487 results on '"Michael J. Pencina"'
Search Results
2. Effects of hybrid comprehensive telerehabilitation on cardiopulmonary capacity in heart failure patients depending on diabetes mellitus: subanalysis of the TELEREH-HF randomized clinical trial
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Renata Główczyńska, Ewa Piotrowicz, Dominika Szalewska, Ryszard Piotrowicz, Ilona Kowalik, Michael J. Pencina, Wojciech Zaręba, Maciej Banach, Piotr Orzechowski, Sławomir Pluta, Robert Irzmański, Zbigniew Kalarus, and Grzegorz Opolski
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Hybrid rehabilitation ,Telerehabilitation ,Heart failure ,Exercise training ,Diabetes mellitus ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Type 2 diabetes mellitus (DM) is one of the most common comorbidities among patients with heart failure (HF) with reduced ejection fraction (HFrEF). There are limited data regarding efficacy of hybrid comprehensive telerehabilitation (HCTR) on cardiopulmonary exercise capacity in patients with HFrEF with versus those without diabetes. Aim The aim of the present study was to analyze effects of 9-week HCTR in comparison to usual care on parameters of cardiopulmonary exercise capacity in HF patients according to history of DM. Methods Clinically stable HF patients with left ventricular ejection fraction [LVEF]
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- 2021
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3. Antiarrhythmic effect of 9-week hybrid comprehensive telerehabilitation and its influence on cardiovascular mortality in long-term follow-up – subanalysis of the TELEREHabilitation in Heart Failure Patients randomized clinical trial
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Piotr Orzechowski, Ryszard Piotrowicz, Wojciech Zareba, Michael J. Pencina, Ilona Kowalik, Ewa Komar, Grzegorz Opolski, Maciej Banach, Renata Główczyńska, Dominika Szalewska, Sławomir Pluta, Robert Irzmański, Zbigniew Kalarus, and Ewa Piotrowicz
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ventricular arrhythmia ,heart failure ,telerehabilitation ,Medicine - Abstract
Introduction Cardiac rehabilitation is a component of heart failure (HF) management, but its effect on ventricular arrhythmias is not well understood. We analyzed the antiarrhythmic effect of a 9-week hybrid comprehensive telerehabilitation (HCTR) program and its influence on long-term cardiovascular mortality in HF patients taken from the TELEREHabilitation in Heart Failure Patients (TELEREH-HF) trial. Material and methods We evaluated the presence of non-sustained ventricular tachycardia (nsVT) and frequent premature ventricular complexes ≥ 10 beats/hour (PVCs ≥ 10) in 24-hour ECG monitoring at baseline and after 9-week HCTR or usual care (UC) of 773 HF patients (NYHA I-III, LVEF ≤ 40%). Functional response for HCTR was assessed by changes – delta (Δ) – in peak oxygen consumption (pVO2) as a result of comparing pVO2 from the beginning and the end of the program. Results Among 143 patients with nsVT, arrhythmia subsided in 30.8% after HCTR. Similarly, among 165 patients randomized to UC who had nsVT 34.5% did not show it after 9 weeks (p = 0.481). There was no significant difference in the decrease in PVC ≥ 10 over 9 weeks between randomization arms (14.9% vs. 17.8%, respectively p = 0.410). Functional response for HCTR in ΔpVO2 > 2.0 ml/kg/min did not affect occurrence of arrhythmias. Multivariable analysis did not identify HCTR as an independent factor determining improvement of nsVT or PVCs ≥ 10. However, only in the HCTR group, the achievement of the antiarrhythmic effect significantly reduced the cardiovascular mortality in 2-year follow-up (p < 0.001). Conclusions Significant improvement in physical capacity after 9 weeks of HCTR did not correlate with the antiarrhythmic effect in terms of incidence of nsVT or PVCs ≥ 10. An antiarrhythmic effect after the 9-week HCTR affected long-term cardiovascular mortality in HF patients.
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- 2021
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4. An aetiology‐based subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) trial
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Dominika Szalewska, Renata Główczyńska, Ryszard Piotrowicz, Ilona Kowalik, Michael J. Pencina, Grzegorz Opolski, Wojciech Zaręba, Maciej Banach, Piotr Orzechowski, Sławomir Pluta, Robert Irzmański, Zbigniew Kalarus, and Ewa Piotrowicz
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Hybrid rehabilitation ,Telerehabilitation ,Heart failure ,Exercise training ,Remote monitoring ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims The aim of our study was to analyse the benefits of a 9 week hybrid comprehensive telerehabilitation (HCTR) programme in heart failure (HF) patients according to aetiology, as a subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) trial. Methods and results Overall, 555 (65.3%) patients with ischaemic (IS) and 295 (34.7%) patients with non‐ischaemic (NIS) HF aetiology were randomized. There were no differences between the effect of HCTR and usual care (UC) on the primary outcome of number of days alive and out of the hospital in 26 months from the time of randomization in either aetiology (Wilcoxon–Mann–Whitney test), and no heterogeneity of effect between the aetiologies was noted (van Elteren test, P = 0.746). In Cox proportional hazards regression analysis, treatment was not independently associated with the secondary outcomes. For all‐cause mortality, the adjusted hazard ratio for HCTR vs. UC was 0.90 (95% confidence interval, 0.54–1.51) in IS and 1.42 (95% confidence interval, 0.69–2.94) in NIS (P interaction = 0.316). Differences between HCTR and UC in terms of change in the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks reached statistical significance in the IS arm (P = 0.015 and P
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- 2021
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5. Assessment of ECG during hybrid comprehensive telerehabilitation in heart failure patients—Subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) randomized clinical trial
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Piotr Orzechowski, Ryszard Piotrowicz, Wojciech Zaręba, Renata Główczyńska, Dominika Szalewska, Sławomir Pluta, Robert Irzmański, Zbigniew Kalarus, Maciej Banach, Grzegorz Opolski, Michael J. Pencina, Ilona Kowalik, and Ewa Piotrowicz
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arrhythmia ,cardiac telerehabilitation ,ECG monitoring ,heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Exercise training in heart failure (HF) patients should be monitored to ensure patients’ safety. Electrocardiographic (ECG) telemonitoring was used to assess the safety of hybrid comprehensive telerehabilitation (HCTR). Objective Analysis of ECG recorded during HCTR in HF patients. Methods The TELEREH‐HF multicenter, randomized, controlled trial enrolled 850 HF patients with New York Heart Association class I‐III and left ventricular ejection fraction of ≤40%. This subanalysis focuses on 386 patients (aged 62 ± 11 years, LVEF 31 ± 7%) randomized to HCTR. HCTR was telemonitored with a device allowing to record 16‐s fragments of ECG and to transmit the data via mobile phone network to the monitoring center. ResultsIn 386 patients, 16,622 HCTR sessions were recorded and 66,488 ECGs fragments were evaluated. Sinus rhythm was present in 320 (83%) and permanent atrial fibrillation (AF) in 66 (17%) patients, respectively. The most common arrhythmias were ventricular and atrial premature beats, recorded in 76.4% and 27.7% of the patients, respectively. Non‐sustained ventricular tachycardia (21 episodes in 8 patients) and paroxysmal AF episodes (6 in 4 patients) were rare. None of the analyzed demographic and clinical characteristics was predictive for onset of the new arrhythmias on exercise. Conclusion Telerehabilitation in HF patients was safe without the evidence for symptomatic arrhythmias requiring discontinuation of telerehabilitation. Only one mildly symptomatic paroxysmal AF episode led to the short‐term suspension of the training program. The most common arrhythmias were atrial and ventricular premature beats. These arrhythmias did not result in any changes in rehabilitation and therapy regimens.
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- 2021
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6. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk
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Julio Rosenstock, Vlado Perkovic, John H. Alexander, Mark E. Cooper, Nikolaus Marx, Michael J. Pencina, Robert D. Toto, Christoph Wanner, Bernard Zinman, David Baanstra, Egon Pfarr, Michaela Mattheus, Uli C. Broedl, Hans-Juergen Woerle, Jyothis T. George, Maximilian von Eynatten, Darren K. McGuire, and CARMELINA® investigators
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Diabetes mellitus, type 2 ,Cardiovascular diseases ,Diabetic nephropathies ,Dipeptidyl-peptidase IV inhibitors ,Linagliptin ,Clinical trial, phase IV ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA® trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. Methods CARMELINA® is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5–10.0% (48–86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, ≥ 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA® was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided α-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. Results Between July 2013 and August 2016, 6980 patients were randomized and took ≥ 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean ± SD age was 65.8 ± 9.1 years, HbA1c 7.9 ± 1.0%, BMI 31.3 ± 5.3 kg/m2, and eGFR 55 ± 25 mL/min/1.73 m2. A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common. Conclusions CARMELINA® will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk. Trial registration ClinicalTrials.gov identifier—NCT01897532; registered July 9, 2013
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- 2018
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7. Multi-category diagnostic accuracy based on logistic regression
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Jialiang Li, Jason P. Fine, and Michael J. Pencina
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hypervolume under the roc manifold ,multi-category classification ,correct classification probability ,net reclassification improvement ,integrated discrimination improvement ,marker evaluation ,r software ,Probabilities. Mathematical statistics ,QA273-280 - Abstract
We provide a detailed review for the statistical analysis of diagnostic accuracy in a multi-category classification task. For qualitative response variables with more than two categories, many traditional accuracy measures such as sensitivity, specificity and area under the ROC curve are no longer applicable. In recent literature, new diagnostic accuracy measures are introduced in medical research studies. In this paper, important statistical concepts for multi-category classification accuracy are reviewed and their utilities are demonstrated with real medical examples. We offer problem-based R code to illustrate how to perform these statistical computations step by step. We expect such analysis tools will become more familiar to practitioners and receive broader applications in biostatistics. Our program can be adapted to many classifiers among which logistic regression may be the most popular approach. We thus base our discussion and illustration completely on the logistic regression in this paper.
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- 2017
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8. A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study
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Julius S. Ngwa, Howard J. Cabral, Debbie M. Cheng, Michael J. Pencina, David R. Gagnon, Michael P. LaValley, and L. Adrienne Cupples
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Time dependent covariate model (TDCM) ,Cross sectional pooling (CSP) ,Pooled logistic regression (PLR) ,Longitudinal and survival data ,Medicine (General) ,R5-920 - Abstract
Abstract Background Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. Methods In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. Results In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. Conclusions We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.
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- 2016
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9. Adaptive Discretization for Event PredicTion (ADEPT).
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Jimmy Hickey, Ricardo Henao, Daniel Wojdyla, Michael J. Pencina, and Matthew Engelhard
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- 2024
10. Translating ethical and quality principles for the effective, safe and fair development, deployment and use of artificial intelligence technologies in healthcare.
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Nicoleta J. Economou-Zavlanos, Sophia Bessias, Michael P. Cary, Armando Bedoya, Benjamin Goldstein 0001, John Eric Jelovsek, Cara O'Brien, Nancy Walden, Matthew Elmore, Amanda B. Parrish, Scott Elengold, Kay S. Lytle, Suresh Balu, Michael E. Lipkin, Afreen Idris Shariff, Michael Gao, David Leverenz, Ricardo Henao, David Y. Ming, David M. Gallagher, Michael J. Pencina, and Eric G. Poon
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- 2024
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11. An Obesity Dietary Quality Index Predicts Abdominal Obesity in Women: Potential Opportunity for New Prevention and Treatment Paradigms
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Dolores M. Wolongevicz, Lei Zhu, Michael J. Pencina, Ruth W. Kimokoti, P. K. Newby, Ralph B. D'Agostino, and Barbara E. Millen
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Internal medicine ,RC31-1245 - Abstract
Background. Links between dietary quality and abdominal obesity are poorly understood. Objective. To examine the association between an obesity-specific dietary quality index and abdominal obesity risk in women. Methods. Over 12 years, we followed 288 Framingham Offspring/Spouse Study women, aged 30–69 years, without metabolic syndrome risk factors, cardiovascular disease, cancer, or diabetes at baseline. An 11-nutrient obesity-specific dietary quality index was derived using mean ranks of nutrient intakes from 3-day dietary records. Abdominal obesity (waist circumference >88 cm) was assessed during follow-up. Results. Using multiple logistic regression, women with poorer dietary quality were more likely to develop abdominal obesity compared to those with higher dietary quality (OR 1.87; 95% CI, 1.01, 3.47; P for trend =.048) independent of age, physical activity, smoking, and menopausal status. Conclusions. An obesity-specific dietary quality index predicted abdominal obesity in women, suggesting targets for dietary quality assessment, intervention, and treatment to address abdominal adiposity.
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- 2010
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12. Calibration and Uncertainty in Neural Time-to-Event Modeling.
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Paidamoyo Chapfuwa, Chenyang Tao, Chunyuan Li, Irfan Khan, Karen Chandross, Michael J. Pencina, Lawrence Carin, and Ricardo Henao
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- 2023
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13. Trans-Balance: Reducing demographic disparity for prediction models in the presence of class imbalance.
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Chuan Hong, Molei Liu, Daniel Wojdyla, Jimmy Hickey, Michael J. Pencina, and Ricardo Henao
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- 2024
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14. An Outcome Model Approach to Translating a Randomized Controlled Trial Results to a Target Population
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Goldstein, Benjamin A., Phelan, Matthew, Pagidipati, Neha J., Holman, Rury R., and Stuart, Michael J. Pencina Elizabeth A
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Statistics - Applications ,Statistics - Machine Learning - Abstract
Participants enrolled into randomized controlled trials (RCTs) often do not reflect real-world populations. Previous research in how best to translate RCT results to target populations has focused on weighting RCT data to look like the target data. Simulation work, however, has suggested that an outcome model approach may be preferable. Here we describe such an approach using source data from the 2x2 factorial NAVIGATOR trial which evaluated the impact of valsartan and nateglinide on cardiovascular outcomes and new-onset diabetes in a pre-diabetic population. Our target data consisted of people with pre-diabetes serviced at our institution. We used Random Survival Forests to develop separate outcome models for each of the 4 treatments, estimating the 5-year risk difference for progression to diabetes and estimated the treatment effect in our local patient populations, as well as sub-populations, and the results compared to the traditional weighting approach. Our models suggested that the treatment effect for valsartan in our patient population was the same as in the trial, whereas for nateglinide treatment effect was stronger than observed in the original trial. Our effect estimates were more efficient than the weighting approach., Comment: 2 Tables, 3 Figures
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- 2018
15. A framework for the oversight and local deployment of safe and high-quality prediction models.
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Armando Bedoya, Nicoleta J. Economou-Zavlanos, Benjamin Alan Goldstein, Allison Young, John Eric Jelovsek, Cara O'Brien, Amanda B. Parrish, Scott Elengold, Kay Lytle, Suresh Balu, Erich Huang, Eric G. Poon, and Michael J. Pencina
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- 2022
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16. Observability and its impact on differential bias for clinical prediction models.
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Mengying Yan, Michael J. Pencina, L. Ebony Boulware, and Benjamin Alan Goldstein
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- 2022
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17. Improving Event Time Prediction by Learning to Partition the Event Time Space.
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Jimmy Hickey, Ricardo Henao, Daniel Wojdyla, Michael J. Pencina, and Matthew M. Engelhard
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- 2023
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18. Enabling counterfactual survival analysis with balanced representations.
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Paidamoyo Chapfuwa, Serge Assaad, Shuxi Zeng, Michael J. Pencina, Lawrence Carin, and Ricardo Henao
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- 2021
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19. Semi-supervised calibration of noisy event risk (SCANER) with electronic health records.
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Chuan Hong, Liang Liang, Qianyu Yuan, Kelly Cho, Katherine P. Liao, Michael J. Pencina, David C. Christiani, and Tianxi Cai
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- 2023
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20. Understanding Algorithmic Bias in Clinical Prediction Models.
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Mengying Yan, Michael J. Pencina, and Benjamin Alan Goldstein
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- 2021
21. An outcome model approach to transporting a randomized controlled trial results to a target population.
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Benjamin Alan Goldstein, Matthew Phelan, Neha J. Pagidipati, Rury R. Holman, Michael J. Pencina, and Elizabeth A. Stuart
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- 2019
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22. Informatics-Enabled Learning Health Systems: Strategies for Success from Four Academic Medical Centers.
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Eric G. Poon, Charles P. Friedman, Philip R. O. Payne, Michael J. Pencina, and Kevin B. Johnson
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- 2019
23. Survival Analysis meets Counterfactual Inference.
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Paidamoyo Chapfuwa, Serge Assaad, Shuxi Zeng, Michael J. Pencina, Lawrence Carin, and Ricardo Henao
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- 2020
24. Microsimulation model to predict incremental value of biomarkers added to prognostic models.
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Karol M. Pencina, Ralph B. D'Agostino, Ramachandran S. Vasan, and Michael J. Pencina
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- 2018
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25. Interplay of Atherogenic Particle Number and Particle Size and the Risk of Coronary Heart Disease
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Karol M Pencina, Michael J Pencina, Patrick R Lawler, James C Engert, Line Dufresne, Paul M Ridker, George Thanassoulis, Samia Mora, and Allan D Sniderman
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Biochemistry (medical) ,Clinical Biochemistry - Abstract
Background We examined the interplay of apolipoprotein B (apoB) and LDL particle size, approximated by the LDL-cholesterol (LDL-C)/apoB ratio, on the risk of new-onset coronary heart disease (CHD). Methods Participants without cardiovascular disease from the UK Biobank (UKB; n = 308 182), the Women’s Health Study (WHS; n = 26 204), and the Framingham Heart Study (FHS; n = 2839) were included. Multivariable Cox models were used to assess the relationship between apoB and LDL-C/apoB ratio and incidence of CHD (14 994 events). Our analyses were adjusted for age, sex (except WHS), HDL-cholesterol (HDL-C), systolic blood pressure, antihypertensive treatment, diabetes, and smoking. Results In all 3 studies, there was a strong positive correlation between apoB and LDL-C (correlation coefficients r = 0.80 or higher) and a weak inverse correlation of apoB with LDL-C/apoB ratio (−0.28 ≤ r ≤ −0.14). For all 3 cohorts, CHD risk was higher for higher levels of apoB. Upon multivariable adjustment, the association between apoB and new-onset CHD remained robust and statistically significant in all 3 cohorts with hazard ratios per 1 SD (95% CI): 1.24 (1.22–1.27), 1.33 (1.20–1.47), and 1.24 (1.09–1.42) for UKB, WHS, and FHS, respectively. However, the association between LDL-C/apoB and CHD was statistically significant only in the FHS cohort: 0.78 (0.64–0.94). Conclusions Our analysis confirms that apoB is a strong risk factor for CHD. However, given the null association in 2 of the 3 studies, we cannot confirm that cholesterol-depleted LDL particles are substantially more atherogenic than cholesterol-replete particles. These results lend further support to routine measurement of apoB in clinical care.
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- 2022
26. Predictive Utility of a Validated Polygenic Risk Score for Long-Term Risk of Coronary Heart Disease in Young and Middle-Aged Adults
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Sadiya S. Khan, Courtney Page, Daniel M. Wojdyla, Yosef Y. Schwartz, Philip Greenland, and Michael J. Pencina
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Young Adult ,Risk Factors ,Physiology (medical) ,Humans ,Coronary Disease ,Genetic Predisposition to Disease ,Middle Aged ,Cardiology and Cardiovascular Medicine ,Risk Assessment ,Proportional Hazards Models - Abstract
Background: Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies. Methods: Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20–39 years [median, 30 years] of age), early midlife (FOS, 40–59 years [median, 43] years of age), and late midlife (ARIC, 45–59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI). Results: Among 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08–3.27], 2.09 [95% CI, 1.83–2.40], and 2.11 [95% CI, 1.96–2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70–2.30], 1.64 [95% CI, 1.47–1.84], and 1.22 [95% CI, 1.15–1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70–0.78], 0.70 [95% CI, 0.67–0.72], and 0.72 [95% CI, 0.70–0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69–0.78], 0.66 [95% CI, 0.62–0.69], and 0.66 [95% CI, 0.64–0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001–0.05), 0.02 (95% CI, −0.002 to 0.037), and 0.002 (95% CI, −0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively. Conclusions: Despite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.
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- 2022
27. The Duke Health Data Science Internship Program: Integrating the Educational Mission into Real-World Research.
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Shelley A. Rusincovitch, Lisa Wruck, Ricardo Henao, Larisa Rodgers, Allison Dunning, Peter Merrill, Hillary Mulder, Robert Overton, Matthew Phelan, Erich Huang, Lawrence Carin, and Michael J. Pencina
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- 2018
28. Predicting mortality over different time horizons: which data elements are needed?
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Benjamin Alan Goldstein, Michael J. Pencina, Maria E. Montez-Rath, and Wolfgang C. Winkelmayer
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- 2017
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29. Opportunities and challenges in developing risk prediction models with electronic health records data: a systematic review.
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Benjamin Alan Goldstein, Ann Marie Navar, Michael J. Pencina, and John P. A. Ioannidis
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- 2017
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30. Assessing electronic health record phenotypes against gold-standard diagnostic criteria for diabetes mellitus.
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Susan E. Spratt, Katherine Pereira, Bradi B. Granger, Bryan C. Batch, Matthew Phelan, Michael J. Pencina, Marie Lynn Miranda, L. Ebony Boulware, Joseph E. Lucas, Charlotte L. Nelson, Benjamin Neely, Benjamin Alan Goldstein, Pamela Barth, Rachel L. Richesson, Isaretta L. Riley, Leonor Corsino, Eugenia R. McPeek Hinz, Shelley A. Rusincovitch, Jennifer Green, Anna Beth Barton, Carly Kelley, Kristen Hyland, Monica Tang, Amanda Elliott, Ewa Ruel, Alexander Clark, Melanie Mabrey, Kay Lyn Morrissey, Jyothi Rao, Beatrice Hong, Marjorie Pierre-Louis, Katherine Kelly, and Nicole E. Jelesoff
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- 2017
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31. Cardiovascular Disease Risk Assessment Using Traditional Risk Factors and Polygenic Risk Scores in the Million Veteran Program
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Jason L. Vassy, Daniel C. Posner, Yuk-Lam Ho, David R. Gagnon, Ashley Galloway, Vidisha Tanukonda, Serena C. Houghton, Ravi K. Madduri, Benjamin H. McMahon, Philip S. Tsao, Scott M. Damrauer, Christopher J. O’Donnell, Themistocles L. Assimes, Juan P. Casas, J. Michael Gaziano, Michael J. Pencina, Yan V. Sun, Kelly Cho, and Peter W.F. Wilson
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Cardiology and Cardiovascular Medicine - Abstract
ImportancePrimary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation.ObjectiveTo determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population.Design, Setting, and ParticipantsThis was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023.ExposuresPRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status.Main Outcomes and MeasuresIncident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events.ResultsA total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, −0.07% to 3.30%).Conclusions and RelevanceStudy results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.
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- 2023
32. An adverse lipoprotein phenotype—hypertriglyceridaemic hyperapolipoprotein B—and the long-term risk of type 2 diabetes: a prospective, longitudinal, observational cohort study
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Karol M, Pencina, Michael J, Pencina, Line, Dufresne, Michael, Holmes, George, Thanassoulis, and Allan D, Sniderman
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Blood Glucose ,Health (social science) ,Lipoproteins ,Cholesterol, HDL ,Cholesterol, LDL ,Cohort Studies ,Psychiatry and Mental health ,Phenotype ,Diabetes Mellitus, Type 2 ,Humans ,Prospective Studies ,Geriatrics and Gerontology ,Family Practice ,Triglycerides ,Apolipoproteins B - Abstract
This study examines the risk of new-onset diabetes in patients with hypertriglyceridaemic hyperapolipoprotein B (high triglycerides, high apolipoprotein B [apoB], low LDL cholesterol to apoB ratio, and low HDL cholesterol). The aim was to establish whether this lipoprotein phenotype identified a substantial group at high risk of developing diabetes over the next 20 years.In this prospective, longitudinal, observational cohort study, we used data from the Framingham Offspring cohort (recruited in Framingham, MA, USA). Participants were aged 40-69 years and free of diabetes and cardiovascular disease at a baseline examination done between April, 1987, and November, 1991, and were followed up until March, 2014. Cox proportional hazards regression with hierarchical adjustment for age and sex, waist circumference, and fasting blood glucose were used to model the relationship between each lipid marker and incident diabetes, as well as the relationship between hypertriglyceridaemic hyperapoB (defined as values greater than sample medians of triglycerides and apoB, and less than medians of HDL cholesterol and LDL cholesterol to apoB ratio) and incident diabetes.Of 3446 individuals aged 40-69 years who completed baseline examination, 2515 participants were eligible and included in all analyses. During median 21·1 years (IQR 11·1-23·1) of follow-up, 402 (16·0%) individuals developed diabetes. Age (p=0·032), waist circumference (p0·0001), fasting blood glucose (p0·0001), and natural logarithm-transformed triglycerides (p0·0001) were associated with new-onset diabetes, as were apoB (p=0·0016), LDL cholesterol to apoB ratio (p=0·0018), and HDL cholesterol (p=0·0016) when added to this model. The age and sex-adjusted incidence of diabetes in the hypertriglyceridaemic hyperapoB group was 32·4% (95% CI 27·8-37·7) versus 5·5% (3·5-8·6) in the optimal lipid phenotype group and 15·5% (13·5-17·7) in the mixed lipid phenotype group. The fully adjusted hazard ratio, including glucose and waist circumference, for individuals with hypertriglyceridaemic hyperapoB was 3·30 (95% CI 2·06-5·30; p=0·0008) and for mixed lipid phenotype was 2·17 (1·38-3·40; p0·0001) compared with those with the optimal lipid phenotype.Our findings suggest that individuals with hypertriglyceridaemic hyperapoB are at high risk of new-onset diabetes and might benefit from intensive measures to prevent diabetes. The association between this phenotype and incident diabetes is consistent with a pro-diabetic effect due to increased clearance of apoB particles from plasma, which could injure pancreatic islet cells. This mechanism might explain the increased risk of diabetes with statin therapy.Doggone Foundation.
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- 2022
33. Needles in a Haystack: Finding Qualitative and Quantitative Collaborators in Academic Medical Centers
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Gina-Maria Pomann, Tracy Truong, Mary Boulos, L. Ebony Boulware, Rebecca N. Brouwer, Lesley H. Curtis, Kristopher Kapphahn, Shokoufeh Khalatbari, Julie McKeel, Shari Messinger, Ruth O’Hara, Michael J. Pencina, Greg P. Samsa, Cathie Spino, Lexie Zidanyue Yang, and Manisha Desai
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General Medicine ,Education - Published
- 2023
34. Developing a framework for a comprehensive data sharing program.
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Asba Tasneem, Karen Chiswell, Brian J. McCourt, Matt Gross, Eric D. Peterson, and Michael J. Pencina
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- 2017
35. Managing Atherosclerotic Cardiovascular Risk in Young Adults
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Neil J. Stone, Sidney C. Smith, Carl E. Orringer, Nancy A. Rigotti, Ann Marie Navar, Sadiya S. Khan, Daniel W. Jones, Ronald Goldberg, Samia Mora, Michael Blaha, Michael J. Pencina, and Scott M. Grundy
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Cardiology and Cardiovascular Medicine - Published
- 2022
36. Cardiovascular Disease Risk Prediction in Young Adults-The Next Frontier
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Sadiya Sana Khan and Michael J. Pencina
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Cardiology and Cardiovascular Medicine - Published
- 2022
37. A Systematic Review of Using Electronic Heath Records to Predict Clinical Events: Assessment of Opportunities and Challenges.
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Benjamin Alan Goldstein, Ann Marie Navar, Michael J. Pencina, and John P. A. Ioannidis
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- 2016
38. Clinical reasoning and prevention of cardiovascular disease
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Sniderman D. Allan, Michael J. Pencina, and George Thanassoulis
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medicine.medical_specialty ,Nutrition and Dietetics ,Statin ,business.industry ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical reasoning ,Disease ,030204 cardiovascular system & hematology ,law.invention ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Epidemiology ,Internal Medicine ,Medicine ,Observational study ,030212 general & internal medicine ,Metric (unit) ,Cardiology and Cardiovascular Medicine ,business ,Intensive care medicine - Abstract
All the major lipid prevention guidelines agree that the 10-year risk of a cardiovascular event should be the primary method to select individuals for statin prevention of a cardiovascular event. They also all rely on LDL cholesterol (LDL-C) as the primary metric to monitor lipid lowering therapy. These two principles form the major instruments on which primary prevention of cardiovascular disease is based worldwide. Their application is based on decades of prospective observational studies and large numbers of randomized clinical trials. Their development and application are milestones in medical progress. But are there limits, which were unseen and unintended, that need to be identified and overcome so that cardiovascular prevention can improve? Based on new insights and old knowledge, this Viewpoint will apply Clinical Reasoning, the process by which we integrate all the relevant knowledge, including the knowledge we have gained from physiology, pathology, epidemiology, metabolism, experimental models of disease, and our clinical experience as well as the results of randomized clinical trials to the analysis of a single case to answer these questions. Moreover, this Viewpoint will challenge the universal practice of relating the clinical outcomes of the major successful lipid lowering trials to the decrease in LDL-C and argue that cardiovascular prevention should move from the Risk model to the Causal Benefit model. This Viewpoint will be framed around a single case because, as caregivers, we make decisions case by case and because, as caregivers, the individual is the true object of our concern.
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- 2021
39. Clinical Trials in the 21st Century — Promising Avenues for Better Studies
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Michael J. Pencina and B. Taylor Thompson
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- 2022
40. An aetiology‐based subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) trial
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Maciej Banach, Renata Główczyńska, Piotr Orzechowski, Michael J. Pencina, Sławomir Pluta, Ryszard Piotrowicz, Dominika Szalewska, Ilona Kowalik, Robert Irzmański, Ewa Piotrowicz, Wojciech Zareba, Grzegorz Opolski, and Zbigniew Kalarus
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lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Randomization ,Walk Test ,030204 cardiovascular system & hematology ,Exercise training ,03 medical and health sciences ,0302 clinical medicine ,Original Research Articles ,Internal medicine ,Telerehabilitation ,Statistical significance ,Cox proportional hazards regression ,medicine ,Humans ,Original Research Article ,030212 general & internal medicine ,Hybrid rehabilitation ,Heart Failure ,business.industry ,Hazard ratio ,medicine.disease ,Confidence interval ,Remote monitoring ,lcsh:RC666-701 ,Heart failure ,Exercise Test ,Quality of Life ,Etiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims The aim of our study was to analyse the benefits of a 9 week hybrid comprehensive telerehabilitation (HCTR) programme in heart failure (HF) patients according to aetiology, as a subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH‐HF) trial. Methods and results Overall, 555 (65.3%) patients with ischaemic (IS) and 295 (34.7%) patients with non‐ischaemic (NIS) HF aetiology were randomized. There were no differences between the effect of HCTR and usual care (UC) on the primary outcome of number of days alive and out of the hospital in 26 months from the time of randomization in either aetiology (Wilcoxon–Mann–Whitney test), and no heterogeneity of effect between the aetiologies was noted (van Elteren test, P = 0.746). In Cox proportional hazards regression analysis, treatment was not independently associated with the secondary outcomes. For all‐cause mortality, the adjusted hazard ratio for HCTR vs. UC was 0.90 (95% confidence interval, 0.54–1.51) in IS and 1.42 (95% confidence interval, 0.69–2.94) in NIS (P interaction = 0.316). Differences between HCTR and UC in terms of change in the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks reached statistical significance in the IS arm (P = 0.015 and P
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- 2021
41. Comparison of Operating Characteristics of Commonly Used Sample Size Re-Estimation Procedures in a Two-Stage Design.
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Sandeep Menon, Joseph Massaro, Michael J. Pencina, Jerry Lewis, and Yong Cheng Wang
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- 2013
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42. The Dose–Response Relationship Between Physical Activity and Cardiometabolic Health in Adolescents
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Eliana M. Perrin, Sarah C. Armstrong, Asheley Cockrell Skinner, Hillary Mulder, Eric D. Peterson, Taruni S. Santanam, Heather R. Frank, Michael J. Pencina, Karishma Sriram, and Charlene A. Wong
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Adult ,Male ,Percentile ,medicine.medical_specialty ,Adolescent ,National Health and Nutrition Examination Survey ,Epidemiology ,Physical activity ,Blood Pressure ,Article ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Total cholesterol ,medicine ,Humans ,030212 general & internal medicine ,Exercise ,business.industry ,Public Health, Environmental and Occupational Health ,Cardiorespiratory fitness ,Nutrition Surveys ,Dose–response relationship ,Cross-Sectional Studies ,Blood pressure ,Cardiorespiratory Fitness ,Cardiovascular Diseases ,Physical therapy ,Female ,business - Abstract
Introduction This study examines the dose–response relationship between moderate-to-vigorous physical activity and cardiometabolic measures in adolescents. Methods Cross-sectional spline analyses were performed using 2003–2016 National Health and Nutrition Examination Survey data among adolescents (aged 12–19 years, N=9,195) on objectively measured (2003–2006) and self-reported (2007–2016) weekly mean minutes of moderate-to-vigorous physical activity and cardiometabolic measures (systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein, BMI, and cardiorespiratory fitness). Inflection points were determined for nonlinear relationships. Results For objective moderate-to-vigorous physical activity, female adolescents had significant nonlinear associations with inflection points at 90 minutes/week for BMI percentile and systolic blood pressure. Male adolescents had inflection points at 150 weekly minutes of objective activity for BMI percentile and cardiorespiratory fitness. BMI percentile was about 7% lower for female and male adolescents at 150 weekly minutes of objectively measured moderate-to-vigorous physical activity than at 0 minutes. For self-reported moderate-to-vigorous physical activity, inflection points were at 375 minutes/week (diastolic blood pressure for female adolescents) and 500 minutes/week (systolic blood pressure for male adolescents). Conclusions Among several significant dose–response relationships between physical activity and cardiometabolic health in adolescents, consistent and often nonlinear relationships were identified for BMI, with inflection points at 90–150 minutes of objective moderate-to-vigorous physical activity. Notable differences in associations and linearity were identified by sex and physical activity measure (objective or self-reported). These results support calls for any increase in physical activity among adolescents and suggest that recommendations closer to the adult guidelines of 150 weekly minutes of physical activity may be health promoting and more attainable for youth than the current recommendation of 420 weekly minutes.
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- 2021
43. Prognostic Impact of Hybrid Comprehensive Telerehabilitation Regarding Diastolic Dysfunction in Patients with Heart Failure with Reduced Ejection Fraction-Subanalysis of the TELEREH-HF Randomized Clinical Trial
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Robert Irzmański, Renata Glowczynska, Maciej Banach, Dominika Szalewska, Ryszard Piotrowicz, Ilona Kowalik, Michael J. Pencina, Wojciech Zareba, Piotr Orzechowski, Slawomir Pluta, Zbigniew Kalarus, Grzegorz Opolski, and Ewa Piotrowicz
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hybrid telerehabilitation ,heart failure with reduced ejection fraction ,diastolic function ,General Medicine - Abstract
Aims: The objective of the study was to evaluate the effects of individually prescribed hybrid comprehensive telerehabilitation (HCTR) implemented at patients’ homes on left ventricular (LV) diastolic function in heart failure (HF) patients. Methods and results: The Telerehabilitation in Heart Failure Patients trial (TELEREH-HF) is a multicenter, prospective, randomized (1:1), open-label, parallel-group, controlled trial involving HF patients assigned either to HCTR involving a remotely monitored home training program in conjunction with usual care (HCTR group) or usual care only (UC group). The patient in the HCTR group underwent a 9-week HCTR program consisting of two stages: an initial stage (1 week) conducted in hospital and the subsequent stage (eight weeks) of home-based HCTR five times weekly. Due to difficulties of proper assessment and differences in the evaluation of diastolic function in patients with atrial fibrillation, we included in our subanalysis only patients with sinus rhythm. Depending on the grade of diastolic dysfunction, patients were assigned to subgroups with mild diastolic (MDD) or severe diastolic dysfunction (SDD), both in HCTR (HCTR-MDD and HCTR-SDD) and UC groups (UC-MDD and UC-SDD). Changes from baseline to 9 weeks in echocardiographic parameters were seen only in A velocities in HCTR-MDD vs. UC-MDD; no significant shifts between groups of different diastolic dysfunction grades were observed after HCTR. All-cause mortality was higher in UC-SDD vs. UC-MDD with no difference between HCTR-SDD and HCTR-MDD. Higher probability of HF hospitalization was observed in HCTR-SDD than HCTR-MDD and in UC-SDD than UC-MDD. No differences in the probability of cardiovascular mortality and hospitalization were found. Conclusions: HCTR did not influence diastolic function in HF patients in a significant manner. The grade of diastolic dysfunction had an impact on mortality only in the UC group and HF hospitalization over a 12–24-month follow-up in HCTR and UC groups.
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- 2022
44. The Expected 30-Year Benefits of Early Versus Delayed Primary Prevention of Cardiovascular Disease by Lipid Lowering
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Michael J. Pencina, George Thanassoulis, Alberico L. Catapano, Karol M. Pencina, Donald M. Lloyd-Jones, and Allan D. Sniderman
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Adult ,Male ,medicine.medical_specialty ,Atherosclerotic cardiovascular disease ,business.industry ,Cholesterol, HDL ,Models, Cardiovascular ,Disease ,Middle Aged ,Atherosclerosis ,Time optimal ,Primary Prevention ,Physiology (medical) ,Primary prevention ,medicine ,Humans ,Female ,Lipid lowering ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Prevention control ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Abstract
Background: Lipid-lowering recommendations for prevention of atherosclerotic cardiovascular disease rely principally on estimated 10-year risk. We sought to determine the optimal time for initiation of lipid lowering in younger adults as a function of expected 30-year benefit. Methods: Data from 3148 National Health and Nutrition Examination Survey (2009–2016) participants, age 30 to 59 years, not eligible for lipid-lowering treatment recommendation under the most recent US guidelines, were analyzed. We estimated the absolute and relative impact of lipid lowering as a function of age, age at initiation, and non–high-density lipoprotein cholesterol (HDL-C) level on the expected rates of atherosclerotic cardiovascular disease over the succeeding 30 years. We modeled expected risk reductions based on shorter-term effects observed in statin trials (model A) and longer-term benefits based on Mendelian randomization studies (model B). Results: In both models, potential reductions in predicted 30-year atherosclerotic cardiovascular disease risk were greater with older age and higher non–HDL-C level. Immediate initiation of lipid lowering (ie, treatment for 30 years) in 40- to 49-year-old patients with non–HDL-C ≥160 mg/dL would be expected to reduce their average predicted 30-year risk of 17.1% to 11.6% (model A; absolute risk reduction [ARR], 5.5%) or 6.5% (model B; ARR 10.6%). Delaying lipid lowering by 10 years (treatment for 20 years) would result in residual 30-year risk of 12.7% (A; ARR 4.4) or 9.9% (B; ARR 7.2%) and delaying by 20 years (treatment for 10 years) would lead to expected mean residual risk of 14.6% (A; ARR 2.6%) or 13.9% (B; ARR 3.2%). The slope of the achieved ARR as a function of delay in treatment was also higher with older age and higher non–HDL-C level. Conclusions: Substantial reduction in expected atherosclerotic cardiovascular disease risk in the next 30 years is achievable by intensive lipid lowering in individuals in their 40s and 50s with non–HDL-C ≥160 mg/dL. For many, the question of when to start lipid lowering might be more relevant than whether to start lipid lowering.
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- 2020
45. The Dose–Response Relationship Between Physical Activity and Cardiometabolic Health in Young Adults
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Asheley Cockrell Skinner, Eliana M. Perrin, Michael J. Pencina, Sarah C. Armstrong, Charlene A. Wong, Eric D. Peterson, Taruni S. Santanam, Heather R. Frank, Hillary Mulder, and Karishma Sriram
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education.field_of_study ,medicine.medical_specialty ,National Health and Nutrition Examination Survey ,business.industry ,Public health ,Population ,Public Health, Environmental and Occupational Health ,Physical activity level ,03 medical and health sciences ,Psychiatry and Mental health ,Dose–response relationship ,0302 clinical medicine ,Blood pressure ,030225 pediatrics ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,030212 general & internal medicine ,Young adult ,education ,business ,Body mass index - Abstract
Purpose Guidelines recommend 150 minutes of weekly moderate-to-vigorous physical activity (MVPA) for all adults, although physical activity level correlation with cardiometabolic health is not well characterized for young adults. We determined the dose–response relationship of MVPA on measures of cardiometabolic health in young adults. Methods We examined young adults (aged 20–29 years; N = 5,395, 47.9% female) in the 2003–2016 National Health and Nutrition Examination Survey. Exposures were objective (accelerometer based) and self-reported weekly mean minutes of MVPA. Cardiometabolic outcome measures were body mass index (BMI), high-density lipoprotein (HDL), total cholesterol, systolic blood pressure, and diastolic blood pressure. The dose–response relationships were assessed with unadjusted spline analyses. Sex-stratified outcomes were modeled using multivariable linear regression with mean estimated change presented for 150-minute dose increases of MVPA. Results Among females, associations between objective activity and cardiometabolic measures were all linear. Compared with no activity, 150 minutes of objective activity was associated with a lower BMI (−1.37 kg/m2) and total cholesterol (−4.89 mg/dL), whereas 150 minutes of self-reported activity was associated with a higher HDL (1 mg/dL) and lower diastolic blood pressure (−.42 mm Hg). Among males, an inflection point was identified in the dose–response curves for objective activity with BMI around 100 minutes. Compared with no activity, 150 self-reported minutes was associated with lower BMI (−.26 kg/m2), higher HDL (.52 mg/dL), and lower total cholesterol (−1.35 mg/dL). Conclusions The dose–response relationships between physical activity and cardiometabolic markers in young adults were predominantly linear, supporting public health calls for any increase in physical activity in this population.
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- 2020
46. The Project Baseline Health Study: a step towards a broader mission to map human health
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Pamela S. Douglas, Terry Schaack, Francois Haddad, Bray Patrick-Lake, Shannon J. McCall, Laura M. Beskow, Themistocles L. Assimes, Suresh Balu, Kristine Arges, Paul Campbell, Susie Spielman, Dominik Fleischmann, Svati H. Shah, Ezra Pak-Harvey, Rebecca McCue, John Hernandez, Ashley A. Dunham, Elizabeth S. Fraulo, Sanjiv S. Gambhir, Millie Das, Vikram S. Bajaj, George W. Sledge, Erich Huang, Martin J. Willemink, Rajan Munshi, Rosalia Blanco, Adrian F. Hernandez, Kenneth W. Mahaffey, Curtis P. Langlotz, William J. Marks, Marie Dockery, Daniel King, Ryan Spitler, Victoria Christian, Yaping Joyce Liao, Robert C. Green, Lawrence H. Muhlbaier, Geeta K. Swamy, Steven Shipes, John K. French, Scarlet Shore, Kelly Marcom, Geoffrey S. Ginsburg, L. Kristin Newby, Reid McCabe, Lynne Hurwitz Koweek, Robert M. Califf, Jessica L. Mega, Charlene A. Wong, David J. Maron, David P. Miller, Michael J. Pencina, Mustafa R. Bashir, Eric D. Peterson, Emily Ford, Fatima Rodriguez, Glenn J. Jaffe, Lawrence Carin, Julie Eckstrand, and Scott W. Cousins
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Population ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Medicine (miscellaneous) ,Health Informatics ,Review Article ,030204 cardiovascular system & hematology ,computer.software_genre ,lcsh:Computer applications to medicine. Medical informatics ,03 medical and health sciences ,Human health ,0302 clinical medicine ,Health Information Management ,Diagnosis ,030212 general & internal medicine ,Longitudinal cohort ,education ,Baseline (configuration management) ,Cancer ,Medical education ,education.field_of_study ,Computer Science Applications ,Data sharing ,Cardiovascular diseases ,Social system ,Cohort ,lcsh:R858-859.7 ,Data integration ,Psychology ,computer ,Biomarkers - Abstract
The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.
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- 2020
47. Prediction Models — Development, Evaluation, and Clinical Application
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Michael J. Pencina, Benjamin A. Goldstein, and Ralph B. D'Agostino
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Models, Statistical ,business.industry ,MEDLINE ,Datasets as Topic ,General Medicine ,Models, Theoretical ,030204 cardiovascular system & hematology ,Machine learning ,computer.software_genre ,Risk Assessment ,Decision Support Techniques ,Machine Learning ,03 medical and health sciences ,0302 clinical medicine ,Development (topology) ,Humans ,Medicine ,Model development ,030212 general & internal medicine ,Artificial intelligence ,business ,computer ,Predictive modelling - Abstract
Prediction Models Prediction models’ newfound importance and the emergence of model development based on machine learning raise questions about how to ensure their safety and efficacy, given their ...
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- 2020
48. Predictive Accuracy of Stroke Risk Prediction Models Across Black and White Race, Sex, and Age Groups
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Chuan Hong, Michael J. Pencina, Daniel M. Wojdyla, Jennifer L. Hall, Suzanne E. Judd, Michael Cary, Matthew M. Engelhard, Samuel Berchuck, Ying Xian, Ralph D’Agostino, George Howard, Brett Kissela, and Ricardo Henao
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General Medicine - Abstract
ImportanceStroke is the fifth-highest cause of death in the US and a leading cause of serious long-term disability with particularly high risk in Black individuals. Quality risk prediction algorithms, free of bias, are key for comprehensive prevention strategies.ObjectiveTo compare the performance of stroke-specific algorithms with pooled cohort equations developed for atherosclerotic cardiovascular disease for the prediction of new-onset stroke across different subgroups (race, sex, and age) and to determine the added value of novel machine learning techniques.Design, Setting, and ParticipantsRetrospective cohort study on combined and harmonized data from Black and White participants of the Framingham Offspring, Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study for Atherosclerosis (MESA), and Reasons for Geographical and Racial Differences in Stroke (REGARDS) studies (1983-2019) conducted in the US. The 62 482 participants included at baseline were at least 45 years of age and free of stroke or transient ischemic attack.ExposuresPublished stroke-specific algorithms from Framingham and REGARDS (based on self-reported risk factors) as well as pooled cohort equations for atherosclerotic cardiovascular disease plus 2 newly developed machine learning algorithms.Main Outcomes and MeasuresModels were designed to estimate the 10-year risk of new-onset stroke (ischemic or hemorrhagic). Discrimination concordance index (C index) and calibration ratios of expected vs observed event rates were assessed at 10 years. Analyses were conducted by race, sex, and age groups.ResultsThe combined study sample included 62 482 participants (median age, 61 years, 54% women, and 29% Black individuals). Discrimination C indexes were not significantly different for the 2 stroke-specific models (Framingham stroke, 0.72; 95% CI, 0.72-073; REGARDS self-report, 0.73; 95% CI, 0.72-0.74) vs the pooled cohort equations (0.72; 95% CI, 0.71-0.73): differences 0.01 or less (P values >.05) in the combined sample. Significant differences in discrimination were observed by race: the C indexes were 0.76 for all 3 models in White vs 0.69 in Black women (all P values P values ≤.001). When stratified by age, model discrimination was better for younger (Conclusions and RelevanceIn this analysis of Black and White individuals without stroke or transient ischemic attack among 4 US cohorts, existing stroke–specific risk prediction models and novel machine learning techniques did not significantly improve discriminative accuracy for new-onset stroke compared with the pooled cohort equations, and the REGARDS self-report model had the best calibration. All algorithms exhibited worse discrimination in Black individuals than in White individuals, indicating the need to expand the pool of risk factors and improve modeling techniques to address observed racial disparities and improve model performance.
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- 2023
49. Claims-based cardiovascular outcome identification for clinical research: Results from 7 large randomized cardiovascular clinical trials
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Joseph S. Ross, John H. Alexander, Sunil V. Rao, Danica Marinac-Dabic, Renato D. Lopes, Daniel A. Canos, Manesh R. Patel, Benjamin C. Eloff, Michael J. Pencina, Sean M. O'Brien, Eric D. Peterson, Yuliya Lokhnygina, J. Matthew Brennan, Tracy Y. Wang, L. Kristin Newby, Lisa M. Wruck, Christopher B. Granger, Mitchell W. Krucoff, Robert M. Califf, Lesley H. Curtis, Kenneth W. Mahaffey, Robert M. Clare, Matthew T. Roe, and Sharon-Lise T. Normand
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Male ,medicine.medical_specialty ,Biomedical Research ,Evaluation system ,Databases, Factual ,medicine.medical_treatment ,Concordance ,Myocardial Infarction ,MEDLINE ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Medicare ,Revascularization ,Insurance Claim Review ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Myocardial Revascularization ,medicine ,Humans ,Multicenter Studies as Topic ,030212 general & internal medicine ,Myocardial infarction ,Coronary Artery Bypass ,Aged ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Inpatients ,business.industry ,Fee-for-Service Plans ,Retrospective cohort study ,medicine.disease ,United States ,Data Accuracy ,Stroke ,Clinical trial ,Clinical research ,Cardiovascular Diseases ,Female ,Medical Record Linkage ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Medicare insurance claims may provide an efficient means to ascertain follow-up of older participants in clinical research. We sought to determine the accuracy and completeness of claims- versus site-based follow-up with clinical event committee (+CEC) adjudication of cardiovascular outcomes. Methods We performed a retrospective study using linked Medicare and Duke Database of Clinical Trials data. Medicare claims were linked to clinical data from 7 randomized cardiovascular clinical trials. Of 52,476 trial participants, linking resulted in 5,839 (of 10,497 linkage-eligible) Medicare-linked trial participants with fee-for-service A and B coverage. Death, myocardial infarction (MI), stroke, and revascularization incidences were compared using Medicare inpatient claims only, site-reported events (+CEC) only, or a combination of the 2. Randomized treatment effects were compared as a function of whether claims-based, site-based (+CEC), or a combined system was used for event detection. Results Among the 5,839 study participants, the annual event rates were similar between claims- and site-based (+CEC) follow-up: death (overall rate 5.2% vs 5.2%; adjusted κ 0.99), MI (2.2% vs 2.3%; adjusted κ 0.96), stroke (0.7% vs 0.7%; adjusted κ 0.99), and any revascularization (7.4% vs 7.9%; adjusted κ 0.95). Of events detected by claims yet not reported by CEC, a minority were reported by sites but negatively adjudicated by CEC (39% of MIs and 18% of strokes). Differences in individual case concordance led to higher event rates when claims- and site-based (+CEC) systems were combined. Randomized treatment effects were similar among the 3 approaches for each outcome of interest. Conclusions Claims- versus site-based (+CEC) follow-up identified similar overall cardiovascular event rates despite meaningful differences in the events detected. Randomized treatment effects were similar using the 2 methods, suggesting claims data could be used to support clinical research leveraging routinely collected data. This approach may lead to more effective evidence generation, synthesis, and appraisal of medical products and inform the strategic approaches toward the National Evaluation System for Health Technology.
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- 2019
50. Cardiovascular risk factor profiles in familial hypercholesterolemia patients with and without genetic mutation compared to a nationally representative sample of adults in a high-risk European country
- Author
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Magdalena Chmara, Marcin Pajkowski, Michael J. Pencina, Rafał Gałąska, Krzysztof Chlebus, Marzena Romanowska Kocejko, Tomasz Zdrojewski, and Marcin Gruchała
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Adult ,Male ,medicine.medical_specialty ,Cross-sectional study ,Population ,Familial hypercholesterolemia ,030204 cardiovascular system & hematology ,Body Mass Index ,Cohort Studies ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,Prevalence ,medicine ,Humans ,Genetic Testing ,030212 general & internal medicine ,Risk factor ,education ,Triglycerides ,Aged ,education.field_of_study ,business.industry ,Cholesterol, HDL ,Smoking ,Blood Pressure Determination ,Cholesterol, LDL ,Middle Aged ,Atherosclerosis ,medicine.disease ,Cross-Sectional Studies ,Mutation ,Cohort ,Female ,Poland ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Cohort study - Abstract
Background There is a paucity of data on the distribution of cardiovascular risk factors in patients with familial hypercholesterolemia (FH) as compared to the general population. The aim of the study was to compare cardiovascular risk factors in a cohort of FH patients to the representative sample of adults in Poland who represent a high–cardiovascular risk European region. Methods We compared the distribution of risk factors in 1,382 individuals with FH phenotype referred for genetic testing between 2006 and 2014 to the National Centre of Familial Hypercholesterolemia in Gdansk, Poland. The cohort was comprised of 637 positive FH(+) and 745 negative FH(−) patients who were compared to a nationally representative sample of 2,413 adults age 18-79, standardized by age and sex, from the NATPOL 2011 study (NATPOL). We analyzed patients' distribution of history of atherosclerotic cardiovascular disease (ASCVD) and standard risk factors including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure (SBP, DBP), body mass index, smoking, and diabetes. Results FH(+) patients (mean age 45.6 years) had the highest LDL-C of 241.7 mg/dL (95% CI 234.8-248.5) compared to 206.1 mg/dL (200.5-211.7) in FH(−) patients (mean age 48.2) and 126.2 mg/dL (124.8-127.6) in NATPOL. Mean SBP was the lowest in FH(+) patients at 128.7 mm Hg (126.7-130.7) compared to 133.4 mm Hg (132.6-134.3) in NATPOL and 134.4 mm Hg (132.3-136.5) in FH(−). No differences were found in the prevalence of diabetes and body mass index. Smoking was less common in FH(+) at 12.4% (9.4-15.4) compared to both FH(−) and NATPOL: 20.4% (16.6-24.1) and 28.4% (26.6-30.2), respectively. The prevalence of individuals with a history of ASCVD in both FH(+) and FH(−) was nearly 3-fold higher compared to NATPOL: 26% (21.8-30.1) and 26.6% (22.2-30.9) versus 9.5% (8.3-10.7), respectively. Conclusions The FH(+) patients had significantly higher mean LDL-C, but the levels of nonlipid factors were lower or similar compared to the other groups. Both FH(+) and FH(−) were characterized by a heavy burden of ASCVD. This suggests that cholesterol, and no other risk factors, is a key contributor to cardiovascular risk in patients with FH, especially those with genetic mutation.
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- 2019
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