Abstract
Background Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. Methods A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 μmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. Results The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P < 0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r = −0.31, P < 0.001), SDANN (r = −0.25, P = 0.002), and logLF (r = −0.18, P = 0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (β = −24.11, P = 0.015) and SDANN (β = −19.88, P = 0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. Conclusions Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.
Highlights
Cardiovascular autonomic neuropathy, the impairment of cardiovascular autonomic nerve function, is one of the most important but overlooked complications of diabetes for its association with cardiovascular morbidity and mortality but mostly asymptomatic in patients with diabetes [1,2,3]
The requirement of specialized personnel of heart rate variability (HRV) test limits its use in general practice, which eventually leads to the failure to decrease overall prevalence and progression of Journal of Diabetes Research cardiovascular autonomic dysfunction [7]
Patients were excluded by the following conditions: (1) arrhythmia, coronary heart disease, and heart failure; (2) taking beta-blockers or glucocorticoid for the past 2 weeks; (3) history of cerebral infarction; (4) severe infection, respiratory illness, or hematologic disease; (5) acute complications of diabetes, including diabetic ketosis acidosis, diabetic hyperosmolar coma, and severe foot ulcer; and (6) serum creatinine higher than 133 μmol/l and estimated glomerular filtration rate eGFR < 60 ml/ min per 1.73 m2 which was considered renal dysfunction [15]
Summary
Cardiovascular autonomic neuropathy, the impairment of cardiovascular autonomic nerve function, is one of the most important but overlooked complications of diabetes for its association with cardiovascular morbidity and mortality but mostly asymptomatic in patients with diabetes [1,2,3]. It is essential to identify cardiovascular autonomic dysfunction at the early stage. It has been reported that cardiovascular autonomic dysfunction could be detected early by reduced HRV [5, 6]. The aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. Multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (β = −24 11, P = 0 015) and SDANN (β = −19 88, P = 0 047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. Serum CysC levels are associated with cardiovascular autonomic dysfunction; CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction
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