Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Novel Small Leucine-Rich Repeat Protein Podocan Is a Negative Regulator of Migration and Proliferation of Smooth Muscle Cells, Modulates Neointima Formation, and Is Expressed in Human Atheroma
- High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice
- Use of Remote Monitoring of Newly Implanted Cardioverter-Defibrillators: Insights From the Patient Related Determinants of ICD Remote Monitoring (PREDICT RM) Study
- Long-Term Evolution and Prognostic Stratification of Biopsy-Proven Active Myocarditis
- C-Reactive Protein, but not Low-Density Lipoprotein Cholesterol Levels, Associate With Coronary Atheroma Regression and Cardiovascular Events After Maximally Intensive Statin Therapy
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Novel Small Leucine-Rich Repeat Protein Podocan Is a Negative Regulator of Migration and Proliferation of Smooth Muscle Cells, Modulates Neointima Formation, and Is Expressed in Human Atheroma
Smooth muscle cells (SMCs) critically influence the clinical course of vascular disease. The close regulation of SMC migration and proliferation within the intimal space is critical in maintaining a delicate balance between insufficient and excessive atherosclerotic plaque repair. When SMC proliferation is too suppressed, the ensuing weakening of the fibrous cap can result in the plaque vulnerability that underlies acute coronary syndrome, and when SMC proliferation is excessive, intimal hyperplasia can follow, such as in restenosis after percutaneous coronary intervention. Although stents have vastly improved on the recoil and constrictive remodeling component of restenosis, the problem of accelerated intimal SMC growth has remained. The current approach of delivering stents that release nonspecific agents that promote cell death or inhibition of proliferation has been successful in reducing the need for recurrent vascular interventions; however, this success comes at the expense of delaying vascular healing, the ultimate long-term clinical impact of which is still being evaluated. Short- and long-term negative effects on the healing arterial wall, such as delayed reendothelialization, increased inflammation, and enhanced thrombogenicity, are undisputed. These side effects of drug-eluting stents are being masked by prolonged and aggressive antiplatelet therapy, which exposes patients, especially the elderly, to increased bleeding risks, complicates clinical decision making through fear of too early treatment cessation, demands rigorous patient compliance, and is costly. These issues are not trivial in daily clinical practice. The possible role of podocan as a novel selective inhibitor of the SMC response and the Wnt-TCF pathway opens the door to modulation of vascular SMCs in a smarter and more physiological way. See p 2351.
High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice
Abnormal glucose metabolism, ranging from insulin resistance to type 2 diabetes mellitus, is a central feature of disorders associated with increased rates of cardiovascular disease. Successfully preventing and treating these disorders resides among the great public health challenges of our times. One of the strongest predictors of cardiovascular disease in the metabolic syndrome is a low level of high-density lipoprotein (HDL) cholesterol and its major protein constituent apolipoprotein A-I (apoA-I). Infusions of reconstituted HDL raising circulating apoA-I levels reduce plasma glucose and promote glucose uptake in skeletal muscle of type 2 diabetes mellitus patients. Our series of discoveries showing that raising HDL levels by overexpressing human apoA-I in mice increases skeletal muscle glycolysis, ATP synthesis and endurance capacity leading to improved glucose metabolism and reduced fat mass is therefore highly relevant. As a matter of fact, our results for the first time link low HDL levels with the mitochondrial dysfunction observed in type 2 diabetes mellitus. ApoA-I analogues are now clinically tested for prevention of atherosclerosis. Based on our findings described herein, these analogs may offer underappreciated potential and offer additional therapeutic opportunities for diabetes mellitus. Efficacious and safe compounds targeting multiple aspects of the metabolic syndrome do not currently exist, but are urgently needed. Moreover, with optimized apoA-I analogues already available, swift translation of our research toward clinical use appears quite doable. See p 2364.
Use of Remote Monitoring of Newly Implanted Cardioverter-Defibrillators: Insights From the Patient Related Determinants of ICD Remote Monitoring (PREDICT RM) Study
Despite guideline recommendation, the use of remote patient monitoring (RPM) technology for implantable cardioverter defibrillators is not universal. Successful use of RPM depends on the enrollment of the patient into an RPM system and subsequent activation of RPM by the enrolled patient. We examined the degree of RPM use and the patient, physician, and institutional determinants of RPM use in patients with newly implanted implantable cardioverter defibrillators by linking information derived from the ALTITUDE database to the National Cardiovascular Data Registry ICD Registry. Hierarchical logistic regression models were developed to predict both RPM enrollment and RPM activation. The selected variables were incorporated into a model to account for clustering of the patients within hospitals, and a hospital-specific median odds ratio was calculated to characterize the variation between hospitals in the propensity to enroll patients in RPM. Among 39 158 patients who received RPM-capable devices, 62% (n=24 113) were enrolled in RPM. Of those enrolled, 76% (n=18 289) activated their device yielding an overall RPM use rate of only 47%. RPM enrollment was highly variable among institutions. The hospital-specific median odds ratio for RPM enrollment was 3.43, indicating that physician/institutional factors were associated with RPM enrollment. Patient age, race, health insurance, geographic location, and other health-related factors were also associated with both RPM enrollment and activation. These results indicate that RPM technology is significantly underused with less than half of eligible patients ultimately using it. Lack of enrollment into RPM systems relating to the local practice environment is the major cause of underuse. See p 2372.
Long-Term Evolution and Prognostic Stratification of Biopsy-Proven Active Myocarditis
Myocarditis is an inflammatory disease of the myocardium characterized by great variability in clinical presentation and significant heterogeneity of long-term evolution, currently representing a demanding challenge for the cardiologist. Although it is often associated with a benign prognosis, myocarditis may present with dramatic scenarios requiring major clinical decisions, such as early referral for heart transplantation or prophylactic implantable cardioverter-defibrillator placement. In this regard, reliable predictors of long-term prognosis are critical for the appropriate, patient-tailored management. Benefiting from the detailed and comprehensive long-term follow-up, this study offers novel insights in the long-term evolution of a large sample of patients with endomyocardial biopsy-proven active myocarditis and proposes clinically simple algorithms identifying early predictors of long-term severe outcome. In particular, current data demonstrate that the structural and functional impairment of the left ventricle, as assessed from left atrium enlargement and left ventricle dysfunction at baseline echocardiogram, are independently associated with the long-term prognosis. Furthermore, the short-term reevaluation of clinical and echocardiographic parameters provided additional incremental predictive value in comparison with the baseline evaluation, allowing a more precise long-term risk stratification of patients with active myocarditis. Taken together, these results underscore the importance of early clinical and echocardiographic reevaluation for the appropriate management of patients with active myocarditis. As such, major clinical decisions should be reconsidered according to the short-term evolution of clinical and instrumental parameters under optimal medical treatment. Promising imaging techniques, such as cardiac magnetic resonance with advanced tissue characterization modalities, will allow an even more accurate management of this disease in the future. See p 2384.
C-Reactive Protein, but not Low-Density Lipoprotein Cholesterol Levels, Associate With Coronary Atheroma Regression and Cardiovascular Events After Maximally Intensive Statin Therapy
Although inflammation appears to be involved in all stages of atherosclerosis, the mechanistic and prognostic role of inflammation in individuals treated with potent statin therapy remains unclear. The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) was the largest serial atherosclerosis imaging study undertaken in >1000 individuals treated with the highest approved doses of 2 of the most potent statins currently available. We thus undertook a prespecified post hoc analysis to determine the prognostic role of changes in C-reactive protein (CRP) in individuals prescribed 2 years of maximally intensive statin therapy, who achieved a mean on-treatment low-density lipoprotein cholesterol of 65.9 mg/dL. Despite potent statin therapy, over one-third of individuals experienced rising on-treatment CRP levels, with a poor correlation between changes in low-density lipoprotein cholesterol and changes in CRP. Decreasing CRP levels independently associated with coronary atheroma regression. Although the absolute change in CRP was nonprognostic, the on-treatment level of CRP independently associated with major adverse cardiovascular events. A stepwise relationship was noted between on-treatment CRP levels and time to first major adverse cardiovascular event. Collectively, these results highlight the potential importance of inflammation mediating residual cardiovascular risk in individuals with coronary artery disease treated according to current lipid-lowering guidelines. Such findings also underscore the importance of clinical trials that will specifically test the inflammatory hypothesis of atherothrombosis. See p 2395.
- © 2013 American Heart Association, Inc.
- Long-Term Evolution and Prognostic Stratification of Biopsy-Proven Active Myocarditis
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