Abstract:
Importance:Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene-drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade. Objective:To determine whether screening for clinical associations with the IL6R SNP in a phenome-wide association study (PheWAS) using EHR biobank data can identify drug effects from IL6R clinical trials. Design, Setting, and Participants:Diagnosis codes and routine laboratory measurements were extracted from the VA Million Veteran Program (MVP); diagnosis codes were mapped to phenotype groups using published PheWAS methods. A PheWAS was performed by fitting logistic regression models for testing associations of the IL6R SNPs with 1342 phenotype groups and by fitting linear regression models for testing associations of the IL6R SNP with 26 routine laboratory measurements. Significance was reported using a false discovery rate of 0.05 or less. Findings were replicated in 2 independent cohorts using UK Biobank and Vanderbilt University Biobank data. The Million Veteran Program included 332 799 US veterans; the UK Biobank, 408 455 individuals from the general population of the United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a tertiary care center. Exposures:IL6R SNPs (rs2228145; rs4129267). Main Outcomes and Measures:Phenotypes defined by International Classification of Diseases, Ninth Revision codes. Results:Of the 332 799 veterans included in the main cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years. The IL6R SNP was most strongly associated with a reduced risk of aortic aneurysm phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed known off-target effects of IL6R blockade from clinical trials (eg, higher hemoglobin level). The reduced risk for aortic aneurysms among those with the IL6R SNP in the MVP was replicated in the Vanderbilt University Biobank, and the reduced risk for coronary heart disease was replicated in the UK Biobank. Conclusions and Relevance:In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.
journal_name
JAMA Cardioljournal_title
JAMA cardiologyauthors
Cai T,Zhang Y,Ho YL,Link N,Sun J,Huang J,Cai TA,Damrauer S,Ahuja Y,Honerlaw J,Huang J,Costa L,Schubert P,Hong C,Gagnon D,Sun YV,Gaziano JM,Wilson P,Cho K,Tsao P,O'Donnell CJ,Liao KP,VA Million Veteran Program.doi
10.1001/jamacardio.2018.2287subject
Has Abstractpub_date
2018-09-01 00:00:00pages
849-857issue
9eissn
2380-6583issn
2380-6591pii
2696438journal_volume
3pub_type
杂志文章相关文献
JAMA Cardiology文献大全abstract:IMPORTANCE:The adverse outcomes associated with atrial fibrillation (AF) have been studied in predominantly white cohorts. Racial differences in outcomes associated with AF merit continued investigation. OBJECTIVE:To evaluate the race-specific associations of AF with stroke, heart failure, coronary heart disease (CHD)...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2016.1025
更新日期:2016-07-01 00:00:00
abstract:Importance:Medicare Advantage (MA), a private insurance plan option, now covers one-third of all Medicare beneficiaries. Although patients with cardiovascular disease enrolled in MA have been reported to receive higher quality of care in the ambulatory setting than patients enrolled in fee-for-service (FFS) Medicare, i...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2020.3638
更新日期:2020-09-02 00:00:00
abstract:Importance:Little is known about the influence of comprehensive public health initiatives according to out-of-hospital cardiac arrest (OHCA) location, particularly at home, where resuscitation efforts and outcomes have historically been poor. Objective:To describe temporal trends in bystander cardiopulmonary resuscita...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.3471
更新日期:2017-11-01 00:00:00
abstract:Importance:One-third of Medicare beneficiaries are enrolled in Medicare Advantage (MA), Medicare's private plan option. Medicare Advantage incentivizes performance on evidence-based care, but limited information exists using reliable clinical data to determine whether this translates into better quality for patients wi...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2019.0007
更新日期:2019-03-01 00:00:00
abstract:Importance:The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER-1) evaluated the durability of long-term efficacy and safety during long-term therapy with evolocumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9). Objective:To determine whether LDL-C level reductions ...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.0747
更新日期:2017-06-01 00:00:00
abstract:Importance:Somatic mutations causing clonal expansion of hematopoietic cells (clonal hematopoiesis of indeterminate potential [CHIP]) are increased with age and associated with atherosclerosis and inflammation. Age and inflammation are the major risk factors for heart failure, yet the association of CHIP with heart fai...
journal_title:JAMA cardiology
pub_type: 临床试验,杂志文章
doi:10.1001/jamacardio.2018.3965
更新日期:2019-01-01 00:00:00
abstract:Importance:Myocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the d...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2020.1555
更新日期:2020-09-01 00:00:00
abstract:Importance:Women are at higher risk of drug-induced torsade de pointes (TdP) than men. Androgens are protective. Influence of oral contraception on drug-induced TdP and QT prolongation is controversial. Objective:To determine if the extent of sotalol-induced corrected QT (QTc) prolongation and specific T-wave morpholo...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2018.2251
更新日期:2018-09-01 00:00:00
abstract:Importance:If we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular phy...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2019.5306
更新日期:2020-03-01 00:00:00
abstract:Importance:High-resolution stratification of risk of sudden cardiac arrest (SCA) in individual patients is a tool that is necessary for achieving effective and efficient application of data generated by population-based research. This concept is at the core of initiatives for merging cost effectiveness with maximized c...
journal_title:JAMA cardiology
pub_type: 杂志文章,评审
doi:10.1001/jamacardio.2017.0266
更新日期:2017-06-01 00:00:00
abstract:Importance:Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accurac...
journal_title:JAMA cardiology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamacardio.2016.2839
更新日期:2016-11-01 00:00:00
abstract:Importance:Quality of percutaneous coronary intervention (PCI) is commonly assessed by risk-adjusted mortality. However, this metric may result in procedural risk aversion, especially for high-risk patients. Objective:To determine correlation and reclassification between hospital-level disease-specific mortality and P...
journal_title:JAMA cardiology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamacardio.2020.0753
更新日期:2020-07-01 00:00:00
abstract:Importance:Racial differences are recognized in multiple cardiovascular parameters, including left ventricular hypertrophy and heart failure, which are 2 major manifestations of hypertrophic cardiomyopathy. The association of race with disease expression and outcomes among patients with hypertrophic cardiomyopathy is n...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2019.4638
更新日期:2020-01-01 00:00:00
abstract:Importance:As many as 10% of women experience natural menopause by the age of 45 years. If confirmed, an increased risk of cardiovascular disease (CVD) and all-cause mortality associated with premature and early-onset menopause could be an important factor affecting risk of disease and mortality among middle-aged and o...
journal_title:JAMA cardiology
pub_type: 杂志文章,meta分析,评审
doi:10.1001/jamacardio.2016.2415
更新日期:2016-10-01 00:00:00
abstract:Importance:With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduc...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.0264
更新日期:2017-05-01 00:00:00
abstract:Importance:The Department of Veterans Affairs (VA) operates a nationwide system of hospitals and hospital-affiliated clinics, providing health care to more than 2 million veterans with cardiovascular disease. While data permitting hospital comparisons of the outcomes of acute cardiovascular care (eg, myocardial infarct...
journal_title:JAMA cardiology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamacardio.2018.1115
更新日期:2018-07-01 00:00:00
abstract:Importance:Recent data support percutaneous revascularization as an alternative to coronary artery bypass grafting in unprotected left main (ULM) coronary lesions. However, the relevance of these trials to current practice is unclear, as patterns and outcomes of ULM percutaneous coronary intervention (PCI) in contempor...
journal_title:JAMA cardiology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamacardio.2018.4376
更新日期:2019-02-01 00:00:00
abstract:Importance:Accurate, real-time case identification is needed to target interventions to improve quality and outcomes for hospitalized patients with heart failure. Problem lists may be useful for case identification but are often inaccurate or incomplete. Machine-learning approaches may improve accuracy of identificatio...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2016.3236
更新日期:2016-12-01 00:00:00
abstract:Importance:Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown. Objective:To determine the association between mental stress-induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and a...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2019.3252
更新日期:2019-10-01 00:00:00
abstract:Importance:Many of the quality measures used to assess accountable care organization (ACO) performance in the Medicare Shared Savings Program (MSSP) focus on disease control and medication use among patients with cardiovascular disease and diabetes. To date, the association between participation in the MSSP by provider...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.2172
更新日期:2017-09-01 00:00:00
abstract:Importance:Bioresorbable scaffolds were designed to provide clinical benefits after their complete bioresorption. Prior studies demonstrated early risks with the Absorb polymeric bioresorbable vascular scaffold (BVS). Whether this risk profile changes over time during the course of its bioresorption is unknown. Object...
journal_title:JAMA cardiology
pub_type: 杂志文章,meta分析
doi:10.1001/jamacardio.2019.4101
更新日期:2019-12-01 00:00:00
abstract:Importance:Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. Objective:To examine whether monthly...
journal_title:JAMA cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1001/jamacardio.2017.0175
更新日期:2017-06-01 00:00:00
abstract:Importance:Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and M...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.2275
更新日期:2017-09-01 00:00:00
abstract:Importance:Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder associated with premature death due to cardiovascular events during the second decade of life. However, because of its rarity (107 identified living patients), the natural history of cardiac disease remains uncharacterized. Therefore, meani...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.5235
更新日期:2018-04-01 00:00:00
abstract:IMPORTANCE:Although survival of patients with in-hospital cardiac arrest varies markedly among hospitals, specific resuscitation practices that distinguish sites with higher cardiac arrest survival rates remain unknown. OBJECTIVE:To identify resuscitation practices associated with higher rates of in-hospital cardiac a...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2016.0073
更新日期:2016-05-01 00:00:00
abstract:Importance:Hospitalizations for worsening heart failure (WHF) represent an enormous public health and financial burden, with physicians, health systems, and payers placing increasing emphasis on hospitalization prevention. In addition, maximizing time out of the hospital is an important patient-centered outcome. In thi...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.5250
更新日期:2018-03-01 00:00:00
abstract:Importance:Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding. Objective:We conducted a meta-analysis of randomized clinical trials that tested...
journal_title:JAMA cardiology
pub_type: 杂志文章,meta分析
doi:10.1001/jamacardio.2019.1870
更新日期:2019-08-01 00:00:00
abstract:Importance:Computed tomography-derived fractional flow reserve (FFR-CT) is a novel, noninvasive test for myocardial ischemia. Clinicians using FFR-CT must be able to interpret individual FFR-CT results to determine subsequent patient care. Objective:To provide clinicians a means of interpreting individual FFR-CT resul...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2017.1314
更新日期:2017-07-01 00:00:00
abstract::P values and hypothesis testing methods are frequently misused in clinical research. Much of this misuse appears to be owing to the widespread, mistaken belief that they provide simple, reliable, and objective triage tools for separating the true and important from the untrue or unimportant. The primary focus in inter...
journal_title:JAMA cardiology
pub_type: 杂志文章
doi:10.1001/jamacardio.2016.3312
更新日期:2016-12-01 00:00:00
abstract:Importance:Use of transcatheter aortic valve replacement (TAVR) for severe aortic stenosis is growing rapidly. However, to our knowledge, the durability of these prostheses is incompletely defined. Objective:To determine the midterm hemodynamic performance of balloon-expandable transcatheter heart valves. Design, Set...
journal_title:JAMA cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1001/jamacardio.2017.3306
更新日期:2017-11-01 00:00:00