Contrast-Associated Acute Kidney Injury Mehran, Roxana; Dangas, George D; Weisbord, Steven D
The New England journal of medicine,
05/2019, Volume:
380, Issue:
22
Journal Article
Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown.
Using a ...polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women's Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet.
The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval CI, 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category.
Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.).
Summary Stable coronary artery disease is the most common clinical manifestation of ischaemic heart disease and a leading cause of mortality worldwide. Myocardial revascularisation is a mainstay in ...the treatment of symptomatic patients or those with ischaemia-producing coronary lesions, and reduces ischaemia to a greater extent than medical treatment. Documentation of ischaemia and plaque burden is fundamental in the risk stratification of patients with stable coronary artery disease, and several invasive and non-invasive techniques are available (eg, fractional flow reserve or intravascular ultrasound) or being validated (eg, instantaneous wave-free ratio and optical coherence tomography). The use of new-generation drug-eluting stents and arterial conduits greatly improve clinical outcome in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is feasible, safe, and effective in many patients with stable coronary artery disease who remain symptomatic despite medical treatment. In patients with multivessel and left main coronary artery disease, the decision between PCI or CABG is guided by the local Heart Team (team of different cardiovascular specialists, including non-invasive and invasive cardiologists, and cardiac surgeons), who carefully judge the possible benefits and risks inherent to PCI and CABG. In specific subsets, such as patients with diabetes and advanced, multivessel coronary artery disease, CABG remains the standard of care in view of improved protection against recurrent ischaemic adverse events.
Atherosclerosis and plaque disruption have a central pathological role in the majority of patients who present with an acute coronary syndrome (ACS), but non-atherosclerotic processes are also ...important contributors to a substantial number of ACS events and require different diagnostic and therapeutic strategies. In the absence of obstructive coronary artery disease, intravascular imaging techniques might be needed to delineate the underlying aetiology, together with a high index of suspicion for other important causes of ACS. In this Review, we discuss five non-atherosclerotic causes of ACS, including spontaneous coronary artery dissection, coronary artery embolism, vasospasm, myocardial bridging and stress-induced cardiomyopathy (Takotsubo syndrome). Important diagnostic findings, management strategies and prognostic data for these non-atherosclerotic mechanisms of ACS are reviewed.
Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among ...older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear.
We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls. To assess causality, we perturbed the function of Tet2, the second most commonly mutated gene linked to clonal hematopoiesis, in the hematopoietic cells of atherosclerosis-prone mice.
In nested case-control analyses from two prospective cohorts, carriers of CHIP had a risk of coronary heart disease that was 1.9 times as great as in noncarriers (95% confidence interval CI, 1.4 to 2.7). In two retrospective case-control cohorts for the evaluation of early-onset myocardial infarction, participants with CHIP had a risk of myocardial infarction that was 4.0 times as great as in noncarriers (95% CI, 2.4 to 6.7). Mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary heart disease. CHIP carriers with these mutations also had increased coronary-artery calcification, a marker of coronary atherosclerosis burden. Hypercholesterolemia-prone mice that were engrafted with bone marrow obtained from homozygous or heterozygous Tet2 knockout mice had larger atherosclerotic lesions in the aortic root and aorta than did mice that had received control bone marrow. Analyses of macrophages from Tet2 knockout mice showed elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis.
The presence of CHIP in peripheral-blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice. (Funded by the National Institutes of Health and others.).
Abstract
Aims
The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for ...transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.
Methods and results
Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.
Conclusions
Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
Graphical Abstract
Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes ...affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.
In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy ...(DAPT) with a P2Y
inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain.
We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y
inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction TIMI criteria or bleeding requiring medical attention).
The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval CI, 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan-Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values for all comparisons were nonsignificant).
In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y
inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy. (Funded by Janssen Scientific Affairs and Bayer Pharmaceuticals; PIONEER AF-PCI ClinicalTrials.gov number, NCT01830543 .).
Prosthetic Heart Valve Thrombosis Dangas, George D., MD, PhD; Weitz, Jeffrey I., MD; Giustino, Gennaro, MD ...
Journal of the American College of Cardiology,
12/2016, Volume:
68, Issue:
24
Journal Article
Peer reviewed
Open access
Abstract Although surgery was the mainstay of treatment for valvular heart disease, transcatheter valve therapies have grown exponentially over the past decade. Two types of artificial heart valve ...exist: mechanical heart valves (MHV), which are implanted surgically, and bioprosthetic heart valves (BHV), which can be implanted via a surgical or transcatheter approach. Whereas long-term anticoagulation is required to prevent thromboembolism after MHV replacement, its value in patients receiving BHVs is uncertain. Patients undergoing transcatheter BHV replacement are at risk for thromboembolism in the first few months, and recent data suggest that the risk continues thereafter. BHV thrombosis provides a substrate for subsequent thromboembolism and may identify a reversible cause of prosthesis dysfunction. Hereafter, the authors: 1) review the data on prosthetic valve thrombosis; 2) discuss the pathophysiological mechanisms that may lead to valve thrombus formation; and 3) provide perspective on the implications of these findings in the era of transcatheter valve replacement.
In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. ...Whether PCI of nonculprit lesions further reduces the risk of such events is unclear.
We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization.
At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval CI, 0.60 to 0.91; P = 0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P = 0.62 and P = 0.27 for interaction for the first and second coprimary outcomes, respectively).
Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.).
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