Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor
- Alternative Strategies to Achieve Cardiovascular Mortality Goals in China and India: A Microsimulation of Target- Versus Risk-Based Blood Pressure Treatment
- Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
- Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry
- Info & Metrics
Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor
Efficient efferocytosis, the process by which apoptotic or necrotic cells are actively removed out of the milieu, is critical to sustain tissue homeostasis by directing the healing of injured tissues. As a consequence, improper clearance of dying cells by activated neighboring phagocytes contributes to the establishment and progression of numerous human diseases. In infarcted heart, alteration of efferocytosis and ineffective elimination of dying cells by galvanized cardiac monocytes/macrophages may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. We showed that Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of the proangiogenic and antifibrotic vascular endothelial growth factor to locally repair the dysfunctional heart. With respect to translation into the clinics, our results are promising, indicating that the modulation of phagocytic activity by recruited or resident cardiac macrophages may counteract adverse left ventricle remodeling. In particular, our work suggests that targeting local factors that promote myeloid cell–derived efferocytosis such as the Mertk/Mfge8 axis may counteract the local mediators of inflammation that drive cardiac dysfunction and maladaptation after myocardial infarction. See p 826.
Alternative Strategies to Achieve Cardiovascular Mortality Goals in China and India: A Microsimulation of Target- Versus Risk-Based Blood Pressure Treatment
In May 2012, the World Health Organization’s (WHO) General Assembly adopted a target of reducing cardiovascular disease (CVD) mortality by 25% by 2025, setting the template for the global Sustainable Development Goals. Achieving such a large reduction in CVD mortality will likely require more extensive blood pressure (BP) treatment. Particularly in rapidly developing countries, a key question is how to achieve the greatest CVD mortality reduction within limited budgets. Here, we sought to compare the population benefits and cost-effectiveness of 3 alternative proposed strategies to treat high BP, using data from China and India on treatment access, BP levels, and other risk factors for CVD. Our research, which uses a modeling strategy, found that a simple treatment approach using calculations of CVD risk to inform treatment decisions was more effective and cost-effective than the common strategy of using BP levels to decide treatment. The risk-based approach recommends treatment for patients with a 10-year combined risk of myocardial infarction and stroke of at least 10%. We also found that the current WHO guidelines were worse than the simple risk-based approach; these guidelines recommend treating individuals with high CVD risk (≥30% risk over 10 years) to a BP of <130/80 mm Hg, and individuals with lower risk (20% to 30% over 10 years) to BP <140/90 mm Hg. Even with poor treatment adherence, the risk-based approach to BP treatment could on its own succeed in achieving between one-quarter and one-third of the CVD mortality goal set by the WHO. See p 840.
Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Clinical cardiovascular disease risk assessment has focused predominantly on the identification of individuals at high absolute cardiovascular disease risk. This holds true for nontraditional risk markers, including novel risk assessment technologies. The literature mostly describes their use to detect additional patients who may benefit from preventive pharmacotherapies. However, in the context of the new American College of Cardiology/American Heart Association prevention guidelines, in which population aging, possible risk overestimation, potential overtreatment of older individuals with few risk factors, and overmedicalization are concerns, the accurate identification of individuals who are truly at low risk may have even greater clinical, economic, and public health implications. For this purpose, we compared the ability of 13 negative risk markers used widely in clinical practice to modify 10-year coronary heart disease and cardiovascular disease risk estimates, and we tested their accuracy for reclassifying individuals below the treatment threshold in a large, multiethnic, contemporary cohort. Among these markers, negative results of atherosclerosis imaging tests, particularly a coronary artery calcium score of 0, resulted in the greatest downward shift in risk estimation and in the largest net risk reclassification. These findings have direct implications for the identification of individuals less likely to receive net benefit from statins and other preventive pharmacotherapies. Moreover, given the lack of guidance in current guidelines for downwardly reclassifying risk, our findings could be used to inform guideline updates. The next research steps should be the definition of which high-risk patients should be tested for presence of negative risk markers and the evaluation of the cost-effectiveness of different “de-risking” strategies. See p 849.
Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry
Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. A European registry was set up in 27 centers to evaluate long-term outcome and outcome predictors in operated and not-operated patients. Six hundred seventy-nine newly diagnosed patients were prospectively included over a 24-month period. Estimated survival at 3 years was 89% in operated patients and only 70% in not-operated patients. In both operated and not-operated patients, pulmonary arterial hypertension–targeted therapy did not affect survival estimates. Mortality was associated with New York Heart Association functional class, right atrial pressure, and a history of cancer. Additional predictors of mortality were bridging therapy with pulmonary arterial hypertension–targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. This article shows that the long-term prognosis of operated patients is nowadays excellent and better than the outcome of not-operated patients. We thereby demonstrate that turning down a patient for surgery is predicting poor survival and support the recommendation that an experienced chronic thromboembolic pulmonary hypertension team should assess operability before medical treatment is considered, even obtaining a second opinion from a more experienced chronic thromboembolic pulmonary hypertension center in cases of borderline operability. See p 859.
- © 2016 American Heart Association, Inc.
- Info & Metrics