The diagnostic value of circulating microRNAs for middle-aged (40–60-year-old) coronary artery disease patients

Sayed, Ali Sheikh Md; Xia, Ke; Li, Fei; Deng, Xu; Salma, Umme; Li, Tingbo; Deng, Hai; Yang, Dafeng; Haoyang, Zhou; Yang, TianLun; Peng, Jun

doi:10.6061/clinics/2015(04)07

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Sumário

CLINICAL SCIENCES • Clinics 70 (4) • Apr 2015 • https://doi.org/10.6061/clinics/2015(04)07 copy

The diagnostic value of circulating microRNAs for middle-aged (40–60-year-old) coronary artery disease patients

Authorship SCIMAGO INSTITUTIONS RANKINGS

OBJECTIVE:

Circulating microRNAs have been recognized as promising biomarkers for various diseases. The present study aimed to explore the potential roles of circulating miR-149, miR-424 and miR-765 as non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged (40–60-year-old) patients.

METHODS:

Sixty-five stable coronary artery disease patients (49–57 years old), 30 unstable coronary artery disease patients (49–58 years old), and 32 non-coronary artery disease patients (49–-57 years old) who were matched for age, sex, smoking habits, hypertension and diabetes were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. Circulating miRNA levels were measured by quantitative real-time polymerase chain reaction.

RESULTS:

Circulating miR-149 levels were decreased 4.49-fold in stable coronary artery disease patients (1.18 ± 0.84) and 5.09-fold in unstable coronary artery disease patients (1.04 ± 0.65) compared with non-coronary artery disease patients (5.30 ± 2.57) (p<0.001). Circulating miR-424 levels were reduced 3.6-fold in stable coronary artery disease patients (1.18 ± 0.60) and 5-fold in unstable coronary artery disease patients (0.86 ± 0.54) compared with non-coronary artery disease patients (4.35 ± 2.20) (p<0.001). In contrast, circulating miR-765 levels were elevated 3.98-fold in stable coronary artery disease patients (6.09 ± 2.27) and 5.33-fold in unstable coronary artery disease patients (8.17 ± 2.77) compared with non-coronary artery disease patients (1.53 ± 0.99) (p<0.001). Receiver operating characteristic curve analysis revealed that the respective areas under the curve for circulating miR-149, miR-424 and miR-765 were 0.938, 0.919 and 0.968 in stable CAD patients and 0.951, 0.960 and 0.977 in unstable coronary artery disease patients compared with non-coronary artery disease patients.

CONCLUSION:

Our results suggest that circulating miR-149, miR-424 and miR-765 might be novel, non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged patients. However, future prospective trials in large patient cohorts are necessary before reaching a solid conclusion.

Circulating microRNAs; Coronary artery disease; Unstable angina; Biomarkers; Non-coronary artery disease

Variable	Non-CAD patients (n ϝ 32)	CAD patients (n ϝ 65)	UA patients (n ϝ 30)	p₁	p₂
Age (years)	53 (49–57)	53 (49–57)	54 (49–58)	0.957	0.471
Male/Female	16/16	38/27	20/12	0.516	0.208
BMI (kg/m²)	22 (20–23)	22 (19–25)	23 (20–27)	0.706	0.124
Active Smoker (%)	59.37	63.07	67	0.825	0.606
Hypertension (%)	56.25	70.76	73.3	0.177	0.192
Dyslipidemia (%)	37.50	41.53	43.33	0.826	0.796
DM (%)	15.63	20	23.33	0.783	0.529
SBP (mmHg)	127 (119–135)	131 (117–146)	134 (122–146)	0.330	0.018
DBP (mmHg)	79 (72–86)	80 (73–86)	82 (75–90)	0.587	0.076
LVEF (%)	66 (60–72)	63 (55–71)	62 (53–70)	0.238	0.075
Medications
Aspirin (%)	34.3	53.84	60	0.086	0.074
β-blocker (%)	40.62	61.53	66.66	0.082	0.047
CCB (%)	31.25	38.46	46.66	0.511	0.298
ACEI/ARB (%)	28.12	35.84	40	0.502	0.423
Statin (%)	46.87	61.53	63.33	0.196	0.213
Diuretic (%)	18.75	24.61	26.66	0.612	0.550

Variable	Non-CAD patients (n ϝ 32)	CAD patients (n ϝ 65)	UA patients (n ϝ 30)	p₁	p₂
FBS (mmol/L)	4.9 (4.3–5.4)	5.1 (4.2–6.1)	5.2 (3.9–6.7)	0.234	0.490
TG (mmol/L)	1.5 (0.5–2.5)	1.6 (0.6–2.7)	1.8 (0.8–2.7)	0.454	0.126
TC (mmol/L)	4.4 (2.9–5.9)	4.9 (3.3–6.5)	5.3 (3.7-7)	0.177	0.038
HDL-C (mmol/L)	0.9 (0.5–1.4)	0.9 (0.4–1.4)	0.9 (0.5–1.3)	0.595	0.746
LDL-C (mmol/L)	2.7 (1.5–3.8)	2.9 (1.4–4.4)	3.2 (2.1–4.3)	0.872	0.024
hs-CRP (mg/L)	1.4 (0.5–2.7)	19.8 (9.9–29.5)	21.3 (15–27.5)	<0.001	<0.001
AST (U/L)	15.3 (6.9–24)	17.7 (8.3–27.1)	19.8 (12.6–27)	0.294	0.019
ALT (U/L)	17.1 (9.1–25)	19.1 (10.7–27.4)	21.5 (13.4–29.6)	0.244	0.042
Cr (umol/L)	71.5 (52.4–90)	74.8 (53.4–96.1)	79.8 (58.6–101.1)	0.602	0.049

miRNA	AUC	Cut-off point	Sensitivity	Specificity	95% CI	p-value
miR-149
Non-CAD vs. CAD	0.938	1.67	71.8%	95.3%	0.894 to 0.983	<0.0001
Non-CAD vs. UA	0.951	1.71	75%	96.6%	0.905 to 0.997	<0.0001
CAD vs. UA	0.539	1.15	75%	40%	0.415 to 0.663	0.540
miR-424
Non-CAD vs. CAD	0.919	1.61	68.7%	92.3%	0.863 to 0.975	<0.0001
Non-CAD vs. UA	0.960	1.77	84.3%	93.3%	0.920 to 1.000	<0.0001
CAD vs. UA	0.682	1.35	89.2%	46.6%	0.559 to 0.805	0.005
miR-765
Non-CAD vs. CAD	0.968	1.75	81.5%	93.7%	0.939 to 996	<0.0001
Non-CAD vs. UA	0.977	1.80	83.3%	96.8%	0.949 to 1.005	<0.0001
CAD vs. UA	0.760	1.57	66.5%	90.7%	0.635 to 0.885	<0.0001

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[1] Sayed AS and Xia K designed the research, performed the experiments and wrote the manuscript. Deng X, Deng H, Yangda F, Li F, Haoyang Z, Li T, and Salma U collected patient samples and assembled the data. Yang T and Peng J supervised the data analysis and revised the manuscript. The work presented in this paper was performed in collaboration with all the authors.