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Renovascular hypertension (RVH) leads to left ventricular (LV) hypertrophy and diastolic dysfunction, associated with increased cardiovascular mortality. Intrarenal delivery of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) improves kidney function in porcine RVH, and the potent anti-inflammatory properties of MSCs may serve to blunt inflammatory mediators in the cardiorenal axis. However, their relative efficacy in attenuating cardiac injury and dysfunction remains unknown. This study tested the hypothesis that the car-dioprotective effect of EPCs and MSCs delivered into the stenotic kidney in experimental RVH are comparable. Pigs ( n = 7 per group) were studied after 10 weeks of RVH or control untreated or treated with a single intrarenal infusion of autologous EPCs or MSCs 4 weeks earlier. Cardiac and renal function (fast CT) and stenotic kidney release of inflammatory mediators (ELISA) were assessed in vivo, and myocardial inflammation, remodeling, and fibrosis ex vivo. After 10 weeks of RVH, blood pressure was not altered in cell-treated groups, yet stenotic kidney glomerular filtration rate (GFR), blunted in RVH, improved in RVH + EPC, and normalized in RVH + MSCs. Stenotic kidney release of monocyte chemoattractant protein (MCP)-1 and its myocardial expression were elevated in RVH + EPC, but normalized only in RVH + MSC pigs. RVH-induced LV hypertrophy was normalized in both EPC- and MSC-treated pigs, while diastolic function (E/A ratio) was restored to normal levels exclusively in RVH + MSCs. RVH-induced myocardial fibrosis and collagen deposition decreased in RVH + EPCs but further decreased in RVH + MSC-treated pigs. Intrarenal delivery of EPCs or MSCs attenuates RVH-induced myocardial injury, yet MSCs restore diastolic function more effectively than EPCs, possibly by greater improvement in renal function or reduction of MCP-1 release from the stenotic kidney. These observations suggest a therapeutic potential for EPCs and MSCs in preserving the myocardium in chronic experimental RVH.

Background— Current risk models for predicting long-term mortality after percutaneous coronary intervention are restricted to all-cause mortality. We sought to develop novel risk models for the prediction of cardiac and noncardiac mortality after percutaneous coronary intervention. Methods and Results— We retrospectively evaluated patients who underwent index percutaneous coronary intervention at Mayo Clinic from 2003 to 2008. Long-term deaths were ascertained through scheduled prospective surveillance. Cause of death was determined via telephone interviews, medical records, and autopsy reports. Fine and Gray extension of Cox proportional hazards models was used to model cause-specific cumulative incidence. Candidate variables and interactions were chosen a priori, without variable selection methods. Resulting models were mapped to an integer-based risk score. The study comprised 6636 patients followed up over a median of 62 months (25th, 75th percentiles: 45, 77 months). There were 1488 deaths, 518 (35%) cardiac, 938 (63%) noncardiac, and 32 (2%) unknown. The 5-year predicted cardiac mortality ranged from 0.6% to 97%, with a corrected c -statistic of 0.82. Risk factors for cardiac death included age, body mass index, ejection fraction, and history of congestive heart failure. The integer score for noncardiac death included age, medicine index, body mass index, current smoker, noncardiac Charlson index and cardiac Charlson index, and accommodated significant age-based interactions for smoking and the 2 Charlson indices. Predicted noncardiac mortality at 5 years ranged from 0.2% to 81%, with a corrected c -statistic of 0.77. Conclusions— We report novel risk models to predict cardiac and noncardiac long-term mortality after percutaneous coronary intervention.

Carotid artery stenosis is a well-established risk factor of ischemic stroke, contributing to up to 10%-20% of strokes or transient ischemic attacks. Many clinical trials over the last 20 years have used measurements of carotid artery stenosis as a means to risk stratify patients. However, with improvements in vascular imaging techniques such as CT angiography and MR angiography, ultrasonography, and PET/CT, it is now possible to risk stratify patients, not just on the degree of carotid artery stenosis but also on how vulnerable the plaque is to rupture, resulting in ischemic stroke. These imaging techniques are ushering in an emerging paradigm shift that allows for risk stratifications based on the presence of imaging features such as intraplaque hemorrhage (IPH), plaque ulceration, plaque neovascularity, fibrous cap thickness, and presence of a lipid-rich necrotic core (LRNC). It is important for the neurosurgeon to be aware of these new imaging techniques that allow for improved patient risk stratification and outcomes. For example, a patient with a low-grade stenosis but an ulcerated plaque may benefit more from a revascularization procedure than a patient with a stable 70% asymptomatic stenosis with a thick fibrous cap. This review summarizes the current state-of-the-art advances in carotid plaque imaging. Currently, MRI is the gold standard in carotid plaque imaging, with its high resolution and high sensitivity for identifying IPH, ulceration, LRNC, and inflammation. However, MRI is limited due to time constraints. CT also allows for high-resolution imaging and can accurately detect ulceration and calcification, but cannot reliably differentiate LRNC from IPH. PET/CT is an effective technique to identify active inflammation within the plaque, but it does not allow for assessment of anatomy, ulceration, IPH, or LRNC. Ultrasonography, with the aid of contrast enhancement, is a cost-effective technique to assess plaque morphology and characteristics, but it is limited in sensitivity and specificity for detecting LRNC, plaque hemorrhage, and ulceration compared with MRI. Also summarized is how these advanced imaging techniques are being used in clinical practice to risk stratify patients with low- and high-grade carotid artery stenosis. For example, identification of IPH on MRI in patients with low-grade carotid artery stenosis is a risk factor for failure of medical therapy, and studies have shown that such patients may fair better with carotid endarterectomy (CEA). MR plaque imaging has also been found to be useful in identifying revascularization candidates who would be better candidates for CEA than carotid artery stenting (CAS), as high intraplaque signal on time of flight imaging is associated with vulnerable plaque and increased rates of adverse events in patients undergoing CAS but not CEA.

Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity.

Hypercholesterolemia (HC) is characterized by increased circulating 8- epi-prostaglandin-F2α(isoprostane), a vasoconstrictor, marker, and mediator of increased oxidative stress, whose vascular effects might be augmented in HC. Anesthetized pigs were studied in vivo with electron beam computed tomography after a 12-wk normal ( n = 8) or HC ( n = 8) diet. Mean arterial pressure (MAP), single-kidney perfusion, and glomerular filtration rate (GFR) were quantified before and during unilateral intrarenal infusions of U46619 (10 ng · kg−1· min−1) or isoprostane (1 μg · kg−1· min−1). Basal renal perfusion and function were similar, and isoprostane infusion elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs. baseline). Both drugs markedly and comparably decreased cortical perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P≤ 0.05). Hence, in HC, renal functional responses to high-dose isoprostane are largely similar to normal, but the systemic circulation exhibits augmented sensitivity to pathophysiological levels of isoprostane and U46619 , which may potentially play a role in development of hypertension and vascular injury associated with increased oxidative stress.