Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Association of Plasma Phospholipid Long-Chain Omega-3 Fatty Acids With Incident Atrial Fibrillation in Older Adults: The Cardiovascular Health Study
- Trends in Use of Implantable Cardioverter-Defibrillator Therapy Among Patients Hospitalized for Heart Failure: Have the Previously Observed Sex and Racial Disparities Changed Over Time?
- Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Standard Care Among Inoperable Patients With Severe Aortic Stenosis: Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B)
- Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting Stent Compared With Early-Generation Drug-Eluting Stents: A Prospective Cohort Study
- Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans
- Rheb is a Critical Regulator of Autophagy During Myocardial Ischemia: Pathophysiological Implications in Obesity and Metabolic Syndrome
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Association of Plasma Phospholipid Long-Chain Omega-3 Fatty Acids With Incident Atrial Fibrillation in Older Adults: The Cardiovascular Health Study
Atrial fibrillation (AF) is the most common chronic arrhythmia in adults, and risk increases markedly with age. Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) from seafood may reduce onset of AF, but most prior studies of n-3 PUFA and new-onset AF in ambulatory populations have used estimates based on dietary questionnaires and were not focused on older adults, the general population at highest risk. We prospectively investigated the associations of circulating blood levels of the n-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incidence of AF among 3,326 older men and women (≥65y) from 4 US communities over a 14-year period. We excluded study subjects taking fish oil supplements. After adjustment for other risk factors, participants in the top quartile of total n-3 PUFA (EPA+DPA+DHA) levels had 29% lower risk of AF, compared with the lowest quartile (P trend <0.004). Among the individual n-3 fatty acids, only DHA was significantly associated with AF, with a 23% lower risk among participants in the highest versus lowest quartile (P=0.01). These associations were consistent among different subgroups, including men and women as well as whites and blacks. Although the observational nature of this study does not prove a causal relationship, these findings suggest that increased dietary intake of total n-3 PUFA or DHA from seafood may reduce incidence of AF in older adults. See p 1084.
Trends in Use of Implantable Cardioverter-Defibrillator Therapy Among Patients Hospitalized for Heart Failure: Have the Previously Observed Sex and Racial Disparities Changed Over Time?
Prior studies have demonstrated low use of implantable cardioverter-defibrillators (ICDs) as primary prevention, particularly among women and blacks relative to their counterparts. The degree to which the overall use of ICD therapy and disparities in use have changed is unclear. We examined 11 880 unique patients with a history of heart failure and left ventricular ejection fraction ≤35% who were ≥65 years of age and enrolled in the Get With the Guidelines–Heart Failure (GWTG-HF) program from January 2005 through December 2009. From 2005 to 2007, overall ICD use increased from 30.2% to 42.4% and then remained unchanged in 2008 to 2009. After adjustment for potential confounders, ICD use increased significantly in the overall study population and in black women, white women, black men, and white men. The increase in ICD use was greatest among blacks. In the GWTG-HF quality improvement program, a significant increase in ICD therapy use was observed over time in all 4 sex and race groups. The previously described racial disparities in ICD use were no longer present by the end of the study period; however, sex differences persisted. See p 1094.
Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Standard Care Among Inoperable Patients With Severe Aortic Stenosis: Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B)
In patients deemed ineligible for cardiac surgery, the Placement of Aortic Transcatheter Valves (PARTNER) trial recently demonstrated a 20% absolute survival difference at 12 months when transcatheter aortic valve replacement (TAVR) was compared with standard nonsurgical therapy. The costs and cost effectiveness of this clinical strategy, which would typically be applied to elderly patients, have not been evaluated previously. Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the PARTNER trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs. Average costs for the initial TAVR procedure and hospital stay were $42 806 and $78 542, respectively, but follow-up costs through 12 months were approximately $24 000 lower per patient with TAVR because of higher rates of cardiovascular hospitalization with standard therapy. We projected that over a patient's lifetime, TAVR would increase life expectancy by 1.9 years (1.6 years after application of a standard 3% discount rate to future costs and benefits) at a discounted lifetime incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained, or $61 889 per quality-adjusted life-year gained, values generally considered acceptable within the context of the US healthcare system. These estimates were only slightly altered when assumptions about future costs and survival were varied within plausible ranges. See p 1102.
Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting Stent Compared With Early-Generation Drug-Eluting Stents: A Prospective Cohort Study
Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with an increased risk of very late stent thrombosis with an annual incidence of 0.5% to 0.6%. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES). A total of 12 339 patients undergoing treatment with either SES, PES, or EES between 2002 and 2009 were followed up for up to 4 years to compare the incidence of stent thrombosis between stent types with particular focus on very late stent thrombosis. The incidence rate of stent thrombosis through 4 years was lower among EES-treated patients (1.4%) compared with patients treated with SES (2.9%; P<0.0001) and PES (4.4%; P<0.0001). The reduction in stent thrombosis was most prominent during the very late time period (>1 year) with a 67% (EES versus SES) and 76% (EES versus PES) risk reduction in favor of EES. The annual incidence rate of very late stent thrombosis amounted to 0.2% in EES, 0.5% with SES, and 0.8% with PES. The lower risk of cardiac death or myocardial infarction with EES compared with PES (hazard ratio, 0.67; 95% confidence interval, 0.58–0.77; P<0.0001) was directly related to the lower risk of stent thrombosis–associated events. Newer-generation EES improve clinical outcome by reducing the risk of stent thrombosis compared with early-generation drug-eluting stents during long-term follow-up. The important reduction of the risk of very late stent thrombosis with the unrestricted use of EES overcomes the principal limitation of early-generation drug-eluting stents and constitutes an important advance in drug-eluting stent safety. See p 1110.
Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans
Insulin resistance is an important mechanism underlying obesity-related disorders, eg, diabetes, hyperlipidemia, and hypertension, collectively called the metabolic syndrome. In particular, inflammation and oxidative stress are well known to play important roles in the pathogenesis of this systemic syndrome and the resultant development of atherosclerosis. A transcription factor, nuclear factor-κB (NF-κB), has been considered to mediate the responses to both inflammation and oxidative stress intracellularly. However, the site(s) at which the NF-κB signaling pathway plays critical roles in these pathological processes remains to be elucidated. This study focused on the roles of endothelial NF-κB signaling. By expressing the dominant-negative IκB mutant in the endothelium using the transgenic procedure, the NF-κB signaling pathway was blocked selectively in endothelial cells. These mice were protected from the development of both obesity- and age-related insulin resistance. Furthermore, importantly, these mice exhibited prolonged lifespans. In addition to the decrease in relatively early deaths, maximum lifespan was shown to be longer in these transgenic mice. Vascular senescence was markedly inhibited by blockade of endothelial NF-κB. Thus, the endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, ultimately impacting lifespan. Blockade of endothelial NF-κB signaling apparently protects the whole body from both fatal morbidities at earlier ages and the development of senescence. Amelioration of insulin resistance and decreased oxidative stress are likely to contribute to these beneficial phenotypes. Therefore, endothelial NF-κB signaling is a potential target not only for treating the metabolic syndrome, but also for anti-aging strategies. See p 1122.
Rheb is a Critical Regulator of Autophagy During Myocardial Ischemia: Pathophysiological Implications in Obesity and Metabolic Syndrome
The incidence of heart failure after acute myocardial infarction (MI) remains very high in patients. This highlights the necessity to clarify the mechanism regulating the survival and death of cardiomyocytes in response to ischemia and to find new cardioprotective therapies reducing ischemic injury. We discovered that Rheb, a small GTP-binding protein, plays a pivotal role in regulating the survival of cardiomyocytes during prolonged myocardial ischemia. Rheb activity is reduced in the ischemic heart, thereby causing the suppression of the mTORC1 pathway. Inhibition of the Rheb/mTORC1 pathway is an adaptive response during ischemia, because forced restoration of cardiac Rheb activity is detrimental under this condition. Rheb inhibition is required for the activation of autophagy, an intracellular degradation process for proteins and organelles, which is protective during energy stress through preservation of cellular energy and relief of ER stress. We discovered that obesity and metabolic syndrome (Ob/MS) are associated with cardiac activation of Rheb/mTORC1 at baseline and during ischemia. In obese mice, autophagy in the heart was suppressed and ischemic injury was exacerbated. Remarkably, inhibition of mTORC1 restores autophagy and reduces infarct size in these animals after prolonged ischemia. Thus, our results suggest that Rheb and mTORC1 may be promising therapeutic targets to reduce myocardial damage after prolonged ischemia in patients with Ob/MS who display deregulated activation of the Rheb/TORC1 pathway and consequent inhibition of autophagy. See p 1134.
- © 2012 American Heart Association, Inc.
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