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1. Intracranial arteriosclerosis and the risk of dementia:A population-based cohort study

Author

van den Beukel, TC, Wolters, FJ, Siebert, U, Spiering, W, Ikram, MA, Vernooij, MW, de Jong, PA, Bos, D, van den Beukel, TC, Wolters, FJ, Siebert, U, Spiering, W, Ikram, MA, Vernooij, MW, de Jong, PA, and Bos, D

Abstract

BACKGROUND The impact of intracranial arteriosclerosis on dementia remains largely unclear. METHODS In 2339 stroke-free and dementia-free participants (52.2% women, mean age 69.5 years) from the general population, we assessed intracranial carotid artery calcification (ICAC) and vertebrobasilar artery calcification (VBAC) as proxy for arteriosclerosis. Associations with dementia were assessed using Cox models. In addition, indirect effects through cerebral small vessel disease (cSVD) and subcortical brain structure volumes were assessed using causal mediation analyses. RESULTS During a median of 13.4 years (25th–75th percentiles 9.9–14.5) of follow-up, 282 participants developed dementia. Both ICAC presence (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 1.00–2.32]) and volume (HR per standard deviation: 1.19, 95% CI: 1.01–1.40) increased dementia risk. For VBAC, severe calcifications increased dementia risk (HR for third vs first volume tertile: 1.89, 95% CI: 1.00–3.59). These effects were mediated partly through increased cSVD (percentage mediated for ICAC: 13% and VBAC: 24%). DISCUSSION Intracranial arteriosclerosis increases the risk of dementia.

Published
2024

2. The prevalence of vertebral fractures in diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis: A systematic review and meta-analysis

Author

Harlianto, N.I., Ezzafzafi, S., Foppen, W., Kuperus, J.S., Horst-Bruinsma, I.E. van der, Jong, Pa. de, Verlaan, J.J., Harlianto, N.I., Ezzafzafi, S., Foppen, W., Kuperus, J.S., Horst-Bruinsma, I.E. van der, Jong, Pa. de, and Verlaan, J.J.

Abstract

Contains fulltext : 305204.pdf (Publisher’s version ) (Open Access), BACKGROUND: Subjects with ankylosing spinal disorders, including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) are more prone to vertebral fractures and frequently present with neurological deficit compared to the patients without an ankylosed spine. Moreover, prevalent vertebral fractures are an important predictor for subsequent fracture risk. However, the pooled fracture prevalence for DISH is unknown and less recent for AS. We aimed to systematically investigate the prevalence and risk of vertebral fractures in DISH and AS populations. METHODS: Publications in Medline and EMBASE were searched from January 1980 until July 2023 for cohort studies reporting vertebral fractures in AS and DISH. Data on prevalence were pooled with random effects modeling after double arcsine transformation. Heterogeneity was assessed with I(2) statistics and we performed subgroup analysis and meta-regression to explore sources of heterogeneity. RESULTS: We included 7 studies on DISH (n = 1,193, total fractures = 231) with a pooled vertebral fracture prevalence of 22.6% (95%CI: 13.4%-33.4%). For AS, 26 studies were included (n = 2,875, total fractures = 460) with a pooled vertebral fracture prevalence of 15.2% (95%CI: 11.6%-19.1%). In general, fracture prevalence for AS remained similar for several study-level and clinically relevant characteristics, including study design, diagnostic criteria, spine level, and patient characteristics in subgroup analysis. AS publications from 2010 to 2020 showed higher fracture prevalence compared to 1990 to 2010 (18.6% vs. 11.6%). Fractures in DISH were most common at the thoracolumbar junction, whereas for AS, the most common location was the mid-thoracic spine. CONCLUSIONS: Vertebral fractures are prevalent in AS and DISH populations. Differences in fracture distribution along the spinal axis exist between the 2 disorders. Additional longitudinal studies are needed for incident fracture assessment in patients with

Published
2024

3. Imaging of intracranial arterial disease: a comparison between MRI and unenhanced CT

Author

Lucci, C., Rissanen, I., Takx, R.A.P., Kolk, A.G. van der, Harteveld, A.A., Dankbaar, J.W., Geerlings, M.I., Jong, Pa. de, Hendrikse, J., Lucci, C., Rissanen, I., Takx, R.A.P., Kolk, A.G. van der, Harteveld, A.A., Dankbaar, J.W., Geerlings, M.I., Jong, Pa. de, and Hendrikse, J.

Abstract

Contains fulltext : 305366.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Arterial calcifications on unenhanced CT scans and vessel wall lesions on MRI are often used interchangeably to portray intracranial arterial disease. However, the extent of pathology depicted with each technique is unclear. We investigated the presence and distribution of these two imaging findings in patients with a history of cerebrovascular disease. MATERIALS AND METHODS: We analyzed CT and MRI data from 78 patients admitted for stroke or TIA at our institution. Vessel wall lesions were assessed on 7 T MRI sequences, while arterial calcifications were assessed on CT scans. The number of vessel wall lesions, severity of intracranial internal carotid artery (iICA) calcifications, and overall presence and distribution of the two imaging findings were visually assessed in the intracranial arteries. RESULTS: At least one vessel wall lesion or arterial calcification was assessed in 69 (88%) patients. Only the iICA and vertebral arteries (VA) showed a substantial number of both calcifications and vessel wall lesions. The other vessels showed almost exclusively vessel wall lesions. The number of vessel wall lesions was associated with the severity of iICA calcification (p = 0.013). CONCLUSIONS: The number of vessel wall lesions increases with the severity of iICA calcifications. Nonetheless, the distribution of vessel wall lesions on MRI and arterial calcifications on CT shows remarkable differences. These findings support the need for a combined approach to examine intracranial arterial disease.

Published
2024

4. Multi-source data approach for personalized outcome prediction in lung cancer screening: update from the NELSON trial.

Author

Sidorenkov, G., Stadhouders, R., Jacobs, C., Mohamed Hoesein, F.A., Gietema, H.A., Nackaerts, K., Saghir, Z., Heuvelmans, M.A., Donker, Hylke C., Aerts, J.G., Vermeulen, R., Uitterlinden, A., Lenters, V., Rooij, J van, Schaefer-Prokop, C.M., Groen, H.J.M., Jong, Pa. de, Cornelissen, R., Prokop, M., Bock, G.H. de, Vliegenthart, R., Sidorenkov, G., Stadhouders, R., Jacobs, C., Mohamed Hoesein, F.A., Gietema, H.A., Nackaerts, K., Saghir, Z., Heuvelmans, M.A., Donker, Hylke C., Aerts, J.G., Vermeulen, R., Uitterlinden, A., Lenters, V., Rooij, J van, Schaefer-Prokop, C.M., Groen, H.J.M., Jong, Pa. de, Cornelissen, R., Prokop, M., Bock, G.H. de, and Vliegenthart, R.

Abstract

01 april 2023, Item does not contain fulltext, Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15-20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40-50%.

Published
2023

5. Smokers with emphysema and small airway disease on computed tomography have lower bone density

Author

Pompe E, de Jong PA, van Rikxoort EM, Gallardo Estrella L, de Jong WU, Vliegenthart R, Oudkerk M, van der Aalst CM, van Ginneken B, Lammers JWJ, and Mohamed Hoesein FAA

Subjects
COPD, Osteoporosis, Computed Tomography, air trapping, emphysema, bone density, Diseases of the respiratory system, RC705-779
Abstract

Esther Pompe,1 Pim A de Jong,2 Eva M van Rikxoort,3 Leticia Gallardo Estrella,3 Werner U de Jong,2 Rozemarijn Vliegenthart,4,5 Matthijs Oudkerk,5 Carlijn M van der Aalst,6 Bram van Ginneken,3 Jan-Willem J Lammers,1 Firdaus AA Mohamed Hoesein2 1Department of Pulmonology, 2Department of Radiology, University Medical Center Utrecht, Utrecht, 3Department of Radiology, Radboud University Medical Center, Nijmegen, 4Center for Medical Imaging-North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 5Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, 6Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands Abstract: Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures. Keywords: phenotyping, computed tomography, air trapping, emphysema, COPD, bone density

Published
2016

7. Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk

Author

Harlianto, N.I., Oosterhof, N., Foppen, W., Hol, M.E., Wittenberg, R., Veen, P.H. van der, Ginneken, B. van, Hoesein, F.A.M., Verlaan, J.J., Jong, Pa. de, Westerink, J., Studygroup, U.S., Harlianto, N.I., Oosterhof, N., Foppen, W., Hol, M.E., Wittenberg, R., Veen, P.H. van der, Ginneken, B. van, Hoesein, F.A.M., Verlaan, J.J., Jong, Pa. de, Westerink, J., and Studygroup, U.S.

Abstract

Item does not contain fulltext, OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0-12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSION: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.

Published
2022

9. Novel method of wafer-level and package-level process simulation for warpage optimization of 2.5D TSV

Author

Jong Pa Hong, Su Chang Lee, Soohyun Nam, Sun woo Han, Park Yu-Kyung, Jongho Lee, Sang kun O, and Dong Ok Kwak

Subjects
Interconnection, Substrate (building), Materials science, Temperature control, business.industry, Residual stress, Interposer, Semiconductor device modeling, Optoelectronics, Wafer, business, Chip
Abstract

2.5D IC packages are typically produced through Chip on Wafer (CoW) or Chip on Substrate (CoS) processes. Among these, 2.5D processing involves bonding the interposer chip and ASIC chip perpendicularly in sequence to the substrate for 2.5D package production. However, due to the large size of the interposer chip and its commensurately large high temperature warpage, attaching the interposer chip to the substrate carries a high risk of interconnection defects (non-wet/short) at the chip-substrate joints arising from the warpage difference. Moreover, the warpage difference between the attached interposer chip and ASIC also leads to a high risk of interconnection defects during bonding. For this reason, accurate prediction of the interposer chip high temperature warpage is of utmost importance in 2.5D packages In package warpage simulation, the reference (stress free) temperature is generally taken from high-T processes such as molding or F/C mounting, as they are most critical in inducing package warpage. However, unlike an IC package, the interposer chip undergoes no dominant process in particular which is critical to its chip warpage. Instead, all device fabrication processes prior to package formation impact the final interposer chip warpage. The initial room temperature warpage is determined by the residual stress from each processing step. The high temperature warpage is determined by the difference in metal density between the regions above and beneath the silicon as the temperature is increased. In the present study, we examine a $28.3\times 18.9\text{mm}$ 4-layer BEOL, 1-layer B-RDL interposer chip in order to predict the final interposer chip warpage via the finite element method (FEM) and thereby more effectively control it. To that end, we obtain the residual stress resulting from the front side (BEOL) and back side (B-RDL) processes through warpage measurement at each step. Moreover, we propose a method to maintain the interposer chip warpage close to zero, by adjusting the metal density and CVD film properties. In addition, we aim to address and improve possible Joint defects (non-wet/short) during ASIC chip bonding by predicting the warpage of the interposer chip attached to the substrate.

Published
2021

11. Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019

Author

Dofferhoff, A.S.M., Piscaer, I., Schurgers, L.J., Visser, M.P.J., Ouweland, J.M.W. van den, Jong, Pa. de, Gosens, R., Hackeng, T.M., Daal, H. van, Lux, P., Maassen, C., Karssemeijer, E.G.A., Vermeer, C., Wouters, E.F.M., Kistemaker, L.E.M., Walk, J., Janssen, R., Dofferhoff, A.S.M., Piscaer, I., Schurgers, L.J., Visser, M.P.J., Ouweland, J.M.W. van den, Jong, Pa. de, Gosens, R., Hackeng, T.M., Daal, H. van, Lux, P., Maassen, C., Karssemeijer, E.G.A., Vermeer, C., Wouters, E.F.M., Kistemaker, L.E.M., Walk, J., and Janssen, R.

Abstract

Item does not contain fulltext, BACKGROUND: Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K-dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography. RESULTS: dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores. CONCLUSIONS: dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.

Published
2021

12. Deep Learning for Lung Cancer Detection on Screening CT Scans: Results of a Large-Scale Public Competition and an Observer Study with 11 Radiologists

Author

Jacobs, C., Setio, A.A.A., Scholten, E.T., Gerke, P.K., Bhattacharya, H., Hoesein, F.A.M., Brink, M., Ranschaert, E., Jong, Pa. de, Silva, M., Geurts, B.H.J., Chung, K., Schalekamp, S., Meersschaert, J., Devaraj, A., Pinsky, P.F., Lam, S.C., Ginneken, B. van, Farahani, K., Jacobs, C., Setio, A.A.A., Scholten, E.T., Gerke, P.K., Bhattacharya, H., Hoesein, F.A.M., Brink, M., Ranschaert, E., Jong, Pa. de, Silva, M., Geurts, B.H.J., Chung, K., Schalekamp, S., Meersschaert, J., Devaraj, A., Pinsky, P.F., Lam, S.C., Ginneken, B. van, and Farahani, K.

Abstract

Contains fulltext : 245169.pdf (Publisher’s version ) (Closed access), Purpose: To determine whether deep learning algorithms developed in a public competition could identify lung cancer on low-dose CT scans with a performance similar to that of radiologists. Materials and Methods: In this retrospective study, a dataset consisting of 300 patient scans was used for model assessment; 150 patient scans were from the competition set and 150 were from an independent dataset. Both test datasets contained 50 cancer-positive scans and 100 cancer-negative scans. The reference standard was set by histopathologic examination for cancer-positive scans and imaging follow-up for at least 2 years for cancer-negative scans. The test datasets were applied to the three top-performing algorithms from the Kaggle Data Science Bowl 2017 public competition: grt123, Julian de Wit and Daniel Hammack (JWDH), and Aidence. Model outputs were compared with an observer study of 11 radiologists that assessed the same test datasets. Each scan was scored on a continuous scale by both the deep learning algorithms and the radiologists. Performance was measured using multireader, multicase receiver operating characteristic analysis. Results: The area under the receiver operating characteristic curve (AUC) was 0.877 (95% CI: 0.842, 0.910) for grt123, 0.902 (95% CI: 0.871, 0.932) for JWDH, and 0.900 (95% CI: 0.870, 0.928) for Aidence. The average AUC of the radiologists was 0.917 (95% CI: 0.889, 0.945), which was significantly higher than grt123 (P = .02); however, no significant difference was found between the radiologists and JWDH (P = .29) or Aidence (P = .26). Conclusion: Deep learning algorithms developed in a public competition for lung cancer detection in low-dose CT scans reached performance close to that of radiologists.Keywords: Lung, CT, Thorax, Screening, Oncology Supplemental material is available for this article. (c) RSNA, 2021.

Published
2021

13. Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2

Author

Bartstra, J.W., Draaisma, F., Zwakenberg, S.R., Lessmann, N., Wolterink, J.M., Schouw, Y.T. van der, Jong, Pa. de, Beulens, J.W., Bartstra, J.W., Draaisma, F., Zwakenberg, S.R., Lessmann, N., Wolterink, J.M., Schouw, Y.T. van der, Jong, Pa. de, and Beulens, J.W.

Abstract

Contains fulltext : 235803.pdf (Publisher’s version ) (Open Access), PURPOSE: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD). METHODS: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 microg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae. RESULTS: 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812-3584) vs 1182 (235-2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (beta [95% CI]: - 0.02 [- 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (beta [95% CI]: - 2.06 [- 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo. CONCLUSION: Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044.

Published
2021

14. Deep Learning-Quantified Calcium Scores for Automatic Cardiovascular Mortality Prediction at Lung Screening Low-Dose CT

Author

Vos, B.D. de, Lessmann, N., Jong, Pa. de, Isgum, I., Vos, B.D. de, Lessmann, N., Jong, Pa. de, and Isgum, I.

Abstract

Item does not contain fulltext, Purpose: To examine the prognostic value of location-specific arterial calcification quantities at lung screening low-dose CT for the prediction of cardiovascular disease (CVD) mortality. Materials and Methods: This retrospective study included 5564 participants who underwent low-dose CT from the National Lung Screening Trial between August 2002 and April 2004, who were followed until December 2009. A deep learning network was trained to quantify six types of vascular calcification: thoracic aorta calcification (TAC); aortic and mitral valve calcification; and coronary artery calcification (CAC) of the left main, the left anterior descending, and the right coronary artery. TAC and CAC were determined in six evenly distributed slabs spatially aligned among chest CT images. CVD mortality prediction was performed with multivariable logistic regression using least absolute shrinkage and selection operator. The methods were compared with semiautomatic baseline prediction using self-reported participant characteristics, such as age, history of smoking, and history of illness. Statistical significance between the prediction models was tested using the nonparametric DeLong test. Results: The prediction model was trained with data from 4451 participants (median age, 61 years; 37.9% women) and then tested on data from 1113 participants (median age, 61 years; 37.9% women). The prediction model using calcium scores achieved a C statistic of 0.74 (95% CI: 0.69, 0.79), and it outperformed the baseline model using only participant characteristics (C statistic, 0.69; P = .049). Best results were obtained when combining all variables (C statistic, 0.76; P < .001). Conclusion: Five-year CVD mortality prediction using automatically extracted image-based features is feasible at lung screening low-dose CT.(c) RSNA, 2021.

Published
2021

15. Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer

Author

Gal, R., Velzen, S.G.M. van, Hooning, M.J., Emaus, M.J., Leij, F. van der, Gregorowitsch, M.L., Blezer, E.L.A., Gernaat, S.A.M., Lessmann, N., Sattler, M.G., Leiner, T., Jong, Pa. de, Teske, A.J., Verloop, J., Penninkhof, J.J., Vaartjes, I., Meijer, H.J.M., Tol-Geerdink, J.J. van, Pignol, J.P., Bongard, D. van den, Isgum, I., Verkooijen, H.M., Gal, R., Velzen, S.G.M. van, Hooning, M.J., Emaus, M.J., Leij, F. van der, Gregorowitsch, M.L., Blezer, E.L.A., Gernaat, S.A.M., Lessmann, N., Sattler, M.G., Leiner, T., Jong, Pa. de, Teske, A.J., Verloop, J., Penninkhof, J.J., Vaartjes, I., Meijer, H.J.M., Tol-Geerdink, J.J. van, Pignol, J.P., Bongard, D. van den, Isgum, I., and Verkooijen, H.M.

Abstract

Contains fulltext : 235298.pdf (Publisher’s version ) (Open Access), Importance: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. Objective: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. Design, Setting, and Participants: In this multicenter cohort study of 15915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Exposures: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Main Outcomes and Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly st

Published
2021

16. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

Author

Koning, H.J. de, Aalst, C.M. van der, Jong, Pa. de, Scholten, E.T., Nackaerts, K., Heuvelmans, M.A., Lammers, J.J., Weenink, C., Yousaf-Khan, U., Horeweg, N., Westeinde, S. van 't, Prokop, M., Mali, W.P., Hoesein, F.A.A.M., Ooijen, PM van, Aerts, J., Bakker, M.A. den, Thunnissen, E., Verschakelen, J., Vliegenthart, R., Walter, J.E., Haaf, K. Ten, Groen, H.J.M., Oudkerk, M., Koning, H.J. de, Aalst, C.M. van der, Jong, Pa. de, Scholten, E.T., Nackaerts, K., Heuvelmans, M.A., Lammers, J.J., Weenink, C., Yousaf-Khan, U., Horeweg, N., Westeinde, S. van 't, Prokop, M., Mali, W.P., Hoesein, F.A.A.M., Ooijen, PM van, Aerts, J., Bakker, M.A. den, Thunnissen, E., Verschakelen, J., Vliegenthart, R., Walter, J.E., Haaf, K. Ten, Groen, H.J.M., and Oudkerk, M.

Abstract

Contains fulltext : 219680.pdf (Publisher’s version ) (Open Access), BACKGROUND: There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS: A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS: Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 person-years in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS: In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and

Published
2020

20. Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

Author

Emaus, MJ, Isgum, I, van Velzen, SGM, van den Bongard, H, Gernaat, S A M, Lessmann, N, Sattler, Margriet, Teske, AJ, Penninkhof, Joan, Meijer, H, Pignol, Jean-Philippe, Verkooijen, HM, Bijlsma, R M, Blezer, ELA, Bots, ML, Bretveld, HJ, Hooning, MJ, Incrocci, Luca, Jong, PA, Leiner, T, van Tol-Geerdink, JJ, Vaartjes, I, Veldhuis, WB, Verloop, J, Viergever, MA, Visseren, FL, Wessels, H, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, and Radiation Oncology

Subjects
medicine.medical_specialty, coronary artery calcifications, medicine.medical_treatment, Breast Neoplasms, Coronary Artery Disease, 030204 cardiovascular system & hematology, Risk Assessment, Cohort Studies, 03 medical and health sciences, breast cancer, Deep Learning, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Cancer Survivors, cardiovascular disease, Trastuzumab, Protocol, medicine, Humans, cardiovascular diseases, Decision Making, Computer-Assisted, Cause of death, Medicine(all), business.industry, Calcinosis, Cancer, prediction, General Medicine, medicine.disease, radiotherapy planning CT-scan, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Radiation therapy, Coronary arteries, medicine.anatomical_structure, Oncology, Case-Control Studies, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Cohort, Female, Radiology, Tomography, X-Ray Computed, business, deep learning algorithm, Cohort study, medicine.drug
Abstract

IntroductionCardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk.Methods and analysisIn a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600).Ethics and disseminationThe Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences.Trial registration numberNCT03206333.

Published
2019

21. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

Author

Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW

Subjects
Male, Myocardial Infarction, genetic risk factor, Coronary Artery Disease, Middle Aged, Article, chromosome 9p21, Gene Frequency, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Genetic Predisposition to Disease, cardiovascular diseases, Chromosomes, Human, Pair 9, secondary prevention
Abstract

Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Published
2019

22. FELIX based readout of the Single-Phase ProtoDUNE detector

Author

Borga, A., Church, E., Filthaut, F., Gamberini, E., Jong, Pa. de, Habraken, R., Miotto, G. Lehmann, Miedema, T., Schreuder, F., Schumacher, J., Sipos, R., Vermeulen, Milo, Wood, L., Borga, A., Church, E., Filthaut, F., Gamberini, E., Jong, Pa. de, Habraken, R., Miotto, G. Lehmann, Miedema, T., Schreuder, F., Schumacher, J., Sipos, R., Vermeulen, Milo, and Wood, L.

Abstract

Contains fulltext : 209214.pdf (publisher's version ) (Open Access)

Published
2019

23. Defining the role of common variation in the genomic and biological architecture of adult human height

Author

Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, 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Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., 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H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker 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Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.

Subjects
Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, Medizin, Genome-wide association study, Adult, Analysis of Variance, Body Height/genetics, European Continental Ancestry Group/genetics, Genetic Variation/genetics, Genetics, Population, Genome-Wide Association Study/methods, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide/genetics, heritability, 0302 clinical medicine, Genome-wide, SNPS, snps, Genetics & Heredity, ddc:616, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, variants, GENETIC-VARIATION, Biological Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], body height, genetic-variation, Life Sciences & Biomedicine, Single Nucleotide/genetics, Human, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, NO, complex traits, 03 medical and health sciences, Genetic variation, heritability, adult, height, Polymorphism, Human height, PAGEGE Consortium, education, Gene, VLAG, 030304 developmental biology, Global Nutrition, Wereldvoeding, genome-wide association study, Science & Technology, Whites, Oligonucleotide Array Sequence Analysi, MUTATIONS, COMPLEX TRAITS, ta1184, Klinisk medicin, population genetics, Genetic Variation, Heritability, ta3121, mutations, Genetic architecture, Body Height, genetic variation, MIGen Consortium, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Clinical Medicine, 030217 neurology & neurosurgery, height, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract

Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Published
2014

24. Sex differences in intracranial and extracranial atherosclerosis in patients with acute ischemic stroke.

Author

Voigt, S, van Os, HJA, van Walderveen, MAA, van der Schaaf, IC, Kappelle, LJ, Broersen, A, Velthuis, BK, de Jong, PA, Kockelkoren, R, Kruyt, ND, Algra, A, and Wermer, MJH

Subjects
STROKE patients, ATHEROSCLEROSIS, ISCHEMIC stroke, INTERNAL carotid artery, COMPUTED tomography
Abstract

Background and aim: To investigate sex differences with respect to presence and location of atherosclerosis in acute ischemic stroke patients. Methods: Participants with acute ischemic stroke were included from the Dutch acute stroke trial, a large prospective multicenter cohort study performed between May 2009 and August 2013. All patients received computed tomography/computed tomography-angiography within 9 h of stroke onset. We assessed presence of atherosclerosis in the intra- and extracranial internal carotid and vertebrobasilar arteries. In addition, we determined the burden of intracranial atherosclerosis by quantifying internal carotid and vertebrobasilar artery calcifications, resulting in calcium volumes. Prevalence ratios between women and men were calculated with Poisson regression analysis and adjusted prevalence ratio for potential confounders (age, hypertension, hyperlipidemia, diabetes, smoking, and alcohol use). Results: We included 1397 patients with a mean age of 67 years, of whom 600 (43%) were women. Presence of atherosclerosis in intracranial vessel segments was found as frequently in women as in men (71% versus 72%, adjusted prevalence ratio 0.95; 95% CI 0.89–1.01). In addition, intracranial calcification volume did not differ between women and men in both intracranial internal carotid (large burden 35% versus 33%, adjusted prevalence ratio 0.93; 95% CI 0.73–1.19) and vertebrobasilar arteries (large burden 26% versus 40%, adjusted prevalence ratio 0.69; 95% CI 0.41–1.12). Extracranial atherosclerosis was less common in women than in men (74% versus 81%, adjusted prevalence ratio 0.86; 95% CI 0.81–0.92). Conclusions: In patients with acute ischemic stroke the prevalence of intracranial atherosclerosis does not differ between women and men, while extracranial atherosclerosis is less often present in women compared with men. [ABSTRACT FROM AUTHOR]

Published
2021
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25. Variable radiological lung nodule evaluation leads to divergent management recommendations

Author

Nair, A, Bartlett, EC, Walsh, SLF, Wells, AU, Navani, N, Hardavella, G, Bhalla, S, Calandriello, L, Devaraj, A, Goo, JM, Klein, JS, MacMahon, H, Schaefer-Prokop, CM, Seo, JB, Sverzellati, N, Desai, SR, Ahlfors, F, Bastos, A, Behr, J, Benes, J, Bozovic, G, Buzan, MT, Castaner, E, Chaves, M, Choi, YW, Dalpiaz, G, David, S, De Jong, PA, Dournes, G, Eberhard, M, Escuissato, D, Farchione, A, Flors, L, Franchi, P, Frauenfelder, T, Fujimoto, K, Gatti, M, Gavelli, G, Grgic, A, Haine, L, Haramati, L, Iiartman, T, Hartmann, I, Hering, JP, Herpels, V, Herraez, I, Hobbs, S, Hochhegger, B, Hursoy, N, Ip, J, Iyengar, S, Jimenez, JA, Johnson, K, Kanne, J, Kapur, S, Karaman, CZ, Karl, R, Kirova, G, Ko, J, Kramer, G, Kul, M, Larici, AR, Lee, Y, Leifels, L, Ley, S, Machnicki, S, Maidas, P, Mak, SM, Mariani, F, Meirelles, G, Hoesein, FAM, Montet, X, Murchison, J, Nath, H, Nenkina, T, Nganga, E, Linh, NKTD, Niemann, T, Nunez, CFM, Occhipiniti, M, Oikonomou, A, Ozawa, Y, Pandher, T, Parkar, AP, Piciucchi, S, Pinheiro, D, Poerio, A, Polverosi, R, Pope, K, Prosch, H, Pulzato, I, Rampinelli, C, Rodrigues, J, Romanos, O, Romei, C, Roos, J, Rossi, S, Ruhtsov, R, Ruggirello, M, Sanchez, M, Santos, MK, Schubert, M, Senbanjo, T, Silva, C, Silva, M, Snoeckx, A, Sonavane, S, Sriharan, M, Stefanidis, K, Taydas, O, Tomiyama, N, Tran, S, Villanueva, A, Williams, M, and Lung Nodule Evaluation Grp

Abstract

Radiological evaluation of incidentally detected lung nodules on computed tomography (CT) influences management. We assessed international radiological variation in 1) pulmonary nodule characterisation; 2) hypothetical guideline-derived management; and 3) radiologists' management recommendations. 107 radiologists from 25 countries evaluated 69 CT-detected nodules, recording: 1) first-choice composition (solid, part-solid or ground-glass, with percentage confidence); 2) morphological features; 3) dimensions; 4) recommended management; and 5) decision-influencing factors. We modelled hypothetical management decisions on the 2005 and updated 2017 Fleischner Society, and both liberal and parsimonious interpretations of the British Thoracic Society 2015 guidelines. Overall agreement for first-choice nodule composition was good (Fleiss' kappa=0.65), but poorest for part-solid nodules (weighted 0.62, interquartile range 0.50-0.71). Morphological variables, including spiculation (kappa=0.35), showed poor-to-moderate agreement (kappa=0.23-0.53). Variation in diameter was greatest at key thresholds (5 mm and 6 mm). Agreement for radiologists' recommendations was poor (kappa=0.30); 21% disagreed with the majority. Although agreement within the four guideline-modelled management strategies was good (kappa=0.63-0.73), 5-10% of radiologists would disagree with majority decisions if they applied guidelines strictly. Agreement was lowest for part-solid nodules, while significant measurement variation exists at important size thresholds. These variations resulted in generally good agreement for guideline-modelled management, but poor agreement for radiologists' actual recommendations.

Published
2018

26. The accuracy of diagnostic Imaging techniques in patients with a suspected Fracture-related Infection (IFI) trial: study protocol for a prospective multicenter cohort study.

Author

Govaert, GAM, primary, Hobbelink, MGG, additional, Reininga, IHF, additional, Bosch, P, additional, Kwee, TC, additional, de Jong, PA, additional, Jutte, PC, additional, Vogely, HC, additional, Dierckx, RAJO, additional, Leenen, LPH, additional, Glaudemans, AWJM, additional, and IJpma, FFA, additional

Published
2019
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27. Computed tomography image quality of aortic stents in patients with aortic coarctation: a multicentre evaluation

Author

Boccalini, Sara, den Harder, AM, Witsenburg, Maarten, Breur, JPJM, Krestin, Gabriel, van Beynum, Ingrid, Attrach, Mohamed, Stagnaro, N, Marasini, M, Jong, PA, Leiner, T, Budde, Ricardo, Boccalini, Sara, den Harder, AM, Witsenburg, Maarten, Breur, JPJM, Krestin, Gabriel, van Beynum, Ingrid, Attrach, Mohamed, Stagnaro, N, Marasini, M, Jong, PA, Leiner, T, and Budde, Ricardo

Published
2018

29. Quantification of growth patterns of screen-detected lung cancers: The NELSON study

Author

Heuvelmans, MA, Vliegenthart, R, de Koning, Harry, Groen, HJM, van Putten, M (Margreet), Yousaf, Uraujh, Weenink, C, Nackaerts, K, Jong, PA, Oudkerk, M, Heuvelmans, MA, Vliegenthart, R, de Koning, Harry, Groen, HJM, van Putten, M (Margreet), Yousaf, Uraujh, Weenink, C, Nackaerts, K, Jong, PA, and Oudkerk, M

Published
2017

33. Automated estimation of progression of interstitial lung disease in CT images

Author

Yulia Arzhaeva, Prokop, M., Murphy, K., Rikxoort, Em, Jong, Pa, Gietema, Ha, Viergever, Ma, and Ginneken, B.

Subjects
Auto-immunity, transplantation and immunotherapy [N4i 4]
Abstract

Contains fulltext : 88430.pdf (Publisher’s version ) (Open Access) PURPOSE: A system is presented for automated estimation of progression of interstitial lung disease in serial thoracic CT scans. METHODS: The system compares corresponding 2D axial sections from baseline and follow-up scans and concludes whether this pair of sections represents regression, progression, or unchanged disease status. The correspondence between serial CT scans is achieved by intrapatient volumetric image registration. The system classification function is trained with two different feature sets. Features in the first set represent the intensity distribution of a difference image between the baseline and follow-up CT sections. Features in the second set represent dissimilarities computed between the baseline and follow-up images filtered with a bank of general purpose texture filters. RESULTS: In an experiment on 74 scan pairs, the system classification accuracies were 76.1% and 79.5% for the two feature sets, respectively, while the accuracies of two observer radiologist were 78.5% and 82%, respectively. The agreements of the system with the reference standard, measured by weighted kappa statistics, were 0.611 and 0.683 for the two feature sets, respectively. CONCLUSIONS: The system employing the second feature set showed good agreement with the reference standard, and its accuracy approached that of two radiologists. 01 januari 2010

Published
2010

35. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: Evidence from genetic analysis and randomised trials

Author

Swerdlow, DI, Preiss, D, Kuchenbaecker, KB, Holmes, MV, Engmann, JEL, Shah, T, Sofat, R, Stender, S, Johnson, PCD, Scott, RA, Leusink, M, Verweij, N, Sharp, SJ, Guo, Y, Giambartolomei, C, Chung, C, Peasey, A, Amuzu, A, Li, K, Palmen, J, Howard, P, Cooper, JA, Drenos, F, Li, YR, Lowe, G, Gallacher, J, Stewart, MCW, Tzoulaki, I, Buxbaum, SG, Van Der A, DL, Forouhi, NG, Onland-Moret, NC, Van Der Schouw, YT, Schnabel, RB, Hubacek, JA, Kubinova, R, Baceviciene, M, Tamosiunas, A, Pajak, A, Topor-Madry, R, Stepaniak, U, Malyutina, S, Baldassarre, D, Sennblad, B, Tremoli, E, De Faire, U, Veglia, F, Ford, I, Jukema, JW, Westendorp, RGJ, De Borst, GJ, De Jong, PA, Algra, A, Spiering, W, Der Zee, AHMV, Klungel, OH, De Boer, A, Doevendans, PA, Eaton, CB, Robinson, JG, Duggan, D, Kjekshus, J, Downs, JR, Gotto, AM, Keech, AC, Marchioli, R, Tognoni, G, Sever, PS, Poulter, NR, Waters, DD, Pedersen, TR, Amarenco, P, Nakamura, H, McMurray, JJV, Lewsey, JD, Chasman, DI, Ridker, PM, Maggioni, AP, Tavazzi, L, Ray, KK, Seshasai, SRK, Manson, JE, Price, JF, Whincup, PH, Morris, RW, and Lawlor, DA

Abstract

© 2015 Swerdlow et al. Open Access article distributed under the terms of CC BY. Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. Funding The funding sources are cited at the end of the paper.

Published
2015

36. Influences of Elastic Stress and Interfacial Kinetic Barrier on Phase Evolution Paths of Thin-Film Diffusion Couples

Author

Jong Pa Hong and Joo Youl Huh

Subjects
Materials science, Computer simulation, Diffusion, Thermodynamics, Condensed Matter Physics, Kinetic energy, Phase evolution, Atomic and Molecular Physics, and Optics, Stress (mechanics), Phase (matter), Finite difference scheme, Physical chemistry, General Materials Science, Thin film
Abstract

An explicit, finite difference scheme was used to examine the effects of coherency stresses and interface kinetic barriers on the phase evolution of a binary, thin-film diffusion couple. Thin-films, initially consisting of alternating layers of two terminal phases, α and γ, were held at a temperature at which the formation of an intermediate phase, β, at α/γ interface was thermodynamically probable. When either the coherency stresses or interface kinetic barriers are present, the interfacial compositions become time-dependent and, thus, the formation of the thermodynamically stable β phase can be kinetically prohibited at the early stage of the evolution. Even if the initial α/γ thin-films have the same overall composition, the coherency constraint can result in different final equilibrium states depending on either the initial compositions of the α and γ phases or the relative magnitudes of the interfacial kinetic barriers. When both the coherency constraint and interfacial kinetic barriers are present, an intermediate phase can repeatedly form and disappear during the evolution.

Published
2006

37. Automatic Coronary Artery Calcium Scoring on Radiotherapy Planning CT Scans of Breast Cancer Patients: Reproducibility and Association with Traditional Cardiovascular Risk Factors

Author

Gernaat, S A M, Isgum, I, de Vos, B D, Takx, RAP, Young-Afat, D A, Rijnberg, N, Grobbee, DE, van der Graaf, Y, Jong, PA, Leiner, T, van den Bongard, D H J, Pignol, Jean-Philippe, Verkooijen, HM, Gernaat, S A M, Isgum, I, de Vos, B D, Takx, RAP, Young-Afat, D A, Rijnberg, N, Grobbee, DE, van der Graaf, Y, Jong, PA, Leiner, T, van den Bongard, D H J, Pignol, Jean-Philippe, and Verkooijen, HM

Published
2016

39. Association of Chronic Obstructive Pulmonary Disease and Smoking Status With Bone Density and Vertebral Fractures in Male Lung Cancer Screening Participants

Author

de Jong, WU, Jong, PA, Vliegenthart, R (Rozemarijn), Isgum, I, Lammers, JWJ, Oudkerk, M, van der Aalst, Carlijn, de Koning, Harry, Hoesein, FAM, Cardiovascular Centre (CVC), Academic Medical Center, Epidemiology, and Public Health

Subjects
RISK, FRACTURE RISK ASSESSMENT, UNITED-STATES, OSTEOPOROSIS, respiratory tract diseases, ATTENUATION, SCANS, SDG 3 - Good Health and Well-being, BONE DENSITY, COPD, MINERAL DENSITY, COMPUTED TOMOGRAPHY, SMOKING, METAANALYSIS, CT
Abstract

We studied the vertebral fracture prevalence on low-dose chest computed tomography (CT) in male lung cancer screening participants and the association of fractures and bone density with chronic obstructive pulmonary disease (COPD) and smoking. 1140 male current and former smokers with >= 16.5 packyears from the NELSON lung cancer screening trial were included. Age, body mass index, and smoking status were registered. CT scans and pulmonary function tests were obtained on the same day. On CT, vertebral fractures and bone density were measured. The cohort had a mean age of 62.5 years (standard deviation 5.2) old; 531 (46.6%) had quit smoking; and 437 (38.3%) had COPD. Of the group, 100 (8.8%) participants had a vertebral fracture. Fracture prevalence was higher in current compared to former smokers (11.3% versus 5.8%, p = 0.001), but similar in participants with COPD compared to those without (9.6% versus 8.3%, p = 0.430). The multivariable adjusted odds ratio for fracture presence was 1.79 (95% CI: 1.13-2.84) in current smokers and 1.08 (95% CI: 0.69-1.67) in COPD participants. Bone density was lower in current compared to former smokers (103.2HU versus 108.7HU, p = 0.006) and in participants with COPD compared to those without [100.7 Hounsfield Units (HU) versus 108.9HU, p < 0.001]. In multivariate analysis, smoking status and COPD status were independently associated with bone density, corrected for age and body mass index. In conclusion, our study shows that lung cancer screening participants have a substantial vertebral fracture burden. Fractures are more common in current smokers, who also have lower bone density. We could not confirm that COPD is independently associated with vertebral fractures. (c) 2014 American Society for Bone and Mineral Research.

Published
2014

40. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data

Author

Holmes, MV, Dale, CE, Zuccolo, L, Silverwood, RJ, Guo, Y, Ye, Z, Prieto-Merino, D, Dehghan, Abbas, Trompet, S, Wong, A, Cavadino, A, Drogan, D, Padmanabhan, S, Li, Shan, Yesupriya, A, Leusink, M, Sundstrom, J, Hubacek, JA, Pikhart, H, Swerdlow, DI, Panayiotou, AG, Borinskaya, SA, Finan, C, Shah, S, Kuchenbaecker, KB, Shah, T, Engmann, J, Folkersen, L, Eriksson, P, Ricceri, F, Melander, O, Sacerdote, C, Gamble, DM, Rayaprolu, S, Ross, OA, McLachlan, S, Vikhireva, O, Sluijs, Iris, Scott, RA, Adamkova, V, Flicker, L, van Bockxmeer, FM, Power, C, Marques-Vidal, P, Meade, T, Marmot, MG, Ferro, JM, Paulos-Pinheiro, S, Humphries, SE, Talmud, PJ, Leach, IM, Verweij, N (Niek), Linneberg, A, Skaaby, T, Doevendans, PA, Cramer, MJ, van der Harst, P, Klungel, OH, Dowling, NF, Dominiczak, AF, Kumari, M, Nicolaides, AN, Weikert, C, Boeing, H, Ebrahim, S, Gaunt, TR, Price, JF, Lannfelt, L, Peasey, A, Kubinova, R, Pajak, A, Malyutina, S, Voevoda, MI, Tamosiunas, A, Zee, AH, Norman, PE, Hankey, GJ, Bergmann, MM, Hofman, Bert, Franco Duran, OH, Cooper, J, Palmen, J, Spiering, W, Jong, PA, Kuh, D, Hardy, R, Uitterlinden, André, Ikram, Arfan, Ford, I, Hyppoenen, E, Almeida, OP, Wareham, NJ, Khaw, KT, Hamsten, A, Husemoen, LLN, Tjonneland, A, Tolstrup, JS, Rimm, E, Beulens, JWJ, Verschuren, WMM, Onland-Moret, NC, Hofker, MH, Wannamethee, SG, Whincup, PH, Morris, R, Vicente, AM, Watkins, H, Farrall, M, Jukema, JW, Meschia, J, Cupples, LA, Sharp, SJ, Fornage, M, Kooperberg, C, Lacroix, AZ, Dai, JY, Lanktree, MB, Siscovick, DS, Jorgenson, E, Spring, B, Coresh, J, Li, YR, Buxbaum, SG, Schreiner, PJ, Ellison, RC, Tsai, MY, Patel, SR, Redline, S, Johnson, AD, Hoogeveen, RC, Rotter, JI, Boerwinkle, E, de Bakker, PIW, Kivimaki, M, Asselbergs, FW, Sattar, N, Lawlor, DA, Whittaker, J, Smith, GD, Mukamal, K, Psaty, BM, Wilson, JG, Lange, LA, Hamidovic, A, Hingorani, AD, Nordestgaard, BG, Bobak, M, Leon, DA, Langenberg, C, Palmer, TM, Reiner, AP, Keating, BJ, Dudbridge, F, Casas, JP, Sub Pharmacotherapy, Theoretical, Pharmacoepidemiology and Clinical Pharmacology, Clinical Genetics, Epidemiology, Erasmus MC other, Internal Medicine, and Radiology & Nuclear Medicine

Subjects
Medicine(all), Alcohol dehydrogenase 1B gene, SDG 3 - Good Health and Well-being, Alcohol consumption, Alcohol abstinence, Clinical Medicine, Medical and Health Sciences
Abstract

Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Published
2014

41. Prognostic value of heart valve calcifications for cardiovascular events in a lung cancer screening population

Author

Willemink, MJ, Takx, RAP, Isgum, I, de Koning, Harry, Oudkerk, M, Mali, WPTM, Budde, Ricardo, Leiner, T, Vliegenthart, R, Jong, PA, Willemink, MJ, Takx, RAP, Isgum, I, de Koning, Harry, Oudkerk, M, Mali, WPTM, Budde, Ricardo, Leiner, T, Vliegenthart, R, and Jong, PA

Abstract

To assess the prognostic value of aortic valve and mitral valve/annulus calcifications for cardiovascular events in heavily smoking men without a history of cardiovascular disease. Heavily smoking men without a cardiovascular disease history who underwent non-contrast-enhanced low-radiation-dose chest CT for lung cancer screening were included. Non-imaging predictors (age, smoking status and pack-years) were collected and imaging-predictors (calcium volume of the coronary arteries, aorta, aortic valve and mitral valve/annulus) were obtained. The outcome was the occurrence of cardiovascular events. Multivariable Cox proportional-hazards regression was used to calculate hazard-ratios (HRs) with 95 % confidence interval (CI). Subsequently, concordance-statistics were calculated. In total 3111 individuals were included, of whom 186 (6.0 %) developed a cardiovascular event during a follow-up of 2.9 (Q1-Q3, 2.7-3.3) years. If aortic (n = 657) or mitral (n = 85) annulus/valve calcifications were present, cardiovascular event incidence increased to 9.0 % (n = 59) or 12.9 % (n = 11), respectively. HRs of aortic and mitral valve/annulus calcium volume for cardiovascular events were 1.46 (95 % CI, 1.09-1.84) and 2.74 (95 % CI, 0.92-4.56) per 500 mm(3). The c-statistic of a basic model including age, pack-years, current smoking status, coronary and aorta calcium volume was 0.68 (95 % CI, 0.63-0.72), which did not change after adding heart valve calcium volume. Aortic valve calcifications are predictors of future cardiovascular events. However, there was no added prognostic value beyond age, number of pack-years, current smoking status, coronary and aorta calcium volume for short term cardiovascular events.

Published
2015

42. Automated Coronary Artery Calcification Scoring in Non-Gated Chest CT: Agreement and Reliability

Author

Takx, RAP, Jong, PA, Leiner, T, Oudkerk, M, de Koning, Harry, Mol, CP, Viergever, MA, Isgum, I, Takx, RAP, Jong, PA, Leiner, T, Oudkerk, M, de Koning, Harry, Mol, CP, Viergever, MA, and Isgum, I

Abstract

Objective: To determine the agreement and reliability of fully automated coronary artery calcium (CAC) scoring in a lung cancer screening population. Materials and Methods: 1793 low-dose chest CT scans were analyzed (non-contrast-enhanced, non-gated). To establish the reference standard for CAC, first automated calcium scoring was performed using a preliminary version of a method employing coronary calcium atlas and machine learning approach. Thereafter, each scan was inspected by one of four trained raters. When needed, the raters corrected initially automaticity-identified results. In addition, an independent observer subsequently inspected manually corrected results and discarded scans with gross segmentation errors. Subsequently, fully automatic coronary calcium scoring was performed. Agatston score, CAC volume and number of calcifications were computed. Agreement was determined by calculating proportion of agreement and examining Bland-Altman plots. Reliability was determined by calculating linearly weighted kappa (k) for Agatston strata and intraclass correlation coefficient (ICC) for continuous values. Results: 44 (2.5%) scans were excluded due to metal artifacts or gross segmentation errors. In the remaining 1749 scans, median Agatston score was 39.6 (P25-P75:0-345.9), median volume score was 60.4 mm(3) (P25-P75:0-361.4) and median number of calcifications was 2 (P25-P75:0-4) for the automated scores. The k demonstrated very good reliability (0.85) for Agatston risk categories between the automated and reference scores. The Bland-Altman plots showed underestimation of calcium score values by automated quantification. Median difference was 2.5 (p25-p75:0.0-53.2) for Agatston score, 7.6 (p25-p75:0.0-94.4) for CAC volume and 1 (p25-p75:0-5) for number of calcifications. The ICC was very good for Agatston score (0.90), very good for calcium volume (0.88) and good for number of calcifications (0.64). Discussion: Fully automated coronary calcium scoring in a lung

Published
2014

45. Theoretical study of phase stability of In<formula><roman>x</roman></formula>Ga<formula><roman>1-x</roman></formula>N alloys

Author

Soo Min Lee, Jong pa Hong, Won Ha Moon, and Dong Woohn Kim

Subjects
Materials science, Indium nitride, business.industry, media_common.quotation_subject, chemistry.chemical_element, Thermodynamics, Flory–Huggins solution theory, Asymmetry, Bond length, chemistry.chemical_compound, Molecular geometry, Optics, chemistry, Gallium, business, Chemical composition, Phase diagram, media_common
Abstract

Molecular-mechanics based simulations are applied to investigate the structures and phase stability of InGaN alloys. The variation of bond lengths and angles with increasing In composition is found. This causes the considerable structural change and the phase separation of InGaN alloys. The interaction parameter (Ω= -1.3435x + 6.1607 (kcal/mol) ) dependent on In composition is also calculated. The phase diagram for InGaN alloys shows an asymmetry with respect to x0.5. The critical temperature for the phase separation is 1392 K at x = 0.44. These results are in agreement with experimental results.

Published
2006

49. Semi-Automatic Quantification of Subsolid Pulmonary Nodules: Comparison with Manual Measurements

Author

Scholten, ET, de Hoop, B, Jacobs, C, van de Vorst, S, Klaveren, RJ, Oudkerk, M, Vliegenthart, R (Rozemarijn), de Koning, Harry, van der Aalst, Carlijn, Mali, WTM, Gietema, HA, Prokop, M, Ginneken, Berbke, Jong, PA, Scholten, ET, de Hoop, B, Jacobs, C, van de Vorst, S, Klaveren, RJ, Oudkerk, M, Vliegenthart, R (Rozemarijn), de Koning, Harry, van der Aalst, Carlijn, Mali, WTM, Gietema, HA, Prokop, M, Ginneken, Berbke, and Jong, PA

Abstract

Rationale: Accurate measurement of subsolid pulmonary nodules (SSN) is becoming increasingly important in the management of these nodules. SSNs were previously quantified with time-consuming manual measurements. The aim of the present study is to test the feasibility of semi-automatic SSNs measurements and to compare the results to the manual measurements. Methods: In 33 lung cancer screening participants with 33 SSNs, the nodules were previously quantified by two observers manually. In the present study two observers quantified these nodules by using semi-automated nodule volumetry software. Nodules were quantified for effective diameter, volume and mass. The manual and semi-automatic measurements were compared using Bland-Altman plots and paired T tests. Observer agreement was calculated as an intraclass correlation coefficient. Data are present Results: Semi-automated measurements were feasible in all 33 nodules. Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311) milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344) milligrams for observer 2, respectively. Agreement between observers and within observer 1 for the semi-automatic measurements was good with an intraclass correlation coefficient >0.89. For observer 1 and observer 2, measured diameter was 8.8% and 10.3% larger (p<0.001), measur Conclusion: Semi-automated measurement of the diameter, volume and mass of SSNs is feasible with good observer agreement. Semi-automated measurement makes quantification of mass and volume feasible in daily practice.

Published
2013

50. Impact of Cardiovascular Calcifications on the Detrimental Effect of Continued Smoking on Cardiovascular Risk in Male Lung Cancer Screening Participants

Author

Jairam, PM, Jong, PA, Mali, WPTM, Isgum, I, de Koning, Harry, van der Aalst, Carlijn, Oudkerk, M, Vliegenthart, R (Rozemarijn), van der Graaf, Y (Yolanda), Jairam, PM, Jong, PA, Mali, WPTM, Isgum, I, de Koning, Harry, van der Aalst, Carlijn, Oudkerk, M, Vliegenthart, R (Rozemarijn), and van der Graaf, Y (Yolanda)

Abstract

Background: Current smokers have an increased cardiovascular disease (CVD) risk compared to ex-smokers due to reversible as well as irreversible effects of smoking. We investigated if current smokers remain to have an increased CVD risk compared to ex-smokers in subjects with a long and intense smoking history. We in addition studied if the effect of smoking continuation on CVD risk is independent of or modified by the presence of cardiovascular calcifications. Methods: The cohort used comprised a sample of 3559 male lung cancer screening trial participants. We conducted a case-cohort study using all CVD cases and a random sample of 10% (n = 341) from the baseline cohort (subcohort). A weighted Cox proportional hazards model was used to estimate the hazard ratios for current smoking status in relation to CVD events. Results: During a median follow-up of 2.6 years (max. 3.7 years), 263 fatal and non-fatal cardiovascular events (cases) were identified. Age, packyears and cardiovascular calcification adjusted hazard ratio of current smokers compared to former smokers was 1.33 (95% confidence interval 1.00-1.77). In additional analyses that incorporated multiplicative interaction terms, neither coronary nor aortic calcifications modified the association between smoking status and cardiovascular risk (P = 0.08). Conclusions: Current smokers have an increased CVD risk compared to former smokers even in subjects with a long and intense smoking history. Smoking exerts its hazardous effects on CVD risk by pathways partly independent of cardiovascular calcifications.

Published
2013

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