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Discordance between Estimate Glomerular Filtration Rate with Creatinine and Cystatin is Associated with Inflammation and Worsened Survival in Heart Failure
S20 Journal of Cardiac Failure Vol. 25 No. 8S August 2019 044 Discordance between Estimate Glomerular Filtration Rate with Creatinine and Cystatin is Associated with Inflammation and Worsened Survival in Heart Failure J. Ivey-Miranda, B. Stewart, N. Gomez, A. Thomas, E. Wycallis, M. Pattoli, G. Struyk, J. Fleming, P. Shamlian, J. Barnett, P. Raghavendra, D. Mahoney, M. Griffin, V. Rao, J. Testani; Yale University, New Haven, CT
Introduction: Glomerular filtration rate (GFR) can be estimated using serum creatinine or cystatin C. At the population level, these equations predict GFR with similar accuracy but can give substantially different results at the level of an individual patient. These within-patient differences may be explained by factors such as inflammation, as cystatin C is associated with higher levels of established inflammatory markers. We sought to determine if the discordance between the two GFR estimates could be attributed to inflammation, and furthermore to examine if this information held prognostic value. Hypothesis: Discordance of estimated GFR (eGFR) using creatinine vs. cystatin C will be affected by inflammation and patients with greater discordance will have worsened survival. Methods: We analyzed an outpatient cohort of patients with chronic stable heart failure (n= 162). CKDEPI-Creatinine and CKDEPI-Cystatin C equations were used to estimate GFR. Discordance of eGFR was calculated as the ratio of eGFRcreatinine to eGFRcystatin. (values higher than 1 represent eGFRcreatinine > eGFRcystatin and lower than 1 represent eGFRcystatin > eGFRcreatinine). Results: In the overall population eGFRcreatinine was 54§28mL/min/m2 and the eGFRcystatin was 43§25mL/min/m2, resulting in an average ratio of 1.3§0.4. There were, however, substantial differences in individual patients with the 10th percentile ratio at 0.9 and 90th percentile a ratio of 1.7. Notably, the ratio was correlated with plasma interleukin-6 (r= 0.24), C-reactive protein (r= 0.23), and ST2 (r= 0.26); p<0.01 for all. In line with the above-mentioned associations, the ratio of eGFR was strongly associated with all-cause mortality in univariate and multivariable analysis (HR 2.4, 95% CI 1.3-4.2; p<0.01). Conclusion: The discordance of eGFR with creatinine and cystatin C was associated with markers of inflammation and holds powerful independent prognostic information. Additional study into the drivers of the discordance in GFR estimates by cystatin C and creatinine is warranted.
045 Elevated Neutrophil-Lymphocyte Ratio is Associated with a Poorer Cardiopulmonary Exercise Test Performance in Patients with Heart Failure Rani Kuttab, Joronia Chery, Katelyn Carr, Amanda R. Vest; Tufts Medical Center, Boston, MA
Background: The neutrophil-lymphocyte ratio (NLR) is an easily-obtained biomarker of systemic inflammation. An elevated NLR represents greater inflammatory activation and has been associated with higher mortality in patients with heart failure (HF), including after left ventricular assist device implantation. We sought to determine whether NLR is associated with the metabolic response to exercise in patients undergoing cardiopulmonary exercise testing (CPET) for diagnostic or prognostic indications. Methods: We retrospectively reviewed CPETs performed between 4/2017 and 11/2018 at a single tertiary center. We included only the first CPET for unique patients, performed for an indication of cardiomyopathy or HF (systolic or diastolic). Patients referred for congenital or valvular heart disease were excluded. Baseline demographics and key CPET parameters were recorded and NLR noted if performed within 100 days of CPET. Pearson correlation coefficients were calculated between NLR and key CPET parameters. Two linear regression models were constructed, to determine the relationship between the NLR and peak oxygen consumption (pkVO2) or minute ventilation/carbon dioxide production slope (VE/VCO2), respectively. Each model was adjusted for age, sex and body mass index (BMI). Results: There were 142 CPETs during the study period, of which 121 met inclusion criteria and 94 had an NLR value. The cohort (n=94) was 30% female, with primary cardiac conditions identified as non-ischemic cardiomyopathy in 42%, ischemic cardiomyopathy in 38%, hypertrophic cardiomyopathy in 13% and HF with preserved ejection fraction in 7%. Median age was 60 years, BMI 29.2 kg/m2 and NLR 2.58 (quartile range 1.76-4.00). The median CPET parameters achieved were exercise time 9.0 min, metabolic equivalents (METS) 5.3, respiratory exchange ratio (RER) 1.10, pkVO2 1.18 L/min, pkVO2 adjusted for weight 14.2 mL/kg/min, VE/VCO2 35. There was a negative correlation between NLR and pkVO2 (r=-0.24, p=0.020) or weight-adjusted pkVO2 (r=-0.22, p=0.033, Fig 1A) and a positive correlation between NLR and VE/VCO2 (r=0.31, p= 0.003, Fig 1B). On multivariable regression, the NLR remained significantly associated with both the pkVO2 (p=0.048) and the VE/VCO2 (p=0.013) after adjustment for age, sex and BMI. Conclusion: Greater systemic inflammation, represented by a higher NLR, is associated with poorer CPET performance in patients with HF, as characterized by a lower pkVO2 and higher VE/VCO2. Systemic inflammation is an important correlate of functional limitations for patients with HF and warrants further investigation as a therapeutic target.
046 Sarcopenia Strongly Affects Serum Levels of Cystatin C in Patients with Heart Failure J. Ivey-Miranda, B. Stewart, N. Gomez, J. Barnett, A. Thomas, E. Wycallis, M. Pattoli, G. Struyk, J. Fleming, P. Shamlian, P. Raghavendra, D. Mahoney, M. Griffin, V. Rao, J. Testani; Yale University, New Haven, CT Introduction: Low muscle mass, or sarcopenia, is commonly seen in patients with heart failure (HF). For any given level of renal function, patients with sarcopenia will have lower levels of serum creatinine because there is less muscle mass to produce creatinine. Thus, the use of creatinine to estimate glomerular filtration rate (GFR) is affected by sarcopenia. In contrast to creatinine, cystatin C is considered a better filtration marker to estimate GFR in the setting of sarcopenia because it not seclusively produced by muscle. However, it has not been demonstrated that serum cystatin C levels are independent of sarcopenia in patients with HF. Hypothesis: Serum cystatin C levels will be minimally influenced by muscle mass in patients with heart failure. Methods: Serum cystatin C and serum creatinine were measured in patients with decompensated heart failure. Strict timed urine collections were used to measure creatinine excretion rate. Muscle mass was estimated with a validated equation based on urine creatinine excretion (Heymsfield). Creatinine clearance was calculated and used as a surrogate for measured GFR. Results: Out of the 295 patients analyzed (average age 65 §14 years), 65% were male and 61% were obese. Baseline levels of serum creatinine were 1.5§0.6 mg/dL and cystatin C were 1.7§0.7 mg/L. In univariate analysis, serum cystatin C showed a negative correlation with muscle mass (rho -0.37, p<0.001). After adjusting for age, sex, and race, the unindexed measured creatinine clearance showed a positive correlation with serum cystatin C (partial correlation 0.29, p<0.001). Similarly, GFR estimated using the CKDEPI-cystatin C equation was significantly affected by the amount of muscle mass (figure). Patients in the lowest tertile of muscle mass showed a median GFR overestimation of 31%. Underestimation occurred in the middle (-3%) and highest tertile (-22%) of muscle mass (p<0.001). Conclusion: Serum cystatin C serum levels are strongly associated with muscle mass in patients with HF. This may lead to inaccuracies when cystatin C is used to estimate GFR.
Introduction: Glomerular filtration rate (GFR) can be estimated using serum creatinine or cystatin C. At the population level, these equations predict GFR with similar accuracy but can give substantially different results at the level of an individual patient. These within-patient differences may be explained by factors such as inflammation, as cystatin C is associated with higher levels of established inflammatory markers. We sought to determine if the discordance between the two GFR estimates could be attributed to inflammation, and furthermore to examine if this information held prognostic value. Hypothesis: Discordance of estimated GFR (eGFR) using creatinine vs. cystatin C will be affected by inflammation and patients with greater discordance will have worsened survival. Methods: We analyzed an outpatient cohort of patients with chronic stable heart failure (n= 162). CKDEPI-Creatinine and CKDEPI-Cystatin C equations were used to estimate GFR. Discordance of eGFR was calculated as the ratio of eGFRcreatinine to eGFRcystatin. (values higher than 1 represent eGFRcreatinine > eGFRcystatin and lower than 1 represent eGFRcystatin > eGFRcreatinine). Results: In the overall population eGFRcreatinine was 54§28mL/min/m2 and the eGFRcystatin was 43§25mL/min/m2, resulting in an average ratio of 1.3§0.4. There were, however, substantial differences in individual patients with the 10th percentile ratio at 0.9 and 90th percentile a ratio of 1.7. Notably, the ratio was correlated with plasma interleukin-6 (r= 0.24), C-reactive protein (r= 0.23), and ST2 (r= 0.26); p<0.01 for all. In line with the above-mentioned associations, the ratio of eGFR was strongly associated with all-cause mortality in univariate and multivariable analysis (HR 2.4, 95% CI 1.3-4.2; p<0.01). Conclusion: The discordance of eGFR with creatinine and cystatin C was associated with markers of inflammation and holds powerful independent prognostic information. Additional study into the drivers of the discordance in GFR estimates by cystatin C and creatinine is warranted.
045 Elevated Neutrophil-Lymphocyte Ratio is Associated with a Poorer Cardiopulmonary Exercise Test Performance in Patients with Heart Failure Rani Kuttab, Joronia Chery, Katelyn Carr, Amanda R. Vest; Tufts Medical Center, Boston, MA
Background: The neutrophil-lymphocyte ratio (NLR) is an easily-obtained biomarker of systemic inflammation. An elevated NLR represents greater inflammatory activation and has been associated with higher mortality in patients with heart failure (HF), including after left ventricular assist device implantation. We sought to determine whether NLR is associated with the metabolic response to exercise in patients undergoing cardiopulmonary exercise testing (CPET) for diagnostic or prognostic indications. Methods: We retrospectively reviewed CPETs performed between 4/2017 and 11/2018 at a single tertiary center. We included only the first CPET for unique patients, performed for an indication of cardiomyopathy or HF (systolic or diastolic). Patients referred for congenital or valvular heart disease were excluded. Baseline demographics and key CPET parameters were recorded and NLR noted if performed within 100 days of CPET. Pearson correlation coefficients were calculated between NLR and key CPET parameters. Two linear regression models were constructed, to determine the relationship between the NLR and peak oxygen consumption (pkVO2) or minute ventilation/carbon dioxide production slope (VE/VCO2), respectively. Each model was adjusted for age, sex and body mass index (BMI). Results: There were 142 CPETs during the study period, of which 121 met inclusion criteria and 94 had an NLR value. The cohort (n=94) was 30% female, with primary cardiac conditions identified as non-ischemic cardiomyopathy in 42%, ischemic cardiomyopathy in 38%, hypertrophic cardiomyopathy in 13% and HF with preserved ejection fraction in 7%. Median age was 60 years, BMI 29.2 kg/m2 and NLR 2.58 (quartile range 1.76-4.00). The median CPET parameters achieved were exercise time 9.0 min, metabolic equivalents (METS) 5.3, respiratory exchange ratio (RER) 1.10, pkVO2 1.18 L/min, pkVO2 adjusted for weight 14.2 mL/kg/min, VE/VCO2 35. There was a negative correlation between NLR and pkVO2 (r=-0.24, p=0.020) or weight-adjusted pkVO2 (r=-0.22, p=0.033, Fig 1A) and a positive correlation between NLR and VE/VCO2 (r=0.31, p= 0.003, Fig 1B). On multivariable regression, the NLR remained significantly associated with both the pkVO2 (p=0.048) and the VE/VCO2 (p=0.013) after adjustment for age, sex and BMI. Conclusion: Greater systemic inflammation, represented by a higher NLR, is associated with poorer CPET performance in patients with HF, as characterized by a lower pkVO2 and higher VE/VCO2. Systemic inflammation is an important correlate of functional limitations for patients with HF and warrants further investigation as a therapeutic target.
046 Sarcopenia Strongly Affects Serum Levels of Cystatin C in Patients with Heart Failure J. Ivey-Miranda, B. Stewart, N. Gomez, J. Barnett, A. Thomas, E. Wycallis, M. Pattoli, G. Struyk, J. Fleming, P. Shamlian, P. Raghavendra, D. Mahoney, M. Griffin, V. Rao, J. Testani; Yale University, New Haven, CT Introduction: Low muscle mass, or sarcopenia, is commonly seen in patients with heart failure (HF). For any given level of renal function, patients with sarcopenia will have lower levels of serum creatinine because there is less muscle mass to produce creatinine. Thus, the use of creatinine to estimate glomerular filtration rate (GFR) is affected by sarcopenia. In contrast to creatinine, cystatin C is considered a better filtration marker to estimate GFR in the setting of sarcopenia because it not seclusively produced by muscle. However, it has not been demonstrated that serum cystatin C levels are independent of sarcopenia in patients with HF. Hypothesis: Serum cystatin C levels will be minimally influenced by muscle mass in patients with heart failure. Methods: Serum cystatin C and serum creatinine were measured in patients with decompensated heart failure. Strict timed urine collections were used to measure creatinine excretion rate. Muscle mass was estimated with a validated equation based on urine creatinine excretion (Heymsfield). Creatinine clearance was calculated and used as a surrogate for measured GFR. Results: Out of the 295 patients analyzed (average age 65 §14 years), 65% were male and 61% were obese. Baseline levels of serum creatinine were 1.5§0.6 mg/dL and cystatin C were 1.7§0.7 mg/L. In univariate analysis, serum cystatin C showed a negative correlation with muscle mass (rho -0.37, p<0.001). After adjusting for age, sex, and race, the unindexed measured creatinine clearance showed a positive correlation with serum cystatin C (partial correlation 0.29, p<0.001). Similarly, GFR estimated using the CKDEPI-cystatin C equation was significantly affected by the amount of muscle mass (figure). Patients in the lowest tertile of muscle mass showed a median GFR overestimation of 31%. Underestimation occurred in the middle (-3%) and highest tertile (-22%) of muscle mass (p<0.001). Conclusion: Serum cystatin C serum levels are strongly associated with muscle mass in patients with HF. This may lead to inaccuracies when cystatin C is used to estimate GFR.