Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review
- Temporal Trends in Percutaneous Coronary Intervention Appropriateness: Insights From the Clinical Outcomes Assessment Program
- Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial
- Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes
- Platelet Extracellular Regulated Protein Kinase 5 Is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion
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Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review
The incidence of sudden cardiac death (SCD) in young people is hotly debated. It is important to have an accurate understanding of the overall incidence in the context of other risks of death to identify groups where additional preventive strategies should be considered. This study confirms earlier findings of a higher rate of SCD in National Collegiate Athletic Association athletes (1 in 53 703) with males (1 in 37 790), blacks (1 in 21 491), and male basketball athletes (1 in 9000) at higher risk. In fact, Division I male basketball players are 5 times more likely to die of SCD than to die in a car accident. This study also demonstrates that the differences in methodology to identify cases will drastically affect results and that media reports are an unreliable way to identify SCD, in particular, in lower-profile athletes. Similarly, the use of insurance claims for case identification detected only a fraction of SCDs in athletes (1/10). This creates challenges to accurately understand the incidence of SCD in high school and youth athletes without better reporting mechanisms. This study found a higher proportion of autopsy-negative sudden unexplained death (25%) than previously described in US athletes and a lower proportion of hypertrophic cardiomyopathy (8%). Standardized autopsies and postmortem genetic testing are needed to better define the causes of SCD. National Collegiate Athletic Association athletes are currently screened at matriculation for cardiovascular disease. Concern has been expressed regarding resource use, but more intensive screening may be warranted in high-risk groups. See p 10.
Temporal Trends in Percutaneous Coronary Intervention Appropriateness: Insights From the Clinical Outcomes Assessment Program
Increasing attention is being given to proper patient selection for elective percutaneous coronary intervention (PCI) to ensure that the clinical benefits outweigh the procedural risks. The appropriate use criteria for coronary revascularization permit a guidelines-concordant approach to assessing the quality of patient selection for PCI. Although previous studies have suggested gaps in the quality of patient selection for PCI, it is unknown whether the appropriateness of elective PCI has changed over time. In this complete cohort of >50 000 PCIs performed in Washington State between 2010 and 2013, the proportion of elective PCIs classified as appropriate increased over time (26% in 2010 to 38% in 2013; P for trend <0.001), whereas the proportion of inappropriate PCI decreased (16% in 2010 to 13% in 2013; P for trend <0.001). The number of PCIs performed for elective indications dropped by nearly 50% during this time period, and this decline in use of elective PCI was larger than in the preceding time period of 2006 to 2009. Together, these findings suggest that there have been improvements in patient selection for PCI in the state of Washington, resulting in less frequent and more appropriate use of elective PCI. However, when evaluated at the hospital level, improvements in PCI appropriateness were limited to a minority of hospitals. Future study of hospitals with low or improving proportions of inappropriate PCI may identify patient selection processes that could be adopted by other hospitals to improve the quality of patient selection for PCI. See p 20.
Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial
The results of this study suggest an important kidney-bone-cardiovascular link. Fibroblast growth factor-23 (FGF23) is made in the bone in response to elevated parathyroid hormone and 1,25(OH)2-vitamin D and increased dietary intake of phosphorus. FGF23 binds to its receptor and klotho coreceptor in the kidney to increase urinary phosphate and to decrease 1,25(OH)2-vitamin D synthesis and in the parathyroid gland to reduce parathyroid hormone secretion as part of a negative feedback loop. In animals, FGF23 directly induces cardiac hypertrophy in a klotho-independent manner. Levels of FGF23 increase with progressive kidney disease and, by the time a patient reaches dialysis, can be 100-fold greater than in individuals without kidney disease. The present study, a secondary analyses of the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, which randomized patients receiving hemodialysis to cinacalcet versus placebo for the treatment of secondary hyperparathyroidism, demonstrates that cinacalcet reduces serum FGF23 levels. Furthermore, in patients randomized to cinacalcet, a ≥30% decrease in FGF23 was associated with a reduction in mortality, heart failure, and nonatherosclerotic cardiovascular events, including sudden cardiac death. The latter is the leading cause of cardiovascular death in patients undergoing hemodialysis. The present study is the first to demonstrate that a reduction in FGF23 in patients receiving cinacalcet is associated with a reduction in hard clinical end points. It is important to emphasize that this is a secondary analyses and that the mechanisms by which a reduction in FGF23 or cinacalcet reduces the risks of heart failure and sudden cardiac death are likely multifactorial and cannot be discerned by this study. See p 27.
Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes
The previously published results of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial have shown that treatment with clopidogrel plus aspirin for 21 days followed by clopidogrel alone for 90 days decreases the 90-day risk of stroke without increasing the risk of hemorrhage in patients with acute minor stroke or high-risk transient ischemic attack. This article reported the 1-year follow-up results of the CHANCE trial and found that the results of 1-year follow-up were similar to the original 3-month efficacy of this study. These data suggested rebound increase in the risk of recurrence of stroke may not occur after the cessation of clopidogrel in the trial, and the early benefit of combination treatment of clopidogrel and aspirin persisted over the duration of 1 year of follow-up. We found that most of the stroke recurrences occurred at the early stage after the onset of the event. Early aggressive dual-antiplatelet therapy may be of benefit to patients with acute minor stroke or high-risk transient ischemic attack for a long time. See p 40.
Platelet Extracellular Regulated Protein Kinase 5 Is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion
Antiplatelet medications such as aspirin and clopidogrel are used to treat myocardial infarction. For unclear reasons, these drugs are not always efficacious. For example, a significant number of patients experiencing ST-segment–elevation myocardial infarction develop the no-reflow phenomenon after percutaneous intervention even though high-dose antiplatelet medications are given. No reflow is proposed to represent continued activation of platelets in the microvasculature. Such dysregulated platelet activity and consequent myocardial tissue ischemia often evade conventional myocardial imaging. No reflow may be caused by an altered platelet phenotype in ischemic disorders such as myocardial infarction and stroke. In this study, we found that the expression of platelet proteins known to promote platelet activation and thrombosis are increased within a few days of myocardial infarction, tipping the balance toward a thrombotic platelet phenotype. Because platelets are anucleate, the changes in platelet protein expression likely represent enhanced protein synthesis from platelet mRNA, impaired degradation, or both. We discovered that platelet extracellular regulated protein kinase 5, a protein traditionally found in the nucleus of other cells, acts as a redox sensor in human and murine platelets. Extracellular regulated protein kinase 5 contributes to enhanced platelet reactivity by altering the expression and release of several proteins known to augment platelet activation and promote myocardial remodeling during the postinfarct period. Our data suggest that platelet extracellular regulated protein kinase 5 activity and its downstream signaling mediators are triggered during myocardial infarction and may represent additional drug targets. In addition, the antiplatelet effect demonstrated by extracellular regulated protein kinase 5 blockade is specific to redox-mediated platelet activation and may therefore avoid bleeding complications common to current antiplatelet agents. See p 47.
- © 2015 American Heart Association, Inc.
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