Faculty Bibliography

BACKGROUND:coronary microvascular dysfunction may underlie the high cardiovascular risk associated with chronic kidney disease (CKD), but the effects of CKD on coronary microvasculature function remain uncertain. METHODS AND RESULTS/RESULTS:we assessed myocardial blood flow changes in mild-to-moderate CKD and analyzed the association between creatinine clearance (CrCl) and peak myocardial blood flow and coronary flow reserve (CFR) measured as the ratio of stress to rest perfusion at baseline and at 1 year in 435 nondiabetic individuals who underwent quantitative rest and pharmacological stress positron emission tomography imaging. At baseline, CFR was significantly associated with CrCl (β per 10 mL/min increase, 0.07; P=0.001). Factors such as age and blood pressure accounted for this association, and it was not significant in adjusted analyses (β=-0.02, P=0.53). Peak flow was not associated with CrCl in either crude or adjusted analyses (β per 10 mL/min=-0.02 mL/min per g, P=0.29). Although change in peak flow at 1 year was similar in patients with and without CKD, CrCl was a strong and independent predictor of a higher rate of change in CFR, with a loss of 0.11 CFR units/y (95% confidence interval, 0.01 to 0.20) for each 10 mL/min drop in CrCl (P=0.03). CONCLUSIONS:these findings demonstrate that mild-to-moderate CKD is not independently associated with a reduction in peak myocardial flow or CFR and suggests that microvascular changes are unlikely to explain the high cardiovascular mortality in mild to moderate CKD. Loss of CFR, however, may accelerate in mild to moderate CKD. Further studies are needed to determine whether these changes lead to more significant reductions that may reduce peak flows and CFR and contribute to cardiovascular risk in more severe CKD.

BACKGROUND:Improved understanding of the incidence and risk factors for operative complications and long-term mortality following coronary artery bypass grafting (CABG) is needed to better define the optimal role for CABG in patients with chronic kidney disease (CKD). METHODS:We analysed 2438 patients who underwent CABG at a single centre between 2005 and 2008. Multivariable regression was used to analyse associations and to generate a CKD-specific predictive tool. RESULTS:Operative mortality was 4.8% in individuals with stage 3 CKD, 7.1% in individuals with stage 4-5 CKD and 2.2% in those without significant CKD (P < 0.001). CKD was associated with post-operative blood transfusion, acute kidney injury, myocardial injury and cardiac arrest, and use of exogenous blood and acute kidney injury were strongly associated with in-hospital death in CKD patients. Patients with stage 3 (HR 1.64, 95% CI 1.30-45.94) and stage 4-5 CKD (HR 2.77, 95% CI 1.00-2.68) were more likely to die during follow-up than those without CKD, but mortality rates were low among patients who survived to discharge-stage 3 (0.006 deaths/year) and stage 4-5 CKD (0.009/year). A scoring system including urgent or emergent surgery (OR 2.30), prior cardiac surgery (OR 3.06), concurrent valve surgery (OR 2.06), preoperative shock (OR 6.18), and prior stroke (OR 1.98) had 96.4% percent specificity for the detection of in-hospital death in patients with CKD. CONCLUSIONS:Perioperative mortality and morbidity remain more frequent in patients with stage 3-5 CKD than patients with preserved renal function, but long-term outcomes in patients surviving hospitalization are favourable. We have developed a predictive tool that holds promise as a means of identifying CKD patients most likely to survive surgery and benefit from CABG.

BACKGROUND:Ischemic cardiomyopathy is the major cause of heart failure and a significant cause of morbidity and mortality. The degree of left ventricular dysfunction in this setting is often out of proportion to the amount of overtly infarcted tissue, and how decreased delivery of oxygen and nutrients leads to impaired contractility remains incompletely understood. The Prolyl Hydroxylase Domain-Containing Protein (PHD) prolyl hydroxylases are oxygen-sensitive enzymes that transduce changes in oxygen availability into changes in the stability of the hypoxia-inducible factor transcription factor, a master regulator of genes that promote survival in a low-oxygen environment. METHODS AND RESULTS/RESULTS:We found that cardiac-specific PHD inactivation causes ultrastructural, histological, and functional changes reminiscent of ischemic cardiomyopathy over time. Moreover, long-term expression of a stabilized hypoxia-inducible factor alpha variant in cardiomyocytes also led to dilated cardiomyopathy. CONCLUSIONS:Sustained loss of PHD activity and subsequent hypoxia-inducible factor activation, as would occur in the setting of chronic ischemia, are sufficient to account for many of the changes in the hearts of individuals with chronic coronary artery disease.

Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD). Due to an explosion in the incidence and the prevalence of Type 2 DM, the burden of CKD is expected to increase proportionately. Both DM and CKD are associated with a high incidence of cardiovascular (CV) morbidity and mortality, and it is important to understand the unique nature of CV disease in patients with the combination of these two conditions. In this report, we review the traditional and nontraditional risk factors that underlie the high risk of CV disease in this population, with a particular focus on vascular calcification, mineral metabolism, and therapeutic paradigms for the treatment of cardiovascular disease in this unique and high-risk population.

BACKGROUND AND OBJECTIVES/OBJECTIVE:In the general population, an early invasive strategy of routine coronary angiography is superior to a conservative strategy of selective angiography in patients who are admitted with unstable angina or non-ST segment elevation myocardial infarction (MI), but the effectiveness of this strategy in individuals with chronic kidney disease (CKD) is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m(2). RESULTS:Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization. CONCLUSIONS:This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non-ST elevation acute coronary syndromes.

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction.