The Association of TWEAK with Coronary Artery Calcification in Patients with Chronic Kidney Disease

Tatlisu, Mustafa Adem; Atici, Adem; Ozcan, Fatma Betul; Çelik, Mehmet; Kirac, Eray; Baycan, Omer Faruk; Caliskan, Mustafa

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Original Article • Arq. Bras. Cardiol. 119 (3) • Sept 2022 • https://doi.org/10.36660/abc.20210599 copy

The Association of TWEAK with Coronary Artery Calcification in Patients with Chronic Kidney Disease

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

The soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a member of the TNF superfamily that plays a critical role in proliferation and inflammation in the arterial circulation.

Objectives

This prospective study aimed to show the relationship between the sTWEAK levels and coronary artery calcification (CAC) in patients with chronic kidney disease (CKD).

Methods

This prospective study included 139 consecutive patients undergoing computed coronary angiography for any reason except for acute coronary syndromes from August 2020 to February 2021. A total of 12 patients were excluded from the study due to exclusion criteria. Patients were divided into two groups with regard to having a CAC score of less than 400 (n=84) and 400 or more (n=43). Significance was assumed at a 2-sided p<0.05.

Results

As the CAC score increased, sTWEAK levels presented a statistically significant decrease, and a strong relationship between sTWEAK levels and the CAC score (r: -0.779, p<0.001) was observed. The ROC analysis revealed that the optimal cut-off level of sTWEAK for predicting the CAC score of 400 was 761 pg/mL with a sensitivity of 71% and a specificity of 73% (AUC: 0.78; 95% CI:0.70-0.85; p < 0.001)

Conclusions

Even though the large-scale studies showed a positive correlation between eGFR and the sTWEAK levels, some studies found the increased sTWEAK levels to be associated with mortality and the severity of the coronary artery system in patients with CKD. Our results support our hypothesis that the sTWEAK level shows coronary calcification rather than other types of atherosclerotic plaques.

Cardiovascular Diseases; Renal Insufficiency,Chronic; Vascular Stiffness; Atherosclerosis; Coronary Artery Disease

	n=127
Age, years	59.9 ± 9.4
Gender (male, %)	49 (39%)
BMI, kg/m²	29.0 ± 3.7
HTN, n(%)	87 (68%)
DM, n(%)	53 (42%)
Smoking, n(%)	35 (27%)
Systolic blood pressure, mmHg	134.2±22.7
Diastolic blood pressure, mmHg	77.4±11.8
Fasting blood glucose, mg/dL	119.4±47.1
Hemoglobin, g/dL	13.8±1.6
PLT, cells/µL	237.7±65.2
WBC, cells/µL	7.5±1.8
Creatinine, mg/dL	1.8±0.2
eGFR, ml/dk/1.73 m²	39.9±13.1
BUN, mg/dL	43.5±8.4
Uric acid, mg/dL	7.4±1.2
Sodium, mmol/L	139.6±2.3
Potassium, mmol/L	4.3±0.4
Calcium, mmol/L	9.4±0.4
AST, U/L	22.4±9.3
ALT, U/L	23.8±11.2
CRP, mg/dL	0.3 (0.1-9.2)
Albumine, g/dL	4.3±0.4
TC, mg/dL	207.3±45.8
LDL, mg/dL	126.7±42.5
HDL, mg/dL	48.7±12.0
Tg, mg/dL	161.3±77.5
sTWEAK , pg/mL	845.0±418.0
CAC score	90 (0-1605)
CAC score <400, n(%)	84 (66%)
CAC score ≥400, n(%)	43 (34%)

	CCS≥400 (n=43)	CCS<400 (n=84)	p
Age, years	61.7 ± 8.8	59.0 ± 9.6	0.126
Gender (male%)	19(44%)	30(35%)	0.353
BMI, kg/m²	29.8 ± 3.8	28.6± 3.6	0.098
HT, n(%)	33(78%)	54(65%)	0.121
DM, n(%)	22(52%)	31(37%)	0.108
Smoking, n(%)	15(36%)	20(25%)	0.198
Systolic blood pressure, mmHg	137.5±20.7	132.4±23.6	0.241
Diastolic blood pressure, mmHg	80.0±11.5	76.0±11.7	0.073
Fasting blood glucose, mg/dL	122.8±62.9	117.5±24.5	0.601
Hemoglobin, g/dL	13.6±1.4	13.9±1.7	0.336
PLT, cells/µL	235.5±68.1	239.0±63.9	0.797
WBC, cells/µL	7.4±1.8	7.5±1.9	0.687
Creatinine, mg/dL	1.8±0.2	1.9±0.1	0.887
Stages of CKD
Stage 2	18	36	0.914
Stage 3a	15	27	0.756
Stage 3b	10	18	0.814
Stage 4	1	2	0.984
eGFR, ml/dk/1.73 m²	39.8±13.6	40.2±12.9	0.890
BUN, mg/dL	36.4±9.3	32.0±7.4	0.009
Uric acid, mg/dL	7.5±1.1	7.3±1.3	0.274
Sodium, mmol/L	139.5±2.2	139.6±2.3	0.825
Potassium, mmol/L	4.2±0.5	4.3±0.3	0.115
Calcium, mmol/L	9.3±0.3	9.4±0.4	0.066
AST, U/L	22.2±8.1	22.6±11.3	0.875
ALT, U/L	23.5±11.1	24.0±10.0	0.898
CRP, mg/dL	0.3 (0.1-9.2)	0.2 (0.1-2.0)	0.009
Albumine, g/dL	4.1±0.5	4.4±0.2	0.005
TC, mg/dL	215.8±41.6	202.9±47.5	0.132
LDL, mg/dL	135.2±40.0	122.4±43.4	0.108
HDL, mg/dL	49.6±13.3	48.3±11.3	0.550
Tg, mg/dL	158.4±59.1	162.8±85.7	0.758
sTWEAK, pg/mL	586.2±286.6	977.5±413.8	<0.001
CAC score	488 (402-1605)	45 (0-312)	<0.001

Variable	Univariate			Multivariate

	OR	95%CI	p	OR	95%CI	p
Age	1.049	1.009-1.091	0.016	1.033	1.016-1.058	0.003
Gender	0.567	0.276-1.166	0.123
HTN	1.093	0.492-2.265	0.877
DM	0.591	0.289-1.209	0.150
CKD	1.105	0.151-8.105	0.922
Smoking	4.552	1.898-10.915	0.001	4.638	1.965-11.236	0.003
BMI	0.969	0.881-1.066	0.513
CRP	2.490	0.802-7.731	0.314
LDL	1.017	1.007-1.027	0.001	1.016	1.005-1.028	0.005
sTWEAK	0.314	0.172-0.507	<0.001	0.345	0.201-0.581	<0.001

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[1] Mailing Address: Mustafa Adem Tatlisu Istanbul Medeniyet University Faculty of Medicine, Cardiology. Istanbul Goztepe Prof Suleyman Yalcin City Hospital Istanbul Istanbul 34722 – Turkey E-mail: ademtatlisu@gmail.com