Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

Marino, Bárbara Campos Abreu; Buljubasic, Nermina; Akkerhuis, Martijn; Cheng, Jin M.; Garcia-Garcia, Hector M.; Regar, Evelyn; Geuns, Robert-Jan van; Serruys, Patrick W.; Boersma, Eric; Kardys, Isabella

doi:10.5935/abc.20180172

Brasil

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Original Article • Arq. Bras. Cardiol. 111 (3) • Sept 2018 • https://doi.org/10.5935/abc.20180172 linkcopy

Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background: Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.

Objective: To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.

Methods: In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.

Results: In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm² (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).

Conclusion: In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Keywords: Adiponectin; Atherosclerosis; Plaque, Atherosclerotic; Ultrasonography, Interventional; Coronary Artery Disease / complications.

	Total (n = 570)	ACS patients (n = 309)	SAP patients (n = 261)
Patient characteristics
Age, years (mean±SD)	61.5 ± 11.4	59.7 ± 11.9	63.6 ± 10.3
Men, n (%)	430 (75.4)	227 (73.5)	203 (77.8)
Diabetes Mellitus, n (%)	99 (17.4)	40 (12.9)	59 (22.6)
Hypertension, n (%)	295 (51.8)	134 (43.4)	161 (61.7)
Hypercholesterolemia, n (%)	317 (55.6)	137 (44.3)	180 (69.0)
Smoking, n (%)	164 (28.8)	115 (37.2)	49 (18.8)
Positive family history, n (%)	293 (51.5)	140 (45.3)	153 (58.6)
Previous MI, n (%)	184 (32.3)	80 (25.9)	104 (58.6)
Previous PCI, n (%)	185 (32.5)	57 (18.4)	128 (49.0)
Previous CABG, n (%)	18 (3.2)	7 (2.3)	11 (4.2)
Previous stroke, n (%)	23 (4.0)	10 (3.2)	13 (5.0)
Peripheral artery disease, n (%)	36 (6.3)	12 (3.9)	24 (9.2)
History of renal insufficiency (%)	32 (5.6)	13 (4.2)	19 (7.3)
History of heart failure, n (%)	19 (3.3)	6 (1.9)	13 (5.0)
Procedural characteristics
Indication for coronary angiography
Acute coronary syndrome, n (%)	309 (54.2)	309 (100)	0 (0)
Myocardial infarction, n (%)	159 (27.9)	159 (51.5)	0 (0)
Unstable angina pectoris, n (%)	150 (26.3)	150 (48.5)	0 (0)
Stable angina pectoris, n (%)	261 (45.8)	0 (0)	261 (100)
Coronary artery disease
No significant stenosis, n (%)	42 (7.4)	18 (5.8)	24 (9.2)
1-vessel disease, n (%)	301 (52.8)	168 (54.4)	133 (51.0)
2-vessel disease, n (%)	166 (29.1)	88 (28.5)	78 (29.9)
3-vessel disease, n (%)	61 (10.7)	35 (11.3)	26 (10.0)
PCI performed, n (%)	501 (87.9)	287 (92.9)	214 (82.0)
IVUS characteristics
Segment length (mm), median (IQR)	44.1 (33.7-55.4)	43.9 [32.9-54.1]	44.8 [34.2-57.2]
Plaque burden (%), median (IQR)	39.2 (30.0-46.4)	37.2 [28.0-45.5]	40.2 [31.8-47.8]
Presence lesion with MLA ≤ 4.0mm²	176 (30.9)	88 (28.7)	88 (33.7)
Presence of VH-TCFA, n (%)	239 (41.9)	140 (45.5)	99 (37.9)
Presence of VH-TCFA with PB ≥ 70%, n (%)	69 (12.1)	32 (10.4)	37 (14.2)
Serum biomarker concentrations
C-reactive protein (mg/L), median [IQR]	2.1 [0.8-5.3]	2.8 [1.1-7.0]	1.5[0.6-3.1]
Adiponectin (µg/mL) median [IQR]	2.8 [1.9-4.0]	2.9 [1.8-4.1]	2.9 [1.9-3.9]

	IVUS characteristics	Unadjusted Model	p	Multivariable model^* * Adjusted for age, gender, diabetes, hypertension, and C-reactive protein (CRP). Additionally adjusted for indication for coronary angiography in the total cohort.	p
	IVUS characteristics	Beta ‡ (95% CI)	p	Beta ‡ (95% CI)	p
All patients (n = 570)	Segment plaque Burden	-0.40 (-2.04 – 1.23)	0.62	-0.95 (-2.74 – 0.85)	0.30
	Dense calcium fraction %	1.35 (0.27 – 2.44)	0.001	0.36 (-0.86 – 1.58)	0.56
	Necrotic core fraction %	0.43 (-0.71 – 1.58)	0.46	0.39 (-0.92 – 1.70)	0.56
	Fibrofatty tissue fraction %	-0.62 (-1.51 – 0.27)	0.17	-0.46 (-1.46 – 0.55)	0.37
	Fibrous tissue fraction %	-1.17 (-2.81 – 0.48)	0.17	-0.29 (-2.16 – 1.58)	0.76
ACS patients (n = 309)	Segment plaque Burden	0.03 (-2.27 – 2.33)	0.98	-0.89 (-3.42 – 1.63)	0.49
	Dense calcium fraction %	2.53 (0.92 – 3.78)	0.001	1.10 (-0.50 – 2.70)	0.18
	Necrotic core fraction %	0.56 (-1.12 – 2.24)	0.51	0.23 (-1.69 – 2.16)	0.81
	Fibrofatty tissue fraction %	-1.47 (-2.78 – -0.15)	0.029	-0.99 (-2.49 – 0.50)	0.19
	Fibrous tissue fraction %	-1.45 (-3.78 – 0.89)	0.22	-0.35 (-3.00 – 2.30)	0.80
SAP patients (n = 261)	Segment plaque Burden	-0.71 (-3.00 – 1.58)	0.54	-0.87 (-3.46 – 1.73)	0.51
	Dense calcium fraction %	0.39 (-1.25 – 2.01)	0.64	-0.41 (-2.28 – 1.47)	0.67
	Necrotic core fraction %	0.24 (-1.29 – 1.77)	0.76	0.57 (-1.20 – 2.35)	0.52
	Fibrofatty tissue fraction %	0.38 (-0.80 – 1.57)	0.52	0.01 (-1.32 – 1.34)	0.99
	Fibrous tissue fraction %	-1.01 (-3.31 – 1.30)	0.39	-0.17 (-2.82 –2.48)	0.90

		Unadjusted Model	p	Multivariable model^* * Adjusted for age, gender, diabetes, hypertension, and C-reactive protein (CRP). Additionally adjusted for indication for coronary angiography in the total cohort. OR: odds ratio; CI: confidence interval of 95%; TCFA: thin-cap fibroatheroma; PB: plaque burden; MLA: minimal luminal area; ACS: acute coronary syndrome; SAP: stable angina pectoris.	p
		OR^† † Odds ratio per unit increase in ln-transformed biomarker concentration (95% CI)	p	OR^† † Odds ratio per unit increase in ln-transformed biomarker concentration (95% CI)	p
Total cohort (n = 570)	TCFA	1.11 (0.84 – 1.49)	0.44	1.23 (0.88 – 1.71)	0.23
	TCFA PB ≥70%	0.88 (0.57 – 1.37)	0.55	0.81 (0.50 – 1.33)	0.42
	Lesion with MLA ≤ 4.0 mm²	0.84 (0.62 – 1.14)	0.25	0.70 (0.49 – 1.00)	0.052
	Lesion with PB ≥70%	1.02 (0.72 – 1.44)	0.93	0.93 (0.63– 1.39)	0.73
ACS patients (n = 309)	TCFA	0.85 (0.58 – 1.26)	0.42	0.90 (0.58 – 1.42)	0.66
	TCFA PB ≥70%	0.90 (0.57 – 1.42)	0.66	0.77 (0.37 – 1.58)	0.48
	Lesion with MLA ≤ 4.0 mm²	1.13 (0.74 – 1.74)	0.57	0.87 (0.53 – 1.44)	0.59
	Lesion with PB ≥70%	1.25 (0.76 – 2.07)	0.38	1.08 (0.60 – 1.94)	0.80
SAP patients (n = 261)	TCFA	1.54 (0.99 – 2.38)	0.057	1.78 (1.06 – 3.00)	0.030
	TCFA PB ≥70%	0.86 (0.48 – 1.52)	0.60	0.87 (0.45 – 1.69)	0.68
	Lesion with MLA ≤ 4.0 mm²	0.62 (0.40 – 0.97)	0.035	0.55 (0.32 – 0.93)	0.025
	Lesion with PB ≥70%	0.86 (0.54 – 1.39)	0.54	0.85 (0.49 – 1.47)	0.56

		Univariable	p	Adjusted for age and gender^† † Additionally adjusted for indication for coronary angiography in the total cohort.	p
		HR^* * Hazard ratio per unit increase in ln-transformed biomarker concentration (95% CI)	p	HR^* * Hazard ratio per unit increase in ln-transformed biomarker concentration (95% CI)	p
Total (n = 570)	MACE (n = 56)	1.28 (0.81 – 2.02)	0.29	1.19 (0.71 – 1.99)	0.52
	Acute MACE (n = 32)	1.77 (0.96 – 3.23)	0.069	1.36 (0.68 – 2.72)	0.38
	Death (n = 19)	3.36 (1.49 – 7.59)	0.004	2.52 (1.02 – 6.23)	0.045
ACS (n = 309)	MACE (n = 26)	1.29 (0.66 – 2.50)	0.46	1.02 (0.48 – 2.19)	0.95
	Acute MACE (n = 20)	1.75 (0.81 – 3.72)	0.14	1.40 (0.59 – 3.29)	0.44
	Death (n = 14)	2.44 (0.98 – 6.06)	0.055	1.87 (0.67 – 5.19)	0.23
SAP (n = 261)	MACE (n = 30)	1.30 (0.69 – 2.46)	0.42	1.43 (0.69 – 2.98)	0.34
	Acute MACE (n = 12)	1.75 (0.61 – 4.94)	0.29	1.33 (0.41 – 4.28)	0.64
	Death (n = 5)	8.15 (1.49 – 44.68)	0.016	8.48 (0.92 – 78.03)	0.058

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[TFN01] ACS: acute coronary syndrome; SAP: stable angina pectoris; SD: standard deviation; MI: myocardial infarction; PCI: percutaneous coronary intervention; CABG: coronary artery bypass grafting; IVUS: intravascular ultrasound; IQR: interquartile range; MLA: minimal luminal area; VH-TCFA: virtual histology thin-cap fibroatheroma; PB: plaque burden.