Low catestatin as a risk factor for cardiovascular disease - assessment in patients with adrenal incidentalomas

Abstract

Background: Catestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease.

Objectives: examining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP).

Materials and methods: In this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed.

Results: Unadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 - 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9- 6.9) vs. 25.7 (5.8-115) ng/ml, p<0.01), and in men compared to women (4.9 (4-7.4) ng/ml vs. 7 (4.8-100), p=0.015). AI patients in the lower half of Cts levels compared to those in the upper had a higher prevalence of hypertension (OR 0.15, 95% CI: 0.041-0.5, p<0.001) and metabolic syndrome (OR 0.15, 95% CI 0.041-0.5, p<0.001). In AI patients Cts correlated positively with high-density lipoprotein cholesterol (Spearman's r=0.31), negatively with BMI (r=-0.31), and 10-year atherosclerotic CV disease risk (r=-0.42).

Conclusions: Our data indicate associations between CV risk factors and Cts. More clinical research is needed to apply serum Cts as a biomarker.

Keywords: adrenal incidentaloma (AI); cardiovascular disease(s); catestatin; metabolic syndrome; risk predictor.

Figure 1

Catestatin distribution in controls and AI patients. Boxplot and data distribution with dots (AI patients) and triangles (controls) indicating individual datapoints. Unadjusted p value was determined using the Mann Whitney U test. AI, adrenal incidentaloma.

Figure 2

Catestatin in male and female controls and AI patients. Boxplot chart. P-value was determined using the Mann-Whitney U test. AI, adrenal incidentaloma.

Figure 3

Catestatin in normotensive and hypertensive in controls and AI patients. Boxplot chart. P-values were determined using the Mann-Whitney U test. AI, adrenal incidentaloma.

Figure 4

Catestatin in subjects without and with metabolic syndrome in controls and AI patients. AI, adrenal incidentaloma; MetS, metabolic syndrome. P-values determined using the Mann-Whitney U test.

Figure 5

Correlations between catestatin and: (A) BMI in AI patients; (B) FHS-ASCVD Risk in AI patients; (C) HDL-C in AI patients and controls. Correlations were computed by the Spearman rank-order method. For HDL-C, correlations were tested separately in subjects with and without statin therapy. AI, adrenal incidentaloma, BMI, body mass index, FHS-ASCVD Risk - 10-year atherosclerotic cardiovascular disease risk calculated based on the Framingham Heart Study; HDL-C, high density lipoprotein cholesterol, ln, natural logarithm.

Figure 6

Summary of research on associations between low catestatin and cardiovascular risk. Superscript numbers indicate references to previous studies; *indicate results of the current study; ^#correlation between uric acid and Cts did not reach significance in AI patients analyzed here, it did upon analyzing AI patients and controls together; ^†significance achieved in AI patients. AI, adrenal incidentaloma, BMI, body mass index; Cts, catestatin; CVD, cardiovascular disease; FHS-ASCVD Risk, 10-year atherosclerotic cardiovascular disease risk calculated based on the Framingham Heart Study; HDL-C, high density lipoprotein cholesterol; HT, hypertension; MetS, Metabolic Syndrome.