Pretransplant cardiac investigations in the Irish renal transplant population--the effectiveness of our current screening techniques in predicting cardiac events

BACKGROUND: Coronary artery disease (CAD) is prevalent among endstage renal failure patients and remains the major cause of mortality following renal transplantation. Death with a functioning transplant institute remains the most common cause of kidney graft failure. In this study we attempt to evaluate the effectiveness of the clinical history and current screening techniques available in predicting posttransplant CAD and also assess the role of coronary angiography as a pretransplant screening technique. METHODS: Clinical data of 190 renal transplant patients was analyzed. Any clinical history of cardiac disease and all preoperative cardiac screening data was recorded for each patient. The study endpoints were the subsequent development of myocardial infarction (MI), undergoing coronary artery bypass graft (CABG) or death. RESULTS: Factors that were significantly associated with reaching a study endpoint included: age at transplant [Hazard Ratio (HR) 1.91, P<0.001], history of heart failure (HR 8.22, P<0.001), presence of CAD on coronary angiography (HR 5.55, P=0.033), anterior Q wave on electrocardiograph (ECG) (HR 8.6, P<0.001), carotid artery disease (HR 3.74, P=0.030) and history of a cerebrovascular accident (HR of 4.32, P=0.008). The screening techniques of exercise stress testing and echocardiography were not conclusive as predictive variables of outcome. CONCLUSION: Clinical history and ECG results are good, practical and low-cost screening methods. In our study exercise stress testing and echocardiography were found to be of limited value. Coronary angiography is appropriate in certain high-risk groups but not necessary as part of screening in all potential renal transplant recipients.     

Acute administration of L-arginine does not improve arterial endothelial function in chronic renal failure.

BACKGROUND: Reduced activity of the nitric oxide (NO) pathway has been implicated in the endothelial dysfunction that occurs in patients with renal failure. NO is generated from L-arginine by NO synthase, and certain uremic toxins including asymmetrical dimethyl-L-arginine (ADMA), inhibit NO synthase and might contribute to endothelial dysfunction. We hypothesized that exogenous L-arginine might improve endothelial function in patients with renal failure by overcoming the effects of uremic toxins. METHODS: Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia (flow-mediated dilation; FMD). Studies were performed before and after administration of L-arginine by intra-arterial infusion (50 micromol/min) in 8 pre-dialysis patients or by intravenous infusion (10 g) in 18 hemodialysis patients. RESULTS: Local L-arginine did not improve the dilator response of forearm resistance vessels (AUC 23.1 +/- 6.4 pre, 23.1 +/- 5.1 post; P = 0.9) or FMD of the radial artery (6.5 +/- 1.2% pre, 6.3 +/- 0.8% post; P = 0.8). Systemic L-arginine did not improve FMD of the brachial artery (4.1 +/- 1.1% pre, 3.0 +/- 1.1% post; P = 0.07). These data demonstrate that acute local or systemic administration of L-arginine did not improve endothelial function in resistance or conduit arteries of patients with chronic renal failure. CONCLUSION: The results suggest that competitive inhibition of nitric oxide synthase (NOS) by circulating inhibitors is not the principal explanation for impaired endothelial dilator function in chronic renal failure.     

Relevance of conventional cardiovascular risk factors for the prediction of coronary artery disease in diabetic patients on renal replacement therapy

Background. Diabetic patients undergoing renal replacement therapy have a high cardiovascular mortality. As the rate of patients with diabetic nephropathy rises, adequate risk stratification subsequent to renal transplantation is warranted. It was the aim of our study to elucidate whether conventional risk factors are valid predictors of coronary artery disease in this group of patients with chronic renal failure subsequent to transplantation. Methods and Results. Between 1989 and 1993, 105 consecutive diabetic patients (70 men, 35 women, 77 type I and 28 type II diabetics, mean age 43±12 years) were examined during the first six months of dialysis treatment. Coronary angiography was performed in all patients regardless of clinical symptoms of coronary artery disease (CAD). In 38 patients (36%) CAD was documented (single-vessel disease: 17 patients, double-vessel disease: 6 patients, triple-vessel disease: 15 patients). Manifestations of coronary atherosclerosis were seen in 49 patients (47%). Angina pectoris was present in 9 out of 38 patients (24%), the sensitivity to detect CAD was 43% and 52% for ST-segment depression assessed at rest. Risk factors for atherosclerosis like hypertension, smoking, cholesterol (total cholesterol, HDL-,LDL-cholesterol), triglycerides as well as concentrations of lipoprotein (a) and fibrinogen were not significantly different in patients with or without coronary artery disease. Atherosclerotic manifestations of cerebral and peripheral arteries as well as manifestations of diabetic microangiopathy like retinopathy did not correlate with the prevalence of CAD. In 11 out of 38 patients (29%) cardiac interventions (3 x CABG, 8 x PTCA) were performed. All of them were defined as transplantable after myocardial revascularisation. Conclusions. Clinical symptoms as well as the cardiovascular risk profile are not valid predictors of CAD in diabetic patients with chronic renal failure. Therefore coronary angiography should be performed in all diabetic patients prior to renal transplantation.     

Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease

Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 micromol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 micromol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with L-arginine but not D-arginine reversed the effect of SDMA on NOS pathway. Our data suggest that SDMA reduced the endothelial NO synthesis, probably by limiting L-arginine supply to NOS. It is concluded that SDMA might be a useful parameter for detecting patients in very early stages of chronic kidney disease and for determining their risk for developing cardiovascular disease.     

Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure

BACKGROUND: Cardiovascular disease is a major cause of mortality amongst patients with chronic renal failure (CRF). L-arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability and in animal models this in turn has attenuated the progression of atherosclerosis. We examined whether dietary L-arginine supplementation improved endothelial function in children with CRF. METHODS: A randomized, double-blind, placebo-controlled, crossover trial of L-arginine was conducted in 21 normotensive children aged 11.5 +/- 3 (7 to 17) years with CRF (GFR 27.4 +/- 13.2 mL/min/1.73 m(2)) in whom endothelial dysfunction had previously been demonstrated. We examined the effect of L-arginineon the endothelial response to shear stress (NO-dependent) using a non-invasive technique of high-resolution ultrasound. Each subject was studied before and after 4 weeks of L-arginine (2.5 g/m(2) or 5 g/m(2) x 3/day) or placebo, separated by a rest period of 4 weeks. Brachial artery diameter was measured at rest, during increased flow (endothelial-dependent dilation) and after 25 microg of glyceryl trinitrate (endothelial-independent dilation) at each visit. RESULTS: After oral L-arginine, plasma L-arginine levels rose from 82 +/- 20 to 179 +/- 110 micromol/L (P < 0.001). No significant change in endothelial-dependent dilation during L-arginine (7.96 +/- 2.35 to 7.71 +/- 3.22%; P> 0.05) or placebo (8.2 +/- 2.89 to 8.3 +/- 3.14%; P> 0.05) was noted. There was no change in endothelial-independent dilation. CONCLUSION: Endothelial function was not improved with L-arginine, suggesting that dietary supplementation is not a useful clinical approach in children with CRF.     

Association of atherosclerotic coronary artery disease and pulse pressure with renal disease progression

BACKGROUND: This study was performed to identify the association of atherosclerotic coronary artery disease (CAD) and pulse pressure with renal disease progression in patients with mild chronic renal disease. METHODS: Eligibility criteria for enrollment in this study included age 18 to 70 years, mild chronic renal disease (CRD), undergoing thallium SPECT and echocardiography and followed longer than three years. Mild CRD was defined as serum creatinine level of 1.5 to 3.0 mg/dL in men and 1.4 to 3.0 mg/dL in women. Patients with serious illness, history of kidney transplantation, ejection fraction less than 40% on echocardiography and development of acute renal failure during follow-up were excluded. RESULTS: A total of 87 patients were included in this study. The underlying renal disease included diabetic nephropathy in 51 patients. Forty-five patients showed positive findings on thallium SPECT and they were classified as having CAD. Coronary angiography showed significant stenosis in 41 of 42 patients studied. Median duration of follow-up was 56 months. During the follow-up period, 40 patients required chronic dialysis therapy and 16 patients showed a doubling of baseline serum creatinine in three years. These 56 patients were classified as progressors. Comparison of clinical and laboratory parameters between progressors and nonprogressors showed a difference in the presence of diabetic nephropathy, mean arterial pressure, 24-h urine protein (p < 0.001), pulse pressure (p < 0.01), total cholesterol and presence of CAD (p < 0.05). There was no association between the progression of CRD and the results of CAD or treatment of CAD. Multivariate logistic regression analysis showed that the presence of diabetic nephropathy and mean arterial pressure > 100 mm Hg were independent predictors of CRD progression. CONCLUSION: Atherosclerotic coronary artery disease and pulse pressure were associated with renal disease progression.     

The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography

BACKGROUND: Renal failure induced by radiographic contrast agents is a known complication of coronary angiography, especially among patients with chronic renal failure. Recently, treatment with N-acetylcysteine (NAC) has been shown to have a protective effect but the mechanisms are unknown. We examined the hypothesis that NAC protected against contrast-induced renal impairment through effects on nitric oxide metabolism and oxidative stress. METHODS: Patients with a serum creatinine concentration above 10(6) micromol/L undergoing coronary angiography were randomly assigned to receive either NAC 1 g (N= 24) or placebo (N= 29) twice daily 24 hours before and after angiography with 0.45% saline hydration in a double-blind study. Creatinine clearance was calculated and urinary nitric oxide and F2-isoprostane excretion were measured at baseline, 24 and 96 hours after angiography. RESULTS: Treatment with NAC significantly improved the effect of contrast media on creatinine clearance, and maximal beneficial effect was observed 24 hours after angiography. Creatinine clearance (mL/min) was 59.5 +/- 4.4, 64.7 +/- 5.8, and 58.7 + 3.9 at baseline, 24, and 96 hours after angiography in the NAC group, respectively, and 65.2 +/- 3.2, 51.5 +/- 3.7, and 53.6 +/- 3.9 in the placebo group, respectively (P < 0.0001). NAC treatment prevented the reduction in urinary nitric oxide after angiography. The urinary nitric oxide/creatinine ratio (micromol/mg) was 0.0058 +/- 0.0004, 0.0057 +/- 0.0004, and 0.0052 +/- 0.0004 at baseline, 24, and 96 hours after angiography in NAC group, respectively, and 0.0057 +/- 0.0007, 0.0031 +/- 0.0005, and 0.0039 +/- 0.0005 in the placebo group, respectively (P= 0.013). NAC had no significant effect on urinary F2-isoprostanes. CONCLUSION: NAC treatment has renoprotective effect in patients with mild chronic renal failure undergoing coronary angiography that may be mediated in part by an increase in nitric oxide production.     

Effects of L-arginine on the endogenous angiogenic response in a model of hypercholesterolemia

BACKGROUND: The angiogenic properties of vascular endothelial growth factor and fibroblast growth factor-2 are mediated in part through nitric oxide release, whose availability is decreased in endothelial dysfunction associated with advanced coronary artery disease. We examined the influence of L-arginine supplementation on the endogenous angiogenic response to ischemia in a porcine model of hypercholesterolemia. METHODS: Eighteen Yucatan pigs were fed either a normal (NORM, n=6) or a high-cholesterol diet, with (CHOL-ARG, n=6) or without (CHOL, n=6) L-arginine (100 mg/kg/day), throughout the experiment. All pigs underwent ameroid constrictor placement on the circumflex artery (LCx). Seven weeks later, endothelium-dependent coronary microvascular responses to fibroblast growth factor-2 and vascular endothelial growth factor were assessed by videomicroscopy. Perfusion was assessed with radioactive microspheres; angiogenesis was evaluated by platelet-endothelial cell adhesion molecule-1 (CD-31) staining. Regional myocardial function was assessed by sonomicrometry. Expression of endothelial nitric oxide synthase and inducible nitric oxide synthase was measured by Western blot analyses. RESULTS: Pigs from the CHOL group showed significant endothelial dysfunction in the LCx territory. The dysfunction was normalized partially by L-arginine supplementation, which restored the response in the LCx territory to the level of the nonischemic anterior wall. L-arginine supplementation resulted in increases of perfusion, density of capillary endothelial, and level of endothelial nitric oxide synthase in the ischemic region. Despite these findings, no improvement in myocardial regional function was found. CONCLUSIONS: L-arginine supplementation can partially restore endothelium-dependent vasorelaxation and improve myocardial perfusion in a swine model of chronic myocardial ischemia with hypercholesterolemia-induced endothelial dysfunction. These findings suggest a putative role for L-arginine in combination with growth factor therapy for end-stage coronary artery disease.     

Pretransplant Cardiac Investigations in the Irish Renal Transplant Population—The Effectiveness of Our Current Screening Techniques in Predicting Cardiac Events

Background. Coronary artery disease (CAD) is prevalent among endstage renal failure patients and remains the major cause of mortality following renal transplantation. Death with a functioning transplant institute remains the most common cause of kidney graft failure. In this study we attempt to evaluate the effectiveness of the clinical history and current screening techniques available in predicting posttransplant CAD and also assess the role of coronary angiography as a pretransplant screening technique. Methods. Clinical data of 190 renal transplant patients was analyzed. Any clinical history of cardiac disease and all preoperative cardiac screening data was recorded for each patient. The study endpoints were the subsequent development of myocardial infarction (MI), undergoing coronary artery bypass graft (CABG) or death. Results. Factors that were significantly associated with reaching a study end‐point included: age at transplant [Hazard Ratio (HR) 1.91, P < 0.001], history of heart failure (HR 8.22, P < 0.001), presence of CAD on coronary angiography (HR 5.55, P = 0.033), anterior Q wave on electrocardiograph {ECG} (HR 8.6, P < 0.001), carotid artery disease (HR 3.74, P = 0.030) and history of a cerebrovascular accident (HR of 4.32, P = 0.008). The screening techniques of exercise stress testing and echocardiography were not conclusive as predictive variables of outcome. Conclusion. Clinical history and ECG results are good, practical and low‐cost screening methods. In our study exercise stress testing and echocardiography were found to be of limited value. Coronary angiography is appropriate in certain high‐risk groups but not necessary as part of screening in all potential renal transplant recipients.     

Prognostic Value of Cardiovascular Screening in Potential Renal Transplant Recipients: A Single-Center Prospective Observational Study

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end-stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twenty-two patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow-up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety-nine patients underwent coronary angiography; 65 had normal or low-grade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.     

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease. Patients with end-stage renal disease (ESRD) are at increased risk of death from coronary artery disease (CAD). The metabolic milieu that results from renal dysfunction appears to accelerate the atherosclerotic process by decades in patients with ESRD. The extremely high prevalence of atherosclerosis in patients with ESRD mandates risk factor identification and treatment. Traditionally, CAD in this patient population has been treated conservatively. Analysis of large databases has highlighted the scope and complexity of this problem; nonetheless, there is a paucity of randomized, controlled trials of CAD in patients with ESRD. In this paper the following issues related to evaluation and treatment of patients with chronic kidney disease are addressed: (1) optimal CAD risk management; (2) evaluation for CAD in patients with ESRD, including the identification of coronary calcification; (3) treatment of CAD with medical therapy and revascularization; (4) relative merits of percutaneous coronary intervention versus bypass surgery. In general, an aggressive approach to medical management of CAD is warranted, even in the setting of subclinical CAD. A low threshold for diagnostic testing should be employed in patients with ESRD. When significant CAD is identified, ESRD patients appear to benefit more from revascularization compared to conservative medical management. Thus, if clinically reasonable, patients with ESRD and CAD should be managed aggressively to improve survival and reduce the incidence of future cardiac events.     

Angiographic progression of coronary artery disease in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have an increased risk of developing coronary artery disease (CAD). The cardiovascular mortality of dialysis patients is 10-15 times higher compared with the general population. The aim of our study was to evaluate the morphological progression of coronary arteriosclerosis in this cardiovascular high-risk group by visual assessment and quantitative coronary angiography. Methods and results. In 26 patients with chronic renal failure (age, 47+/-11 years; 15 male; duration of dialysis, 23+/-25 months) the severity of CAD and degree of coronary stenoses were assessed in two coronary angiograms after a mean follow-up interval of 30+/-15 months (12-60). Baseline angiography revealed CAD in 13/22 patients (59%). The second angiography was performed as screening procedure prior to renal transplantation (n=20) and/or as follow-up angiography after coronary angioplasty (n=10). Visual assessment showed a progression defined by the development of haemodynamically relevant stenosis of >50% luminal diameter in 13 patients. Quantitative angiographic evaluation was performed in a total of 45 segments showing >25% narrowing at the second angiogram. A progression (>15% luminal reduction) was found in 17 of 45 segments, a new lesion (initial luminal diameter <20%) was detected in nine segments, resulting in progression or new lesion in 16 patients (62%). Patients with or without progression did not differ in age, duration of dialysis treatment, number of cardiovascular risk factors, or serum total cholesterol and fibrinogen levels. After percutaneous transluminal coronary angioplasty (PTCA) a restenosis was seen in seven of 16 primarily successfully dilated segments. After the second angiography, myocardial revascularization was performed in eight patients (1 PTCA, 7 coronary artery bypass graft). CONCLUSIONS: Patients with end-stage renal disease have a high prevalence of CAD. In line with the clinical course, CAD patients on maintenance dialysis undergo rapid angiographic progression of CAD, which results in a high rate of subsequent myocardial revascularizations.     

Apelin, a Novel Adipocytokine, in Relation to Endothelial Function and Inflammation in Kidney Allograft Recipients

Apelin, a newly discovered adipocytokine produced by white adipose tissue, is also expressed in kidney and heart. It has been reported that apelin is related to echocardiographic features in hemodialyzed patients. Cardiovascular disease is a major contributor to the mortality and morbidity among patients with chronic renal failure as well as kidney allograft recipients. The aim of this study was to assess the association between apelin and coronary artery disease (CAD) among kidney allograft recipients. We investigated plasma apelin levels in 100 clinically stable, kidney allograft recipients with versus without CAD. We also assessed markers of endothelial cell injury—von Villebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of inflammation—high-sensitivity-reactive protein (hsCRP); other hemostatic parameters—tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well as other adipocytokines—adiponectin and resistin—using commercially available kits. Markers of endothelial dysfunction and inflammation were significantly elevated among patients with CAD levels, as well as with CAD or diabetes, compared with those without CAD. Apelin was significantly lower among patients with CAD, but higher in diabetic patients. Apelin content was similar in hypertensive versus normotensive kidney allograft recipients. We observed significant correlations between apelin and ICAM, resistin, adiponectin, calcium, phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes. Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were predictors of apelin. Apelin was significantly reduced in kidney allograft recipients with CAD; its level was predicted by the presence of CAD, endothelial damage, or inflammation. Apelin and other adipocytokines may be associated with inflammation and its clinical consequences.     

Prevalence and predictors of renal artery stenosis in patients undergoing peripheral and coronary angiography

Background

Renal artery stenosis is a potential cause of secondary hypertension, ischemic nephropathy and end-stage renal disease. Atherosclerosis is by far the most common etiology of renal artery stenosis in elderly. We investigated whether the presence of significant atherosclerotic renal artery stenosis (ARAS) with luminal diameter narrowing ≥50 % could be predicted in patients undergoing peripheral and coronary angiography.

Methods

The records of 3,500 consecutive patients undergoing simultaneous renal angiography along with peripheral and coronary angiography were reviewed. The patients with known renal artery disease were excluded.

Results

Prevalence of ARAS was 5.7 %. Significant ARAS (luminal diameter narrowing ≥50 %) was present in 139 patients (3.9 %). Hypertension with altered serum creatinine and triple-vessel CAD were associated with significant renal artery stenosis in multivariate analysis. No significant relationship between the involved coronary arteries like left anterior descending, left circumflex, right coronary artery and ARAS was found. Only hypertension and altered serum creatinine were associated with bilateral ARAS. Extent of CAD or risk factors like diabetes, hyperlipidemia or smoking did not predict the unilateral or bilateral ARAS.

Conclusion

Prevalence of ARAS among the patients in routine cardiac catheterization was 5.7 %. Hypertension is closely associated with significant ARAS. Significant CAD in the form of triple-vessel disease and altered renal function tests are closely associated with ARAS. They predict the presence of significant renal artery stenosis in patients undergoing routine peripheral and coronary angiography. Moreover, hypertension and altered renal functions predict bilateral ARAS.     

Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease

BACKGROUND: It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear. PATIENTS AND METHODS: Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization. RESULTS: Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = -0.756, p < 0.0001). CONCLUSIONS: Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.     

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

De Lima JJG, Gowdak LHW, de Paula FJ, Arantes RL, Ianhez LE, Ramires JAF, Krieger EM. Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients.
Clin Transplant 2010: 24: 474–480.
© 2009 John Wiley & Sons A/S. Abstract: Background: The best strategy for pre‐transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log‐rank = 0.0002) and deaths (log‐rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007–5.11; p = 0.04). The incidence of cardiac events (log‐rank = 0.349) and deaths (log‐rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline‐oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre‐emptive myocardial revascularization for renal transplant candidates.     

Normalization of coronary microvascular reactivity and improvement in myocardial perfusion by surgical vascular endothelial growth factor therapy combined with oral supplementation of l-arginine in a porcine model of endothelial dysfunction

OBJECTIVE: Vascular endothelial growth factor acts in part through nitric oxide release, the availability of which is decreased in endothelial dysfunction associated with advanced coronary artery disease. This could explain the relatively disappointing results of vascular endothelial growth factor therapy in clinical studies compared with animal studies. We examined the influence of L-arginine supplementation to vascular endothelial growth factor therapy on myocardial microvascular reactivity and perfusion in a porcine model of endothelial dysfunction. METHODS: Twenty-four pigs were fed either a normal (NORM, n = 8) or high-cholesterol diet with (CHOL-ARG, n = 8) or without (CHOL, n = 8) L-arginine. All pigs underwent ameroid placement on the circumflex artery and then 3 weeks later received surgical vascular endothelial growth factor treatment. Four weeks after treatment, endothelial-dependent coronary microvascular responses and lateral myocardial perfusion were assessed. Endothelial cell density was determined by means of immunohistochemistry. Vascular endothelial growth factor, endothelial nitric oxide synthase, and Akt levels were determined by means of immunoblotting. RESULTS: Pigs from the CHOL group showed endothelial dysfunction in the circumflex territory, which was normalized by L-arginine supplementation. Vascular endothelial growth factor treatment was ineffective in the CHOL group (circumflex/left anterior descending coronary artery blood flow ratios: 0.95 [rest] and 0.74 [pace] before-after treatment; P < .05 compared with the NORM group). Addition of L-arginine restored the angiogenic effect of vascular endothelial growth factor (ratios: 1.13 [rest] and 1.20 [pace]; P < .05) and was associated with increased endothelial cell density, as well as vascular endothelial growth factor, endothelial nitric oxide synthase, and Akt protein levels in the ischemic territory. CONCLUSIONS: L-Arginine supplementation can restore normal endothelium-dependent vasorelaxation and angiogenic response to vascular endothelial growth factor in a swine model of chronic myocardial ischemia with hypercholesterolemia-induced endothelial dysfunction. These findings suggest a putative role for L-arginine in combination with vascular endothelial growth factor therapy for end-stage coronary artery disease.     

Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.     

A single chinese center investigation of renal artery stenosis in 141 consecutive cases with coronary angiography

BACKGROUND: There is an increasing prevalence of ischemic nephropathy in the aging population of the world. However, the exact incidence of ischemic nephropathy in the Chinese population is still uncertain. The present study investigated the incidence of renal artery stenosis (RAS) in patients with suspected coronary artery disease (CAD) using renal angiography. METHODS: Renal angiography was performed immediately after coronary artery angiography in 141 patients with suspected CAD, including 59 males and 82 females whose mean ages were 59 +/- 10 years. Comorbidities included hypertension (n = 69), diabetes mellitus (n = 21), hyperlipidemia (n = 19), hypokalemia (n = 7) and preoperative renal insufficiency (Cr >132 micromol/l; n = 14). The patients were divided into CAD (luminal narrowing of > or =50%) and non-CAD (luminal narrowing of <50%) subgroups, and RAS (luminal narrowing of > or =50%) and non-RAS subgroups. In the RAS group, there were 11 patients (5 males, 6 females) in whom percutaneous transluminal renal angioplasty was performed in conjunction with stent implantation due to refractory hypertension. RESULTS: The incidence of RAS was 18.4% (26/141) in all cases and 30.8% (16/52) in patients with CAD identified by coronary artery angiography. Ten cases with RAS were found among the 89 cases with normal coronary arteries (11.2%). The incidence of RAS in patients with CAD was higher than that in patients without CAD (30.8 vs. 11.2%, p< 0.05). In 52 cases with CAD, the incidence of RAS with three vessel lesions was significantly higher than that with one or two vessel lesions. Hypertension, CAD, renal insufficiency, hyperlipidemia and hypokalemia were associated with a higher risk of RAS. CONCLUSIONS: This study suggests that RAS is very common in the elderly Chinese population, specifically for those with three vessel lesions in CAD. For early detection of potential ischemic nephropathy, renal angiography is necessary in patients who receive coronary artery angiography.     

Association of Atherosclerotic Coronary Artery Disease and Pulse Pressure with Renal Disease Progression

Background.?This study was performed to identify the association of atherosclerotic coronary artery disease (CAD) and pulse pressure with renal disease progression in patients with mild chronic renal disease. Methods.?Eligibility criteria for enrollment in this study included age 18 to 70 years, mild chronic renal disease (CRD), undergoing thallium SPECT and echocardiography and followed longer than three years. Mild CRD was defined as serum creatinine level of 1.5 to 3.0 mg/dL in men and 1.4 to 3.0 mg/dL in women. Patients with serious illness, history of kidney transplantation, ejection fraction less than 40% on echocardiography and development of acute renal failure during follow-up were excluded. Results.?A total of 87 patients were included in this study. The underlying renal disease included diabetic nephropathy in 51 patients. Forty-five patients showed positive findings on thallium SPECT and they were classified as having CAD. Coronary angiography showed significant stenosis in 41 of 42 patients studied. Median duration of follow-up was 56 months. During the follow-up period, 40 patients required chronic dialysis therapy and 16 patients showed a doubling of baseline serum creatinine in three years. These 56 patients were classified as progressors. Comparison of clinical and laboratory parameters between progressors and nonprogressors showed a difference in the presence of diabetic nephropathy, mean arterial pressure, 24-h urine protein (p<0.001), pulse pressure (p<0.01), total cholesterol and presence of CAD (p<0.05). There was no association between the progression of CRD and the results of CAD or treatment of CAD. Multivariate logistic regression analysis showed that the presence of diabetic nephropathy and mean arterial pressure ≥100 mm Hg were independent predictors of CRD progression. Conclusion.?Atherosclerotic coronary artery disease and pulse pressure were associated with renal disease progression.