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doi: 10.1111/j.1365-2796.2008.02007.x
Introduction
Coronary heart disease (CHD) continues to be the
leading cause of premature mortality and morbidity
worldwide [1]. The stratication of CHD risk amongst
asymptomatic individuals as well as those with overt
disease continues to be one of the major priorities of
Results. Levels of adiponectin decreased in an ordinal fashion across tertiles of increasing CAS
(P = 0.047), but were nonsignicantly correlated to
absolute values of CAS (P = 0.06). Adiponectin levels were unrelated to left ventricular dysfunction
related measures of RWMA or EF. On multivariate
analysis, (including factors relating to CHD risk,
history and medication) adiponectin levels were
independently inversely associated with triglycerides
(P = 0.001), CAS tertiles (P = 0.01) and positively
with age (P < 0.001).
Conclusion. Levels of adiponectin decreased with
coronary artery disease severity, without impact
from systolic dysfunction, but levels may be
moderated through established CHD risk factors
such as smoking and triglycerides. Further work is
warranted as to the clinical prognostic utility of this
marker amongst CHD patients.
Keywords:
adiponectin, atheroma score, cardiac
function, coronary heart disease, ejection fraction.
593
J. V. Patel et al.
Adipocytokines are hormones produced by adipocytes, which elicit a diverse range of metabolic
changes that are implicated in the pathophysiology of
atherosclerosis. Importantly, circulating concentrations
of adipocytokines are of both diagnostic and prognostic potential with respect to the cardiovascular disease
continuum [38]. Of the adipocytokines, the collagenlike protein adiponectin has received the most intense
evaluation as a potential cardiovascular biomarker [9],
where low levels are used to explicate increased CHD
risk [10, 11] in both healthy [12, 13] and high-risk
populations [14]. There are also emerging data that
adiponectin elicits a favourable effect on postmyocardial infarction left ventricular (LV) remodelling [15],
with the potential to attenuate cardiac myocyte hypertrophy [16] as well as to protect against the progression of heart failure [17]. Given that cardiac function
deteriorates in the presence of longstanding CHD, we
tested the hypothesis that plasma adiponectin levels
would be signicantly correlated to indices of coronary artery disease (CAD) severity [coronary atheroma scores (CAS)], ejection fraction (EF) and
regional wall motion abnormalities (RWMA) therein.
Methods
We measured plasma adiponectin levels in 204 consecutive patients (3481 years) with symptomatic, but
stable CAD, who were undergoing diagnostic coronary angiography at University Hospital of North
Staffordshire (Stoke, UK). Those patients with a
recent clinical history (within the last 3 months) of
acute coronary syndrome, coronary intervention or
cerebral vascular accident were excluded. Patients
were also excluded if they had a history of malignant
disease, chronic inammatory disease or major concomitant noncardiovascular disease (e.g. renal impairment, liver impairment, connective tissue disease,
etc). All the patients underwent a complete cardiovascular assessment on the day of their attendance for
cardiac catheterization. Left heart catheters were
inserted via the femoral or radial approach, and
images were digitally recorded.
Left ventricular function and the severity of CAD
were assessed by an experienced cardiologist blinded
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Laboratory
Blood samples were collected before angiography.
Plasma was separated by centrifugation (4 C,
20 min, 3000 rpm), aliquoted and stored at )70 C
for batch analysis. Adiponectin levels were measured
by enzyme-linked immunosorbent assay (ELISA)
using commercially available antibodies (R&D Systems, Abingdon, UK). Intra-assay coefcients of variation were 3% and inter-assay variance was 5%. The
lower limit of detection by this ELISA was
62.5 pg mL)1.
J. V. Patel et al.
Results
Patient characteristics by CAS tertile strata are presented in Table 1. Individuals with higher score were
more likely to be male and they smoke and have
Bottom
Middle
Top
P-value
Age (years)
60.0 (9.8)
63.5 (8.6)
63.0 (8.4)
0.073
Male gender
15 (23.8)
21 (47.7)
55 (77.5)
<0.001
Current smoker
2 (3.2)
11 (25)
11 (15.7)
0.005
Hypertension
22 (36.1)
17 (39.5)
34 (49.3)
0.289
Diabetes mellitus
14.5 (9)
22.7 (10)
31.4 (22)
0.072
141 (18.9)
142 (18.1)
143 (19.9)
0.878
81 (11.2)
77.2 (9.6)
77.6 (12.3)
0.122
28.9 (6.4)
29.3 (5.59)
28.4 (4.39)
0.719
61 (14.7)
58.1 (15.4)
51.5 (18.9)
0.005
4.89 (1.12)
4.91 (1.07)
4.41 (1.05)
0.021
1.4 (1.01.9)
1.8 (1.52.6)
1.6 (1.32.5)
0.003a
Adiponectin (ng ml )
287 (195409)
240 (182404)
206 (153302)
0.047a
37 (60.7)
37 (86.0)
55 (78.6)
0.008
36 (59.0)
29 (67.4)
54 (77.1)
0.08
17 (27.9)
19 (44.2)
22 (31.4)
0.20
9 (14.5)
9 (20.9)
14 (20.3)
0.62
41 (67.2)
32 (74.4)
52 (74.3)
0.61
0.29
)1
13 (21.0)
6 (13.6)
10 (14.3)
II
14 (22.6)
12 (27.3)
10 (14.3)
III
1 (1.6)
3 (6.8)
2 (2.9)
23 (36.5)
25 (56.8)
49 (71.0)
<0.001
ACE, angiotensin converting enzyme; IQR, interquartile range; RWMA, regional wall motion abnormalities.
One-way anova, aKruskallWallis test. Data are mean (SD), number (%) or median (IQR).
2008 Blackwell Publishing Ltd Journal of Internal Medicine 264; 593598 595
J. V. Patel et al.
Bottom
60 (95.2)
0 (0)
2 (3.2)
0 (0)
1 (1.6)
Middle
40 (90.9)
3 (6.8)
1 (2.3)
0 (0)
0 (0)
Top
57 (82.6)
4 (5.8)
5 (7.2)
2 (2.9)
1 (1.4)
NS
NS
NS
NS
NS
coefcient (P-value)
0.265 (0.001)
)0.186 (0.009)
Weight (kg)
)0.185 (0.009)
)0.124 (0.083)
)0.191 (0.007)
Hypertension (%)
0.032 (0.661)
)0.236 (0.001)
)0.159 (0.026)
)0.013 (0.86)
0.006 (0.933)
)0.279 (0.001)
0.111 (0.123)
0.076 (0.292)
)0.047 (0.516)
)0.025 (0.733)
)0.120 (0.095)
)0.021 (0.768)
0.082 (0.254)
)0.078 (0.276)
)0.002 (0.982)
)0.166 (0.02)
)0.047 (0.098)
0.139 (0.053)
)0.134 (0.061)
(absolute numbers)
Discussion
Given the diverse metabolic remit relating to the regulatory role of adiponectin (insulin-sensitization, free
J. V. Patel et al.
fatty acid oxidation, gluconeogenesis, anti-inammatory modulation of the endothelium and counter
action of pro-inammatory cytokines to name just a
few [18]), there is increasing interest in the utility of
this biomarker in CHD. Indeed, many of these
effects could contribute to protection against atherosclerosis. Moreover, several other vascular and myocardial effects of adiponectin have been described,
including the modulation of angiogenesis and apoptosis, attenuation of LV hypertrophy, brosis and postmyocardial infarction remodelling as well as possible
regulation of myocardial ischaemia and reperfusion
injury [15, 16].
Whilst this biomarker appears to be physiologically
specic for CHD, there is confusion as to the clinical
signicance of circulating levels especially across
the cardiovascular disease spectrum from asymptomatic individuals to patients with end stage heart failure. For example, several studies conducted in
patients with CHF have found a direct correlation
between adiponectin and brain-type natriuretic peptides [1921], where high, not low adiponectin levels
independently predicted mortality [20, 21]. There are
also the lack of compelling prospective data on adiponectin levels as a predictor of recurrent cardiovascular
events, although relatively small studies in patients
with end stage renal disease [22], diabetes mellitus
[23] and CHD [24] have been published some with
conicting ndings [2527]. However, a recent prospective study in Japanese CHD patients reported that
the measurement of adiponectin was of clinical utility
with respect to predicting future clinical outcomes
following percutaneous coronary intervention [22].
The positive association between age and adiponectin
was not expected. However, amongst hospital
patients, adiponectin has been implicated in the ageing process, where increased levels in the elderly may
reect a physiological protective response to combat
low level inammation and oxidative stress [28]. The
absence of association between absolute scores of
CAS and adiponectin levels may reect the presence
of a nonlinear relationship, that is, levels of adiponectin falls dramatically amongst extreme thresholds of
CAS. Alternatively, we may have been underpowered
Acknowledgements
We thank Dr R Butler and Ms Julie Machin for their
help. We also acknowledge the support of the Sandwell
and West Birmingham Hospitals NHS Trust for the
Haemostasis Thrombosis and Vascular Biology Unit.
References
1 Reddy KS, Yusuf S. Emerging epidemic of cardiovascular
disease in developing countries. Circulation 1998; 97: 596601.
2008 Blackwell Publishing Ltd Journal of Internal Medicine 264; 593598 597
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