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Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.

Introduction:Cardiovascular disease, including atherosclerosis is the leading cause of mortality in the Western world. We have reported that insulin-like growth factor I (IGF-1) reduced atherosclerosis in the murine model, however it is unknown whether IGF-1 exerts protective effect on human-like atherosclerosis.Hypothesis:Rapacz pigs with familial hypercholesterolemia (FH pigs) fed with high-cholesterol diet develop human-like advanced plaques in coronary arteries. We hypothesize that IGF-1 suppresses atherosclerosis in FH pigs.Methods:Human recombinant IGF-1 (50 ug/kg) or saline (control) was injected daily into high-fat diet fed FH swine (n=9/group) for 6 months. Atherosclerotic burden was quantified by intravascular ultrasound (IVUS) at basal level (T0), after 3 months on diet (T3) and at sacrificing (T6).Results:IGF-1-injected pigs had 2.6-fold increase in total plasma IGF-1 (ELISA, p<0.001 vs. control pigs). Pigs in IGF-1 and control groups had a gradual increase in vessel volume in the right coronary artery (RCA), and left anterior descending artery (LAD) with time as quantified by IVUS. However, IGF-1-injected pigs had a larger increase in vessel volume after 3 and 6 months compared to controls suggesting vascular hypertrophy. The atherosclerotic burden was increased in RCA, and LAD in both groups after 3 and 6 months of injections compared to the pre-injection time point. We found a significant reduction in atherosclerotic burden in RCA and LAD in IGF-1 group compared to control at 6 months’ time-point (RCA: IGF-1, 203±13%, vs. control, 244±8; LAD: IGF-1, 200±6%, vs. control, 228±11%). The lumen volume of coronaries was decreased in both groups, however, coronaries in IGF-1-injected pigs had on average 24±3% larger lumen volume compared to control pigs at 6 months’ time-point.Conclusions:We found that IGF-1 increased total volume of pig coronaries suggesting hypertrophy and these data are consistent with growth-stimulating effects of IGF-1. We found reduction in atherosclerotic burden and increase in lumen volume in coronaries in the IGF-1 group after 6 months of injections consistent with an anti-atherosclerotic effect of IGF-1. Our data support the feasibility of using IGF-1 for as an anti-atherogenic therapy.

Introduction:Collagen content in atherosclerotic plaque is a hallmark of plaque stability. We have shown that insulin-like growth factor-1 (IGF1) increased collagen content in atherosclerotic plaques of Apoe-/-mice. We have identified LARP6 (La Ribonucleoprotein Domain Family, Member 6), a type I collagen mRNA-binding protein, as a mediator of IGF1-dependent type I collagen upregulation and increased mature fibril formation by smooth muscle cells (SMC), however specific mechanism has not been elucidated yet.Methods and Results:Micro-RNAs, including miR-1976 have been shown to bind to LARP6 mRNA. We found that SMC treatment with IGF1 significantly downregulated miR-1976 by 41±5% after 3h (P&lt;0.05), consistent with the IGF1-induced LARP6 upregulation. In fact, miR-1976 mimic (20 nM) decreased LARP6 by 67% (P&lt;0.05) and reduced type I procollagen protein levels by 85% (P&lt;0.05). MiR-1976 mimic inhibits IGF1-induced LARP6 upregulation showing miR-1976 involvement in IGF1 effect on LARP6. It has been reported that LARP6-mediated promotion of procollagen synthesis may be regulated by phosphorylation of LARP6, therefore we investigated whether IGF1 induces LARP6 phosphorylation in cultured human aortic SMCs. For this experiment, SMCs were serum-starved and treated for 0-48h with 10 ng/mL IGF1. LARP6 protein was detected by immunoblots as a single 67kDa band in untreated SMC. However, after 6h of IGF1 treatment there was additional phosphorylated LARP6 band detected at 70 kDa. The levels of 70kDa LARP6 time-dependently increased up to 18h of treatment, with a concomitant increase of type I procollagen and collagen expression levels.Conclusions:In summary, our data suggests that (i) IGF1 downregulates miR-1976, thereby increasing LARP6 expression levels and (ii) IGF1 induces phosphorylation of LARP6, thereby promoting LARP6 activity. Our study revealed novel mechanisms underlying IGF1-induced type I collagen upregulation in vascular SMC and potentially in atherosclerotic plaques.

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To determine the prolonged effect of Hurricane Katrina on the incidence and timing of acute myocardial infarction (AMI) in the city of New Orleans.

Breast arterial calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, with increasing age. The aim of this review is to discuss relevant literature examining relation between BAC and atherosclerosis. After a thorough literature search, in OVID and PubMed, 199 studies were identified, of which 25 were relevant to our review. Data were abstracted from each study and statistical analysis was done, including calculation of odds ratios and construction of forest plots. A total of 35,542 patients were enrolled across 25 studies looking at an association between BAC and coronary artery disease, cardiovascular disease, stroke, cerebral artery disease, carotid and peripheral artery diseases, and coronary artery calcification. A majority of the studies showed a statistically significant relation between BAC and presence of coronary artery disease cardiovascular disease and associated mortality. Sensitivity of BAC in predicting cardiovascular events was low, but specificity was high. BAC was predictive of incident and prevalent stroke but not mortality of stroke. Similarly, BAC was predictive of cerebral, carotid, and peripheral artery diseases. The role of BAC as a surrogate marker of coronary and systemic atherosclerosis is currently uncertain. Its role may be further elucidated by more large-scale prospective studies and clinical experience.

ABSTRACTBackground:In August 2005, New Orleans was hit by Hurricane Katrina, the costliest natural disaster in US history. Previous studies have shown an increase in acute myocardial infarction (AMI) in the immediate hours to weeks after natural disasters. The goals of our study were to detect any long-term increase in the incidence of AMI after Katrina and to investigate any pertinent contributing factors.Methods:This was a single-center retrospective cohort observational study. Patients admitted with AMI to Tulane Health Sciences Center hospital in the 2 years before Katrina and in the 2 years after the hospital reopened (5 months after Katrina) were identified from hospital records. The 2 groups (pre- and post-Katrina) were compared for prespecified demographic and clinical data.Results:In the post-Katrina group, there were 246 admissions for AMI, out of a total census of 11,282 patients (2.18%), as compared with 150 AMI admissions out of a total of 21,229 patients (0.71%) in the pre-Katrina group (P< 0.0001). The post-Katrina group had a significantly higher prevalence of unemployment (P= 0.0003), lack of medical insurance (P< 0.0001), medication noncompliance (P= 0.0001), smoking (P= 0.001), substance abuse (P= 0.03), first-time hospitalization (P< 0.001), local residents rather than visitors affected (P< 0.0001), and people living in temporary housing (P= 0.003).Discussion:The role of chronic stress in the pathogenesis of AMI is poorly understood, especially in the aftermath of natural disasters. Our data suggest that Katrina was associated with prolonged loss of employment and insurance, decreased access to preventive health services, and an increased incidence of AMI. In addition, it appears that chronic stress after a natural disaster can be associated with tobacco abuse and medication and therapeutic noncompliance.Conclusions:We found a 3-fold increased incidence of AMI more than 2 years after Hurricane Katrina. Even allowing for the loss of some local hospitals after the disaster, this represents a significant change in overall health of the study population and supports the need for further study into the health effects of chronic stress. (Disaster Med Public Health Preparedness. 2009;3:144–150)

Introduction:We have previously shown left ventricular (LV) structural and hemodynamic differences in two models of rat pressure overload induced moderate remodeling and early systolic dysfunction (MOD) and overt systolic heart failure (SHF). The MOD and SHF phenotypes develop 8 weeks post ascending aortic banding via a vascular clip, area of 2 mm2and 1.5 mm2, respectively.Hypothesis:Metabolic remodeling play significant role in the development of MOD and SHF phenotypes, but is more evident in SHF than MOD.Methods:Shotgun proteomics and phospho-(p)-proteomics and non-targeted metabolomics analysis was performed in LV myocardium tissue from Sham, MOD and SHF using liquid chromatography mass spectrometry (LC-MS); n=3 biological samples per group. Raw proteomics, p-proteomics and metabolomics MS data were uploaded into Qlucore bioinformatics software for statistical analysis and data visualization. Statistically analyzed data were then uploaded into Ingenuity Pathway Analysis bioinformatics software for data validation and assessment of highly enriched canonical pathways related to metabolism that were up or down-regulated in MOD and SHF relative to Sham. Some of the proteomics and p-proteomics data were validated by immunoblotting.Results:Canonical pathways of oxidative phosphorylation, fatty acid β-oxidation, Kreb’s cycle, branched-chain amino acid and amino acid (Glutamine and Tryptophan) degradation were downregulated in MOD vs Sham and were further downregulated in SHF vs MOD. Whilst glycogen degradation and glucose degradation were upregulated in MOD and SHF vs Sham, but more so in MOD than SHF. Metabolomics data revealed that long chain and very long chain acyl-carnitines were decreased in abundance in MOD and SHF relative to Sham, while short and medium chain acyl-carnitines were decreased in abundance in SHF only. Moreover, Isoleucine degradation and glycolysis decreased and Taurine biosynthesis increased in SHF vs MOD. p-Proteomics data showed mild decrease in protein kinase A (PKA) and AMPK signaling in MOD vs Sham, which were more profoundly decreased in SHF than MOD.Conclusion:The interplay between PKA and AMPK signaling play an important role in metabolic remodeling and transitioning from MOD to SHF phenotype.

Increased bioavailability of Insulin Like Growth Factor I (IGF1) has been shown to reduce cardiovascular events. Systemic IGF1 administration in ApoE deficient (Apoe-/-) mice fed a high fat diet reduced atherosclerosis and reduced plaque macrophages. Results of our previous in vitroexperiments suggest that macrophages play a predominant role in mediating IGF1 effects in atherosclerotic plaque. We hypothesized that increasing IGF1 levels strictly in macrophages will prevent atherosclerosis. After breeding a novel macrophage-specific IGF1 overexpressing transgenic mouse to an Apoe-/-background (MF-IGF1 mice), we assessed atherosclerotic plaque burden, stability, and monocyte recruitment. Macrophage IGF1 overexpression downregulated plaque burden by 30% (P<0.01), reduced plaque macrophages by 47% (P<0.001) and promoted a stable plaque phenotype. Monocyte recruitment was reduced by 70% (P<0.05) in MF-IGF1 mice and was associated with a decrease in circulating levels of CXC Chemokine Ligand 12 (CXCL12) (27% reduction, P<0.05). CXCL12 protein levels were reduced in plaque and peritoneal macrophages in MF-IGF1 mice. IGF1 completely blocked oxidized low-density lipoprotein (oxLDL)-dependent increase of CXCL12 mRNA transcription (98% reduction, P<0.01) and IGF1 treatment reduced CXCL12 protein (56% decrease, P<0.001) in vitro.ATP-binding cassette transporter A1 (ABCA1) is the key cholesterol transporter mediating macrophage cholesterol efflux and CXCL12 reduces its expression. We found that peritoneal macrophages isolated from MF-IGF1 mice have a 2 fold increase in ABCA1 protein levels. We loaded peritoneal macrophages with oxLDL to measure changes in cholesterol efflux and found that MF-IGF1 mice have a 42% increase in efflux (P<0.01). We also found a 27% increase in cholesterol efflux in IGF1 (100 ng/mL) treated THP-1 cells (P<0.01) with Apolipoprotein AI as a cholesterol acceptor. Overall, our results indicate that macrophage IGF1 reduces atherosclerosis and decreases CXCL12, a chemokine newly implicated in atheroprogression. IGF1 potentially exerts its atheroprotective effect via this reduction in CXCL12 by reducing monocyte recruitment and by increasing ABCA1, thereby increasing cholesterol efflux capacity.

Congestive heart failure is increasing in prevalence and represents a major public health problem. The syndrome of advanced heart failure often includes muscle wasting, commonly termed cardiac cachexia, which is a predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood, but there is recent evidence that increased angiotensin II, interacting with the insulin-like growth factor-1 system, plays an important role.

Coronary artery disease is the major cause of death worldwide. Hypertension is a major risk factor for developing coronary disease. It is now recognized that endothelial dysfunction is an early marker of coronary artery disease before structural changes to the vessel wall are apparent on angiography or intravascular ultrasound and that it has a prognostic value in predicting cardiovascular events in hypertensive patients. This review addresses recent developments in hypertension-induced endothelial dysfunction.

Peptide growth factors induce vascular smooth muscle cell (SMC) proliferation and migration after vascular injury, leading to arterial stenosis. Estrogen provides vasculoprotective effects by regulating endothelial and vascular SMC function.

Insulin-like growth factor-1 (IGF-1) plays an important role in migration, cell cycle progression and survival of vascular smooth muscle cells (VSMC). We investigated the specific localization of IGF-1 and its receptor (IGF-1R) and their association with apoptosis and the expression of apoptosis-related proteins in early and advanced atherosclerotic lesions. Human atherosclerotic plaques (n=23) from patients undergoing aortic, carotid or femoral arterial surgery were studied. Immunohistochemistry and in situhybridization revealed significantly higher expression of IGF-1 and IGF-1R in the media than in the intima of early atherosclerotic lesions (P<0.01). Medial VSMC positive for BAX, a proapoptotic protein of the B-cell CLL/lymphoma 2 (BCL2) family, showed colocalization of IGF-1. Apoptosis, as detected by DNA in situterminal deoxynucleotidyl transferase end labeling (TUNEL), was not present in these early lesions. In advanced atherosclerotic plaques, the expression of IGF-1 and IGF-1R was significantly lower in the intimal regions with macrophage infiltration than in those without macrophage infiltration or than in the media (P<0.01). Furthermore, IGF-1 and IGF-1R immunoreactivity was markedly lower in intimal TUNEL-positive VSMC compared with intimal BAX-positive and medial VSMC (P<0.01). We conclude that IGF-1 and IGF-1R expression are reduced in the deep intima of early atherosclerotic lesions and in areas of advanced plaques with macrophage infiltration. Since IGF-1 is a potent survival factor for VSMC, poor expression of IGF-1 and IGF-1R in intimal regions with macrophage infiltration would likely contribute to triggering VSMC apoptosis potentially leading to plaque weakening, plaque rupture and acute coronary events.

Severe acute respiratory syndrome coronavirus 2 is highly contagious, and the global spread has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures (including contact tracing, isolation, and quarantine) are critical for deterring viral transmission, preventing infection progression, and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitrostudies have indicated that the amount of virus isolated from infected people affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We aimed to examine, from a diagnostic point of view, whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the nonspreaders in a population of college students. Our results indicate that although at the population level the Ct value is lower (suggesting a higher viral load) in the symptomatic spreaders than in the asymptomatic nonspreaders, there is significant overlap in the Ct values between the two groups. Thus, the Ct value, or the viral load, at the individual level could not predict transmissibility. Our studies also suggest that a sensitive method to detect the presence of virus is needed to identify asymptomatic persons who may carry a low viral load but can still be infectious.

An abnormal electrocardiographic stress test is typically characterized by ST segment depression. In rare cases, ST segment elevation is observed, which, in the absence of diagnostic Q waves, has anatomic specificity for localized myocardial ischemia. Most instances of ST elevation occurring during cardiac stress testing have been observed with exercise, with only six cases reported with pharmacologic stress. Despite different physiologic mechanisms for inducing myocardial ischemia, development of ST segment elevation during pharmacologic stress, as illustrated by the present case, may also be indicative of critical coronary stenoses, warranting urgent coronary arteriography.

Various electrocardiographic changes have been reported in the setting of acute neurological events, among them large, upright U waves. In contrast, the occurrence of inverted U waves is strongly suggestive of cardiovascular disease, most commonly hypertension, coronary artery disease, or valvular abnormalities. Presented herein is the case of a 29-year-old man with previous anoxic brain injury (but without apparent cardiovascular disease) whose electrocardiogram demonstrated persistent giant inverted U waves.