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Coronary Artery Disease (CAD) and Chronic Kidney Disease (CKD)
S140 Journal of Cardiac Failure Vol. 15 No. 7S September 2009
Symposium 2 S2-1 Biomarkers That Links to Cardiorenal Connection YOSHIHIKO SAITO The First Department of Internal Medicine, Nara Medical University Recently, the concept, cardio-renal connection, is widely accepted in both cardiologists and nephrologists. However, molecular mechanism that links kidney diseases and cardiovascular diseases has not been fully understood. I supposed that there are three types of molecules that are involved in the mechanism. The first one consists of the sympathetic nervous system and renin-angiotensin aldosterone system that target both heart and kidney. The second one is natretic peptide system, which is synthesized in and secreted from the heart and regulates natriuresis and dieresis. The third type of the molecules is produced by kidney and affects cardiovascular homeostasis. Erythropoietin is a member of the third type of molecules. Here we will show the clinical significance of new candidates belonging to the third type of molecules, soluble Flt-1 (sFlt-1). We found that sFlt-1, which is alternatively spliced form of Flt and antagonizes PLGF and VEGF actions, is released from the kidney and its plasma levels are decreased in accordance of renal dysfunction. The ratio of PlGF to sFLT is parallel to the severity of coronary artery diseases in patients with renal dysfunction. Better understanding of the molecular mechanism of cardiorenal connection would leads to development of new biomarkers that link to cardiorenal connection.
S2-2 Type 1 Cardiorenal Syndrome in Acute Coronary Syndrome NAOKI SATO1, KEIJI TANAKA1, KYOICHI MIZUNO2 Intensive and Cardiac Care Unit, Nippon Medical School, Tokyo, Japan, 2 Department of Internal Medicine, Division of Cardiology, Hepatology, Geriatrics, and Integrated Medicine
1
Ronco et al have recently suggested a more articulated definition to explore the complex nature of cardiorenal syndrome (CRS) with five types. Type 1 CRS is characterized by a rapid worsening of cardiac function, leading to acute kidney injury (AKI). In acute coronary syndrome (ACS) patients, there are two critical factors in terms of pathophysiology and management of CRS, i.e., cardiovascular function and radiocontrast. Data from ATTEND (Acute decompensated heart failure syndromes) registry confirmed that the lower systolic blood pressure at admission, the worse renal function, which suggested cardiovascular function would be correlated closely to renal function. Therefore, one of key factors is blood pressure during hospitalization. Furthermore, arterial oxygenation, control of renin-angiotensin-aldosterone system, and how to use concomitant diuretics are important for renal protection. We will summarize pathophysiology and management of AKI in acute heart failure. Second issue is radiocontrast. Coronary intervention is performed in most of patients with ACS. Therefore, it is important how we can detect and prevent radiocontrast-induced nephropathy (CIN). We have already demonstrated usefulness of cystatin C, a most predictable CIN marker, and urinary L-type fatty acid binding protein, a most detectable CIN marker. Using these data, we will also summarize how we can manage CIN. Taken together, we would like to clarify what we know and what we do not know in this field.
S2-3 Coronary Artery Disease (CAD) and Chronic Kidney Disease (CKD) YASUNOBU HIRATA, ARIHIRO KIYOSUE, MAKOTO SAHARA, RYOZO NAGAI Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan It is well established that incidence of cardiovascular events increases as renal function decreases. Although several mechanisms have been suggested, details are still unclear. Not only in western countries but also in Japan CAD is one of the leading cardiovascular events in patients with renal dysfunction. We analyzed the relation
between the severity of CAD and renal function. As a result, the severity of CAD increased as estimated GFR on the basis of Cr and age decreased, that is, patients with CKD had more stenotic coronary arteries. At the same time CKD patients showed higher blood pressure than those with preserved renal function. Furthermore, even in non-CKD patients the severity of CAD was greater in patients with elevated plasma cystatin C levels than in those with normal cystatin C. We followed renal function of these patients for three years and analyzed the factors influencing changes in GFR. Among various factors prevalence of diabetes mellitus and the severity of CAD are important determinants of deterioration rates of GFR. Thus, progression of CAD seems to be affected by renal function and should be carefully watched in the early phase of renal dysfunction using some diagnostic tools.
S2-4 Catheter Based Diagnosis and Intervention of the Patients With Chronic Kidney Disease HITOSHI MATSUO1, KATSUMI UENO1, TAKAHIKO SUZUKI2 1 The Department of Cardiology, Gifu Heart Center, Gifu, Japan, 2The Department of Cardiology, Toyohashi Heart Center, Aichi, Japan Catheter based diagnosis and coronary intervention of the coronary artery disease is still the main stream in the cardiology field. Revascularization therapy reduced the absolute and relative risk of cardiac death more than medical therapy especially in patients with moderate to large amounts of inducible ischemia. However, preexisting renal disease is known to be one of the predisposing factor of contrast induced nephropathy [CIN] which is a marker of increased mortality. Thus, physicians should weigh the risk and benefit to use contrast media. In high-risk patients with CIN, such as patients with CKD, each patients risk should be well evaluated by other modality to elucidate the benefit of catheter therapy. Once decided, all patients, if afforded, should receive adequate hydration. In the cath lab, the total dose of the contrast agent should be kept to a minimum by utilizing anatomical information obtained by IVUS, as well as physiological information obtained by pressure wire. In this symposium, we introduce real world of catheter diagnosis and therapy for the patients with reduced renal function.
S2-5 Cardiovascular Disease in Chronic Kidney Disease TETSUO SHOJI Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan Background People with chronic kidney disease (CKD) have an increased risk for death from cardiovascular disease (CVD), and there is an urgent need to prevent it. [CVD in predialysis CKD] The increased risk for CVD is attributable to morphological and functional changes in arterial wall and the heart. The alterations in arterial wall are in parallel with the stages of CKD. [CVD in patients starting dialysis] At the initiation of dialysis therapy, coronary artery disease (CAD) is present in almost half of the patients even without cardiac symptoms. The presence of CAD at the start of dialysis is the most powerful predictor of major cardiovascular events thereafter. [CVD in maintenance dialysis] In the Japanese chronic dialysis population, myocardial infarction (MI) and congestive heart failure (CHF) represent 2.9% and 23.9%, respectively, of the total deaths, suggesting the relative importance of CHF over MI in dialysis patients. Two large clinical trials failed to reduce the risk of CVD with strong statins in hemodialysis patients, whereas statins significantly reduced such risk in those with stages 1-3 CKD. Conclusions These data indicate the importance of timely prevention of atherosclerosis in earlier stages of CKD, screening for CAD at the start of dialysis, and prevention and care for CHF in the maintenance dialysis stage.
Symposium 2 S2-1 Biomarkers That Links to Cardiorenal Connection YOSHIHIKO SAITO The First Department of Internal Medicine, Nara Medical University Recently, the concept, cardio-renal connection, is widely accepted in both cardiologists and nephrologists. However, molecular mechanism that links kidney diseases and cardiovascular diseases has not been fully understood. I supposed that there are three types of molecules that are involved in the mechanism. The first one consists of the sympathetic nervous system and renin-angiotensin aldosterone system that target both heart and kidney. The second one is natretic peptide system, which is synthesized in and secreted from the heart and regulates natriuresis and dieresis. The third type of the molecules is produced by kidney and affects cardiovascular homeostasis. Erythropoietin is a member of the third type of molecules. Here we will show the clinical significance of new candidates belonging to the third type of molecules, soluble Flt-1 (sFlt-1). We found that sFlt-1, which is alternatively spliced form of Flt and antagonizes PLGF and VEGF actions, is released from the kidney and its plasma levels are decreased in accordance of renal dysfunction. The ratio of PlGF to sFLT is parallel to the severity of coronary artery diseases in patients with renal dysfunction. Better understanding of the molecular mechanism of cardiorenal connection would leads to development of new biomarkers that link to cardiorenal connection.
S2-2 Type 1 Cardiorenal Syndrome in Acute Coronary Syndrome NAOKI SATO1, KEIJI TANAKA1, KYOICHI MIZUNO2 Intensive and Cardiac Care Unit, Nippon Medical School, Tokyo, Japan, 2 Department of Internal Medicine, Division of Cardiology, Hepatology, Geriatrics, and Integrated Medicine
1
Ronco et al have recently suggested a more articulated definition to explore the complex nature of cardiorenal syndrome (CRS) with five types. Type 1 CRS is characterized by a rapid worsening of cardiac function, leading to acute kidney injury (AKI). In acute coronary syndrome (ACS) patients, there are two critical factors in terms of pathophysiology and management of CRS, i.e., cardiovascular function and radiocontrast. Data from ATTEND (Acute decompensated heart failure syndromes) registry confirmed that the lower systolic blood pressure at admission, the worse renal function, which suggested cardiovascular function would be correlated closely to renal function. Therefore, one of key factors is blood pressure during hospitalization. Furthermore, arterial oxygenation, control of renin-angiotensin-aldosterone system, and how to use concomitant diuretics are important for renal protection. We will summarize pathophysiology and management of AKI in acute heart failure. Second issue is radiocontrast. Coronary intervention is performed in most of patients with ACS. Therefore, it is important how we can detect and prevent radiocontrast-induced nephropathy (CIN). We have already demonstrated usefulness of cystatin C, a most predictable CIN marker, and urinary L-type fatty acid binding protein, a most detectable CIN marker. Using these data, we will also summarize how we can manage CIN. Taken together, we would like to clarify what we know and what we do not know in this field.
S2-3 Coronary Artery Disease (CAD) and Chronic Kidney Disease (CKD) YASUNOBU HIRATA, ARIHIRO KIYOSUE, MAKOTO SAHARA, RYOZO NAGAI Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan It is well established that incidence of cardiovascular events increases as renal function decreases. Although several mechanisms have been suggested, details are still unclear. Not only in western countries but also in Japan CAD is one of the leading cardiovascular events in patients with renal dysfunction. We analyzed the relation
between the severity of CAD and renal function. As a result, the severity of CAD increased as estimated GFR on the basis of Cr and age decreased, that is, patients with CKD had more stenotic coronary arteries. At the same time CKD patients showed higher blood pressure than those with preserved renal function. Furthermore, even in non-CKD patients the severity of CAD was greater in patients with elevated plasma cystatin C levels than in those with normal cystatin C. We followed renal function of these patients for three years and analyzed the factors influencing changes in GFR. Among various factors prevalence of diabetes mellitus and the severity of CAD are important determinants of deterioration rates of GFR. Thus, progression of CAD seems to be affected by renal function and should be carefully watched in the early phase of renal dysfunction using some diagnostic tools.
S2-4 Catheter Based Diagnosis and Intervention of the Patients With Chronic Kidney Disease HITOSHI MATSUO1, KATSUMI UENO1, TAKAHIKO SUZUKI2 1 The Department of Cardiology, Gifu Heart Center, Gifu, Japan, 2The Department of Cardiology, Toyohashi Heart Center, Aichi, Japan Catheter based diagnosis and coronary intervention of the coronary artery disease is still the main stream in the cardiology field. Revascularization therapy reduced the absolute and relative risk of cardiac death more than medical therapy especially in patients with moderate to large amounts of inducible ischemia. However, preexisting renal disease is known to be one of the predisposing factor of contrast induced nephropathy [CIN] which is a marker of increased mortality. Thus, physicians should weigh the risk and benefit to use contrast media. In high-risk patients with CIN, such as patients with CKD, each patients risk should be well evaluated by other modality to elucidate the benefit of catheter therapy. Once decided, all patients, if afforded, should receive adequate hydration. In the cath lab, the total dose of the contrast agent should be kept to a minimum by utilizing anatomical information obtained by IVUS, as well as physiological information obtained by pressure wire. In this symposium, we introduce real world of catheter diagnosis and therapy for the patients with reduced renal function.
S2-5 Cardiovascular Disease in Chronic Kidney Disease TETSUO SHOJI Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan Background People with chronic kidney disease (CKD) have an increased risk for death from cardiovascular disease (CVD), and there is an urgent need to prevent it. [CVD in predialysis CKD] The increased risk for CVD is attributable to morphological and functional changes in arterial wall and the heart. The alterations in arterial wall are in parallel with the stages of CKD. [CVD in patients starting dialysis] At the initiation of dialysis therapy, coronary artery disease (CAD) is present in almost half of the patients even without cardiac symptoms. The presence of CAD at the start of dialysis is the most powerful predictor of major cardiovascular events thereafter. [CVD in maintenance dialysis] In the Japanese chronic dialysis population, myocardial infarction (MI) and congestive heart failure (CHF) represent 2.9% and 23.9%, respectively, of the total deaths, suggesting the relative importance of CHF over MI in dialysis patients. Two large clinical trials failed to reduce the risk of CVD with strong statins in hemodialysis patients, whereas statins significantly reduced such risk in those with stages 1-3 CKD. Conclusions These data indicate the importance of timely prevention of atherosclerosis in earlier stages of CKD, screening for CAD at the start of dialysis, and prevention and care for CHF in the maintenance dialysis stage.