ABSTRACT
BACKGROUND/AIMS: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM). So this study was designed to investigate the effects of Neuregulin-1 (NRG-1) treatment on myocardial angiogenesis and the changes of VEGF/Flk1 and Ang-1/Tie-2 signaling in the rat model of DCM. METHODS: Diabetic rats were induced by a single intraperitoneal injection of Streptozotocin. 12 weeks after the diabetes induction, the rats with NRG-1 treatment were treated with tail vein injection of NRG-1 at the dose of 10µg/kg/d for consecutive 10 days. Cardiac function was assessed using catheter MPA cardiac function analysis system. Myocardial blood flow (MBF) was assessed with stable-isotope labeled microspheres. Capillary density was measured by CD31 immunohistochemistry. The protein expression and receptors phosphorylation were assessed using western blot. RESULTS: Left ventricular function, capillary density and MBF were significantly reduced in DCM group when compared with those in the control group (P< 0.01, P< 0.01 and P< 0.05 respectively). Left ventricular function and capillary density were significantly increased in NRG-1 treatment group when compared with those in the DCM group (P< 0.05 and P< 0.05 respectively). The expression of VEGF and Ang-1 and the phosphorylation of Flk1 and Tie-1 were significantly decreased in DCM group as compared with those in the control group. However, those in the NRG-1 treatment group were significantly increased as compared with those in the DCM group. In vitro, NRG-1 treatment increased significantly the expression of VEGF and Ang-1 in human coronary artery smooth muscle cells. CONCLUSIONS: NRG-1 can increase the myocardial angiogenesis of DCM, probably via the direct effects of NRG-1 and via the increasing expression of VEGF and Ang-1. These findings may contribute to developing a novel approach to reverse the impaired angiogenic responses in diabetes or coronary artery disease.
Subject(s)
Diabetes Mellitus, Experimental/pathology , Diabetic Cardiomyopathies/pathology , Myocardium/pathology , Neovascularization, Pathologic/pathology , Neuregulin-1/metabolism , Angiopoietin-1/analysis , Angiopoietin-1/metabolism , Animals , Cells, Cultured , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetic Cardiomyopathies/complications , Diabetic Cardiomyopathies/metabolism , Male , Myocardium/metabolism , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/metabolism , Neuregulin-1/analysis , Rats , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Biological N2 fixation sustains the global inventory of nitrogenous nutrients essential for the productivity of terrestrial and marine ecosystems. Like most metabolic processes, rates of biological N2 fixation vary strongly with temperature, making it sensitive to climate change, but a global projection across land and ocean is lacking. Here we use compilations of field and laboratory measurements to reveal a relationship between N2 fixation rates and temperature that is similar in both domains despite large taxonomic and environmental differences. Rates of N2 fixation increase gradually to a thermal optimum around ~25°C, and decline more rapidly toward a thermal maximum, which is lower in the ocean than on land. In both realms, the observed temperature sensitivities imply that climate warming this century could decrease N2 fixation rates by ~50% in the tropics while increasing rates by ~50% in higher latitudes. We propose a conceptual framework for understanding the physiological and ecological mechanisms that underpin and modulate the observed temperature dependence of global N2 fixation rates, facilitating cross-fertilization of marine and terrestrial research to assess its response to climate change.
Subject(s)
Climate Change , Ecosystem , Nitrogen Fixation , Oceans and Seas , Temperature , Global Warming , Seawater/chemistry , Nitrogen/metabolismABSTRACT
Trichodesmium is the dominant photoautotrophic dinitrogen (N2) fixer (diazotroph) in the ocean. Iron is an important factor limiting growth of marine diazotrophs including Trichodesmium mainly because of high iron content of its N2-fixing enzyme, nitrogenase. However, it still lacks a quantitative understanding of how dynamic iron allocation among physiological processes acts to regulate growth and N2 fixation in Trichodesmium. Here, we constructed a model of Trichodesmium trichome in which intracellular iron could be dynamically re-allocated in photosystems and nitrogenase during the daytime. The results demonstrate that the dynamic iron allocation enhances modeled N2 fixation and growth rates of Trichodesmium, especially in iron-limited conditions, albeit having a marginal impact under high iron concentrations. Although the reuse of iron during a day is an apparent cause that dynamic iron allocation can benefit Trichodesmium under iron limitation, our model reveals two important mechanisms. First, the release of iron from photosystems downregulates the intracellular oxygen (O2) production and reduces the demand of respiratory protection, a process that Trichodesmium wastefully respires carbohydrates to create a lower O2 window for N2 fixation. Hence, more carbohydrates can be used in growth. Second, lower allocation of iron to nitrogenase during early daytime, a period when photosynthesis is active and intracellular O2 is high, reduces the amount of iron that is trapped in the inactivated nitrogenase induced by O2. This mechanism further increases the iron use efficiency in Trichodesmium. Overall, our study provides mechanistic and quantitative insight into the diurnal iron allocation that can alleviate iron limitation to Trichodesmium.
ABSTRACT
Diatoms, one of the most important phytoplankton groups, fulfill their carbon demand from seawater mainly by obtaining passively diffused carbon dioxide (CO2) and/or actively consuming intracellular energy to acquire bicarbonate (HCO3 -). An anthropogenically induced increase in seawater CO2 reduces the HCO3 - requirement of diatoms, potentially saving intracellular energy and benefitting their growth. This effect is commonly speculated to be most remarkable in larger diatoms that are subject to a stronger limitation of CO2 supply because of their smaller surface-to-volume ratios. However, we constructed a theoretical model for diatoms and revealed a unimodal relationship between the simulated growth rate response (GRR, the ratio of growth rates under elevated and ambient CO2) and cell size, with the GRR peaking at a cell diameter of â¼7 µm. The simulated GRR of the smallest diatoms was low because the CO2 supply was nearly sufficient at the ambient level, while the decline of GRR from a cell diameter of 7 µm was simulated because the contribution of seawater CO2 to the total carbon demand greatly decreased and diatoms became less sensitive to CO2 increase. A collection of historical data in CO2 enrichment experiments of diatoms also showed a roughly unimodal relationship between maximal GRR and cell size. Our model further revealed that the "optimal" cell size corresponding to peak GRR enlarged with the magnitude of CO2 increase but diminished with elevating cellular carbon demand, leading to projection of the smallest optimal cell size in the equatorial Pacific upwelling zone. Last, we need to emphasize that the size-dependent effects of increasing CO2 on diatoms are multifaceted, while our model only considers the inorganic carbon supply from seawater and optimal allocation of intracellular energy. Our study proposes a competitive advantage of middle-sized diatoms and can be useful in projecting changes in the diatom community in the future acidified high-CO2 ocean.
ABSTRACT
Viruses, the most abundant microorganisms in the ocean, play important roles in marine ecosystems, mainly by killing their hosts and contributing to nutrient recycling. However, in models simulating ecosystems in real marine environments, the virus-mediated mortality (VMM) rates of their hosts are implicitly represented by constant parameters, thus ignoring the dynamics caused by interactions between viruses and hosts. Here, we construct a model explicitly representing marine viruses and the VMM rates of major hosts, heterotrophic bacteria, and apply it to two sites in the oligotrophic North Pacific and the more productive Arabian Sea. The impacts of the viral processes were assessed by comparing model results with the viral processes enabled and disabled. For reliable assessments, a data assimilation method was used to objectively optimize the model parameters in each run. The model generated spatiotemporally variable VMM rates, generally decreasing in the subsurface but increasing at the surface. Although the dynamics introduced by viruses could be partly stabilized by the ecosystems, they still caused substantial changes to the bacterial abundance, primary production and carbon export, with the changes greater at the more productive site. Our modeling experiments reveal the importance of explicitly simulating dynamic viral processes in marine ecological models.
Subject(s)
Ecosystem , Viruses , Bacteria , Carbon , Heterotrophic Processes , SeawaterABSTRACT
The dominant marine filamentous N2 fixer, Trichodesmium, conducts photosynthesis and N2 fixation during the daytime. Because N2 fixation is sensitive to O2, some previous studies suggested that spatial segregation of N2 fixation and photosynthesis is essential in Trichodesmium. However, this hypothesis conflicts with some observations where all the cells contain both photosystems and the N2-fixing enzyme nitrogenase. Here, we construct a systematic model simulating Trichodesmium metabolism, showing that the hypothetical spatial segregation is probably useless in increasing the Trichodesmium growth and N2 fixation, unless substances can efficiently transfer among cells with low loss to the environment. The model suggests that Trichodesmium accumulates fixed carbon in the morning and uses that in respiratory protection to reduce intracellular O2 during the mid-daytime, when photosynthesis is downregulated, allowing the occurrence of N2 fixation. A cell membrane barrier against O2 and alternative non-O2 evolving electron transfer also contribute to maintaining low intracellular O2. Our study provides a mechanism enabling N2 fixation despite the presence of photosynthesis across Trichodesmium. IMPORTANCE The filamentous Trichodesmium is a globally prominent marine nitrogen fixer. A long-standing paradox is that the nitrogen-fixing enzyme nitrogenase is sensitive to oxygen, but Trichodesmium conducts both nitrogen fixation and oxygen-evolving photosynthesis during the daytime. Previous studies using immunoassays reported that nitrogenase was limited in some specialized Trichodesmium cells (termed diazocytes), suggesting the necessity of spatial segregation of nitrogen fixation and photosynthesis. However, attempts using other methods failed to find diazocytes in Trichodesmium, causing controversy on the existence of the spatial segregation. Here, our physiological model shows that Trichodesmium can maintain low intracellular O2 in mid-daytime and achieve feasible nitrogen fixation and growth rates even without the spatial segregation, while the hypothetical spatial segregation might not be useful if substantial loss of substances to the environment occurs when they transfer among the Trichodesmium cells. Our study then suggests a possible mechanism by which Trichodesmium can survive without the spatial segregation.
Subject(s)
Trichodesmium , Trichodesmium/metabolism , Nitrogen Fixation/physiology , Photosynthesis , Nitrogenase/metabolism , Nitrogen/metabolism , Oxygen/metabolismABSTRACT
Growth of the prominent nitrogen-fixing cyanobacterium Trichodesmium is often limited by phosphorus availability in the ocean. How nitrogen fixation by phosphorus-limited Trichodesmium may respond to ocean acidification remains poorly understood. Here, we use phosphate-limited chemostat experiments to show that acidification enhanced phosphorus demands and decreased phosphorus-specific nitrogen fixation rates in Trichodesmium. The increased phosphorus requirements were attributed primarily to elevated cellular polyphosphate contents, likely for maintaining cytosolic pH homeostasis in response to acidification. Alongside the accumulation of polyphosphate, decreased NADP(H):NAD(H) ratios and impaired chlorophyll synthesis and energy production were observed under acidified conditions. Consequently, the negative effects of acidification were amplified compared to those demonstrated previously under phosphorus sufficiency. Estimating the potential implications of this finding, using outputs from the Community Earth System Model, predicts that acidification and dissolved inorganic and organic phosphorus stress could synergistically cause an appreciable decrease in global Trichodesmium nitrogen fixation by 2100.
Subject(s)
Cyanobacteria , Trichodesmium , Nitrogen/pharmacology , Hydrogen-Ion Concentration , Seawater/chemistry , Nitrogen Fixation , Phosphorus/pharmacology , Homeostasis , Polyphosphates , Oceans and SeasABSTRACT
Prochlorococcus is the key primary producer in marine ecosystems, and the high-light-adapted clade II (HLII) is the most abundant ecotype. However, the genomic and ecological basis of Prochlorococcus HLII in the marine environment has remained elusive. Here, we show that the ecologically coherent subclade differentiation of HLII corresponds to genomic and ecological characteristics on the basis of analyses of 31 different strains of HLII, including 12 novel isolates. Different subclades of HLII with different core and accessory genes were identified, and their distribution in the marine environment was explored using the TARA Oceans metagenome database. Three major subclade groups were identified, viz., the surface group (HLII-SG), the transition group (HLII-TG), and the deep group (HLII-DG). These subclade groups showed different temperature ranges and optima for distribution. In regression analyses, temperature and nutrient availability were identified as key factors affecting the distribution of HLII subclades. A 35% increase in the relative abundance of HLII-SG by the end of the 21st century was predicted under the Representative Concentration Pathway 8.5 scenario. Our results show that the ubiquity and distribution of Prochlorococcus HLII in the marine environment are associated with the differentiation of diverse subclades. These findings provide insights into the large-scale shifts in the Prochlorococcus community in response to future climate change. IMPORTANCEProchlorococcus is the most abundant oxygenic photosynthetic microorganism on Earth, and high-light-adapted clade II (HLII) is the dominant ecotype. However, the factors behind the dominance of HLII in the vast oligotrophic oceans are still unknown. Here, we identified three distinct groups of HLII subclades, viz., the surface group (HLII-SG), the transition group (HLII-TG), and the deep group (HLII-DG). We further demonstrated that the ecologically coherent subclade differentiation of HLII corresponds to genomic and ecological characteristics. Our study suggests that the differentiation of diverse subclades underlies the ubiquity and distribution of Prochlorococcus HLII in the marine environment and provides insights into the shifts in the Prochlorococcus community in response to future climate change.
Subject(s)
Prochlorococcus , Ecosystem , Genome, Bacterial , Oceans and Seas , Phylogeny , Prochlorococcus/genetics , Prochlorococcus/metabolismABSTRACT
OBJECTIVE: To study the correlation between the clinical features and the prognosis in elderly patients with unprotected left main coronary artery disease (ULMCA) after coronary artery bypass grafting (CABG). METHODS: The clinical parameters and prognosis data from 176 patients received CABG for ULM were retrospectively analyzed for comparison of elderly (age≥65) and against non-elderly (age < 65). RESULTS: The elderly patients were found to have significantly higher level of blood high density lipoprotein cholesterin (HDL-C, mmol/L: 28.36 ± 17.20 vs. 13.68 ± 7.78, P < 0.01), lower level of blood low density lipoprotein cholesterin (LDL-C, mmol/L: 1.21 ± 0.77 vs. 2.48 ± 1.27, P < 0.01) and higher level of coronary stenosis [(94.56 ± 8.01)% vs. (87.96 ± 11.10)%, P < 0.01]. The incidence of multi-vessel disease (75.9% vs. 58.1%, P < 0.05) and chronic total occlusion (55.4% vs. 29.0%, P < 0.05) were both significantly higher in the elderly. No significant difference was found between the two groups in major adverse cardiac and cerebral events (MACCE), cerebral infarction, myocardial infarction, cardiac mortality, and total mortality (16.9% vs 17.2%, 3.6% vs 3.2%, 3.6% vs 5.4%, 6.0% vs 9.7%, and 12.0% vs 8.6%, all P > 0.05). CONCLUSION: In the elderly ULMCA patients the coronary lesions are more severe, but CABG is still a safe and efficient therapy for these patients.
Subject(s)
Coronary Artery Bypass , Coronary Artery Disease/surgery , Adult , Aged , Aged, 80 and over , Coronary Artery Disease/pathology , Coronary Vessels/pathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To observe the angiographic characteristics and the long-term clinical outcomes following coronary stenting in non-diabetic (non-DM) and type 2 diabetic (DM) patients with coronary artery disease. METHODS: This cohort study enrolled 1172 consecutive patients with coronary heart disease underwent elective coronary stenting (249 type 2 DM and 923 non-DM). The angiographic characteristics and the long-term clinical follow-up results were compared between non-DM and DM patients. RESULTS: The follow-up period was (39.2 +/- 6.4) months (6 - 83 months), follow-up rate was 90.3% in DM and 91.0% in non-DM group (P > 0.05). Compared with non-diabetic patients, there were significantly higher incidences of 2-vessel (P = 0.029) and 3-vessel (P = 0.013) diseases of coronary artery, severe stenosis lesion (P = 0.012), chronic total obstructive lesion (P = 0.044) and long lesion (P = 0.001), in-stent restenosis (ISR, P = 0.000) and revascularization (P = 0.000) and MACE (P = 0.000) in DM patients. COX multiple factorial analysis showed that DM is independent risk factor for ISR (P = 0.000), revascularization (P = 0.001) and MACE (P = 0.003). CONCLUSIONS: CHD patients with type 2 DM are associated with multi- and more severe vessel lesions. Type 2 DM is also an independent risk factor for increased ISR, revascularization and MACE post stenting.
Subject(s)
Coronary Disease/therapy , Diabetes Mellitus, Type 2/therapy , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , Coronary Disease/complications , Diabetes Mellitus, Type 2/complications , Female , Follow-Up Studies , Humans , Male , Middle Aged , Stents , Treatment OutcomeABSTRACT
The response of the prominent marine dinitrogen (N2)-fixing cyanobacteria Trichodesmium to ocean acidification (OA) is critical to understanding future oceanic biogeochemical cycles. Recent studies have reported conflicting findings on the effect of OA on growth and N2 fixation of Trichodesmium. Here, we quantitatively analyzed experimental data on how Trichodesmium reallocated intracellular iron and energy among key cellular processes in response to OA, and integrated the findings to construct an optimality-based cellular model. The model results indicate that Trichodesmium growth rate decreases under OA primarily due to reduced nitrogenase efficiency. The downregulation of the carbon dioxide (CO2)-concentrating mechanism under OA has little impact on Trichodesmium, and the energy demand of anti-stress responses to OA has a moderate negative effect. We predict that if anthropogenic CO2 emissions continue to rise, OA could reduce global N2 fixation potential of Trichodesmium by 27% in this century, with the largest decrease in iron-limiting regions.
Subject(s)
Nitrogen Fixation/physiology , Nitrogen/metabolism , Nitrogenase/metabolism , Trichodesmium/metabolism , Carbon Dioxide/metabolism , Carbon Dioxide/pharmacology , Computer Simulation , Energy Metabolism/drug effects , Ferredoxins/metabolism , Hydrogen-Ion Concentration , Iron/metabolism , Models, Theoretical , Oceans and Seas , Seawater/chemistry , Seawater/microbiology , Trichodesmium/drug effects , Trichodesmium/enzymology , Trichodesmium/growth & developmentABSTRACT
The origin of the recalcitrant dissolved organic carbon (RDOC) reservoir in the deep ocean remains enigmatic. The structural recalcitrance hypothesis suggests that RDOC is formed by molecules that are chemically resistant to bacterial degradation. The dilution hypothesis claims that RDOC is formed from a large diversity of labile molecules that escape bacterial utilization due to their low concentrations, termed as RDOCc . To evaluate the relative contributions of these two mechanisms in determining the long-term persistence of RDOC, we model the dynamics of both structurally recalcitrant DOC and RDOCc based on previously published data that describes deep oceanic DOC degradation experiments. Our results demonstrate that the majority of DOC (84.5 ± 2.2%) in the deep ocean is structurally recalcitrant. The intrinsically labile DOC (i.e., labile DOC that rapidly consumed and RDOCc ) accounts for a relatively small proportion and is consumed rapidly in the incubation experiments, in which 47.8 ± 3.2% of labile DOC and 21.9 ± 4.6% of RDOCc are consumed in 40 days. Our results suggest that the recalcitrance of RDOC is largely related to its chemical properties, whereas dilution plays a minor role in determining the persistence of deep-ocean DOC.
Subject(s)
Carbon/chemistry , Seawater/chemistry , Seawater/microbiology , Carbon/metabolism , Carbon Cycle , Models, BiologicalABSTRACT
Acidification of seawater caused by anthropogenic carbon dioxide (CO2) is anticipated to influence the growth of dinitrogen (N2)-fixing phytoplankton, which contribute a large fraction of primary production in the tropical and subtropical ocean. We found that growth and N2-fixation of the ubiquitous cyanobacterium Trichodesmium decreased under acidified conditions, notwithstanding a beneficial effect of high CO2 Acidification resulted in low cytosolic pH and reduced N2-fixation rates despite elevated nitrogenase concentrations. Low cytosolic pH required increased proton pumping across the thylakoid membrane and elevated adenosine triphosphate production. These requirements were not satisfied under field or experimental iron-limiting conditions, which greatly amplified the negative effect of acidification.
Subject(s)
Nitrogen Fixation , Nitrogen/metabolism , Seawater/chemistry , Seawater/microbiology , Trichodesmium/growth & development , Trichodesmium/metabolism , Carbon Dioxide/metabolism , Hydrogen-Ion Concentration , Iron Deficiencies , Nitrogenase/metabolism , Oceans and Seas , Proton Pumps/metabolismABSTRACT
BACKGROUND: There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events. METHODS: All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups. RESULTS: Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3-8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group. CONCLUSIONS: During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.
Subject(s)
Coronary Artery Bypass , Coronary Artery Disease/therapy , Drug-Eluting Stents , Percutaneous Coronary Intervention , Aged , Coronary Artery Disease/physiopathology , Female , Humans , Male , Middle Aged , Stroke VolumeABSTRACT
Arrieta et al. (Reports, 17 April 2015, p. 331) propose that low concentrations of labile dissolved organic carbon (DOC) preclude prokaryotic consumption of a substantial fraction of DOC in the deep ocean and that this dilution acts as an alternative mechanism to recalcitrance for long-term DOC storage. Here, we show that the authors' data do not support their claims.
Subject(s)
Carbon Cycle , Carbon Dioxide/chemistry , Oceans and Seas , Seawater/chemistry , Seawater/microbiologyABSTRACT
BACKGROUND: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery Score II (SS-II) can well predict 4-year mortality in patients with complex coronary artery disease (CAD), and guide decision-making between coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). However, there is lack of data regarding the utility of the SS-II in patients with three-vessel CAD undergoing PCI treated with second-generation drug-eluting stents (DES). The purpose of the present study was to evaluate the ability of the SS-II to predict long-term mortality in patients with three-vessel CAD undergoing PCI with second-generation DES. METHODS: Totally, 573 consecutive patients with de novo three-vessel CAD who underwent PCI with second-generation DES were retrospectively studied. According to the tertiles of the SS-II, the patients were divided into three groups: The lowest SS-II tertile (SS-II ≤20), intermediate SS-II tertile (SS-II of 21-31), and the highest SS-II tertile (SS-II ≥32). The survival curves of the different groups were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relationship between the SS-II and 5-year mortality. The performance of the SS-II with respect to predicting the rate of mortality was studied by calculating the area under the receiver operator characteristic (ROC) curve. The predictive ability of the SS-II for 5-year mortality was evaluated and compared with the SS alone. RESULTS: The overall SS-II was 27.6 ± 9.0. Among patients in the lowest, intermediate and the highest SS-II tertiles, the 5-year rates of mortality were 1.6%, 3.2%, and 8.6%, respectively (P = 0.003); the cardiac mortality rates were 0.5%, 1.9%, and 5.2%, respectively (P = 0.014). By multivariable analysis, adjusting for the potential confounders, the SS-II was an independent predictor of 5-year mortality (hazard ratio: 2.45, 95% confidence interval: 1.38-4.36; P = 0.002). The SS-II demonstrated a higher predictive accuracy for 5-year mortality compared with the SS alone (the area under the ROC curve was 0.705 and 0.598, respectively). CONCLUSION: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.
Subject(s)
Coronary Disease/mortality , Coronary Disease/surgery , Drug-Eluting Stents , Percutaneous Coronary Intervention/mortality , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: The Syntax score was recently developed as a comprehensive, angiographic tool grading the complexity of coronary artery disease (CAD). It aims to assist in patient selection and risk stratification of patients with extensive CAD undergoing revascularization. However, the prognostic value of the Syntax score in patients undergoing percutaneous coronary intervention (PCI) has not been validated. The aim of this study was to evaluate its role in predicting long-term incidences of major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing PCI for 3-vessel disease. METHODS: Two hundred and three consecutive patients with de novo 3-vessel CAD undergoing PCI with sirolimus-eluting stents were studied. Their angiograms were scored according to the Syntax score. The patients were divided into tertiles according to the Syntax score: lowest Syntax score tertile (Syntax score ≤ 22), intermediate Syntax score tertile (Syntax score of 23 to 32), and the highest Syntax score tertile (Syntax score ≥ 33). During the 1-year follow-up, the MACCE-free survival curves were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the Syntax score and the incidence of MACCE. Performance of the Syntax score was studied with respect to predicting the rate of MACCE by receiver operator characteristic (ROC) curves with an area under the curve. RESULTS: The overall Syntax score ranged from 6 to 66 with mean ± standard deviation of 27.9 ± 12.6 and a median of 26. At 1 year, the Syntax score significantly predicted the risk of MACCE (HR 1.07/U increase, 95%CI 1.04 to 1.11, P < 0.001). The rate of MACCE was significantly increased among patients in the highest Syntax score tertile (17.9%) as compared with those with the lowest Syntax score tertile (1.4%, P < 0.001) or intermediate Syntax score tertile (6.2%, P = 0.041). After the adjustment for all potential confounders, the Syntax score remained a significant predictor of the rate of MACCE (adjusted HR 1.12/U increase, 95%CI 1.05 to 1.20, P < 0.001). The Syntax score accurately predicted MACCE with an area under the receiver operator curve of 0.77 (95%CI 0.65 to 0.90, P < 0.001). A Syntax score of 29.5 was identified as the optimal cutoff to predict MACCE with a sensitivity of 82.4% and specificity of 65.6%. CONCLUSION: The Syntax score predicts the risk of MACCE in patients with 3-vessel disease undergoing PCI.