Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial
- Ideal Cardiovascular Health and Mortality From All Causes and Diseases of the Circulatory System Among Adults in the United States
- Healthy Lifestyle Through Young Adulthood and the Presence of Low Cardiovascular Disease Risk Profile in Middle Age: The Coronary Artery Risk Development in (Young) Adults (CARDIA) Study
- Percutaneous Coronary Intervention in Patients With Severe Aortic Stenosis: Implications for Transcatheter Aortic Valve Replacement
- C/EBP Homologous Protein-10 (CHOP-10) Limits Postnatal Neovascularization Through Control of Endothelial Nitric Oxide Synthase Gene Expression
- Coronary Vasospasm Induced in Transgenic Mouse With Increased Phospholipase C-δ1 Activity
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Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial
The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. We examined the relationship between prior PPI use and 1-year cardiovascular events in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel; however, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events. With recognition of the inherent limitations of nonrandomized comparisons, our findings do not support the need to avoid concomitant PPI use with clopidogrel or ticagrelor. See p 978.
Ideal Cardiovascular Health and Mortality From All Causes and Diseases of the Circulatory System Among Adults in the United States
In 2010, the American Heart Association presented a set of 7 metrics that were designed to promote cardiovascular health: smoking status, body mass index, physical activity, healthy dietary score, total cholesterol, blood pressure, and fasting plasma glucose. For each metric, 3 levels of health were defined (poor, intermediate, and ideal health). The state of ideal health for each metric emphasizes the concept of primordial prevention. Using data from a nationally representative cohort of US adults, we found that about half of adults had 3 or 4 ideal health metrics (only ≈1% met the ideal health criteria for all 7 metrics). Furthermore, we observed a strong dose-response relationship between the number of ideal health metrics and mortality from all causes and diseases of the circulatory system. Clinicians can reduce cardiovascular morbidity and mortality in their patient populations not only by helping their patients maximize the number of attained ideal cardiovascular health metrics but also by helping patients with poor health for some metrics transition to intermediate health. Optimizing cardiovascular health involves addressing key lifestyle behaviors of smoking, diet, and physical activity. Besides the resources in their practices, clinicians can opt to draw on available institutional, clinical, and community resources. An implication of the AHA goals and our findings is that the cardiovascular health of patients should be monitored from an early age. Clinicians should strive to maximize the numbers of patients with hypercholesterolemia, hypertension, and hyperglycemia who require pharmacological management who are on treatment and under control. See p 987.
Healthy Lifestyle Through Young Adulthood and the Presence of Low Cardiovascular Disease Risk Profile in Middle Age: The Coronary Artery Risk Development in (Young) Adults (CARDIA) Study
Low cardiovascular disease risk profile (no prior myocardial infarction and the simultaneous presence of untreated cholesterol <200 mg/dL, untreated blood pressure <120/80 mm Hg, no smoking, and no diabetes mellitus) in middle age has been demonstrated to be associated with lower mortality and morbidity rates, higher life expectancy, lower lifetime risk for cardiovascular disease, higher quality of life, and lower Medicare charges in older age. However, the prevalence of a low risk profile in middle-aged and older people is very low. Using data from the Coronary Artery Risk Development in (Young) Adults (CARDIA) Study, we demonstrated that 5 healthy lifestyle factors—body mass index <25 kg/m2, no smoking, vigorous or moderate physical activity at least 5 times per week, no excessive alcohol drinking, and a Dietary Approaches to Stop Hypertension–like diet—during young adulthood to middle age are strongly associated with achievement of the low risk profile in middle age. The study indicated that the more healthy lifestyle factors are adopted and maintained during young adulthood, the higher the prevalence of a low risk profile in middle age. The results also demonstrated that those who did not adopt a healthy lifestyle initially but did so later on could still benefit from the improvement of their lifestyle. These data suggest that physicians should encourage their patients to adopt a healthy lifestyle starting at a young age or to improve their lifestyle as early as possible to maximize the benefits of the low cardiovascular risk profile in terms of healthy longevity. See p 996.
Percutaneous Coronary Intervention in Patients With Severe Aortic Stenosis: Implications for Transcatheter Aortic Valve Replacement
Outcomes of percutaneous coronary intervention (PCI) in patients with severe aortic stenosis (AS) and coronary artery disease are largely unknown. With the advent of transcatheter aortic valve replacement (TAVR), PCI in patients with severe AS warrants a fresh appraisal. In this study, we identified that the risk of PCI in patients with severe AS is similar to that in other high-risk PCI populations. The highest 30-day mortality risk was seen in patients with low ejection fraction (≤30%) and high Society of Thoracic Surgeons score (≥10). These results provide some insight for the management of patients with severe coronary artery disease and AS who present for TAVR. In patients with very low ejection fraction or severe multiple comorbidities, performing TAVR first to improve cardiac hemodynamics and function could be life-saving, although the 12-month mortality of 24% in high-risk but operable TAVR patients in the Placement of Aortic Transcatheter Valve Trial (PARTNER) suggests that there is much to learn about patient selection. In selected patients, PCI may have to be performed before TAVR to improve procedural safety of TAVR. For some patients, combined TAVR and PCI can be considered with or without adjunctive use of support devices. The optimal approach to patients with severe AS and coronary artery disease should be individualized on the basis of the relative impact of coronary artery disease and AS on the clinical presentation and the nature of the comorbidities. We hope that, as the volume of experience in TAVR increases and more data become available, evidence-based treatment strategies for patients with severe AS and coronary artery disease will emerge. See p 1005.
C/EBP Homologous Protein-10 (CHOP-10) Limits Postnatal Neovascularization Through Control of Endothelial Nitric Oxide Synthase Gene Expression
Understanding the molecular and cellular mechanisms involved in the regulation of vessel growth and maturation in the setting of tissue ischemia is of major importance and may trigger the development of innovative strategies of therapeutic angiogenesis in the treatment of ischemic diseases. In the present study, we analyzed the role of C/EBP homologous protein-10 (CHOP-10) in postischemic revascularization. CHOP-10 is a novel developmentally regulated nuclear protein that emerges as a critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. This study identifies CHOP-10 as a major modulator of vessel formation and maturation. The physiological significance of CHOP-10 in the vasculature is validated by the observation that ischemia and diabetes mellitus–induced oxidative stress upregulated CHOP-10 levels and that CHOP-10 deficiency markedly improved postischemic vessel growth in control animals but also in a pathological setting, such as diabetes mellitus. Finally, our data demonstrated that the transcriptional repression of endothelial nitric oxide synthase by CHOP-10 greatly contributes to the antiangiogenic effects of CHOP-10. In conclusion, this work suggests that CHOP-10 functions as an important regulator of postnatal neovascularization. Because downregulation of CHOP-10 promoted neovascularization, the regulation of CHOP-10 expression and activity may pave the way for new therapeutic strategies designed to increase vessel growth in the setting of ischemia. In contrast, forced expression or activation of CHOP-10 might limit unwanted neovascularization associated with tumor development or retinopathy. See p 1014.
Coronary Vasospasm Induced in Transgenic Mouse With Increased Phospholipase C-δ1 Activity
Coronary spasm is involved in the pathogenesis of not only variant angina, but the other acute coronary syndromes; however, its precise mechanism still remains unclear. We reported that phospholipase C (PLC)-δ1 activity in cultured skin fibroblasts obtained from patients with coronary spastic angina (CSA) was increased 3-fold compared with that from control subjects. We also detected R257H variant PLC-δ1 in CSA patients, which was associated with the increased PLC-δ1 enzymatic activity. We further found that p122 protein, a positive regulator of PLC-δ1, was upregulated in CSA patients. Thus, the increased PLC-δ1 activity caused by either structural mutation or increased positive regulator is likely to be related to the pathogenesis of coronary spasm. However, there has been no proof for a direct contribution of increased PLC-δ1 to enhanced coronary vasomotility. In this study, we generated transgenic mice with increased PLC-δ1 activity in vascular smooth muscle cells by overexpressing human R257H variant PLC-δ1. Our transgenic mouse showed increased PLC enzymatic activity in the coronary artery and enhanced coronary vasoconstrictor response to ergometrine compared with the wild-type mouse. In particular, intravenous ergometrine administration induced ST elevation on ECG and focal coronary artery narrowing such as that seen in CSA patients in the transgenic but not in the wild-type mouse. Thus, this transgenic mouse is a novel animal model of CSA and would provide a novel tool for revealing the mechanism for coronary spasm and investigating the treatment of CSA. See p 1027.
- © 2012 American Heart Association, Inc.
- Coronary Vasospasm Induced in Transgenic Mouse With Increased Phospholipase C-δ1 Activity
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