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1.  Effect of Late Revascularization of a Totally Occluded Coronary Artery After Myocardial Infarction on Mortality Rates in Patients with Renal Impairment 
The American journal of cardiology  2012;110(7):954-960.
Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention (PCI) to medical therapy in MI patients with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to PCI with optimal medical therapy in 2201 high risk patients with an occluded infarct artery >24 hours post-MI with serum creatinine ≤2.5 mg/dl. The primary endpoint was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out utilizing estimated glomerular filtration rates (eGFR) as a continuous variable and by eGFR categories. Long term follow up data (maximum 9 years) were used for this analysis. Lower eGFR (ml/min/1.73m2) was associated with development of the primary outcome (6-year life-table rate 16.9% in eGFR>90; 19.2% in eGFR 60–89; 34.9% in eGFR<60; p-value <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariable analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary endpoint regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from PCI in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase post MI.
PMCID: PMC3439588  PMID: 22728005
Myocardial Infarction; Stents and Kidney Disease
2.  Determinants of vascular function in patients with type 2 diabetes 
Type 2 diabetes mellitus (T2DM) is independently associated with an increased risk for cardiovascular diseases that is primarily due to the early development of advanced atherosclerotic vascular changes. The aim of our study was to investigate the predictors of vascular dysfunction in T2DM patients.
We studied 165 T2DM patients without known macrovascular or microvascular disease. Standard demographic (age, gender, cardiovascular risk factors, medications), clinical (body mass index, blood pressure) and laboratory (glucose, glycated hemoglobin, lipids, renal function) parameters were included in analyses. Brachial artery flow-mediated dilation (FMD), nitrate mediated dilation (NMD) and Carotid-Femoral Pulse Wave Velocity (PWV) were measured.
Median age was 66 years and duration since T2DM diagnosis was 10 years, 70% were females and 79% hypertensives, while only 10% had a glycated hemoglobin <7%. FMD was positively associated with NMD (r 0.391, P < 0.001), while PWV was inversely associated with FMD (r -0.218, P = 0.014) and NMD (r -0.309, P < 0.001). Time since diagnosis of diabetes was the single independent predictor of FMD (β -0.40, P = 0.003). Increased age and fasting glucose and the presence of hypertension were independent predictors of decreased NMD (P < 0.001). Increased age and systolic blood pressure were independently associated with increased PWV (P < 0.001).
In T2DM patients, impairment of endothelium-dependent vasodilation was independently associated only with longer diabetes duration while no association with other established risk factors was found. Vascular smooth muscle dysfunction and increased arterial stiffness were more prominent in older T2DM patients with hypertension. Worse glycemic control was associated with impaired vascular smooth muscle function.
PMCID: PMC3490819  PMID: 23062182
Type 2 diabetes mellitus; Pulse wave velocity; Flow-mediated dilation; Nitrate-mediated dilation; Atherosclerosis
3.  Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities 
Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques.
PMCID: PMC3039561  PMID: 21276268
4.  Lack of effects of pioglitazone on cardiac function in patients with type 2 diabetes and evidence of left ventricular diastolic dysfunction: a tissue doppler imaging study 
Thiazolidinediones, used for the treatment of patients with type 2 diabetes mellitus (DM2), are associated with an increased incidence of heart failure. We sought to investigate the effects of pioglitazone on novel echocardiographic indices of left ventricular (LV) diastolic function in DM2 patients with LV diastolic dysfunction (LVDD).
Eighty-eight asymptomatic DM2 patients on metformin and/or sulfonylureas, aged 64.5 ± 7.7 years, without known cardiovascular disease, with normal LV systolic function and evidence of LVDD were randomly assigned to pioglitazone 30 mg/day (n = 42) or an increase in dose of other oral agents (n = 39) for 6 months. All patients underwent transthoracic conventional and Tissue Doppler Imaging echocardiography at baseline and follow-up. The primary end-point was change in early diastolic velocity of the mitral annulus (E').
Improvement of glycaemic control was similar in the 2 groups. A significant difference (p < 0.05) between the 2 groups was found in the treatment-induced changes in fasting insulin, the insulin resistance index HOMA, HDL cholesterol, triglycerides, diastolic blood pressure (all in favor of pioglitazone) and in body weight (increase with pioglitazone). No significant changes were observed in any echocardiographic parameter in either group and did not differ between groups (p = NS for all). E' increased non-significantly and to a similar extent in both groups (p = NS).
In asymptomatic DM2 patients with LVDD, the addition of pioglitazone to oral conventional treatment for 6 months does not induce any adverse or favorable changes in LV diastolic or systolic function despite improvements in glycaemic control, insulin sensitivity, lipid profile, and blood pressure.
PMCID: PMC2955641  PMID: 20863381
5.  Percutaneous coronary intervention in the Occluded Artery Trial: Procedural success, hazard, and outcomes over 5 years 
American heart journal  2009;158(3):408.
The Occluded Artery Trial (OAT) was a 2,201-patient randomized clinical trial comparing routine stent-based percutaneous coronary intervention (PCI) versus optimal medical therapy alone in stable myocardial infarction (MI) survivors with persistent infarct-related artery occlusion identified day 3 to 28 post MI. Intent-to-treat analysis showed no difference between strategies with respect to the incidence of new class IV congestive heart failure, MI, or death. The influence of PCI failure, procedural hazard, and crossover on trial results has not been reported.
Study angiograms were analyzed and adjudicated centrally. Factors associated with PCI failure were examined. Time-to-event analysis using the OAT primary outcome was performed by PCI success status. Landmark analysis (up to and beyond 30 days) partitioned early hazard versus late outcome according to treatment received.
Percutaneous coronary intervention was adjudicated successful in >87%. Percutaneous coronary intervention failure rates were similar in US and non-US sites, and did not significantly influence outcome at 60 months (hazard ratio for success vs fail 0.79, 99% CI 0.45–1.40, P = .29). Partitioning of early procedural hazard revealed no late benefit for PCI (hazard ratio for PCI success vs medical therapy alone 1.06, 99% CI 0.75–1.50, P = .66).
Percutaneous coronary intervention failure and complication rates in the OAT were low. Neither PCI failure nor early procedural hazard substantively influenced the primary trial results.
PMCID: PMC2820255  PMID: 19699864
6.  Hsp70 translocates to the nuclei and nucleoli, binds to XRCC1 and PARP-1, and protects HeLa cells from single-strand DNA breaks 
Cell Stress & Chaperones  2008;14(4):391-406.
For many years, there has been uncertainty concerning the reason for Hsp70 translocation to the nucleus and nucleolus. Herein, we propose that Hsp70 translocates to the nucleus and nucleoli in order to participate in pathways related to the protection of the nucleoplasmic DNA or ribosomal DNA from single-strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing (knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore, HeLa Hsp70 depleted cells were very sensitive in heat treatment and their DNA breaks were multiple compared to that of control HeLa cells. The molecular mechanism with which Hsp70 performs its role at the level of nucleus and nucleolus during stress was examined. Hsp70 co-localizes with PARP1 in the nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain of PARP1 as was revealed with protein–protein interaction assays. It was also found that Hsp70 binds simultaneously to XRCC1 and PARP-1, indicating that Hsp70 function takes place at the level of DNA repair and possibly at the base excision repair system. Making a hypothetical model, we have suggested that Hsp70 is the molecule that binds and interrelates with PARP1 creating the repair proteins simultaneously, such as XRCC1, at the single-strand DNA breaks. Our data partially clarify a previously unrecognized cellular response to heat stress. Finally, we can speculate that Hsp70 plays a role in the quality and integrity of DNA.
PMCID: PMC2728274  PMID: 19089598
Hsp70; PARP-1; XRCC1; DNA damage; DNA repair; DNA breaks; Apoptosis; Heat shock

Results 1-6 (6)