HR ] range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation. |
C.E. Welsh; Paul Welsh; Pardeep Jhund; Christian Delles; C. Celis-Morales; J.D. Lewsey; S. Gray; D. Lyall; S. Iliodromiti; J.M.R. Gill; Naveed Sattar; Patrick B. Mark In: Hypertension, 2019. Abstract | Links | BibTeX | Tags: 9310, blood pressure, cardiovascular disease, sodium @article{Welsh2019, title = {Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease}, author = {C.E. Welsh and Paul Welsh and Pardeep Jhund and Christian Delles and C. Celis-Morales and J.D. Lewsey and S. Gray and D. Lyall and S. Iliodromiti and J.M.R. Gill and Naveed Sattar and Patrick B. Mark }, url = {https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.119.12726?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed}, year = {2019}, date = {2019-06-01}, journal = {Hypertension}, abstract = {Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.}, keywords = {9310, blood pressure, cardiovascular disease, sodium}, pubstate = {published}, tppubtype = {article} } Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake. |
Alice R Carter; and Dipender Gill; Neil M Davies; and Amy E Taylor; Taavi Tillmann; Julien Vaucher; Robyn E Wootton; Marcus R Munafò; Gibran Hemani; Rainer Malik; Sudha Seshadri and Daniel Woo; Stephen Burgess; George Davey Smith; Michael V Holmes; Ioanna Tzoulaki; Laura D Howe; Abbas Dehghan Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study Journal Article In: BMJ, 2019. Abstract | Links | BibTeX | Tags: 10953, cardiovascular disease, education, genetics @article{Carter2019, title = {Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study}, author = {Alice R Carter and and Dipender Gill and Neil M Davies and and Amy E Taylor and Taavi Tillmann and Julien Vaucher and Robyn E Wootton and Marcus R Munafò and Gibran Hemani and Rainer Malik and Sudha Seshadri and Daniel Woo and Stephen Burgess and George Davey Smith and Michael V Holmes and Ioanna Tzoulaki and Laura D Howe and Abbas Dehghan}, url = {https://www.bmj.com/content/365/bmj.l1855.long}, year = {2019}, date = {2019-05-22}, journal = {BMJ}, abstract = {Objectives To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. Design Mendelian randomisation study. Setting UK Biobank and international genome-wide association study data. Participants Predominantly participants of European ancestry. Exposure Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. Main outcomes measure The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. Results Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. Conclusions BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.}, keywords = {10953, cardiovascular disease, education, genetics}, pubstate = {published}, tppubtype = {article} } Objectives To investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes. Design Mendelian randomisation study. Setting UK Biobank and international genome-wide association study data. Participants Predominantly participants of European ancestry. Exposure Educational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation. Main outcomes measure The risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively. Results Each additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease. Conclusions BMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation. |
Ahmed M. Alaa; Thomas Bolton; Emanuele Di Angelantonio; James H. F. Rudd; Mihaela van der Schaar Cardiovascular disease risk prediction using automated machine learning: A prospective study of 423,604 UK Biobank participants Journal Article In: PloS one, 2019. Abstract | Links | BibTeX | Tags: 26865, cardiovascular disease, machine learning @article{Alaa2019, title = {Cardiovascular disease risk prediction using automated machine learning: A prospective study of 423,604 UK Biobank participants}, author = {Ahmed M. Alaa and Thomas Bolton and Emanuele Di Angelantonio and James H. F. Rudd and Mihaela van der Schaar }, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213653}, year = {2019}, date = {2019-05-15}, journal = {PloS one}, abstract = {Identifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventative cardiology. Risk prediction models currently recommended by clinical guidelines are typically based on a limited number of predictors with sub-optimal performance across all patient groups. Data-driven techniques based on machine learning (ML) might improve the performance of risk predictions by agnostically discovering novel risk predictors and learning the complex interactions between them. We tested (1) whether ML techniques based on a state-of-the-art automated ML framework (AutoPrognosis) could improve CVD risk prediction compared to traditional approaches, and (2) whether considering non-traditional variables could increase the accuracy of CVD risk predictions.}, keywords = {26865, cardiovascular disease, machine learning}, pubstate = {published}, tppubtype = {article} } Identifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventative cardiology. Risk prediction models currently recommended by clinical guidelines are typically based on a limited number of predictors with sub-optimal performance across all patient groups. Data-driven techniques based on machine learning (ML) might improve the performance of risk predictions by agnostically discovering novel risk predictors and learning the complex interactions between them. We tested (1) whether ML techniques based on a state-of-the-art automated ML framework (AutoPrognosis) could improve CVD risk prediction compared to traditional approaches, and (2) whether considering non-traditional variables could increase the accuracy of CVD risk predictions. |
Hao Ma; Xiang Li; Dianjianyi Sun; Tao Zhou; Sylvia H Ley; Jeanette Gustat; Yoriko Heianza; Lu Qi Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank Journal Article In: BMJ, 2019. Abstract | Links | BibTeX | Tags: 29256, cardiovascular disease, glucosamine @article{Ma2019, title = {Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank}, author = {Hao Ma and Xiang Li and Dianjianyi Sun and Tao Zhou and Sylvia H Ley and Jeanette Gustat and Yoriko Heianza and Lu Qi}, url = {https://www.bmj.com/content/365/bmj.l1628.long}, year = {2019}, date = {2019-05-14}, journal = {BMJ}, abstract = {Objective To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. Design Prospective cohort study. Setting UK Biobank. Participants 466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. Main outcome measures Incident CVD events, including CVD death, coronary heart disease, and stroke. Results During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00). Conclusion Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events. }, keywords = {29256, cardiovascular disease, glucosamine}, pubstate = {published}, tppubtype = {article} } Objective To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events. Design Prospective cohort study. Setting UK Biobank. Participants 466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016. Main outcome measures Incident CVD events, including CVD death, coronary heart disease, and stroke. Results During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00). Conclusion Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events. |
Robert Robinson; Vanya V. Valindria; Wenjia Bai; Ozan Oktay; Bernhard Kainz; Hideaki Suzuki; Mihir M. Sanghvi; Nay Aung; José Miguel Paiva; Filip Zemrak; Kenneth Fung; Elena Lukaschuk; Aaron M. Lee; Valentina Carapella; Young Jin Kim; Stefan K. Piechnik; Stefan Neubauer; Steffen E. Petersen; Chris Page; Paul M. Matthews; Daniel Rueckert; Ben Glocker Automated quality control in image segmentation: application to the UK Biobank cardiovascular magnetic resonance imaging study Journal Article In: Journal of Cardiovascular Magnetic Resonance, 2019. Abstract | Links | BibTeX | Tags: 18545, 2964, cardiovascular disease, imaging, MRI @article{Robinson2019, title = {Automated quality control in image segmentation: application to the UK Biobank cardiovascular magnetic resonance imaging study}, author = {Robert Robinson and Vanya V. Valindria and Wenjia Bai and Ozan Oktay and Bernhard Kainz and Hideaki Suzuki and Mihir M. Sanghvi and Nay Aung and José Miguel Paiva and Filip Zemrak and Kenneth Fung and Elena Lukaschuk and Aaron M. Lee and Valentina Carapella and Young Jin Kim and Stefan K. Piechnik and Stefan Neubauer and Steffen E. Petersen and Chris Page and Paul M. Matthews and Daniel Rueckert and Ben Glocker}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416857/}, year = {2019}, date = {2019-03-14}, journal = {Journal of Cardiovascular Magnetic Resonance}, abstract = {The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale. However, it is important to be able to automatically detect when a segmentation method fails in order to avoid inclusion of wrong measurements into subsequent analyses which could otherwise lead to incorrect conclusions. Methods To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4800 cardiovascular magnetic resonance (CMR) scans. We then apply our method to a large cohort of 7250 CMR on which we have performed manual QC. Results We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using the predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4800 scans for which manual segmentations were available. We mimic real-world application of the method on 7250 CMR where we show good agreement between predicted quality metrics and manual visual QC scores. Conclusions We show that Reverse classification accuracy has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study.}, keywords = {18545, 2964, cardiovascular disease, imaging, MRI}, pubstate = {published}, tppubtype = {article} } The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale. However, it is important to be able to automatically detect when a segmentation method fails in order to avoid inclusion of wrong measurements into subsequent analyses which could otherwise lead to incorrect conclusions. Methods To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4800 cardiovascular magnetic resonance (CMR) scans. We then apply our method to a large cohort of 7250 CMR on which we have performed manual QC. Results We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using the predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4800 scans for which manual segmentations were available. We mimic real-world application of the method on 7250 CMR where we show good agreement between predicted quality metrics and manual visual QC scores. Conclusions We show that Reverse classification accuracy has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study. |
A Zhou; E Hyppönen In: The American Journal of Clinical Nutrition, 2019. Abstract | Links | BibTeX | Tags: 20175, cardiovascular disease, coffee, genetics @article{Zhou2019, title = {Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: a prospective analysis of up to 347,077 individuals and 8368 cases}, author = {A Zhou and E Hyppönen }, url = {https://www.ncbi.nlm.nih.gov/pubmed/30838377}, year = {2019}, date = {2019-03-01}, journal = {The American Journal of Clinical Nutrition}, abstract = {BACKGROUND: Coffee is one of the most widely consumed stimulants worldwide and is generally considered to be safe or even beneficial for health. However, increased risk of myocardial infarction and hypertension has been suggested for individuals who carry a functional variant at cytochrome P450 1A2 (CYP1A2), which makes them less effective at metabolizing caffeine. OBJECTIVES: The aim of this study was to examine if the CYP1A2 genotype or a genetic score for caffeine metabolism (caffeine-GS) modifies the association between habitual coffee consumption and the risk of cardiovascular disease (CVD). METHODS: Genetic data and information on habitual coffee intake and relevant covariates were available for 347,077 individuals in the UK Biobank, including 8368 incident CVD cases. We used logistic regression to test for the association between coffee intake and CVD risk, and whether the association varies with CYP1A2 genotype or caffeine-GS. RESULTS: The association between habitual coffee intake and CVD risk was nonlinear, and, compared with participants drinking 1-2 cups/day, the risk of CVD was elevated for nondrinkers, drinkers of decaffeinated coffee, and those who reported drinking >6 cups/day (increase in odds by 11%, 7%, and 22%, respectively, P-curvature = 0.013). CYP1A2 genotype and caffeine-GS were not associated with CVD (P ≥ 0.22 for all comparisons). There was no evidence for an interaction between the CYP1A2 genotype or caffeine-GS and coffee intake with respect to risk of CVD (P ≥ 0.53). CONCLUSIONS: Heavy coffee consumption was associated with a modest increase in CVD risk, but this association was unaffected by genetic variants influencing caffeine metabolism.}, keywords = {20175, cardiovascular disease, coffee, genetics}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Coffee is one of the most widely consumed stimulants worldwide and is generally considered to be safe or even beneficial for health. However, increased risk of myocardial infarction and hypertension has been suggested for individuals who carry a functional variant at cytochrome P450 1A2 (CYP1A2), which makes them less effective at metabolizing caffeine. OBJECTIVES: The aim of this study was to examine if the CYP1A2 genotype or a genetic score for caffeine metabolism (caffeine-GS) modifies the association between habitual coffee consumption and the risk of cardiovascular disease (CVD). METHODS: Genetic data and information on habitual coffee intake and relevant covariates were available for 347,077 individuals in the UK Biobank, including 8368 incident CVD cases. We used logistic regression to test for the association between coffee intake and CVD risk, and whether the association varies with CYP1A2 genotype or caffeine-GS. RESULTS: The association between habitual coffee intake and CVD risk was nonlinear, and, compared with participants drinking 1-2 cups/day, the risk of CVD was elevated for nondrinkers, drinkers of decaffeinated coffee, and those who reported drinking >6 cups/day (increase in odds by 11%, 7%, and 22%, respectively, P-curvature = 0.013). CYP1A2 genotype and caffeine-GS were not associated with CVD (P ≥ 0.22 for all comparisons). There was no evidence for an interaction between the CYP1A2 genotype or caffeine-GS and coffee intake with respect to risk of CVD (P ≥ 0.53). CONCLUSIONS: Heavy coffee consumption was associated with a modest increase in CVD risk, but this association was unaffected by genetic variants influencing caffeine metabolism. |
Lewis Steell; Frederick K Ho; Anne Sillars; Fanny Petermann-Rocha; Hiu Li1; Donald M Lyall; Stamatina Iliodromiti; Paul Welsh; Jana Anderson; Daniel F MacKay; Jill P Pell; Naveed Sattar; Jason MR Gill; Stuart Robert Gray; Carlos A Celis-Morales In: British Journal of Sports Medicine, 2019. Abstract | Links | BibTeX | Tags: 7155, cancer, cardiorespiratory fitness, cardiovascular disease, respiratory disease @article{Steell2019, title = {Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: the UK Biobank cohort study}, author = {Lewis Steell and Frederick K Ho and Anne Sillars and Fanny Petermann-Rocha and Hiu Li1 and Donald M Lyall and Stamatina Iliodromiti and Paul Welsh and Jana Anderson and Daniel F MacKay and Jill P Pell and Naveed Sattar and Jason MR Gill and Stuart Robert Gray and Carlos A Celis-Morales}, url = {https://www.ncbi.nlm.nih.gov/pubmed/30796106}, year = {2019}, date = {2019-02-22}, journal = {British Journal of Sports Medicine}, abstract = {OBJECTIVE: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence. DESIGN: Prospective population-based study. SETTING: UK Biobank. PARTICIPANTS: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up. MAIN OUTCOME MEASURES: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test. RESULTS: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up. CONCLUSIONS: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer.}, keywords = {7155, cancer, cardiorespiratory fitness, cardiovascular disease, respiratory disease}, pubstate = {published}, tppubtype = {article} } OBJECTIVE: To investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence. DESIGN: Prospective population-based study. SETTING: UK Biobank. PARTICIPANTS: Of the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3-5.7) follow-up. MAIN OUTCOME MEASURES: All-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test. RESULTS: The HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up. CONCLUSIONS: Higher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer. |
2018 |
Tianxi Cai; Yichi Zhang; Yuk-Lam Ho; Nicholas Link; Jiehuan Sun; Jie Huang; Tianrun A Cai; Scott; Damrauer; Yuri Ahuja; Jacqueline Honerlaw; Jie; Huang; Lauren Costa; Petra Schubert; Chuan; Hong; David Gagnon; Yan V Sun; Michael J Gaziano; Peter Wilson; Kelly Cho; Philip Tsao; Christopher J O’Donnell; Katherine Liao Veteran P Program Association of Interleukin 6 Receptor Variant With Cardiovascular Disease Effects of Interleukin 6 Receptor Blocking Therapy Journal Article In: JAMA Cardiology, 2018. Abstract | Links | BibTeX | Tags: 34031, cardiovascular disease, PheWAS @article{Cai2018b, title = {Association of Interleukin 6 Receptor Variant With Cardiovascular Disease Effects of Interleukin 6 Receptor Blocking Therapy}, author = {Tianxi Cai and Yichi Zhang and Yuk-Lam Ho and Nicholas Link and Jiehuan Sun and Jie Huang and Tianrun A Cai and Scott and Damrauer and Yuri Ahuja and Jacqueline Honerlaw and Jie and Huang and Lauren Costa and Petra Schubert and Chuan and Hong and David Gagnon and Yan V Sun and Michael J Gaziano and Peter Wilson and Kelly Cho and Philip Tsao and Christopher J O’Donnell and Katherine Liao Veteran P Program}, url = {https://jamanetwork.com/journals/jamacardiology/article-abstract/2696438}, year = {2018}, date = {2018-08-08}, journal = {JAMA Cardiology}, abstract = {Importance Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene–drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade. Objective To determine whether screening for clinical associations with the IL6R SNP in a phenome-wide association study (PheWAS) using EHR biobank data can identify drug effects from IL6R clinical trials. Design, Setting, and Participants Diagnosis codes and routine laboratory measurements were extracted from the VA Million Veteran Program (MVP); diagnosis codes were mapped to phenotype groups using published PheWAS methods. A PheWAS was performed by fitting logistic regression models for testing associations of the IL6R SNPs with 1342 phenotype groups and by fitting linear regression models for testing associations of the IL6R SNP with 26 routine laboratory measurements. Significance was reported using a false discovery rate of 0.05 or less. Findings were replicated in 2 independent cohorts using UK Biobank and Vanderbilt University Biobank data. The Million Veteran Program included 332 799 US veterans; the UK Biobank, 408 455 individuals from the general population of the United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a tertiary care center. Exposures IL6R SNPs (rs2228145; rs4129267). Main Outcomes and Measures Phenotypes defined by International Classification of Diseases, Ninth Revision codes. Results Of the 332 799 veterans included in the main cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years. The IL6R SNP was most strongly associated with a reduced risk of aortic aneurysm phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed known off-target effects of IL6R blockade from clinical trials (eg, higher hemoglobin level). The reduced risk for aortic aneurysms among those with the IL6R SNP in the MVP was replicated in the Vanderbilt University Biobank, and the reduced risk for coronary heart disease was replicated in the UK Biobank. Conclusions and Relevance In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.}, keywords = {34031, cardiovascular disease, PheWAS}, pubstate = {published}, tppubtype = {article} } Importance Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene–drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade. Objective To determine whether screening for clinical associations with the IL6R SNP in a phenome-wide association study (PheWAS) using EHR biobank data can identify drug effects from IL6R clinical trials. Design, Setting, and Participants Diagnosis codes and routine laboratory measurements were extracted from the VA Million Veteran Program (MVP); diagnosis codes were mapped to phenotype groups using published PheWAS methods. A PheWAS was performed by fitting logistic regression models for testing associations of the IL6R SNPs with 1342 phenotype groups and by fitting linear regression models for testing associations of the IL6R SNP with 26 routine laboratory measurements. Significance was reported using a false discovery rate of 0.05 or less. Findings were replicated in 2 independent cohorts using UK Biobank and Vanderbilt University Biobank data. The Million Veteran Program included 332 799 US veterans; the UK Biobank, 408 455 individuals from the general population of the United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a tertiary care center. Exposures IL6R SNPs (rs2228145; rs4129267). Main Outcomes and Measures Phenotypes defined by International Classification of Diseases, Ninth Revision codes. Results Of the 332 799 veterans included in the main cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years. The IL6R SNP was most strongly associated with a reduced risk of aortic aneurysm phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed known off-target effects of IL6R blockade from clinical trials (eg, higher hemoglobin level). The reduced risk for aortic aneurysms among those with the IL6R SNP in the MVP was replicated in the Vanderbilt University Biobank, and the reduced risk for coronary heart disease was replicated in the UK Biobank. Conclusions and Relevance In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm. |
Abdullah M Said; Niek Verweij; Pim van der Harst Associations of Combined Genetic and Lifestyle Risks With Incident Cardiovascular Disease and Diabetes in the UK Biobank Study Journal Article In: JAMA Cardiology, 2018. Abstract | Links | BibTeX | Tags: 15031, cardiovascular disease, diabetes, genetics @article{Said2018b, title = {Associations of Combined Genetic and Lifestyle Risks With Incident Cardiovascular Disease and Diabetes in the UK Biobank Study}, author = {Abdullah M Said and Niek Verweij and Pim van der Harst}, url = {https://jamanetwork.com/journals/jamacardiology/article-abstract/2686129}, year = {2018}, date = {2018-06-27}, journal = {JAMA Cardiology}, abstract = {Importance Genetic and lifestyle factors both contribute to the risk of developing cardiovascular disease, but whether poor health behaviors are associated with similar increases in risk among individuals with low, intermediate, or high genetic risk is unknown. Objective To investigate the association of combined health behaviors and factors within genetic risk groups with coronary artery disease, atrial fibrillation, stroke, hypertension, and type 2 diabetes as well as to investigate the interactions between genetic risk and lifestyle. Design, Setting, and Participants The UK Biobank cohort study includes more than 500 000 participants aged 40 to 70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. A total of 339 003 unrelated individuals of white British descent with available genotype and matching genetic data and reported sex were included in this study from the UK Biobank population-based sample. Individuals were included in the analyses of 1 or more new-onset diseases. Data were analyzed from April 2006 to March 2015. Main Outcomes and Measures Risks of new-onset cardiovascular disease and diabetes associated with genetic risk and combined health behaviors and factors. Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4), or high (quintile 5). Within each genetic risk group, the risks of incident events associated with ideal, intermediate, or poor combined health behaviors and factors were investigated and compared with low genetic risk and ideal lifestyle. Results Of 339 003 individuals, 181 702 (53.6%) were female, and the mean (SD) age was 56.86 (7.99) years. During follow-up, 9771 of 325 133 participants (3.0%) developed coronary artery disease, 7095 of 333 637 (2.1%) developed atrial fibrillation, 3145 of 332 971 (0.9%) developed stroke, 11 358 of 234 651 (4.8%) developed hypertension, and 4379 of 322 014 (1.4%) developed diabetes. Genetic risk and lifestyle were independent predictors of incident events, and there were no interactions for any outcome. Compared with ideal lifestyle in the low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 4.54 (95% CI, 3.72-5.54) for coronary artery disease, 5.41 (95% CI, 4.29-6.81) for atrial fibrillation, 4.68 (95% CI, 3.85-5.69) for hypertension, 2.26 (95% CI, 1.63-3.14) for stroke, and 15.46 (95% CI, 10.82-22.08) for diabetes in the high genetic risk group. Conclusions and Relevance In this large contemporary population, genetic composition and combined health behaviors and factors had a log-additive effect on the risk of developing cardiovascular disease. The relative effects of poor lifestyle were comparable between genetic risk groups. Behavioral lifestyle changes should be encouraged for all through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on the genetic risk.}, keywords = {15031, cardiovascular disease, diabetes, genetics}, pubstate = {published}, tppubtype = {article} } Importance Genetic and lifestyle factors both contribute to the risk of developing cardiovascular disease, but whether poor health behaviors are associated with similar increases in risk among individuals with low, intermediate, or high genetic risk is unknown. Objective To investigate the association of combined health behaviors and factors within genetic risk groups with coronary artery disease, atrial fibrillation, stroke, hypertension, and type 2 diabetes as well as to investigate the interactions between genetic risk and lifestyle. Design, Setting, and Participants The UK Biobank cohort study includes more than 500 000 participants aged 40 to 70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. A total of 339 003 unrelated individuals of white British descent with available genotype and matching genetic data and reported sex were included in this study from the UK Biobank population-based sample. Individuals were included in the analyses of 1 or more new-onset diseases. Data were analyzed from April 2006 to March 2015. Main Outcomes and Measures Risks of new-onset cardiovascular disease and diabetes associated with genetic risk and combined health behaviors and factors. Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4), or high (quintile 5). Within each genetic risk group, the risks of incident events associated with ideal, intermediate, or poor combined health behaviors and factors were investigated and compared with low genetic risk and ideal lifestyle. Results Of 339 003 individuals, 181 702 (53.6%) were female, and the mean (SD) age was 56.86 (7.99) years. During follow-up, 9771 of 325 133 participants (3.0%) developed coronary artery disease, 7095 of 333 637 (2.1%) developed atrial fibrillation, 3145 of 332 971 (0.9%) developed stroke, 11 358 of 234 651 (4.8%) developed hypertension, and 4379 of 322 014 (1.4%) developed diabetes. Genetic risk and lifestyle were independent predictors of incident events, and there were no interactions for any outcome. Compared with ideal lifestyle in the low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 4.54 (95% CI, 3.72-5.54) for coronary artery disease, 5.41 (95% CI, 4.29-6.81) for atrial fibrillation, 4.68 (95% CI, 3.85-5.69) for hypertension, 2.26 (95% CI, 1.63-3.14) for stroke, and 15.46 (95% CI, 10.82-22.08) for diabetes in the high genetic risk group. Conclusions and Relevance In this large contemporary population, genetic composition and combined health behaviors and factors had a log-additive effect on the risk of developing cardiovascular disease. The relative effects of poor lifestyle were comparable between genetic risk groups. Behavioral lifestyle changes should be encouraged for all through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on the genetic risk. |
D Zanetti; E Tikkanen; S Gustafsson; JR Priest; S Burgess; E Ingelsson Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease: Addressing the Barker Hypothesis With Mendelian Randomization Journal Article In: Circulation, Genomic and Precision Medicine, 2018. Abstract | Links | BibTeX | Tags: 13721, cardiovascular disease, diabetes @article{Zanetti2018b, title = {Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease: Addressing the Barker Hypothesis With Mendelian Randomization}, author = {D Zanetti and E Tikkanen and S Gustafsson and JR Priest and S Burgess and E Ingelsson}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29875125}, year = {2018}, date = {2018-06-11}, journal = {Circulation, Genomic and Precision Medicine}, abstract = {Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. METHODS: We performed regression analyses to assess associations of birthweight with cardiovascular disease and T2D in 237 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. RESULTS: In the observational analyses, birthweight showed inverse associations with systolic and diastolic blood pressure (β, -0.83 and -0.26; per raw unit in outcomes and SD change in birthweight; 95% confidence interval [CI], -0.90 to -0.75 and -0.31 to -0.22, respectively), T2D (odds ratio, 0.83; 95% CI, 0.79-0.87), lipid-lowering treatment (odds ratio, 0.84; 95% CI, 0.81-0.86), and coronary artery disease (hazard ratio, 0.85; 95% CI, 0.78-0.94), whereas the associations with adult body mass index and body fat (β, 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03-0.04 and 0.01-0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. CONCLUSIONS: Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension.}, keywords = {13721, cardiovascular disease, diabetes}, pubstate = {published}, tppubtype = {article} } Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. METHODS: We performed regression analyses to assess associations of birthweight with cardiovascular disease and T2D in 237 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. RESULTS: In the observational analyses, birthweight showed inverse associations with systolic and diastolic blood pressure (β, -0.83 and -0.26; per raw unit in outcomes and SD change in birthweight; 95% confidence interval [CI], -0.90 to -0.75 and -0.31 to -0.22, respectively), T2D (odds ratio, 0.83; 95% CI, 0.79-0.87), lipid-lowering treatment (odds ratio, 0.84; 95% CI, 0.81-0.86), and coronary artery disease (hazard ratio, 0.85; 95% CI, 0.78-0.94), whereas the associations with adult body mass index and body fat (β, 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03-0.04 and 0.01-0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. CONCLUSIONS: Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension. |
C Welsh; P Welsh; PB Mark; CA Celis-Morales; J Lewsey; SR Gray; DM Lyall; S Iliodromiti; JMR Gill; J Pell; PS Jhund; N Sattar Association of Total and Differential Leukocyte Counts With Cardiovascular Disease and Mortality in the UK Biobank Journal Article In: Arteriosclerosis Thrombosis and Vascular Biology, 2018. Abstract | Links | BibTeX | Tags: 9310, cardiovascular disease @article{Welsh2018, title = {Association of Total and Differential Leukocyte Counts With Cardiovascular Disease and Mortality in the UK Biobank}, author = {C Welsh and P Welsh and PB Mark and CA Celis-Morales and J Lewsey and SR Gray and DM Lyall and S Iliodromiti and JMR Gill and J Pell and PS Jhund and N Sattar}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29699973}, year = {2018}, date = {2018-06-01}, journal = {Arteriosclerosis Thrombosis and Vascular Biology}, abstract = {OBJECTIVE: Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD. APPROACH AND RESULTS: Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7.0 years (interquartile range, 6.3-7.6). In Cox models, deciles of leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) were examined using the fifth decile as the referent group. Models were stratified by sex and adjusted for a range of classical risk factors. A sensitivity analysis excluded participants with baseline comorbidites and the first 2 years of follow-up. Men (hazard ratio [HR], 1.59; 95% confidence interval, 1.22-2.08) and women (HR, 2.15; 95% confidence interval, 1.38-3.35) in the highest decile of neutrophil count were at higher risk of CVD mortality and nonfatal CVD (men HR, 1.28; 95% confidence interval, 1.16-1.42 and women HR, 1.21; 95% confidence interval, 1.06-1.38). In the sensitivity analysis, the power to investigate CVD mortality was limited, but for both sexes combined, the linear HRs for a 1×109/L cell count increase in white blood cell count and neutrophils, respectively, was 1.05 (1.03-1.07) and 1.07 (1.04-1.11). CONCLUSIONS: Among circulating leukocyte subpopulations, neutrophil count in men was most consistently associated with fatal and nonfatal CVD. Further studies of interventions that lower circulating neutrophils, such as canakinumab, are required to investigate causality.}, keywords = {9310, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } OBJECTIVE: Elevated white blood cell count is associated with a higher risk of cardiovascular disease (CVD). We aimed to investigate whether specific leukocyte subpopulations, which may more closely indicate a specific inflammatory pathway, are specifically associated with CVD. APPROACH AND RESULTS: Participants (478 259) from UK Biobank with data for white blood cell count were included. Death because of CVD (n=1377) and non-CVD causes (n=8987) occurred during median follow-up time of 7.0 years (interquartile range, 6.3-7.6). In Cox models, deciles of leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils) were examined using the fifth decile as the referent group. Models were stratified by sex and adjusted for a range of classical risk factors. A sensitivity analysis excluded participants with baseline comorbidites and the first 2 years of follow-up. Men (hazard ratio [HR], 1.59; 95% confidence interval, 1.22-2.08) and women (HR, 2.15; 95% confidence interval, 1.38-3.35) in the highest decile of neutrophil count were at higher risk of CVD mortality and nonfatal CVD (men HR, 1.28; 95% confidence interval, 1.16-1.42 and women HR, 1.21; 95% confidence interval, 1.06-1.38). In the sensitivity analysis, the power to investigate CVD mortality was limited, but for both sexes combined, the linear HRs for a 1×109/L cell count increase in white blood cell count and neutrophils, respectively, was 1.05 (1.03-1.07) and 1.07 (1.04-1.11). CONCLUSIONS: Among circulating leukocyte subpopulations, neutrophil count in men was most consistently associated with fatal and nonfatal CVD. Further studies of interventions that lower circulating neutrophils, such as canakinumab, are required to investigate causality. |
Mary C Schooling; Shan Luo; Shiu Lun Au Yeung; Deborah J Thompson; Savita Karthikeyan; Thomas R Bolton; Amy M Mason; Erik Ingelsson; Stephen Burgess; Stephen Burgess Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation Journal Article In: International Journal of Cardiology, 2018. Abstract | Links | BibTeX | Tags: 13721, 14864, cardiovascular disease, genetics @article{Schooling2018, title = {Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation}, author = {Mary C Schooling and Shan Luo and Shiu Lun Au Yeung and Deborah J Thompson and Savita Karthikeyan and Thomas R Bolton and Amy M Mason and Erik Ingelsson and Stephen Burgess and Stephen Burgess}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29804699}, year = {2018}, date = {2018-05-18}, journal = {International Journal of Cardiology}, abstract = {BACKGROUND: Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. METHODS AND RESULTS: We assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases). Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81-1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01-1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. CONCLUSIONS: Sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain.}, keywords = {13721, 14864, cardiovascular disease, genetics}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. METHODS AND RESULTS: We assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases). Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81-1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01-1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. CONCLUSIONS: Sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain. |
E Tikkanen; S Gustafsson; E Ingelsson In: Circulation, 2018. Abstract | Links | BibTeX | Tags: 13721, cardiovascular disease, genetic risk, genetics, physical activity @article{Tikkanen2018b, title = {Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study}, author = {E Tikkanen and S Gustafsson and E Ingelsson}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29632216}, year = {2018}, date = {2018-04-09}, journal = {Circulation}, abstract = {Background -Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases. Methods -We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference. Results -Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77- 0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73- 0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (Ptrend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases. Conclusions - Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.}, keywords = {13721, cardiovascular disease, genetic risk, genetics, physical activity}, pubstate = {published}, tppubtype = {article} } Background -Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases. Methods -We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference. Results -Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77- 0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73- 0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (Ptrend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases. Conclusions - Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases. |
Stamatina Iliodromiti; Carlos A Celis-Morales; Donald M Lyall; Jana Anderson; Stuart R Gray; Daniel F Mackay; Scott M Nelson; Paul Welsh; Jill P Pell; Jason M R Gill; Naveed Sattar In: European Heart Journal, 2018. Abstract | Links | BibTeX | Tags: BMI, cardiovascular disease @article{Iliodromiti2018, title = {The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent}, author = {Stamatina Iliodromiti and Carlos A Celis-Morales and Donald M Lyall and Jana Anderson and Stuart R Gray and Daniel F Mackay and Scott M Nelson and Paul Welsh and Jill P Pell and Jason M R Gill and Naveed Sattar}, url = {https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehy057/4937957}, year = {2018}, date = {2018-03-16}, journal = {European Heart Journal}, abstract = {Aims The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals. Methods and results A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass. Conclusion Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged.}, keywords = {BMI, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } Aims The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals. Methods and results A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass. Conclusion Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged. |
Yutong Cai; SusanHodgson; Marta Blangiardo; John Gulliver; David Morley; Daniela Fecht; DanielleVienneau; Kees de Hoogh; Tim Key; Kristian Hveem; Paul Elliott; Anna L.Hansell Road traffic noise, air pollution and incident cardiovascular disease: A joint analysis of the HUNT, EPIC-Oxford and UK Biobank cohorts Journal Article In: Environment International, 2018. Abstract | Links | BibTeX | Tags: 5179, cardiovascular disease, pollution, road noise @article{Cai2018b, title = {Road traffic noise, air pollution and incident cardiovascular disease: A joint analysis of the HUNT, EPIC-Oxford and UK Biobank cohorts}, author = {Yutong Cai and SusanHodgson and Marta Blangiardo and John Gulliver and David Morley and Daniela Fecht and DanielleVienneau and Kees de Hoogh and Tim Key and Kristian Hveem and Paul Elliott and Anna L.Hansell}, url = {https://www.sciencedirect.com/science/article/pii/S0160412017320548?via%3Dihub}, year = {2018}, date = {2018-03-05}, journal = {Environment International}, abstract = {This study aimed to investigate the effects of long-term exposure to road traffic noise and air pollution on incident cardiovascular disease (CVD) in three large cohorts: HUNT, EPIC-Oxford and UK Biobank. Methods In pooled complete-case sample of the three cohorts from Norway and the United Kingdom (N = 355,732), 21,081 incident all CVD cases including 5259 ischemic heart disease (IHD) and 2871 cerebrovascular cases were ascertained between baseline (1993–2010) and end of follow-up (2008–2013) through medical record linkage. Annual mean 24-hour weighted road traffic noise (Lden) and air pollution (particulate matter with aerodynamic diameter ≤ 10 μm [PM10], ≤2.5 μm [PM2.5] and nitrogen dioxide [NO2]) exposure at baseline address was modelled using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU) and European-wide Land Use Regression models. Individual-level covariate data were harmonised and physically pooled across the three cohorts. Analysis was via Cox proportional hazard model with mutual adjustments for both noise and air pollution and potential confounders. Results No significant associations were found between annual mean Lden and incident CVD, IHD or cerebrovascular disease in the overall population except that the association with incident IHD was significant among current-smokers. In the fully adjusted models including adjustment for Lden, an interquartile range (IQR) higher PM10 (4.1 μg/m3) or PM2.5 (1.4 μg/m3) was associated with a 5.8% (95%CI: 2.5%–9.3%) and 3.7% (95%CI: 0.2%–7.4%) higher risk for all incident CVD respectively. No significant associations were found between NO2 and any of the CVD outcomes. Conclusions We found suggestive evidence of a possible association between road traffic noise and incident IHD, consistent with current literature. Long-term particulate air pollution exposure, even at concentrations below current European air quality standards, was significantly associated with incident CVD.}, keywords = {5179, cardiovascular disease, pollution, road noise}, pubstate = {published}, tppubtype = {article} } This study aimed to investigate the effects of long-term exposure to road traffic noise and air pollution on incident cardiovascular disease (CVD) in three large cohorts: HUNT, EPIC-Oxford and UK Biobank. Methods In pooled complete-case sample of the three cohorts from Norway and the United Kingdom (N = 355,732), 21,081 incident all CVD cases including 5259 ischemic heart disease (IHD) and 2871 cerebrovascular cases were ascertained between baseline (1993–2010) and end of follow-up (2008–2013) through medical record linkage. Annual mean 24-hour weighted road traffic noise (Lden) and air pollution (particulate matter with aerodynamic diameter ≤ 10 μm [PM10], ≤2.5 μm [PM2.5] and nitrogen dioxide [NO2]) exposure at baseline address was modelled using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU) and European-wide Land Use Regression models. Individual-level covariate data were harmonised and physically pooled across the three cohorts. Analysis was via Cox proportional hazard model with mutual adjustments for both noise and air pollution and potential confounders. Results No significant associations were found between annual mean Lden and incident CVD, IHD or cerebrovascular disease in the overall population except that the association with incident IHD was significant among current-smokers. In the fully adjusted models including adjustment for Lden, an interquartile range (IQR) higher PM10 (4.1 μg/m3) or PM2.5 (1.4 μg/m3) was associated with a 5.8% (95%CI: 2.5%–9.3%) and 3.7% (95%CI: 0.2%–7.4%) higher risk for all incident CVD respectively. No significant associations were found between NO2 and any of the CVD outcomes. Conclusions We found suggestive evidence of a possible association between road traffic noise and incident IHD, consistent with current literature. Long-term particulate air pollution exposure, even at concentrations below current European air quality standards, was significantly associated with incident CVD. |
MA Said; RN Eppinga; E Lipsic; N Verweij; P van der Harst Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality. Journal Article In: Journal of American Heart Association, 2018. Abstract | Links | BibTeX | Tags: 12006, 12010, arterial stiffness, blood pressure, cardiovascular disease @article{Said2018b, title = {Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular Disease and Mortality.}, author = {MA Said and RN Eppinga and E Lipsic and N Verweij and P van der Harst}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29358193}, year = {2018}, date = {2018-01-22}, journal = {Journal of American Heart Association}, abstract = {Vascular aging results in stiffer arteries and may have a role in the development of cardiovascular disease (CVD). Arterial stiffness index (ASI), measured by finger photoplethysmography, and pulse pressure (PP) are 2 independent vascular aging indices. We investigated whether ASI or PP predict new-onset CVD and mortality in a large community-based population. METHODS AND RESULTS: We studied 169 613 UK Biobank participants (mean age 56.8 years; 45.8% males) who underwent ASI measurement and blood pressure measurement for PP calculation. Mean±SD ASI was 9.30±3.1 m/s and mean±SD PP was 50.98±13.2 mm Hg. During a median disease follow-up of 2.8 years (interquartile range 1.4-4.0), 18 190 participants developed CVD, of which 1587 myocardial infarction (MI), 4326 coronary heart disease, 1192 heart failure, and 1319 stroke. During a median mortality follow-up of 6.1 years (interquartile range 5.8-6.3), 3678 participants died, of which 1180 of CVD. Higher ASI was associated with increased risk of overall CVD (unadjusted hazard ratio 1.27; 95% confidence interval [CI], 1.25-1.28), myocardial infarction (1.38; 95% CI, 1.32-1.44), coronary heart disease (1.31; 95% CI, 1.27-1.34), and heart failure (1.31; 95% CI 1.24-1.37). ASI also predicted mortality (all-cause, CVD, other). Higher PP was associated with overall CVD (1.57; 95% CI, 1.55-1.59), myocardial infarction (1.48; 95% CI, 1.42-1.54), coronary heart disease (1.47; 95% CI, 1.43-1.50), heart failure (1.47; 95% CI, 1.40-1.55), and CVD mortality (1.47; 95% CI, 1.40-1.55). PP improved risk reclassification of CVD in a non-laboratory-based Framingham Risk Score by 5.4%, ASI by 2.3%. CONCLUSIONS: ASI and PP are independent predictors of CVD and mortality outcomes. Although both improved risk prediction for new-onset disease, PP appears to have a larger clinical value than ASI.}, keywords = {12006, 12010, arterial stiffness, blood pressure, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } Vascular aging results in stiffer arteries and may have a role in the development of cardiovascular disease (CVD). Arterial stiffness index (ASI), measured by finger photoplethysmography, and pulse pressure (PP) are 2 independent vascular aging indices. We investigated whether ASI or PP predict new-onset CVD and mortality in a large community-based population. METHODS AND RESULTS: We studied 169 613 UK Biobank participants (mean age 56.8 years; 45.8% males) who underwent ASI measurement and blood pressure measurement for PP calculation. Mean±SD ASI was 9.30±3.1 m/s and mean±SD PP was 50.98±13.2 mm Hg. During a median disease follow-up of 2.8 years (interquartile range 1.4-4.0), 18 190 participants developed CVD, of which 1587 myocardial infarction (MI), 4326 coronary heart disease, 1192 heart failure, and 1319 stroke. During a median mortality follow-up of 6.1 years (interquartile range 5.8-6.3), 3678 participants died, of which 1180 of CVD. Higher ASI was associated with increased risk of overall CVD (unadjusted hazard ratio 1.27; 95% confidence interval [CI], 1.25-1.28), myocardial infarction (1.38; 95% CI, 1.32-1.44), coronary heart disease (1.31; 95% CI, 1.27-1.34), and heart failure (1.31; 95% CI 1.24-1.37). ASI also predicted mortality (all-cause, CVD, other). Higher PP was associated with overall CVD (1.57; 95% CI, 1.55-1.59), myocardial infarction (1.48; 95% CI, 1.42-1.54), coronary heart disease (1.47; 95% CI, 1.43-1.50), heart failure (1.47; 95% CI, 1.40-1.55), and CVD mortality (1.47; 95% CI, 1.40-1.55). PP improved risk reclassification of CVD in a non-laboratory-based Framingham Risk Score by 5.4%, ASI by 2.3%. CONCLUSIONS: ASI and PP are independent predictors of CVD and mortality outcomes. Although both improved risk prediction for new-onset disease, PP appears to have a larger clinical value than ASI. |
SA Peters; M Woodward Women's reproductive factors and incident cardiovascular disease in the UK Biobank. Journal Article In: Heart, 2018. Abstract | Links | BibTeX | Tags: 2495, cardiovascular disease, womens reproductive health @article{Peters2018c, title = {Women's reproductive factors and incident cardiovascular disease in the UK Biobank.}, author = {SA Peters and M Woodward}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29335253}, year = {2018}, date = {2018-01-15}, journal = {Heart}, abstract = {BACKGROUND: Studies have suggested that women's reproductive factors are associated with the risk of cardiovascular disease (CVD); however, findings are mixed. We assessed the relationship between reproductive factors and incident CVD in the UK Biobank. METHODS: Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40-69 years across the UK. During 7 years of follow-up, 9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267 440 women and 215 088 men without a history of CVD at baseline. Cox regression models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated with reproductive factors. RESULTS: Adjusted HRs (95% CI) for CVD were 1.10 (1.01 to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14 (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women and 1.03 (1.02 to 1.05) in men. CONCLUSIONS: Early menarche, early menopause, earlier age at first birth, and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life. The relationship between the number of children and incident CVD was similar for men and women.}, keywords = {2495, cardiovascular disease, womens reproductive health}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Studies have suggested that women's reproductive factors are associated with the risk of cardiovascular disease (CVD); however, findings are mixed. We assessed the relationship between reproductive factors and incident CVD in the UK Biobank. METHODS: Between 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40-69 years across the UK. During 7 years of follow-up, 9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267 440 women and 215 088 men without a history of CVD at baseline. Cox regression models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated with reproductive factors. RESULTS: Adjusted HRs (95% CI) for CVD were 1.10 (1.01 to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14 (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women and 1.03 (1.02 to 1.05) in men. CONCLUSIONS: Early menarche, early menopause, earlier age at first birth, and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life. The relationship between the number of children and incident CVD was similar for men and women. |
2017 |
MC Magnus; S Iliodromiti; DA Lawlor DA; JM Catov; SM Nelson; A Fraser Number of Offspring and Cardiovascular Disease Risk in Men and Women: The Role of Shared Lifestyle Characteristics. Journal Article In: Epidemiology, 2017. Abstract | Links | BibTeX | Tags: 6326, cardiovascular disease @article{Magnus2017, title = {Number of Offspring and Cardiovascular Disease Risk in Men and Women: The Role of Shared Lifestyle Characteristics.}, author = {MC Magnus and S Iliodromiti and DA Lawlor DA and JM Catov and SM Nelson and A Fraser}, url = {https://www.ncbi.nlm.nih.gov/pubmed/28696997}, year = {2017}, date = {2017-07-10}, journal = {Epidemiology}, abstract = {BACKGROUND: Previous studies of the number of offspring and cardiovascular disease (CVD) report conflicting findings. We re-examined this association in both sexes to clarify the role of the cardiometabolic changes that women experience during pregnancy versus shared lifestyle characteristics. METHODS: We studied 180,626 women and 133,259 men participating in the UK Biobank cohort who were free of CVD at baseline. CVD events were obtained from hospital and death registers. Analyses were conducted using Cox proportional hazards regression. RESULTS: The incidence rates of overall CVD were 6 per 1,000 person years for women and 9 per 1,000 person years for men. Number of children showed an association with risk of CVD among women; the adjusted HR (95% CI) was 1.2 (1.1, 1.3) for one, 1.1 (1.0, 1.2) for two, 1.2 (1.1, 1.3) for three and 1.2 (1.1, 1.4) for four or more as compared to none. Number of children was also associated with CVD among men; the adjusted HR (95% CI) was 1.1 (1.0, 1.2) for one, 1.0 (0.96, 1.1) for two, 1.1 (1.0, 1.2) for three and 1.1 (1.0, 1.3) for four or more as compared to none. There was no evidence of heterogeneity in the associations between sexes (p-value interaction 0.80). Number of offspring showed similar associations with ischemic heart disease and hypertensive disorders in both sexes. CONCLUSIONS: We observed similar associations between number of offspring and CVD in both sexes. The association among women might therefore be largely explained by unobserved behavioral and lifestyle characteristicsThis is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.}, keywords = {6326, cardiovascular disease}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Previous studies of the number of offspring and cardiovascular disease (CVD) report conflicting findings. We re-examined this association in both sexes to clarify the role of the cardiometabolic changes that women experience during pregnancy versus shared lifestyle characteristics. METHODS: We studied 180,626 women and 133,259 men participating in the UK Biobank cohort who were free of CVD at baseline. CVD events were obtained from hospital and death registers. Analyses were conducted using Cox proportional hazards regression. RESULTS: The incidence rates of overall CVD were 6 per 1,000 person years for women and 9 per 1,000 person years for men. Number of children showed an association with risk of CVD among women; the adjusted HR (95% CI) was 1.2 (1.1, 1.3) for one, 1.1 (1.0, 1.2) for two, 1.2 (1.1, 1.3) for three and 1.2 (1.1, 1.4) for four or more as compared to none. Number of children was also associated with CVD among men; the adjusted HR (95% CI) was 1.1 (1.0, 1.2) for one, 1.0 (0.96, 1.1) for two, 1.1 (1.0, 1.2) for three and 1.1 (1.0, 1.3) for four or more as compared to none. There was no evidence of heterogeneity in the associations between sexes (p-value interaction 0.80). Number of offspring showed similar associations with ischemic heart disease and hypertensive disorders in both sexes. CONCLUSIONS: We observed similar associations between number of offspring and CVD in both sexes. The association among women might therefore be largely explained by unobserved behavioral and lifestyle characteristicsThis is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Kurmi Parish Yang Arnold Guo Bian Wang Chen Meijer Sansome McDonnell Collins Li Chen O S M M Y Z L Y R S J R L Z R Clarke H Du; China Kadoorie Biobank Collaborative Group. Burden of carotid artery atherosclerosis in Chinese adults: Implications for future risk of cardiovascular diseases. Journal Article In: European Journal of Preventitive Cardiology, 2017. Abstract | Links | BibTeX | Tags: 10061, cardiovascular disease, carotid artery, chinese adults @article{Clarke2017, title = {Burden of carotid artery atherosclerosis in Chinese adults: Implications for future risk of cardiovascular diseases.}, author = {Kurmi Parish Yang Arnold Guo Bian Wang Chen Meijer Sansome McDonnell Collins Li Chen O S M M Y Z L Y R S J R L Z R Clarke H Du and China Kadoorie Biobank Collaborative Group.}, url = {https://www.ncbi.nlm.nih.gov/pubmed/28128654}, year = {2017}, date = {2017-01-01}, journal = {European Journal of Preventitive Cardiology}, abstract = {Background Population-based studies of ultrasound measures of carotid atherosclerosis are informative about future risks of cardiovascular disease. Design Cross-sectional studies of carotid artery atherosclerosis in 24,822 Chinese adults from the China Kadoorie Biobank and 2579 Europeans from the UK Biobank. Methods Mean intima-media thickness of the common carotid arteries and presence of carotid artery plaque were examined in the China Kadoorie Biobank study. The carotid intima-media thickness (cIMT) findings in Chinese (mean age 59 years) were compared with a European population (mean age 62 years). Results Overall, the mean cIMT in Chinese was 0.70 mm (SD 0.16) and increased with age by 0.08 mm (SE 0.008) per 10-years older age. About 31% of the Chinese had carotid plaques and the prevalence varied 10-fold with age (6% at 40-49 to 63% at 70-89 years) and four-fold by region (range, 14%-57%). After adjustment for age, sex and region, plaque prevalence was higher in smokers than in non-smokers (36% vs. 28%) and two-fold higher in individuals with systolic blood pressure ≥160 mmHg than those with systolic blood pressure <120 mmHg (44% vs. 22%) in the China Kadoorie Biobank study. Mean cIMT was similar in the younger Chinese and European adults, but increased more steeply with age in the Chinese ( p = 0.002). Conclusions About one-third of Chinese adults had carotid plaques. The rate of progression of carotid atherosclerosis with age was more extreme in the Chinese compared with the European population, highlighting the need for more intensive strategies for cardiovascular disease prevention in China.}, keywords = {10061, cardiovascular disease, carotid artery, chinese adults}, pubstate = {published}, tppubtype = {article} } Background Population-based studies of ultrasound measures of carotid atherosclerosis are informative about future risks of cardiovascular disease. Design Cross-sectional studies of carotid artery atherosclerosis in 24,822 Chinese adults from the China Kadoorie Biobank and 2579 Europeans from the UK Biobank. Methods Mean intima-media thickness of the common carotid arteries and presence of carotid artery plaque were examined in the China Kadoorie Biobank study. The carotid intima-media thickness (cIMT) findings in Chinese (mean age 59 years) were compared with a European population (mean age 62 years). Results Overall, the mean cIMT in Chinese was 0.70 mm (SD 0.16) and increased with age by 0.08 mm (SE 0.008) per 10-years older age. About 31% of the Chinese had carotid plaques and the prevalence varied 10-fold with age (6% at 40-49 to 63% at 70-89 years) and four-fold by region (range, 14%-57%). After adjustment for age, sex and region, plaque prevalence was higher in smokers than in non-smokers (36% vs. 28%) and two-fold higher in individuals with systolic blood pressure ≥160 mmHg than those with systolic blood pressure <120 mmHg (44% vs. 22%) in the China Kadoorie Biobank study. Mean cIMT was similar in the younger Chinese and European adults, but increased more steeply with age in the Chinese ( p = 0.002). Conclusions About one-third of Chinese adults had carotid plaques. The rate of progression of carotid atherosclerosis with age was more extreme in the Chinese compared with the European population, highlighting the need for more intensive strategies for cardiovascular disease prevention in China. |
