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2. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author

Schillemans, T., Tragante, V., Maitusong, B., Gigante, B., Cresci, S., Laguzzi, F., Vikstrom, M., Richards, M., Pilbrow, A., Cameron, V., Foco, L., Doughty, R.N., Kuukasjarvi, P., Allayee, H., Hartiala, J.A., Tang, W.H.W., Lyytikainen, L.P., Nikus, K., Laurikka, J.O., Srinivasan, S., Mordi, I.R., Trompet, S., Kraaijeveld, A., Setten, J. van, Gijsberts, C.M., Maitland-van der Zee, A.H., Saely, C.H., Gong, Y., Johnson, J.A., Cooper-DeHoff, R.M., Pepine, C.J., Casu, G., Leiherer, A., Drexel, H., Horne, B.D., Laan, S.W. van der, Marziliano, N., Hazen, S.L., Sinisalo, J., Kahonen, M., Lehtimaki, T., Lang, C.C., Burkhardt, R., Scholz, M., Jukema, J.W., Eriksson, N., Akerblom, A., James, S., Held, C., Hagstrom, E., Spertus, J.A., Algra, A., Faire, U. de, Akesson, A., Asselbergs, F.W., Patel, R.S., Leander, K., HUS Heart and Lung Center, Department of Medicine, Clinicum, University of Helsinki, Pulmonology, Paediatric Pulmonology, APH - Personalized Medicine, ACS - Heart failure & arrhythmias, Tampere University, Department of Clinical Chemistry, Clinical Medicine, and TAYS Heart Centre

Subjects
RISK, ARCHITECTURE, Kardiologi, HYPERTENSION, PGC-1-ALPHA, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], VARIANT, 1184 Genetics, developmental biology, physiology, meta-analysis, PGC-1, cohort studies, PGC1-ALPHA, PPARGC1A, GLY482SER POLYMORPHISM, ARTERY-DISEASE, Cardiac and Cardiovascular Systems, 3111 Biomedicine, PPAR-GAMMA, coronary heart disease, polymorphisms, SNPs
Abstract

Contains fulltext : 283506.pdf (Publisher’s version ) (Open Access) Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Published
2022

4. Factors Associated with Change in Health-Related Quality of Life from Before to 24 Months After Surgery

Author

Grady, K.L., primary, Kao, A., additional, Spertus, J.A., additional, Hsich, E., additional, Dew, M., additional, Pham, D., additional, Hartupee, J., additional, Petty, M., additional, Cotts, W., additional, Pamboukian, S.V., additional, Pagani, F.D., additional, Lampert, B., additional, Johnson, M., additional, Murray, M., additional, Takeda, K., additional, Yuzefpolskaya, M., additional, Silvestry, S., additional, Kirklin, J.K., additional, Elenbaas, C., additional, Andrei, A., additional, Baldridge, A.S., additional, Warzecha, A., additional, and Yancy, C., additional

Published
2022
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6. Redevelopment and validation of the SYNTAX score II to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease: secondary analysis of the multicentre randomised controlled SYNTAXES trial with external cohort validation

Author

Takahashi, K., Serruys, P.W., Fuster, V., Farkouh, M.E., Spertus, J.A., Cohen, D.J., Park, S.J., Park, D.W., Ahn, J.M., Kappetein, A.P., Head, S.J., Thuijs, D.J.F.M., Onuma, Y., Kent, D.M., Steyerberg, E.W., Klaveren, D. van, SYNTAXES Trial Investigator, FREEDOM Trial Investigator, BEST Trial Investigator, PRECOMBAT Trial Investigator, Graduate School, ACS - Heart failure & arrhythmias, Cardiothoracic Surgery, and Public Health

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, medicine.medical_treatment, Population, Absolute risk reduction, Percutaneous coronary intervention, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, law.invention, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Conventional PCI, medicine, 030212 general & internal medicine, Myocardial infarction, Outcomes research, business, education
Abstract

Summary Background Randomised controlled trials are considered the gold standard for testing the efficacy of novel therapeutic interventions, and typically report the average treatment effect as a summary result. As the result of treatment can vary between patients, basing treatment decisions for individual patients on the overall average treatment effect could be suboptimal. We aimed to develop an individualised decision making tool to select an optimal revascularisation strategy in patients with complex coronary artery disease. Methods The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries between March, 2005, and April, 2007. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to either the percutaneous coronary intervention (PCI) group or coronary artery bypass grafting (CABG) group. The SYNTAXES study ascertained 10-year all-cause deaths. We used Cox regression to develop a clinical prognostic index for predicting death over a 10-year period, which was combined, in a second stage, with assigned treatment (PCI or CABG) and two prespecified effect-modifiers, which were selected on the basis of previous evidence: disease type (three-vessel disease or left main coronary artery disease) and anatomical SYNTAX score. We used similar techniques to develop a model to predict the 5-year risk of major adverse cardiovascular events (defined as a composite of all-cause death, non-fatal stroke, or non-fatal myocardial infarction) in patients receiving PCI or CABG. We then assessed the ability of these models to predict the risk of death or a major adverse cardiovascular event, and their differences (ie, the estimated benefit of CABG versus PCI by calculating the absolute risk difference between the two strategies) by cross-validation with the SYNTAX trial (n=1800 participants) and external validation in the pooled population (n=3380 participants) of the FREEDOM, BEST, and PRECOMBAT trials. The concordance (C)-index was used to measure discriminative ability, and calibration plots were used to assess the degree of agreement between predictions and observations. Findings At cross-validation, the newly developed SYNTAX score II, termed SYNTAX score II 2020, showed a helpful discriminative ability in both treatment groups for predicting 10-year all-cause deaths (C-index=0·73 [95% CI 0·69–0·76] for PCI and 0·73 [0·69–0·76] for CABG) and 5-year major adverse cardiovascular events (C-index=0·65 [0·61–0·69] for PCI and C-index=0·71 [0·67–0·75] for CABG). At external validation, the SYNTAX score II 2020 showed helpful discrimination (C-index=0·67 [0·63–0·70] for PCI and C-index=0·62 [0·58–0·66] for CABG) and good calibration for predicting 5-year major adverse cardiovascular events. The estimated treatment benefit of CABG over PCI varied substantially among patients in the trial population, and the benefit predictions were well calibrated. Interpretation The SYNTAX score II 2020 for predicting 10-year deaths and 5-year major adverse cardiovascular events can help to identify individuals who will benefit from either CABG or PCI, thereby supporting heart teams, patients, and their families to select optimal revascularisation strategies. Funding The German Heart Research Foundation and the Patient-Centered Outcomes Research Institute.

Published
2020

11. Minimal clinically important difference in quality of life scores for patients with heart failure and reduced ejection fraction

Author

Butler, J. Khan, M.S. Mori, C. Filippatos, G.S. Ponikowski, P. Comin-Colet, J. Roubert, B. Spertus, J.A. Anker, S.D.

Subjects
humanities
Abstract

Aims: While the associations of health-related quality of life scores in heart failure (HF) [e.g. the Kansas City Cardiomyopathy Questionnaire (KCCQ)] with clinical outcomes are well established, their interpretation in the context of what magnitudes of change are clinically important to patients is less clear. The main objective of this study was to correlate the changes in the KCCQ and Patient Global Assessment (PGA) in patients with HF with reduced ejection fraction (HFrEF) to determine minimal clinically important difference (MCID). Methods and results: We analysed data from 459 patients of the FAIR-HF trial. Both KCCQ and PGA were assessed at 4 and 24 weeks after enrolment. An anchor-based approach was used to calculate MCID at week 4 and 24. PGA was chosen as the clinical anchor against which changes in the KCCQ scores were calibrated. For each category of change in PGA, the corresponding differences were calculated by the mean scores of various domains of KCCQ along with 95% confidence intervals (CIs). There was fair correlation between PGA and changes in overall summary scores (OSS) (r = 0.31; P < 0.001), clinical summary scores (CSS) (r = 0.36; P < 0.001) and physical limitation scores (PLS) (r = 0.31; P < 0.001) from baseline to week 4. KCCQ OSS, CSS and PLS MCID for ‘little improvement’ at week 4 were 3.6 (1.0–6.2), 4.5 (1.8–7.2) and 4.7 (1.4–8.0) points, respectively. OSS, CSS and PLS MCID for ‘little improvement’ at week 24 were 4.3 (0.2–8.4), 4.5 (0.5–8.5) and 4.0 (−0.9–9.0) points, respectively. Conclusion: The MCID threshold for KCCQ score was generally consistent and numerically lower than the threshold of 5-point change considered for clinical outcome prognosis and were stable between 4 and 24 weeks. This suggests that even changes smaller than the traditional 5-point improvements in KCCQ may be clinically meaningful. Also, these results can aid in the clinical interpretation of patient-reported outcomes, and better endpoint selection in future studies. © 2020 European Society of Cardiology

Published
2020

12. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data

Author

Patel, R.S., Schmidt, A.F., Tragante, V., McCubrey, R.O., Holmes, M.V., Howe, L.J., Direk, K., Akerblom, A., Leander, K., Virani, S.S., Kaminski, K.A., Muehlschlegel, J.D., Dube, M.P., Allayee, H., Almgren, P., Alver, M., Baranova, E.V., Behlouli, H., Boeckx, B., Braund, P.S., Breitling, L.P., Delgado, G., Duarte, N.E., Dufresne, L., Eriksson, N., Foco, L., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Hubacek, J.A., Kleber, M., Kofink, D., Kuukasjarvi, P., Lee, V.V., Leiherer, A., Lenzini, P.A., Levin, D., Lyytikainen, L.P., Martinelli, N., Mons, U., Nelson, C.P., Nikus, K., Pilbrow, A.P., Ploski, R., Sun, Y.V., Tanck, M.W.T., Tang, W.H.W., Trompet, S., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Anselmi, C.V., Vlachopoulou, E., Boerwinkle, E., Briguori, C., Carlquist, J.F., Carruthers, K.F., Casu, G., Deanfield, J., Deloukas, P., Dudbridge, F., Fitzpatrick, N., Gigante, B., James, S., Lokki, M.L., Lotufo, P.A., Marziliano, N., Mordi, I.R., Muhlestein, J.B., Cheh, C.N., Pitha, J., Saely, C.H., Samman-Tahhan, A., Sandesara, P.B., Teren, A., Timmis, A., Werf, F. van de, Wauters, E., Wilde, A.A.M., Ford, I., Stott, D.J., Algra, A., Andreassi, M.G., Ardissino, D., Arsenault, B.J., Ballantyne, C.M., Bergmeijer, T.O., Bezzina, C.R., Body, S.C., Bogaty, P., Borst, G.J. de, Brenner, H., Burkhardt, R., Carpeggiani, C., Condorelli, G., Cooper-DeHoff, R.M., Cresci, S., Faire, U. de, Doughty, R.N., Drexel, H., Engert, J.C., Fox, K.A.A., Girelli, D., Hagstrom, E., Hazen, S.L., Held, C., Hemingway, H., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Jong, P.A. de, Jukema, J.W., Kaczor, M.P., Kahonen, M., Kettner, J., Kiliszek, M., Klungel, O.H., Lagerqvist, B., Lambrechts, D., Laurikka, J.O., Lehtimaki, T., Lindholm, D., Mahmoodi, B.K., Maitland-van der Zee, A.H., McPherson, R., Melander, O., Metspalu, A., Pepinski, W., Olivieri, O., Opolski, G., Palmer, C.N., Pasterkamp, G., Pepine, C.J., Pereira, A.C., Note, L., Quyyumi, A.A., Richards, A.M., Sanak, M., Scholz, M., Siegbahn, A., Sinisalo, J., Smith, J.G., Spertus, J.A., Stewart, A.F.R., Szczeklik, W., Szpakowicz, A., Berg, J.M. ten, Thanassoulis, G., Thieiy, J., Graaf, Y. van der, Visseren, F.L.J., Waltenberger, J., Harst, P. van der, Tardif, J.C., Sattar, N., Lang, C.C., Pare, G., Brophy, J.M., Anderson, J.L., Marz, W., Wallentin, L., Cameron, V.A., Horne, B.D., Samani, N.J., Hingorani, A.D., Asselbergs, F.W., and CARDIo-GRAMPlusC4D Consortium

Subjects
myocardial infarction, risk factor, cardiovascular diseases, chromosome, genetic, variation, secondary prevention
Abstract

BACKGROUND: 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.METHODS: 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.RESULTS: 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 (GENIUSCHD 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 interaction < 0.001 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).CONCLUSIONS: 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

13. Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Author

Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., Patel, R.S., Mahmoodi, B.K., Tragante, V., Kleber, M.E., Holmes, M.V., Schmidt, A.F., McCubrey, R.O., Howe, L.J., Direk, K., Allayee, H., Baranova, E.V., Braund, P.S., Delgado, G.E., Eriksson, N., Gijsberts, C.M., Gong, Y., Hartiala, J., Heydarpour, M., Pasterkamp, G., Kotti, S., Kuukasjärvi, P., Lenzini, P.A., Levin, D., Lyytikäinen, L.P., Muehlschlegel, J.D., Nelson, C.P., Nikus, K., Pilbrow, A.P., Tang, W.H., Laan, S.W. van der, Setten, J. van, Vilmundarson, R.O., Deanfield, J., Deloukas, P., Dudbridge, F., James, S., Mordi, I.R., Teren, A., Bergmeijer, T.O., Body, S.C., Bots, M., Burkhardt, R., Cooper-DeHoff, R.M., Cresci, S., Danchin, N., Doughty, R.N., Grobbee, D.E., Hagström, E., Hazen, S.L., Held, C., Hoefer, I.E., Hovingh, G.K., Johnson, J.A., Kaczor, M.P., Kähönen, M., Klungel, O.H., Laurikka, J.O., Lehtimäki, T., Maitland-van der Zee, A.H., McPherson, R., Palmer, C.N., Kraaijeveld, A.O., Pepine, C.J., Sanak, M., Sattar, N., Scholz, M., Simon, T., Spertus, J.A., Stewart, A.F., Szczeklik, W., Thiery, J., Visseren, F.L., Waltenberger, J., Richards, A.M.S., Lang, C.C., Cameron, V.A., Åkerblom, A., Pare, G., März, W., Samani, N.J., Hingorani, A.D., Berg, J.M. ten, Wallentin, L., Asselbergs, F.W., and Patel, R.S.

Abstract

Contains fulltext : 235380.pdf (Publisher’s version ) (Closed access), BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I(2)=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, card

Published
2020

14. Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With Renal Dysfunction.

Author

Al Badarin F., Moses J., Lombardi W., Karmpaliotis D., Nicholson W.J., Salisbury A.C., Malik A.O., Spertus J.A., Grantham J.A., Peri-Okonny P., Gosch K., Sapontis J., Al Badarin F., Moses J., Lombardi W., Karmpaliotis D., Nicholson W.J., Salisbury A.C., Malik A.O., Spertus J.A., Grantham J.A., Peri-Okonny P., Gosch K., and Sapontis J.

Abstract

Although contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is performed with high success rates, 10% to 13% of patients presenting with CTOs have chronic kidney disease (CKD), and the comparative safety, efficacy, and health status benefit of CTO PCI in these patients, has not been well defined. We examined the association of baseline renal function with periprocedural major adverse cardiovascular and cerebral events and health status outcomes in 957 consecutive patients (mean age 65.3 +/- 10.3 years, 19.4% women, 90.3% white, 23.6 CKD [estimated glomerular filtration rate {eGFR} < 60]) in the OPEN-CTO (Outcomes, Patients Health Status, and Efficiency in Chronic Total Occlusions Registry) study. Hierarchical multivariable regression models were used to examine the independent association of baseline eGFR with technical success, periprocedural complications and change in health status, using Seattle Angina Questionnaire (SAQ) over 1 year. Crude rates of acute kidney injury were higher (13.5% vs 4.4%, p <0.001) and technical success lower (81.8% vs 88.4%, p = 0.01) in patients with CKD. There were no significant differences in other periprocedural complications. After adjustment for confounding factors, there was no significant association of baseline eGFR with technical success or periprocedural major adverse cardiovascular and cerebral events (death, myocardial infarction, emergent bypass surgery, stroke, perforation), whereas patients with lower eGFR had higher rates of acute kidney injury. The difference in SAQ summary score, between patients on the 10th and 90th percentile for baseline eGFR distribution was not clinically significant (1 month: -0.91; 1 year: -3.06 points). In conclusion, CTO PCI success, complication rates, and the health status improvement after CTO PCI are similar in patients across a range of baseline eGFRs.Copyright © 2020 Elsevier Inc.

Published
2020

16. De-escalation of antianginal medications after successful chronic total occlusion percutaneous coronary intervention: Frequency and relationship with health status.

Author

Grantham J.A., Qintar M., Hirai T., Arnold S.V., Sheehy J., Salisbury A.C., Sapontis J., Jones P., Tang Y., Lombardi W., Karmpaliotis D., Moses J., Patterson C., Nicholson W.J., Cohen D.J., Spertus J.A., Grantham J.A., Qintar M., Hirai T., Arnold S.V., Sheehy J., Salisbury A.C., Sapontis J., Jones P., Tang Y., Lombardi W., Karmpaliotis D., Moses J., Patterson C., Nicholson W.J., Cohen D.J., and Spertus J.A.

Abstract

Background: Successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can markedly reduce angina symptom burden, but many patients often remain on multiple antianginal medications (AAMs) after the procedure. It is unclear when, or if, AAMs can be de-escalated to prevent adverse effects or limit polypharmacy. We examined the association of de-escalation of AAMs after CTO PCI with long-term health status. Method(s): In a 12-center registry of consecutive CTO PCI patients, health status was assessed at 6 months after successful CTO PCI with the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Among patients with technical CTO PCI success, we examined the association of AAM de-escalation with 6-month health status using multivariable models adjusting for revascularization completeness and predicted risk of post-PCI angina (using a validated risk model). We also examined predictors and variability of AAMs de-escalation. Result(s): Of 669 patients with technical success of CTO PCI, AAMs were de-escalated in 276 (35.9%) patients at 1 month. Patients with AAM de-escalation reported similar angina and dyspnea rates at 6 months compared with those whose AAMs were reduced (any angina: 22.5% vs 20%, P = .43; any dyspnea: 51.8% vs 50.1%, P = .40). In a multivariable model adjusting for complete revascularization and predicted risk of post-PCI angina, de-escalation of AAMs at 1 month was not associated with an increased risk of angina, dyspnea, or worse health status at 6 months. Conclusion(s): Among patients with successful CTO PCI, de-escalation of AAMs occurred in about one-third of patients at 1 month and was not associated with worse long-term health status.Copyright © 2019 Elsevier Inc.

Published
2019

17. Anti-anginal medication titration among patients with residual angina 6-months after chronic total occlusion percutaneous coronary intervention: Insights from OPEN CTO registry.

Author

Spertus J.A., Nicholson W.J., Grantham J.A., Salisbury A.C., Sheehy J.P., Qintar M., Arnold S.V., Hirai T., Sapontis J., Jones P.G., Tang Y., Lombardi W., Karmpaliotis D., Moses J.W., Patterson C., Cohen D.J., Amin A.P., Spertus J.A., Nicholson W.J., Grantham J.A., Salisbury A.C., Sheehy J.P., Qintar M., Arnold S.V., Hirai T., Sapontis J., Jones P.G., Tang Y., Lombardi W., Karmpaliotis D., Moses J.W., Patterson C., Cohen D.J., and Amin A.P.

Abstract

Aims: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been shown to reduce angina and improve quality of life, but the frequency of new or residual angina after CTO PCI and its relationship with titration of anti-anginal medications (AAMs) has not been described. Methods and Results: Among consecutive CTO PCI patients treated at 12 US centres in the OPEN CTO registry, angina was assessed 6 months after the index PCI using the Seattle Angina Questionnaire (SAQ) Angina Frequency scale (a score <100 defined new or residual angina). We then compared the proportion of patients with AAM escalation (defined as an increase in the number or dosage of AAMs between discharge and follow-up) between those with and without 6-month angina. Of 901 patients who underwent CTO PCI, 197 (21.9%) reported angina at 6-months, of whom 80 (40.6%) had de-escalation, 66 (33.5%) had no change, and only 51 (25.9%) had escalation of their AAM by the 6-month follow-up. Rates of AAM escalation were similar when stratifying patients by the ultimate success of the CTO PCI, completeness of physiologic revascularization, presence or absence of angina at baseline, history of heart failure, and by degree of symptomatic improvement after CTO PCI. Conclusion(s): One in five patients reported angina 6 months after CTO PCI. Although patients with new or residual angina were more likely to have escalation of AAMs in follow-up compared with those without residual symptoms, only one in four patients with residual angina had escalation of AAMs. Although it is unclear whether this finding reflects maximal tolerated therapy at baseline or therapeutic inertia, these findings suggest an important potential opportunity to further improve symptom control in patients with complex stable ischaemic heart disease.Copyright © 2019 Published on behalf of the European Society of Cardiology. All rights reserved.

Published
2019

18. Dyspnea among Patients with Chronic Total Occlusions Undergoing Percutaneous Coronary Intervention: Prevalence and Predictors of Improvement.

Author

Arnold S.V., Qintar M., Grantham J.A., Sapontis J., Gosch K.L., Lombardi W., Karmpaliotis D., Moses J., Salisbury A.C., Cohen D.J., Spertus J.A., Arnold S.V., Qintar M., Grantham J.A., Sapontis J., Gosch K.L., Lombardi W., Karmpaliotis D., Moses J., Salisbury A.C., Cohen D.J., and Spertus J.A.

Abstract

Background - Dyspnea is a common angina equivalent that adversely affects quality of life, but its prevalence in patients with chronic total occlusions (CTOs) and predictors of its improvement after CTO percutaneous coronary intervention (PCI) are unknown. We examined the prevalence of dyspnea and predictors of its improvement among patients selected for CTO PCI. Methods and Results - In the OPEN CTO registry (Outcomes, Patient health status, and Efficiency iN Chronic Total Occlusion) of 12 US experienced centers, 987 patients undergoing CTO PCI (procedure success 82%) were assessed for dyspnea with the Rose Dyspnea Scale at baseline and 1 month after CTO PCI. Rose Dyspnea Scale scores range from 0 to 4 with higher scores indicating more dyspnea with common activities. A total of 800 (81%) reported some dyspnea at baseline with a mean (+/-SD) Rose Dyspnea Scale of 2.8+/-1.2. Dyspnea improvement was defined as a >=1 point decrease in Rose Dyspnea Scale from baseline to 1 month. Predictors of dyspnea improvement were examined with a modified Poisson regression model. Patients with dyspnea were more likely to be female, obese, smokers, and to have more comorbidities and angina. Among patients with baseline dyspnea, 70% reported less dyspnea at 1 month after CTO PCI. Successful CTO PCI was associated with more frequent dyspnea improvement than failure, even after adjustment for other clinical variables. Anemia, depression, and lung disease were associated with less dyspnea improvement after PCI. Conclusions - Dyspnea is a common symptom among patients undergoing CTO PCI and improves significantly with successful PCI. Patients with other potentially noncardiac causes of dyspnea reported less dyspnea improvement after CTO PCI.Copyright ©2017 American Heart Association, Inc.

Published
2017

19. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Author

Schunkert, H. König, I.R. Kathiresan, S. Reilly, M.P. Assimes, T.L. Holm, H. Preuss, M. Stewart, A.F.R. Barbalic, M. Gieger, C. Absher, D. Aherrahrou, Z. Allayee, H. Altshuler, D. Anand, S.S. Andersen, K. Anderson, J.L. Ardissino, D. Ball, S.G. Balmforth, A.J. Barnes, T.A. Becker, D.M. Becker, L.C. Berger, K. Bis, J.C. Boekholdt, S.M. Boerwinkle, E. Braund, P.S. Brown, M.J. Burnett, M.S. Buysschaert, I. Carlquist, J.F. Chen, L. Cichon, S. Codd, V. Davies, R.W. Dedoussis, G. Dehghan, A. Demissie, S. Devaney, J.M. Diemert, P. Do, R. Doering, A. Eifert, S. Mokhtari, N.E.E. Ellis, S.G. Elosua, R. Engert, J.C. Epstein, S.E. De Faire, U. Fischer, M. Folsom, A.R. Freyer, J. Gigante, B. Girelli, D. Gretarsdottir, S. Gudnason, V. Gulcher, J.R. Halperin, E. Hammond, N. Hazen, S.L. Hofman, A. Horne, B.D. Illig, T. Iribarren, C. Jones, G.T. Jukema, J.W. Kaiser, M.A. Kaplan, L.M. Kastelein, J.J.P. Khaw, K.-T. Knowles, J.W. Kolovou, G. Kong, A. Laaksonen, R. Lambrechts, D. Leander, K. Lettre, G. Li, M. Lieb, W. Loley, C. Lotery, A.J. Mannucci, P.M. Maouche, S. Martinelli, N. McKeown, P.P. Meisinger, C. Meitinger, T. Melander, O. Merlini, P.A. Mooser, V. Morgan, T. Mühleisen, T.W. Muhlestein, J.B. Münzel, T. Musunuru, K. Nahrstaedt, J. Nelson, C.P. Nöthen, M.M. Olivieri, O. Patel, R.S. Patterson, C.C. Peters, A. Peyvandi, F. Qu, L. Quyyumi, A.A. Rader, D.J. Rallidis, L.S. Rice, C. Rosendaal, F.R. Rubin, D. Salomaa, V. Sampietro, M.L. Sandhu, M.S. Schadt, E. Scḧsignfer, A. Schillert, A. Schreiber, S. Schrezenmeir, J. Schwartz, S.M. Siscovick, D.S. Sivananthan, M. Sivapalaratnam, S. Smith, A. Smith, T.B. Snoep, J.D. Soranzo, N. Spertus, J.A. Stark, K. Stirrups, K. Stoll, M. Tang, W.H.W. Tennstedt, S. Thorgeirsson, G. Thorleifsson, G. Tomaszewski, M. Uitterlinden, A.G. Van Rij, A.M. Voight, B.F. Wareham, N.J. Wells, G.A. Wichmann, H.-E. Wild, P.S. Willenborg, C. Witteman, J.C.M. Wright, B.J. Ye, S. Zeller, T. Ziegler, A. Cambien, F. Goodall, A.H. Cupples, L.A. Quertermous, T. Mäsignrz, W. Hengstenberg, C. Blankenberg, S. Ouwehand, W.H. Hall, A.S. Deloukas, P. Thompson, J.R. Stefansson, K. Roberts, R. Thorsteinsdottir, U. O'Donnell, C.J. McPherson, R. Erdmann, J. Samani, N.J.

Subjects
cardiovascular diseases
Abstract

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. © 2011 Nature America, Inc. All rights reserved.

Published
2011

20. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author

Strawbridge, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Haeften, T.W. Van Herpt, T. Van Vliet-Ostaptchouk, J.V. Walters, G.B. Wijmenga, C. Witteman, J.C.M. Bergman, R.N. Cauchi, S. Collins, F.S. Gloyn, A.L. Gyllensten, U. Hansen, T. Hide, W.A. Hitman, G.A. Hofman, A. Hunter, D.J. Hveem, K. Laakso, M. Mohlke, K.L. Morris, A.D. Palmer, C.N.A. Pramstaller, P.P. Rudan, I. Sijbrands, E. Stein, L.D. Tuomilehto, J. Uitterlinden, A.G. Wareham, N.J. Watanabe, R.M. Abecasis, G.R. Boehm, B.O. Campbell, H. Daly, M.J. Hattersley, A.T. Hu, F.B. Meigs, J.B. Pankow, J.S. Pedersen, O. Wichmann, H.-E. Barroso, I. Groop, L. Sladek, R. Thorsteinsdottir, U. Wilson, J.F. Illig, T. Froguel, P. Van Duijn, C.M. Stefansson, K. Altshuler, D. Boehnke, M. McCarthy, M.I. Speliotes, E.K. Berndt, S.I. Monda, K.L. Allen, H.L. Magi, R. Randall, J.C. Vedantam, S. Winkler, T.W. Workalemahu, T. Heid, I.M. Wood, A.R. Weyant, R.J. Estrada, K. Liang, L. Nemesh, J. Park, J.-H. Kilpelainen, T.O. Yang, J. Esko, T. Feitosa, M.F. Kutalik, Z. Mangino, M. Scherag, A. Smith, A.V. Zhao, J.H. Aben, K.K. Absher, D.M. Dixon, A.L. Fisher, E. Glazer, N.L. Goddard, M.E. Heard-Costa, N.L. Hoesel, V. Hottenga, J.-J. Johansson, A. Johnson, T. Ketkar, S. Lamina, C. Li, S. Moffatt, M.F. Myers, R.H. Peters, M.J. Preuss, M. Ripatti, S. Rivadeneira, F. Sandholt, C. Timpson, N.J. Tyrer, J.P. Van Wingerden, S. White, C.C. Wiklund, F. Barlassina, C. Chasman, D.I. Cooper, M.N. Jansson, J.-O. Lawrence, R.W. Pellikka, N. Shi, J. Thiering, E. Alavere, H. Alibrandi, M.T.S. Arnold, A.M. Aspelund, T. Atwood, L.D. Balmforth, A.J. Ben-Shlomo, Y. Bergmann, S. Biebermann, H. Blakemore, A.I.F. Boes, T. Bornstein, S.R. Brown, M.J. Buchanan, T.A. Busonero, F. Cappuccio, F.P. Cavalcanti-Proenca, C. Chen, Y.-D.I. Chen, C.-M. Clarke, R. Coin, L. Connell, J. Day, I.N.M. Den Heijer, M. Duan, J. Ebrahim, S. Elliott, P. Elosua, R. Eiriksdottir, G. Facheris, M.F. Felix, S.B. Fischer-Posovszky, P. Folsom, A.R. Friedrich, N. Freimer, N.B. Fu, M. Gaget, S. Gejman, P.V. Geus, E.J.C. Gjesing, A.P. Goyette, P. Grasler, J. Greenawalt, D.M. Gudnason, V. Hartikainen, A.-L. Hall, A.S. Havulinna, A.S. Hayward, C. Heath, A.C. Hengstenberg, C. Hicks, A.A. Hinney, A. Homuth, G. Hui, J. Igl, W. Iribarren, C. Jacobs, K.B. Jarick, I. Jewell, E. John, U. Jousilahti, P. Jula, A. Kaakinen, M. Kaplan, L.M. Kathiresan, S. Kettunen, J. Kinnunen, L. Knowles, J.W. Kolcic, I. König, I.R. Koskinen, S. Kovacs, P. Kvaloy, K. Laitinen, J. Lantieri, O. Lanzani, C. Launer, L.J. Lecoeur, C. Lehtimaki, T. Lettre, G. Liu, J. Lokki, M.-L. Lorentzon, M. Luben, R.N. Ludwig, B. Manunta, P. Marek, D. Martin, N.G. McArdle, W.L. McCarthy, A. McKnight, B. Melander, O. Meyre, D. Montgomery, G.W. Mulic, R. Ngwa, J.S. Nelis, M. Neville, M.J. Nyholt, D.R. O'Donnell, C.J. O'Rahilly, S. Ong, K.K. Oostra, B. Pare, G. Parker, A.N. Perola, M. Pichler, I. Pietilainen, K.H. Platou, C.G.P. Polasek, O. Pouta, A. Rafelt, S. Raitakari, O. Rayner, N.W. Ridderstrale, M. Rief, W. Ruokonen, A. Rzehak, P. Salomaa, V. Sanders, A.R. Sandhu, M.S. Sanna, S. Saramies, J. Savolainen, M.J. Scherag, S. Schipf, S. Schreiber, S. Schunkert, H. Silander, K. Sinisalo, J. Siscovick, D.S. Smit, J.H. Soranzo, N. Sovio, U. Stephens, J. Surakka, I. Tammesoo, M.-L. Tardif, J.-C. Teder-Laving, M. Teslovich, T.M. Thompson, J.R. Thomson, B. Tonjes, A. Van Meurs, J.B.J. Van Ommen, G.-J. Vatin, V. Viikari, J. Visvikis-Siest, S. Vitart, V. Vogel, C.I.G. Waite, L.L. Wallaschofski, H. Widen, E. Wiegand, S. Wild, S.H. Willemsen, G. Witte, D.R. Xu, J. Zhang, Q. Zgaga, L. Ziegler, A. Zitting, P. Beilby, J.P. Farooqi, I.S. Hebebrand, J. Huikuri, H.V. James, A.L. Kahonen, M. Levinson, D.F. Macciardi, F. Nieminen, M.S. Ohlsson, C. Palmer, L.J. Ridker, P.M. Stumvoll, M. Beckmann, J.S. Boeing, H. Boomsma, D.I. Caulfield, M.J. Chanock, S.J. Cupples, L.A. Smith, G.D. Erdmann, J. Gronberg, H. Hall, P. Harris, T.B. Hayes, R.B. Heinrich, J. Jarvelin, M.-R. Kaprio, J. Karpe, F. Khaw, K.-T. Kiemeney, L.A. Krude, H. Lawlor, D.A. Metspalu, A. Munroe, P.B. Ouwehand, W.H. Penninx, B.W. Peters, A. Quertermous, T. Reinehr, T. Rissanen, A. Samani, N.J. Schwarz, P.E.H. Shuldiner, A.R. Spector, T.D. Uda, M. Valle, T.T. Wabitsch, M. Waeber, G. Watkins, H. Wright, A.F. Zillikens, M.C. Chatterjee, N. Purcell, S. Schadt, E.E. Visscher, P.M. Assimes, T.L. Borecki, I.B. Deloukas, P. Haritunians, T. Kaplan, R.C. O'Connell, J.R. Peltonen, L. Schlessinger, D. Strachan, D.P. North, K.E. Hirschhorn, J.N. Ingelsson, E. Parts, L. Glass, D. Nisbet, J. Barrett, A. Sekowska, M. Potter, S. Grundberg, E. Small, K. Hedman, A.K. Bataille, V. Bell, J.T. Surdulescu, G. Ingle, C. Nestle, F.O. Di Meglio, P. Min, J.L. Wilk, A. Hammond, C.J. Yang, T.-P. Montgomery, S.B. Zondervan, K.T. Durbin, R. Ahmadi, K. Dermitzakis, E.T. Reilly, M.P. Holm, H. Stewart, A.F.R. Barbalic, M. Aherrahrou, Z. Allayee, H. Anand, S.S. Andersen, K. Anderson, J.L. Ardissino, D. Ball, S.G. Barnes, T.A. Becker, D.M. Becker, L.C. Berger, K. Bis, J.C. Boekholdt, S.M. Braund, P.S. Burnett, M.S. Buysschaert, I. Carlquist, J.F. Chen, L. Codd, V. Davies, R.W. Cichon, S. Dedoussis, G.V. Demissie, S. Dehghan, A. Devaney, J.M. Diemert, P. Do, R. Doering, A. Eifert, S. El Mokhtari, N.E. Ellis, S.G. Engert, J.C. Epstein, S.E. De Faire, U. Fischer, M. Freyer, J. Gigante, B. Girelli, D. Gretarsdottir, S. Gulcher, J.R. Halperin, E. Hammond, N. Hazen, S.L. Horne, B.D. Jones, G.T. Jukema, J.W. Kaiser, M.A. Kastelein, J.J.P. Kolovou, G. Laaksonen, R. Lambrechts, D. Leander, K. Li, M. Lieb, W. Loley, C. Lotery, A.J. Mannucci, P.M. Maouche, S. Martinelli, N. McKeown, P.P. Meisinger, C. Merlini, P.A. Mooser, V. Morgan, T. Mühleisen, T.W. Muhlestein, J.B. Münzel, T. Musunuru, K. Nahrstaedt, J. Nelson, C.P. Nöthen, M.M. Olivieri, O. Patel, R.S. Patterson, C.C. Peyvandi, F. Qu, L. Quyyumi, A.A. Rader, D.J. Rallidis, L.S. Rice, C. Rosendaal, F.R. Rubin, D. Sampietro, M.L. Sandhu, M.S. Schadt, E. Schäfer, A. Schillert, A. Schrezenmeir, J. Schwartz, S.M. Sivananthan, M. Sivapalaratnam, S. Smith, T.B. Snoep, J.D. Spertus, J.A. Stark, K. Stoll, M. Wilson Tang, W.H. Tennstedt, S. Thorgeirsson, G. Tomaszewski, M. Van Rij, A.M. Wells, G.A. Wild, P.S. Willenborg, C. Wright, B.J. Ye, S. Zeller, T. Cambien, F. Goodall, A.H. Marz, W. Blankenberg, S. Roberts, R. McPherson, R. Hopewell, J.C. Parish, S. Offer, A. Bowman, L. Sleight, P. Armitage, J. Peto, R. Collins, R. Chambers, J.C. Ahmed, N. Donnelly, P. Kooner, A.S. Scott, J. Sehmi, J. Zhang, W. Kooner, J. Sabater-Lleal, M. Mälarstig, A. Hellénius, M.-L. Olsson, G. Rust, S. Assmann, G. Seedorf, U. Barlera, S. Tognoni, G. Franzosi, M.G. Linksted, P. Ongen, H. Kyriakou, T. Green, F. Farrall, M. Saleheen, D. Rasheed, A. Zaidi, M. Shah, N. Samuel, M. Mallick, N. Azhar, M. Zaman, K. Samad, A. Ishaq, M. Gardezi, A. Memon, F.-U.-R. Frossard, P. Danesh, J. Östenson, C.-G. Lind, L. Cooper, C.C. Serrano-Ríos, M. Ferrannini, E. Forsen, T.J. Pattou, F. Langenberg, C. Hamsten, A. Florez, J.C.

Subjects
endocrine system, endocrine system diseases, nutritional and metabolic diseases
Abstract

OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10-8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/ C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 3 10-4), improved b-cell function (P = 1.1 × 10-5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10-6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS - We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis. © 2011 by the American Diabetes Association.

Published
2011

21. Gender differences in health status and adverse outcomes among patients with peripheral arterial disease

Author

Dreyer, R.P., van Zitteren, M., Beltrame, J.F., Fitridge, R., Denollet, J., Spertus, J.A., Smolderen, K.G.E., Vriens, Patrick W, Dreyer, R.P., van Zitteren, M., Beltrame, J.F., Fitridge, R., Denollet, J., Spertus, J.A., Smolderen, K.G.E., and Vriens, Patrick W

Abstract

Background Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self‐reported health status at PAD diagnosis and 12‐months later, and explored (2) whether outcomes in women with PAD differ with regard to long‐term major adverse events. Methods and Results A A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form‐12 (SF‐12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12‐months later. Women had similar ages and clinical characteristics, but poorer socio‐economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental (MCS: 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12‐months, women still reported a poorer overall PCS score (41±12 versus 46±11, P=0.006) and MCS score (42±14 versus 49±12, P=0.002). Female gender was an independent determinant of a poorer baseline and 12‐month PCS and MCS scores. However, there were no significant differences by gender on either mortality (unadjusted hazard ratio [HR]=0.93, 95% CI 0.60;1.44, P=0.74) or major adverse events (unadjusted HR=0.90, 95% CI 0.63;1.29, P=0.57), after a median follow‐up of 3.2 years. Conclusions Women's physical and mental health status is compromised both at initial PAD diagnosis and at 12‐month follow‐up, despite experiencing a similar magnitude of change in their health scores throughout the first 12‐months after diagnosis.

Published
2015

25. Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Author

Butterworth, A.S., Braund, P.S., Hardwick, R.J., Saleheen, D., Peden, J.F., Soranzo, N., Chambers, J.C., Kleber, M.E., Keating, B., Qasim, A., Klopp, N., Erdmann, J., Basart, H., Baumert, J.H., Bezzina, C.R., Boehm, B.O., Brocheton, J., Bugert, P., Cambien, F., Collins, R., Couper, D., Jong, J.S. de, Diemert, P., Ejebe, K., Elbers, C.C., Elliott, P., Fornage, M., Frossard, P., Garner, S., Hunt, S.E., Kastelein, J.J., Klungel, O.H., Kluter, H., Koch, K., Konig, I.R., Kooner, A.S., Liu, K., McPherson, R., Musameh, M.D., Musani, S., Papanicolaou, G., Peters, A., Peters, B.J., Potter, S., Psaty, B.M., Rasheed, A., Scott, J., Seedorf, U., Sehmi, J.S., Sotoodehnia, N., Stark, K., Stephens, J., Schoot, C.E. van der, Schouw, Y.T. van der, Harst, P. van der, Vasan, R.S., Wilde, A.A., Willenborg, C., Winkelmann, B.R., Zaidi, M., Zhang, W., Ziegler, A., Koenig, W., Matz, W., Trip, M.D., Reilly, M.P., Kathiresan, S., Schunkert, H., Hamsten, A., Hall, A.S., Kooner, J.S., Thompson, S.G., Thompson, J.R., Watkins, H., Danesh, J., Barnes, T., Rafelt, S., Codd, V., Bruinsma, N., Dekker, L.R., Henriques, J.P., Koch, K.T., Winter, R.J. de, Alings, M., Allaart, C.F., Gorgels, A.P., Verheugt, F.W.A., Mueller, M., Meisinger, C., DerOhannessian, S., Mehta, N.N., Ferguson, J., Hakonarson, H., Matthai, W., Wilensky, R., Hopewell, J.C., Parish, S., Linksted, P., Notman, J., Gonzalez, H., Young, A., Ostley, T., Munday, A., Goodwin, N., Verdon, V., Shah, S., Edwards, C., Mathews, C., Gunter, R., Benham, J., Davies, C., Cobb, M., Cobb, L., Crowther, J., Richards, A., Silver, M., Tochlin, S., Mozley, S., Clark, S., Radley, M., Kourellias, K., Olsson, P., Barlera, S., Tognoni, G., Rust, S., Assmann, G., Heath, S., Zelenika, D., Gut, I., Green, F., Farrall, M., Goel, A., Ongen, H., Franzosi, M.G., Lathrop, M., Clarke, R., Aly, A., Anner, K., Bjorklund, K., Blomgren, G., Cederschiold, B., Danell-Toverud, K., Eriksson, P., Grundstedt, U., Heinonen, M., Hellenius, M.L., Hooft, F. van 't, Husman, K., Lagercrantz, J., Larsson, A., Larsson, M., Mossfeldt, M., Malarstig, A., Olsson, G., Sabater-Lleal, M., Sennblad, B., Silveira, A., Strawbridge, R., Soderholm, B., Ohrvik, J., Zaman, K.S., Mallick, N.H., Azhar, M., Samad, A., Ishaq, M., Shah, N., Samuel, M., Kathiresan, S.C., Assimes, T.L., Holm, H., Preuss, M., Stewart, A.F., Barbalic, M., Gieger, C., Absher, D., Aherrahrou, Z., Allayee, H., Altshuler, D., Anand, S., Andersen, K., Anderson, J.L., Ardissino, D., Ball, S.G., Balmforth, A.J., Barnes, T.A., Becker, L.C., Becker, D.M., Berger, K., Bis, J.C., Boekholdt, S.M., Boerwinkle, E., Brown, M.J., Burnett, M.S., Buysschaert, I., Carlquist, J.F., Chen, L., Davies, R.W., Dedoussis, G., Dehghan, A., Demissie, S., Devaney, J., Do, R., Doering, A., El Mokhtari, N.E., Ellis, S.G., Elosua, R., Engert, J.C., Epstein, S., Faire, U. de, Fischer, M., Folsom, A.R., Freyer, J., Gigante, B., Girelli, D., Gretarsdottir, S., Gudnason, V., Gulcher, J.R., Tennstedt, S., Halperin, E., Hammond, N., Hazen, S.L., Hofman, A., Horne, B.D., Illig, T., Iribarren, C., Jones, G.T., Jukema, J.W., Kaiser, M.A., Kaplan, L.M., Khaw, K.T., Knowles, J.W., Kolovou, G., Kong, A., Laaksonen, R., Lambrechts, D., Leander, K., Li, M., Lieb, W., Lettre, G., Loley, C., Lotery, A.J., Mannucci, P.M., Martinelli, N., McKeown, P.P., Meitinger, T., Melander, O., Merlini, P.A., Mooser, V., Morgan, T., Muhleisen T.W., ., Muhlestein, J.B., Musunuru, K., Nahrstaedt, J., Nothen, Markus, Olivieri, O., Peyvandi, F., Patel, R.S., Patterson, C.C., Qu, L., Quyyumi, A.A., Rader, D.J., Rallidis, L.S., Rice, C., Roosendaal, F.R., Rubin, D., Salomaa, V., Sampietro, M.L., Sandhu, M.S., Schadt, E., Schafer, A., Schillert, A., Schreiber, S., Schrezenmeir, J., Schwartz, S.M., Siscovick, D.S., Sivananthan, M., Sivapalaratnam, S., Smith, A.V., Smith, T.B., Snoep, J.D., Spertus, J.A., Stefansson, K., Stirrups, K., Stoll, M., Tang, W.H., Thorgeirsson, G., Thorleifsson, G., Tomaszewski, M., Uitterlinden, A.G., Rij, A.M. van, Voight, B.F., Wareham, N.J., AWells, G., Wichmann, H.E., Witteman, J.C., Wright, B.J., Ye, S., Cupples, L.A., Quertermous, T., Marz, W., Blankenberg, S., Thorsteinsdottir, U., Roberts, R., O'Donnell, C.J., Onland-Moret, N.C., Setten, J. van, Bakker, P.I. de, Verschuren, W.M., Boer, J.M., Wijmenga, C., Hofker, M.H., Maitland-van der Zee, A.H., Boer, A. de, Grobbee, D.E., Attwood, T., Belz, S., Cooper, J., Crisp-Hihn, A., Deloukas, P., Foad, N., Goodall, A.H., Gracey, J., Gray, E., Gwilliams, R., Heimerl, S., Hengstenberg, C., Jolley, J., Krishnan, U., Lloyd-Jones, H., Lugauer, I., Lundmark, P., Maouche, S., Moore, J.S., Muir, D., Murray, E., Nelson, C.P., Neudert, J., Niblett, D., O'Leary, K., Ouwehand, W.H., Pollard, H., Rankin, A., Rice, C.M., Sager, H., Samani, N.J., Sambrook, J., Schmitz, G., Scholz, M., Schroeder, L., Syvannen, A.C., Wallace, C., Butterworth, A.S., Braund, P.S., Hardwick, R.J., Saleheen, D., Peden, J.F., Soranzo, N., Chambers, J.C., Kleber, M.E., Keating, B., Qasim, A., Klopp, N., Erdmann, J., Basart, H., Baumert, J.H., Bezzina, C.R., Boehm, B.O., Brocheton, J., Bugert, P., Cambien, F., Collins, R., Couper, D., Jong, J.S. de, Diemert, P., Ejebe, K., Elbers, C.C., Elliott, P., Fornage, M., Frossard, P., Garner, S., Hunt, S.E., Kastelein, J.J., Klungel, O.H., Kluter, H., Koch, K., Konig, I.R., Kooner, A.S., Liu, K., McPherson, R., Musameh, M.D., Musani, S., Papanicolaou, G., Peters, A., Peters, B.J., Potter, S., Psaty, B.M., Rasheed, A., Scott, J., Seedorf, U., Sehmi, J.S., Sotoodehnia, N., Stark, K., Stephens, J., Schoot, C.E. van der, Schouw, Y.T. van der, Harst, P. van der, Vasan, R.S., Wilde, A.A., Willenborg, C., Winkelmann, B.R., Zaidi, M., Zhang, W., Ziegler, A., Koenig, W., Matz, W., Trip, M.D., Reilly, M.P., Kathiresan, S., Schunkert, H., Hamsten, A., Hall, A.S., Kooner, J.S., Thompson, S.G., Thompson, J.R., Watkins, H., Danesh, J., Barnes, T., Rafelt, S., Codd, V., Bruinsma, N., Dekker, L.R., Henriques, J.P., Koch, K.T., Winter, R.J. de, Alings, M., Allaart, C.F., Gorgels, A.P., Verheugt, F.W.A., Mueller, M., Meisinger, C., DerOhannessian, S., Mehta, N.N., Ferguson, J., Hakonarson, H., Matthai, W., Wilensky, R., Hopewell, J.C., Parish, S., Linksted, P., Notman, J., Gonzalez, H., Young, A., Ostley, T., Munday, A., Goodwin, N., Verdon, V., Shah, S., Edwards, C., Mathews, C., Gunter, R., Benham, J., Davies, C., Cobb, M., Cobb, L., Crowther, J., Richards, A., Silver, M., Tochlin, S., Mozley, S., Clark, S., Radley, M., Kourellias, K., Olsson, P., Barlera, S., Tognoni, G., Rust, S., Assmann, G., Heath, S., Zelenika, D., Gut, I., Green, F., Farrall, M., Goel, A., Ongen, H., Franzosi, M.G., Lathrop, M., Clarke, R., Aly, A., Anner, K., Bjorklund, K., Blomgren, G., Cederschiold, B., Danell-Toverud, K., Eriksson, P., Grundstedt, U., Heinonen, M., Hellenius, M.L., Hooft, F. van 't, Husman, K., Lagercrantz, J., Larsson, A., Larsson, M., Mossfeldt, M., Malarstig, A., Olsson, G., Sabater-Lleal, M., Sennblad, B., Silveira, A., Strawbridge, R., Soderholm, B., Ohrvik, J., Zaman, K.S., Mallick, N.H., Azhar, M., Samad, A., Ishaq, M., Shah, N., Samuel, M., Kathiresan, S.C., Assimes, T.L., Holm, H., Preuss, M., Stewart, A.F., Barbalic, M., Gieger, C., Absher, D., Aherrahrou, Z., Allayee, H., Altshuler, D., Anand, S., Andersen, K., Anderson, J.L., Ardissino, D., Ball, S.G., Balmforth, A.J., Barnes, T.A., Becker, L.C., Becker, D.M., Berger, K., Bis, J.C., Boekholdt, S.M., Boerwinkle, E., Brown, M.J., Burnett, M.S., Buysschaert, I., Carlquist, J.F., Chen, L., Davies, R.W., Dedoussis, G., Dehghan, A., Demissie, S., Devaney, J., Do, R., Doering, A., El Mokhtari, N.E., Ellis, S.G., Elosua, R., Engert, J.C., Epstein, S., Faire, U. de, Fischer, M., Folsom, A.R., Freyer, J., Gigante, B., Girelli, D., Gretarsdottir, S., Gudnason, V., Gulcher, J.R., Tennstedt, S., Halperin, E., Hammond, N., Hazen, S.L., Hofman, A., Horne, B.D., Illig, T., Iribarren, C., Jones, G.T., Jukema, J.W., Kaiser, M.A., Kaplan, L.M., Khaw, K.T., Knowles, J.W., Kolovou, G., Kong, A., Laaksonen, R., Lambrechts, D., Leander, K., Li, M., Lieb, W., Lettre, G., Loley, C., Lotery, A.J., Mannucci, P.M., Martinelli, N., McKeown, P.P., Meitinger, T., Melander, O., Merlini, P.A., Mooser, V., Morgan, T., Muhleisen T.W., ., Muhlestein, J.B., Musunuru, K., Nahrstaedt, J., Nothen, Markus, Olivieri, O., Peyvandi, F., Patel, R.S., Patterson, C.C., Qu, L., Quyyumi, A.A., Rader, D.J., Rallidis, L.S., Rice, C., Roosendaal, F.R., Rubin, D., Salomaa, V., Sampietro, M.L., Sandhu, M.S., Schadt, E., Schafer, A., Schillert, A., Schreiber, S., Schrezenmeir, J., Schwartz, S.M., Siscovick, D.S., Sivananthan, M., Sivapalaratnam, S., Smith, A.V., Smith, T.B., Snoep, J.D., Spertus, J.A., Stefansson, K., Stirrups, K., Stoll, M., Tang, W.H., Thorgeirsson, G., Thorleifsson, G., Tomaszewski, M., Uitterlinden, A.G., Rij, A.M. van, Voight, B.F., Wareham, N.J., AWells, G., Wichmann, H.E., Witteman, J.C., Wright, B.J., Ye, S., Cupples, L.A., Quertermous, T., Marz, W., Blankenberg, S., Thorsteinsdottir, U., Roberts, R., O'Donnell, C.J., Onland-Moret, N.C., Setten, J. van, Bakker, P.I. de, Verschuren, W.M., Boer, J.M., Wijmenga, C., Hofker, M.H., Maitland-van der Zee, A.H., Boer, A. de, Grobbee, D.E., Attwood, T., Belz, S., Cooper, J., Crisp-Hihn, A., Deloukas, P., Foad, N., Goodall, A.H., Gracey, J., Gray, E., Gwilliams, R., Heimerl, S., Hengstenberg, C., Jolley, J., Krishnan, U., Lloyd-Jones, H., Lugauer, I., Lundmark, P., Maouche, S., Moore, J.S., Muir, D., Murray, E., Nelson, C.P., Neudert, J., Niblett, D., O'Leary, K., Ouwehand, W.H., Pollard, H., Rankin, A., Rice, C.M., Sager, H., Samani, N.J., Sambrook, J., Schmitz, G., Scholz, M., Schroeder, L., Syvannen, A.C., and Wallace, C.

Abstract

Contains fulltext : 98050.pdf (publisher's version ) (Open Access), Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in approximately 2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5x10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other approximately 4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular f

Published
2011

26. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Author

Schunkert, H. (Heribert), König, I.R. (Inke), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Assimes, T.L. (Themistocles), Holm, H. (Hilma), Preuss, M. (Michael), Stewart, A.F.R. (Alexandre), Barbalic, M. (maja), Gieger, C. (Christian), Absher, D. (Devin), Aherrahrou, Z. (Zouhair), Allayee, H. (Hooman), Altshuler, D. (David), Anand, S.S. (Sonia), Andersen, K.K. (Karl), Anderson, J.L. (Jeffrey), Ardissino, D. (Diego), Ball, S.G. (Stephen), Balmforth, A.J. (Anthony), Barnes, T.A. (Timothy), Becker, D.M. (Diane), Berger, K. (Klaus), Bis, J.C. (Joshua), Boekholdt, S.M. (Matthijs), Boerwinkle, E.A. (Eric), Braund, P.S. (Peter), Brown, M.J. (Morris), Burnett, M.S., Buysschaert, I. (Ian), Carlquist, J.F. (John), Chen, L. (Li), Cichon, S. (Sven), Codd, V. (Veryan), Davies, R.W. (Robert), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Devaney, J. (Joseph), Diemert, P. (Patrick), Do, R. (Ron), Doering, A. (Angela), Eifert, S. (Sandra), Mokhtari, N.E.E., Ellis, S.G. (Stephen), Elosua, R. (Roberto), Engert, J.C. (James), Epstein, S.E. (Stephen), Faire, U. (Ulf) de, Fischer, M. (Marcus), Folsom, A.R. (Aaron), Freyer, J. (Jennifer), Gigante, B. (Bruna), Girelli, D. (Domenico), Gretarsdottir, S. (Solveig), Gudnason, V. (Vilmundur), Gulcher, J.R. (Jeffrey), Halperin, E. (Eran), Hammond, N. (Naomi), Hazen, S.L. (Stanley), Hofman, A. (Albert), Horne, B.D. (Benjamin), Illig, T. (Thomas), Iribarren, C. (Carlos), Jones, G.T. (Gregory), Jukema, J.W. (Jan Wouter), Kaiser, M.A. (Michael), Kaplan, R.C. (Robert), Khaw, K-T. (Kay-Tee), Knowles, J.W. (Joshua), Kolovou, G. (Genovefa), Kong, A. (Augustine), Laaksonen, R. (Reijo), Lambrechts, D. (Diether), Leander, K. (Karin), Lettre, G. (Guillaume), Lieb, W. (Wolfgang), Loley, C. (Christina), Lotery, A.J. (Andrew), Mannucci, P.M. (Pier), Maouche, S. (Seraya), Martinelli, N. (Nicola), McKeown, P.P. (Pascal), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Merlini, P.A., Mooser, V. (Vincent), Morgan, T. (Thomas), Mühleisen, T.W. (Thomas), Muhlestein, J.B. (Joseph), Münzel, T. (Thomas), Musunuru, K. (Kiran), Nahrstaedt, J. (Janja), Nelson, C.P. (Christopher P.), Nöthen, M.M. (Markus), Olivieri, O. (Oliviero), Patel, R.S. (Riyaz), Patterson, C.C. (Chris), Peters, A. (Annette), Peyvandi, F. (Flora), Qu, L. (Liming), Quyyumi, A.A. (Arshed), Rader, D.J. (Daniel), Rallidis, L.S. (Loukianos), Rice, C. (Catherine), Rosendaal, F.R. (Frits), Rubin, D. (Diana), Salomaa, V. (Veikko), Sampietro, M.L. (Maria Lourdes), Sandhu, M.S. (Manj), Schadt, E.E. (Eric), Schillert, A. (Arne), Schreiber, S. (Stefan), Schrezenmeir, J. (Jürgen), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Sivananthan, M. (Mohan), Sivapalaratnam, S. (Suthesh), Smith, A.V. (Albert Vernon), Snoep, J.D. (Jaapjan), Soranzo, N. (Nicole), Spertus, J.A. (John), Stark, K. (Klaus), Stirrups, K. (Kathy), Stoll, M. (Monika), Tang, W.H.W. (Wilson), Tennstedt, S. (Stephanie), Thorgeirsson, G. (Gudmundur), Thorleifsson, G. (Gudmar), Tomaszewski, M. (Maciej), Uitterlinden, A.G. (André), Rij, A.M. (Andre) van, Voight, B.F. (Benjamin), Wareham, N.J. (Nick), Wells, G.A. (George), Wichmann, H.E. (Heinz Erich), Wild, P.S. (Philipp), Willenborg, C. (Christina), Witteman, J.C.M. (Jacqueline), Wright, B.J. (Benjamin), Ye, S. (Shu), Zeller, T. (Tanja), Ziegler, A. (Andreas), Cambien, F. (François), Goodall, A.H. (Alison), Cupples, L.A. (Adrienne), Quertermous, T. (Thomas), Mäsignrz, W. (Winfried), Hengstenberg, C. (Christian), Blankenberg, S. (Stefan), Ouwehand, W.H. (Willem), Hall, A.S. (Alistair), Kastelein, J.J.P. (John), Deloukas, P. (Panagiotis), Thompson, J.R. (John), Stefansson, K. (Kari), Roberts, R. (Robert), Li, M. (Mingyao), Thorsteinsdottir, U. (Unnur), O'Donnell, C.J. (Christopher), McPherson, R. (Ruth), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), Schäffer, A. (Arne), Schunkert, H. (Heribert), König, I.R. (Inke), Kathiresan, S. (Sekar), Reilly, M.P. (Muredach), Assimes, T.L. (Themistocles), Holm, H. (Hilma), Preuss, M. (Michael), Stewart, A.F.R. (Alexandre), Barbalic, M. (maja), Gieger, C. (Christian), Absher, D. (Devin), Aherrahrou, Z. (Zouhair), Allayee, H. (Hooman), Altshuler, D. (David), Anand, S.S. (Sonia), Andersen, K.K. (Karl), Anderson, J.L. (Jeffrey), Ardissino, D. (Diego), Ball, S.G. (Stephen), Balmforth, A.J. (Anthony), Barnes, T.A. (Timothy), Becker, D.M. (Diane), Berger, K. (Klaus), Bis, J.C. (Joshua), Boekholdt, S.M. (Matthijs), Boerwinkle, E.A. (Eric), Braund, P.S. (Peter), Brown, M.J. (Morris), Burnett, M.S., Buysschaert, I. (Ian), Carlquist, J.F. (John), Chen, L. (Li), Cichon, S. (Sven), Codd, V. (Veryan), Davies, R.W. (Robert), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Demissie, S. (Serkalem), Devaney, J. (Joseph), Diemert, P. (Patrick), Do, R. (Ron), Doering, A. (Angela), Eifert, S. (Sandra), Mokhtari, N.E.E., Ellis, S.G. (Stephen), Elosua, R. (Roberto), Engert, J.C. (James), Epstein, S.E. (Stephen), Faire, U. (Ulf) de, Fischer, M. (Marcus), Folsom, A.R. (Aaron), Freyer, J. (Jennifer), Gigante, B. (Bruna), Girelli, D. (Domenico), Gretarsdottir, S. (Solveig), Gudnason, V. (Vilmundur), Gulcher, J.R. (Jeffrey), Halperin, E. (Eran), Hammond, N. (Naomi), Hazen, S.L. (Stanley), Hofman, A. (Albert), Horne, B.D. (Benjamin), Illig, T. (Thomas), Iribarren, C. (Carlos), Jones, G.T. (Gregory), Jukema, J.W. (Jan Wouter), Kaiser, M.A. (Michael), Kaplan, R.C. (Robert), Khaw, K-T. (Kay-Tee), Knowles, J.W. (Joshua), Kolovou, G. (Genovefa), Kong, A. (Augustine), Laaksonen, R. (Reijo), Lambrechts, D. (Diether), Leander, K. (Karin), Lettre, G. (Guillaume), Lieb, W. (Wolfgang), Loley, C. (Christina), Lotery, A.J. (Andrew), Mannucci, P.M. (Pier), Maouche, S. (Seraya), Martinelli, N. (Nicola), McKeown, P.P. (Pascal), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Merlini, P.A., Mooser, V. (Vincent), Morgan, T. (Thomas), Mühleisen, T.W. (Thomas), Muhlestein, J.B. (Joseph), Münzel, T. (Thomas), Musunuru, K. (Kiran), Nahrstaedt, J. (Janja), Nelson, C.P. (Christopher P.), Nöthen, M.M. (Markus), Olivieri, O. (Oliviero), Patel, R.S. (Riyaz), Patterson, C.C. (Chris), Peters, A. (Annette), Peyvandi, F. (Flora), Qu, L. (Liming), Quyyumi, A.A. (Arshed), Rader, D.J. (Daniel), Rallidis, L.S. (Loukianos), Rice, C. (Catherine), Rosendaal, F.R. (Frits), Rubin, D. (Diana), Salomaa, V. (Veikko), Sampietro, M.L. (Maria Lourdes), Sandhu, M.S. (Manj), Schadt, E.E. (Eric), Schillert, A. (Arne), Schreiber, S. (Stefan), Schrezenmeir, J. (Jürgen), Schwartz, S.M. (Stephen), Siscovick, D.S. (David), Sivananthan, M. (Mohan), Sivapalaratnam, S. (Suthesh), Smith, A.V. (Albert Vernon), Snoep, J.D. (Jaapjan), Soranzo, N. (Nicole), Spertus, J.A. (John), Stark, K. (Klaus), Stirrups, K. (Kathy), Stoll, M. (Monika), Tang, W.H.W. (Wilson), Tennstedt, S. (Stephanie), Thorgeirsson, G. (Gudmundur), Thorleifsson, G. (Gudmar), Tomaszewski, M. (Maciej), Uitterlinden, A.G. (André), Rij, A.M. (Andre) van, Voight, B.F. (Benjamin), Wareham, N.J. (Nick), Wells, G.A. (George), Wichmann, H.E. (Heinz Erich), Wild, P.S. (Philipp), Willenborg, C. (Christina), Witteman, J.C.M. (Jacqueline), Wright, B.J. (Benjamin), Ye, S. (Shu), Zeller, T. (Tanja), Ziegler, A. (Andreas), Cambien, F. (François), Goodall, A.H. (Alison), Cupples, L.A. (Adrienne), Quertermous, T. (Thomas), Mäsignrz, W. (Winfried), Hengstenberg, C. (Christian), Blankenberg, S. (Stefan), Ouwehand, W.H. (Willem), Hall, A.S. (Alistair), Kastelein, J.J.P. (John), Deloukas, P. (Panagiotis), Thompson, J.R. (John), Stefansson, K. (Kari), Roberts, R. (Robert), Li, M. (Mingyao), Thorsteinsdottir, U. (Unnur), O'Donnell, C.J. (Christopher), McPherson, R. (Ruth), Erdmann, J. (Jeanette), Samani, N.J. (Nilesh), and Schäffer, A. (Arne)

Abstract

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

Published
2011
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43. Impact of obesity on disease-specific health status after percutaneous coronary intervention in coronary disease patients.

Author

Poston, W.S. Carlos, Haddock, C. Keith, Conard, M., and Spertus, J.A.

Subjects
OBESITY, CORONARY disease, TRANSLUMINAL angioplasty, CORONARY artery bypass, BODY weight, QUALITY of life
Abstract

OBJECTIVE:: Several investigators have focused on obesity as a specific risk factor for mortality in patients undergoing bypass surgery, but few have examined it as a risk factor among patients undergoing percutaneous coronary interventions (PCI). In addition, none have evaluated the impact of obesity on post-PCI quality of life or disease-specific health status. This study examined whether obesity is a risk factor for poor quality of life or diminished health status 12-months postprocedure among a large cohort of PCI patients. RESEARCH METHODS AND PROCEDURES:: A total of 1631 consecutive PCI patients were enrolled into the study and classified as underweight (BMI <20?kg/m2), normal weight range (BMI =20 and <25?kg/m2), overweight (BMI =25 and <30?kg/m2), class I obese (BMI =30?kg/m2), or class II and III obese (BMI =35?kg/m2). The 12-month postprocedure outcomes included need for repeat procedure, survival, quality of life and health status, assessed using the Seattle Angina Questionnaire (SAQ) and the Short Form-12. RESULTS:: Obese patients with and without a history of revascularization were significantly younger than overweight, normal weight range, or underweight patients at the time of PCI. However, obese patients demonstrated similar long-term recovery and improved disease-specific health status and quality of life when compared to patients in the normal weight range after PCI. In addition, mortality and risk for repeat procedure was similar to those patients in the normal weight range patients at 12-months postrevascularization. Underweight patients who had no previous history of revascularization reported lower quality of life (F=3.02; P=0.018) and poorer physical functioning (F=2.82; P=0.024) than other BMI groups. CONCLUSION:: Obese patients presenting for revascularization were younger when compared to patients in the normal weight range, regardless of previous history of revascularization. However, weight status was not a significant predictor of differences in long-term disease-specific health status, quality of life, repeat procedures, or survival. Underweight patients demonstrated less improvement in quality of life and physical functioning than other BMI groups.International Journal of Obesity (2004) 28, 1011-1017. doi:10.1038/sj.ijo.0802703 Published online 22 June 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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44. Review of Available Instruments and Methods for Assessing Quality of Life in Anti-Anginal Trials.

Author

Bliven, B.D., Green, C.P., and Spertus, J.A.

Subjects
CORONARY heart disease treatment, QUALITY of life, CLINICAL trials
Abstract

Collection of patient-centred health status is a method for quantifying patient outcome in the context of clinical trials for the treatment of coronary artery disease (CAD). Traditional clinical trial end-points, such as morbidity and mortality, fail to adequately measure the health-related outcomes of disease states for which death is a rare occurrence. Health-related quality of life (QOL) and functional status surveys allow measurement of the general, and/or disease-specific, health-related limitations experienced by patients. Measures of patient preference, in turn, quantify the effects these health-related limitations have on the overall value patients ascribe to their current health state. Together, these outcomes measures may provide a more accurate appraisal of the benefit conferred by treatment. Currently, selection of the appropriate outcomes measures and methodological approaches for a clinical trial is complicated by the lack of consensus on a single quality of life measure for use with patients with (CAD). This article outlines the use of QOL measures in anti-anginal trials done to date and summarises the approaches currently available for assessing QOL, including the differences between psychometric and preference-based techniques, and general and disease-specific health measures. In conclusion, a framework is provided for selecting the appropriate instruments and methodology in the context of the clinical trial. [ABSTRACT FROM AUTHOR]

Published
1998
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45. Clinically important differences in health status for patients with heart disease: an expert consensus panel report

Author

Wyrwich, K.W., Spertus, J.A., Kroenke, K., Tierney, W.M., Babu, A.N., and Wolinsky, F.D.

Abstract

Background: The purpose of the study was to develop clinically important difference (CID) standards for patients with coronary artery disease and congestive heart failure that identify small, moderate, and large intraindividual changes with time in a modified version of the Chronic Heart Failure Questionnaire (CHQ) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, version 2). Prior work in ascertaining important difference standards for the CHQ have centered on patient-perceived changes. No important difference standards for the SF-36 have been published for patients with heart disease. This development of CIDs would facilitate the use of health status measures in daily clinical decision-making. Methods: We used a modification of the RAND Appropriateness Method to assemble and guide a 9-member consensus panel of physicians with substantial experience in using the CHQ or the SF-36 among patients with heart disease. Results: On the basis of their own experience using these measures and an extensive review of articles describing the development and use of these instruments, the expert panel achieved consensus on small, medium, and large clinically relevant changes in scores for the CHQ and SF-36. The CID standards established by this panel were slightly higher than the minimal important difference standards previously established for the CHQ using patient-perceived changes. Conclusions: The CID standards established by this expert panel provide an important and useful tool for determining whether routine clinical health status assessments will benefit patients and enhance physicians' decision-making capacity in clinical settings.

Published
2004
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49. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura 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Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C 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Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020
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50. Health status after invasive or conservative care in coronary and advanced kidney disease

Author

Spertus J. A., Jones P. G., Maron D. J., Mark D. B., O'Brien S. M., Fleg J. L., Reynolds H. R., Stone G. W., Sidhu M. S., Chaitman B. R., Chertow G. M., Hochman J. S., Bangalore S, ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anandaroop Lahiri, Anastasia M Kuzmina-Krutetskaya, Anastasia Vamvakidou, Andras Vertes, Andre Gabriel, Andrea Bartykowszki, Andrea Lorimer, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew Starovoytov, Andrzej Łabyk, Anelise Kawakami, Angela Hoye, Angelo Nobre, Anjali Acharya, Anjali Anand, Anjana Rishmawi, Ann Banfield, Ann Luyten, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Teresinska, Anne Marie Webb, Anne Heath, Anoop Mathew, Antonia Vega, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anu Tharini, Anupama Rao, Aquiles Valdespino-Estrada, Ariel Diaz, Arif Asif, Arnold H Seto, Arturo S Campos-Santaolalla, Asim N Cheema, Asker Ahmed, Atul Mathur, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Balaji Srinivasan, Baljeet Kaur, Balram Bhargava, Bandula Guruge, Barbara Wicklund, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Benoy N Shah, Bernard de Bruyne, Beth Abramson, Beth Stefanchik, Bethany Harvey, Bharati Shivalkar, 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Siddharth Gadage, Sik-Yin V Tan, Sílvia Zottis Poletti, Silvia Valbuena, Simone Savaris, Solomon Yakubov, Songlin Zhu, Sonika Gupta, Sorin Brener, Sothinathan Gurunathan, Soundarya Nayak, Sowjanya Reddy, Stanley E Cobos, Stefan Weikl, Stephanie M Lane, Stephanie Ferket, Stephanie Mavromichalis, Stephen Fremes, Steven A Fein, Steven P Sedlis, Steven Giovannone, Steven Weitz, Subhash Banerjee, Sudhanva S Hegde, Suellen Hosino, Sulagna Mookherjee, Suman Singh, Sumith Abeygunasekara, Sundeep Mishra, Sunil Kumar Verma, Suresh Kumar, Suryaprakash Narayanappa, Susan K Milbrandt, Susana Silva, Susanna Stevens, Suvarna Kolhe, Suzana Tavares, Suzanne Welsh, T A Kishore, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarek Rashid, Tarun K Mittal, Tauane Bello Duarte, Téodora Dutoiu, Teresa Delgadillo, Terrance Chua, Terrance Welch, Theodoros Kofidis, Thierry Lefevre, Tiago Silva, Timea Boros, Titus Lau, Tiziana Formisano, Tomasz Ciurus, Tomasz Tarchalski, Tracy Tan, Umesh Lingaraj, V K Bahl, V S 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H.R., Stone G.W., Sidhu M.S., Chaitman B.R., Chertow G.M., Hochman J.S., Bangalore S, and ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anandaroop Lahiri, Anastasia M Kuzmina-Krutetskaya, Anastasia Vamvakidou, Andras Vertes, Andre Gabriel, Andrea Bartykowszki, Andrea Lorimer, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew Starovoytov, Andrzej Łabyk, Anelise Kawakami, Angela Hoye, Angelo Nobre, Anjali Acharya, Anjali Anand, Anjana Rishmawi, Ann Banfield, Ann Luyten, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Teresinska, Anne Marie Webb, Anne Heath, Anoop Mathew, Antonia Vega, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anu Tharini, Anupama Rao, Aquiles Valdespino-Estrada, Ariel Diaz, Arif Asif, Arnold H Seto, Arturo S Campos-Santaolalla, Asim N Cheema, Asker Ahmed, Atul Mathur, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Balaji Srinivasan, Baljeet Kaur, Balram Bhargava, Bandula Guruge, Barbara Wicklund, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Benoy N Shah, Bernard de Bruyne, Beth Abramson, Beth Stefanchik, Bethany Harvey, Bharati Shivalkar, Bilal Malik, Binoy Mannekkattukudy Kurian, Bougrida Hammouche, Branko D Beleslin, Bruce Ferguson, Bruce McManus, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Carl-Éric Gagné, Carly Ohmart, Carol M Kartje, Caroline Alsweiler, Caroline Rodgers, Caroline Spindler, Carolyn J Gruber, Catherine Albert, Catherine Bone, Catherine Lemay, Cezary Kepka, Chandini Suvarna, Chantale Mercure, Charlene Wiyarand, Chetan Patel, Chiara Attanasio, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Buller, Christel Vassaliere, Christiaan Vrints, Christian Witzke, Christie Ballantyne, Christina Björklund, Christine Roraff, Christophe Laure, Christophe Thuaire, Christopher Chan, Christopher Fordyce, Christopher Kinsey, Chunli Xia, Cidney Schultz, Claes Held, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Clemens T Kadalie, Corine Thobois, Courtney Page, Cristina Bare, Dalisa Espinosa, Dan Gao, Dana Rizk, Daniela Puzhevsky, Data Analyst, David M Charytan, David O Williams, David Booth, David Charytan, David Cohen, David DeMets, David Foo, David Goldfarb, David Schlichting, David Sisson, David Taggart, David Waters, David Wheeler, David Williams, Davis Vo, Dawid Teodorczyk, Dawn D Shelstad, Dean Kereiakes, Deborah Yip, Deepa Ramaswamy, Deirdre Mattina, Deirdre Murphy, Dengke Jiang, Derek Cyr, Diana Cukali, Diane Camara, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Doreen Reimann, Doron Schwartz, Duarte Cacela, Dwayne S G Conway, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Eduardo Gomes Lima, Eduardo Hernandez-Rangel, Edward D Nicol, Edyta Kaczmarska, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise van Dongen, Elissa Restelli Piloto, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizaveta V Zbyshevskaya, Ellie Fridell, Ellis W Lader, Elvira Gosmanova, Emilie Tachot, Emma Howard, Emmanuel Sorbets, Encarnación Alonso-Álvarez, Eric Daugas, Erick Alexánderson Rosas, Estelle Montpetit, Eugene Passamani, Evgeny Shutov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, Fabio Fimiani, Fadi Hage, Fahim Haider Jafary, Fang Feng, Fatima Ranjbaran, Fausto J Pinto, Fernando Caeiro, Fernando Nolasco, Filipa Silva, Filippo Ottani, Firas Al Solaiman, Flávia Egydio, Florina Chereches, Francesca De Micco, Francesca Bianchini, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francisca Patuleia Figueiras, François Madore, Frank Harrell, Frank Rockhold, Frans Van de Werf, Franziska Guenther, Fred Mohr, G Karthikeyan, Gabriel Galeote, Gabriel Grossmann, Gabriel Steg, Gabriela Guzman, Gabriele Gabrielli, Gang Chen, Gautam Sharma, Gaylin Petty, Gelmina Mikolaitiene, Gennie Yee, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Girish Mishra, Gonzalo Barge-Caballero, Grace M Young, Graciela Scaro, Graham Wong, Gregg Pressman, Gregor Simonis, Gudrun Steinmaurer, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillermo Garcia-Garcia, Guoqin Wang, Gurpreet S Wander, Gurpreet Gulati, Haibo Zhang, Halina Marciniak, Hao Dai, Haojian Dong, Harold Franch, Harvey White, Hatem Elabd, Hayley Pomeroy, Heather Golden, Heidi Wilson, Helene Abergel, Hemalata Siddaram, Hemant Shakhar Mahapatra, Henry C Stokes, Hermine Osseni, Herwig Schuchlenz, Hicham Skali, Holly Mattix-Kramer, Hong Cheng, Hossam Mahrous, Hristo Pejkov, Hugo Marques, Hui Zhong, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ikraam Hassan, Ileana L Pina, Ilona Tamasauskiene, Inês Zimbarra Cabrita, Ines Rodrigues, Inga Soveri, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Isabelle Roy, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, Jacek Kusmierek, Jackie Chow, Jaekyeong Heo, Jakub Maksym, James E Davies, James J Jang, James Hirsch, James Tatoulis, Jan Henzel, Janaina Oliveira, Janani Rangaswami, Jane Eckstein, Janitha Raj, Jaqueline Pozzibon, Jaroslaw Drozdz, Jason Loh Kwok Kong, Jason T Call, Jason Linefsky, Javier J Garcia, Jay Meisner, Jayne Scales, Jean Michel Juliard, Jean Diodati, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeff Leimberger, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Stojkovic, Jenne M Jose, Jennifer L Stanford, Jennifer Hogan, Jennifer Horst, Jennifer Isaacs, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jerry Yee, Jessica Berg, Jesus Peteiro, Jesús Peteiro, Jia Li, Jiamin Liu, Jianxin Zhang, Jill Marcus, Jim Blankenship, Jing Dong, Jiyan Chen, Jo Evans, Joaquín V Peñafiel, Joe Sabik, Johann Christopher, John B Kostis, John Joseph Graham, John Doan, John Jose, John Kotter, John Lehman, John Middleton, John Pownall, Jonathan M Gleadle, Jonathan S Chavez-Iñiguez, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Lebowitz, Jonean Thorsen, Jorge Carrillo Calvillo, Jorge Escobedo, José A Ortega-Ramírez, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Costa Vieira, José M Flores-Palacios, Jose Fragata, Jose Lopes, Jose Lopez-Sendon, José Lopez-Sendon, Jose Rueda, Joseph B Selvanayagam, Joseph Sacco, Joshua P Loh, Joy Burkhardt, Juan Manuel López Quijano, Juan Gaztanaga, Judit Sebo, Judith Wright, Juergen Stumpf, Julia de Aveiro Morata, Julio César Figal, Julio Hernandez Jaras, Junqing Yang, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Karen Calfas, Karen Petrosyan, Karen Servilla, Karen Swan, Karin Ploetze, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Katharina Knaut, Katherine Martin, Kathleen Claes, Kathryn Mason, Ken Mahaffey, Kenneth Gin, Kerry Lee, Kerstin Bonin, Kerstin Mikes, Kevin R Bainey, Kevin T Harley, Kevin Marzo, Kevin McMahon, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khrystyna Kushniriuk, Kian-Keong Poh, Kim Holland, Kimberly E Halverson, Kinnari Murphy, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kreton Mavromatis, Krishnakumar Hongalgi, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristine Arges, Kristine Teoh, Krzysztof Drzymalski, Lalathaksha Kumbar, Laszlone Matics, LaTonya J Hickson, Laura Keinaite, Laura Sarti, Laura True, Lawrence M Phillips, Lawrence Friedman, Leandro C Maranan, Leda Lotaif, Lekshmi Dharmarajan, Leo A Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Li Hai Yan, Li Li, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilian Mazza Barbosa, Liljana Tozija, Linda Arcand, Lino Patricio, Liping Zhang, Lisa Hatch, Lixin Jiang, Liz Low, Loay Salman, Lorena Lopez, Lori Pritchard, Luis Bernanrdes, Luis Guzman, Lynette L Teo, M Sowjanya Reddy, Maarten Simoons, Maayan Konigstein, Mafalda Selas, Magdalena Madero, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdy Abdelhamid, Magid Fahim, Mahevamma Mylarappa, Majo X Joseph, Malgorzata Frach, Manjula Rani, Marcello Galvani, Marcin Demkow, Marcin Szkopiak, Marco De Fabritis, Marco Magnoni, Marco Marini, Marco Sicuro, Marek Roik, Maria A Alfonso, Maria Antonieta Pereira de Moraes, María Dolores Martínez-Ruíz, Maria Eugenia Canziani, Maria Eugenia Martin, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Andreasson, Maria Posada, Marianna D A Dracoulakis, Mariano Rubio, Marija T Petrovic, Marina Vieira, Mario J Garcia, Mario D'arezzo, Maris Orgera, Marius Miglinas, Mark Garand, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Swiderek, Martha Meyer, Martina Ceseri, Martinia Tricoli, Mary Wiilliams, Mary Ann Champagne, Mary Streif, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Shinseki, Matthew Weir, Maura Carina Nédio, Max-Paul Winter, Mayil S Krishnam, Meenakshi Mishra, Mei Hwang, Melemadathil Srilatha, Melissa LeFevre, Mengistu Simegn, Michael A Gibson, Michael B Rubens, Michael D Shapiro, Michael Chobanian, Michael Davidson, Michael Farkouh, Michael Mack, Michal Wlodarczyk, Michel G Khouri, Michelle Crowder, Michelle Ratliff, Miguel Borges Santos, Miguel Nobre Menezes, Miguel Perez Fontan, Miguel Barrero, Mihaly Tapolyai, Mikhail T Torosoff, Milan R Dobric, Milind Avdhoot Gadkari, Min Tun Kyaw, Miri Revivo, Mitchel B Lustre, Mohamed Adel, Mohamed Hassan, Mohammad El-Hajjar, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Monika Laukyte, Muhamed Saric, Myrthes Emy Takiuti, Nadia Asif, Nagaraja Moorthy, Naima L Ogletree, Nana O Katamadze, Nandita Nataraj, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Nathalie Brosens, Naved Aslam, Naveed Akhtar, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Neesh Pannu, Neill Duncan, Nevena Garcevic, Ngaire Meadows, Nicholas Danchin, Nicole Deming, Nikola N Boskovic, Nikolaos Karogiannis, Ning Zhang, Nirmal Kumar, Niruta Sharma, Nitika Chadha, Nitish Naik, Noelle M Durfee, Nora M Cosgrove, Norbert Urbanski, Norma Hogg, Olga Walesiak, Olga Zdończyk, Olga Zhdanova, Olivia Anaya, Olugbenga Bello, Omar Almousalli, Omar Thompson, Orit Kliuk, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, Pablo Raffaele, Page Salanger, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Ouyang, Pamela Woodard, Paola Emanuela Poggio Smanio, Paola Smanio, Paolo Calabro, Patricia K Nguyen, Patricia Alarie, Patricia Carrilho, Patricia Endsley, Patricia Pellikka, Patrycja Lebioda, Paul Der Mesropian, Paul Hauptman, Paula García-González, Paula Wilson, Paulo Cury Rezende, Paulo Novis Rocha, Pedro Canas Silva, Pedro Farto E Abreu, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peiyu He, Peter A McCullough, Peter H Stone, Peter Douglass, Peter Sizeland, Peter Voros, Philippe Gabriel Steg, Philippe Genereux, Philippe Généreux, Philippe Menasche, Philippe Rheault, Piero Tassinario, Pierre Gervais, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Poay-Huan Loh, Pouneh Samadi, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puneet Sodhi, Pushpa Naik, Qi Zhong, Qian Zhao, Qianqian Yuan, Qiulan Xie, Rachel Murphy, Radmila Lyubarova, Radmilar Lyubarova, Raewyn Fisher, Rafael Diaz, Rafael Maldonado, Rafael Selgas, Raffaele Bugiardini, Rafia Chaudhry, Raisa Kavalakkat, Rajalekshmi Vs, Rajesh Gopalan Nair, Rajiv Narang, Rakesh Yadav, Ramiro Carvalho, Ramon de Jesús-Pérez, Ran Leng, Ranjan Kachru, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Reinette Hampson, Renato Abdala Karam Kalil, Renato D Lopes, Renato George Eick, Renato Lopes, Reshma Ravindran, Reto Andreas Gamma, Ricardo Costa, Richa Bhatt, Richard H J Trimlett, Risha Patel, Rita Coram, Robert K Riezebos, Robert M Donnino, Robert Guyton, Robert Harrington, Robert Malecki, Roberto 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Patel, Shruti Pandey, Shuyang Zhang, Siddharth Gadage, Sik-Yin V Tan, Sílvia Zottis Poletti, Silvia Valbuena, Simone Savaris, Solomon Yakubov, Songlin Zhu, Sonika Gupta, Sorin Brener, Sothinathan Gurunathan, Soundarya Nayak, Sowjanya Reddy, Stanley E Cobos, Stefan Weikl, Stephanie M Lane, Stephanie Ferket, Stephanie Mavromichalis, Stephen Fremes, Steven A Fein, Steven P Sedlis, Steven Giovannone, Steven Weitz, Subhash Banerjee, Sudhanva S Hegde, Suellen Hosino, Sulagna Mookherjee, Suman Singh, Sumith Abeygunasekara, Sundeep Mishra, Sunil Kumar Verma, Suresh Kumar, Suryaprakash Narayanappa, Susan K Milbrandt, Susana Silva, Susanna Stevens, Suvarna Kolhe, Suzana Tavares, Suzanne Welsh, T A Kishore, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarek Rashid, Tarun K Mittal, Tauane Bello Duarte, Téodora Dutoiu, Teresa Delgadillo, Terrance Chua, Terrance Welch, Theodoros Kofidis, Thierry Lefevre, Tiago Silva, Timea Boros, Titus Lau, Tiziana Formisano, Tomasz Ciurus, Tomasz Tarchalski, Tracy Tan, Umesh Lingaraj, V K Bahl, V S Narain, Valentina Pellu, Valentine Lobo, Valerie Robesyn, Vandana Yadav, Veerabhadra Gupta, Verghese Mathew, Vicente Miro, Victoria Gumerova, Victoria Hernandez, Vijay Kher, Vijay Kumar, Vikas Makkar, Vikranth Reddy, Viktoria Bulkley, Vinoi George David, Virendra Misra, Virginia Fernández-Figares, Vladimir Ryasniansky, Vojislav L Giga, Wael A Almahmeed, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Wayne Pennachi, Wei Ling Lau, Weibing Xing, Weijing Bian, Wendy L Stewart, Wendy Drewes, Whady Hueb, William Weintraub, Winnie C Sia, Xacobe Flores-Ríos, Xiang Ma, Xiangqiong Gu, Xiaomei Li, Xiaoyi Xu, Xin Fu, Xuemei Li, Xutong Wang, Yanek Pépin-Dubois, Yaron Arbel, Yechen Han, Yiming Lit, Ying Tung Sia, Ying Wang, Yining Yang, Yitong Ma, Yolayfi Peralta, Yves Smets, Yvonne Taul, Zalina Kudzoeva, Zeljko Z Markovic, Zhangsuo Liu, Zhenyu Liu, Zhiming Ye, Zixiang Yu, Zoltan Davidovits, Zvezdana Petronijevic

Subjects
Male, Intention to Treat Analysi, medicine.medical_treatment, Health Status, Myocardial Ischemia, 030204 cardiovascular system & hematology, Coronary Angiography, law.invention, Health Statu, 0302 clinical medicine, Randomized controlled trial, law, Surveys and Questionnaires, Odds Ratio, Surveys and Questionnaire, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, medicine.diagnostic_test, General Medicine, Middle Aged, Intention to Treat Analysis, Cardiology, Female, Human, medicine.medical_specialty, Revascularization, Follow-Up Studie, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, cardiovascular diseases, Healthy Lifestyle, Renal Insufficiency, Chronic, Proportional Hazards Models, Aged, Intention-to-treat analysis, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Odds ratio, medicine.disease, Angiography, Exercise Test, Proportional Hazards Model, business, Kidney disease, Follow-Up Studies
Abstract

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of

Published
2020

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