Association of Cystatin C With Left Ventricular Structure and Function The Dallas Heart Study

Division of Cardiology, Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9047, USA.
Circulation Heart Failure (Impact Factor: 5.89). 03/2009; 2(2):98-104. DOI: 10.1161/CIRCHEARTFAILURE.108.807271
Source: PubMed


Cystatin C, a novel marker of renal function, has been associated with heart failure and cardiovascular mortality in older individuals. We tested the hypothesis that cystatin C is associated with preclinical cardiac structural and functional abnormalities in a younger population-based sample.
The study included participants in the Dallas Heart Study (ages 30 to 65 years) who had measurements of cystatin C and cardiac MRI. The associations of cystatin C with left ventricular (LV) mass, LV end-systolic and -diastolic volumes, concentricity (LV mass/LV end-diastolic volume), LV wall thickness, and LV ejection fraction were evaluated. Cystatin C levels ranged from 0.46 to 6.55 mg/L. In univariable analyses, increasing levels of cystatin C correlated with higher LV mass, concentricity, and wall thickness (P<0.001), but not with LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction. After adjustment with traditional covariates and estimated glomerular filtration rate by the modification of diet in renal disease formula, log-transformed cystatin C remained independently associated with LV mass (P<0.001), concentricity (P=0.027), and wall thickness (P<0.001). These associations persisted when creatinine or estimated glomerular filtration rate by the Cockcroft-Gault formula were included in the models.
Higher levels of cystatin C were associated with increased LV mass and a concentric LV hypertrophy phenotype. These findings were independent of potential confounding variables including standard measurements of renal function, supporting the hypothesis that cystatin C may be useful to identify individuals with preclinical structural heart abnormalities.

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Available from: Jody A Rule, Sep 29, 2015
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    • "First, CyC seems to be a better measure of kidney function than sCr and GFR [16] [24] [28]. Second, CyC may provide prognostic information beyond its role as an index of kidney function and, also, may be a better overall measure of the spectrum of pathophysiologic abnormalities that accompany kidney disease [29] [30] [31]. Table 2: Ideal marker of contrast-induced acute kidney injury. "
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    ABSTRACT: Biomarkers of acute kidney injury (AKI) may be classified in 2 groups: (1) those representing changes in renal function (e.g., serum creatinine or cystatin C and urine flow rate) and (2) those reflecting kidney damage (e.g., kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, etc.). According to these 2 fundamental criteria, 4 subgroups have been proposed: (1) no marker change; (2) damage alone; (3) functional change alone; and (4) combined damage and functional change. Therefore, a new category of patients with "subclinical AKI" (that is, an increase in damage markers alone without simultaneous loss of kidney function) has been identified. This condition has been associated with higher risk of adverse outcomes (including renal replacement therapy and mortality) at followup. The ability to measure these physiological variables may lead to identification of patients at risk for AKI and early diagnosis of AKI and may lead to variables, which may inform therapeutic decisions.
    BioMed Research International 05/2014; 2014:568738. DOI:10.1155/2014/568738 · 2.71 Impact Factor
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    • "Thus, Cys C was used to evaluate renal function in the study. Although Cys C is less dependent on factors such as age, sex, race and body mass index when compared to creatinine-based GFR estimation, it can be affected by other factors such as body composition (lean mass), thyroid dysfunction, cancer and left ventricular mass [35-38]. It is possible that GFR –independent factors could account for decreases in serum cystatin in some individuals, but these factors were not apparent during the follow-up of our patients and were unlikely to account for the changes in serum cystatin C in the group as a whole. "
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    ABSTRACT: Enhanced external counterpulsation (EECP) enhances coronary perfusion and reduces left ventricular afterload. However, the role of EECP on renal function in cardiac patients is unknown. Our aim was to assess renal function determined by serum cystatin C in cardiac patients before and after EECP treatment. A prospective observational longitudinal study was conducted in order to evaluate renal function using serum cystatin C (Cys C) and estimated glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30 patients with chronic stable angina and/or heart failure. The median (IQR) time for follow-up period after starting EECP treatment was 16 (10--24) months. Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27) mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27 (49.02-91.46) mL/min/1.73 m2 (p = 0.006) after EECP treatment. Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m2 or NT-proBNP >125 pg/mL had a significant decrease in Cys C when compared to other groups (p < 0.01). The study demonstrated that EECP could improve long-term renal function in cardiac patients especially in cases with declined renal function or with high NT-proBNP.Trial registration: The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number ISRCTN11560035.
    BMC Nephrology 09/2013; 14(1):193. DOI:10.1186/1471-2369-14-193 · 1.69 Impact Factor
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    • "CystC has been recognized as a sensitive marker for potential renal dysfunction and injury and as an independent predictor of cardiac outcomes in patients with heart failure.85,86 High serum CystC levels are associated with increased left ventricular hypertrophy and dysfunction.87 A comparison of the serum levels of patients with AAA to those of patients with normal aortas showed decreased levels of serum CystC in the patients with AAA.48 "
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    ABSTRACT: Until recently, the role of lysosomal cysteine protease cathepsins in intracellular protein degradation was believed to be mainly restricted to scavenging. However, recent studies have revealed nontraditional roles for cysteine protease cathepsins in the extracellular space during the development and progression of cardiovascular disease. Although the precise mechanisms are unknown, data from animal studies suggest that members of the cathepsin family, like other extracellular proteases, contribute to extracellular matrix protein remodeling and interstitial matrix degradation, as well as to cell signaling and cell apoptosis in heart disease. Inflammatory cytokines and hormones regulate the expression and secretion of cathepsins in cultured cardiovascular cells and macrophages. Serum levels of cathepsins L, S, and K and their endogenous inhibitor cystatin C may be useful predictive biomarkers in patients with coronary artery disease and cardiac disease. Furthermore, in vivo pharmacological intervention with a synthetic cathepsin inhibitor and cardiovascular drugs (including statins and angiotensin II type 1 receptor antagonists) has the potential for pharmacologic targeting of cathepsins in cardiovascular disease. This review focuses on cathepsin biology (structure, synthesis, processing, activation, secretion, activity regulation, and function) and the involvement of cysteinyl cathepsins in the pathogenesis of several heart and vessel diseases, especially with respect to their potential application as diagnostic and prognostic markers and drug targets to prevent inappropriate proteolysis in cardiovascular disease.
    08/2012; 48(2):77-85. DOI:10.4068/cmj.2012.48.2.77
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