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1
Plasma Omentin Predicts Cardiovascular Events Independently From the
Presence and Extent of Angiographically Determined Atherosclerosis
Christoph H. Saely, MD*
a,b,c
, Andreas Leiherer, PHD*
b,c
, Axel Muendlein, PHD
b,c
,
Alexander Vonbank, MD
a,b,c
, Philipp Rein, MD-PHD
a,b,c
, Kathrin Geiger, PHD
b,c
, Cornelia
Malin, PHD
a,b
, and Heinz Drexel, MD
a,b,c,d
a
Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
b
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
c
Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
d
Drexel College University of Medicine, Philadelphia, PA, USA
*CHS and AL contributed equally to this work.
Correspondence to / reprints from:
Heinz Drexel, MD, FESC, FAHA, FRCP; Chairman, Department of Medicine and Cardiology and
VIVIT Institute, Academic Teaching Hospital, Feldkirch, Austria;
Dean and Full Professor of Medicine, Private University of the Principality of Liechtenstein, Triesen,
Liechtenstein
Feldkirch, Carinagasse 47, A-6807 Feldkirch, Austria
Tel: +43/5522/303/2670, FAX: +43/5522/303/7533, E-Mail: vivit@lkhf.at
Word count: 2968, tables: 1; figures: 2
Abstract, Title Page, Manuscript, References, Legends
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Abstract
Background and aims: No prospective data on the power of the adipocytokine omentin to
predict cardiovascular events are available. We aimed at investigating i) the association of
plasma omentin with cardiometabolic risk markers, ii) its association with angiographically
determined coronary atherosclerosis, and iii) its power to predict cardiovascular events.
Methods: We measured plasma omentin in a series of 295 patients undergoing coronary
angiography for the evaluation of established or suspected stable coronary artery disease
(CAD), of whom 161 had significant CAD with coronary artery stenoses ³50% and 134 did
not have significant CAD.
Results: Over a mean period of 3.5 years, 17.6% of our patients suffered cardiovascular
events, corresponding to an annual event rate of 5.0%. At baseline, plasma omentin was not
significantly associated with metabolic syndrome stigmata; it also did not differ significantly
between patients with and subjects without significant CAD (17.2±13.6 ng/ml vs. 17.5±15.1
ng/ml; p=0.783). Prospectively, however, omentin significantly predicted cardiovascular
events after adjustment for age, gender, body mass index, diabetes, hypertension, LDL
cholesterol, HDL cholesterol and smoking (standardized adjusted hazard ratio (HR) 1.41
[95% CI 1.16-1.72]; p<0.001), as well as after additional adjustment for the presence and
extent of CAD at baseline (HR 1.59 [95% CI 1.29-1.97, p<0.001).
Conclusion: From this first prospective evaluation of the cardiovascular risk associated with
omentin we conclude that elevated plasma omentin significantly predicts cardiovascular
events independently from the presence and extent of angiographically determined baseline
CAD.
Key words: omentin, adipokines, atherosclerosis, coronary angiography, prognostic factor,
prospective cohort study
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Introduction
Visceral adipose tissue is a major endocrine organ, which regulates energy homeostasis and
other physiological processes by releasing adipokines. Among these, the 40 kDa large
omentin, previously identified as intelectin has attracted increasing interest. This secretory
factor is specific for the visceral fat-depot
1
and has been suggested to be involved in innate
immune response and pathogen recognition and thus in the development of chronic
inflammatory diseases
2;3
.
Reports from the literature also suggest an association of omentin with metabolic parameters.
Omentin levels have been reported to be decreased in obesity and to correlate negatively with
body mass index (BMI), waist circumference and insulin resistance, and positively with high
density lipoprotein (HDL) cholesterol and plasma adiponectin
4
. These are markers of the
metabolic syndrome (MetS) and given the established role of the MetS as a risk factor for
cardiovascular disease (CVD)
5-7
also omentin may be linked to CVD. However, reports on a
potential association of omentin with CVD are sparse
8-10
, and most importantly, prospective
data regarding its impact on atherothrombotic events are not available.
We therefore aimed at investigating i) the association of plasma omentin with cardiometabolic
risk markers, ii) its association with angiographically determined coronary atherosclerosis,
and iii) its power to predict cardiovascular events.
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Methods
Study design and study subjects
We measured plasma omentin in 295 sex-matched Caucasian patients, 161 with significant
coronary artery disease (CAD), and 134 without significant CAD, who except for CAD status
and sex were randomly drawn from a large cohort of 1751 patients referred to coronary
angiography for the evaluation of established or suspected stable CAD. Patients undergoing
coronary angiography for other reasons were not enrolled. In particular, no patients with acute
coronary syndromes were included. The present study has been approved by the Ethics
Committee of the University of Innsbruck; written informed consent was given by all
participants.
Information on conventional cardiovascular risk factors was obtained by a standardized
interview; weight, height and waist circumference were recorded, and systolic/diastolic blood
pressure was measured by the Riva–Rocci method under resting conditions in a sitting
position at the day of hospital entry at least 5 h after hospitalization. Hypertension was
defined according to the Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure
11
, and type 2 diabetes mellitus
(T2DM) was diagnosed according to World Health Organization criteria
12
. BMI was
calculated as body weight (kg)/height (m
2
).
The MetS was diagnosed according to National Cholesterol Education Programme ATP-III
criteria
13
, as described previously
14
. The HOMA index of insulin resistance was calculated
by the formula fasting insulin [µU/ml] x fasting glucose [mg/dl] / 405
15
. Coronary
angiography was performed with the Judkins technique and the severity of stenosis was
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assessed by visual inspection by a team of two investigators who were blinded to biochemical
assays. Coronary artery stenoses with lumen narrowing ˻50% were considered significant
and the extent of coronary artery disease (CAD) was defined as the number of significant
coronary stenoses in a given patient. Coronary arteries were defined as normal in the absence
of any visible lumen narrowing at angiography as has been described previously
16-19
.
Laboratory analyses
Venous blood samples were collected after an overnight fast of 12 h before angiography was
performed and laboratory measurements were performed from fresh plasma samples, as
described previously
20
. Serum triglycerides, total cholesterol, low density lipoprotein (LDL)
cholesterol, and HDL cholesterol were determined on a Cobas 8000 (Roche, Basel,
Switzerland). Plasma omentin levels were determined with a commercial omentin enzyme-
linked immunosorbent assay (ELISA) kit (Aviscera Bioscience, CA, USA), specific for
omentin-1 with an inter-assay variation less than 10%.
Prospective study
Follow-up visits to our institution were scheduled at 3 years after the baseline investigation.
During this follow-up period we recorded fatal and non-fatal cardiovascular events, including
coronary death (fatal myocardial infarction, sudden cardiac death, mortality from congestive
heart failure due to CAD); fatal ischemic stroke; non-fatal myocardial infarction; non-fatal
ischemic stroke; and need for coronary artery bypass grafting (CABG), percutaneous
coronary intervention (PCI), or revascularization in the carotid or peripheral arterial beds.
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Time and causes of death were regularly obtained from a national survey (Statistik Austria,
Vienna, Austria) or from hospital records. In order to assess endpoints among survivors, we
conducted standardized interviews; additionally, hospital records were reviewed. Coronary
angioplasty and bypass surgery were considered as end points unless they were planned as a
consequence of the baseline angiography and therefore were not “future” events. A follow-up
rate of 95% was achieved.
Statistical analysis
Differences in baseline characteristics were tested for statistical significance with Chi-squared
tests for categorical and Jonckheere-Terpstra tests for continuous variables, respectively.
Correlation analyses were performed calculating non-parametric Spearman rank correlation
coefficients. In addition, analysis of covariance (ANCOVA) models were built using a
general linear model approach. Adjusted hazard ratios for the incidence of first vascular
events were derived from Cox proportional hazards models; for these calculations continuous
variables were z-transformed. Results are given as mean (with standard deviation) if not
denoted otherwise. All statistical analyses were performed with the software package SPSS
22.0 for Macintosh, IBM SPSS; Chicago, IL.
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Results
General characteristics of the study population
Among our 295 patients, 52.5% were men and 47.5% women, the mean age was 66.5 years,
and the prevalence of T2DM (26.1%), hypertension (76.3%) and smoking (56.3%) was high.
Mean plasma omentin was 17.4 ± 14.3 ng/ml, with tertiles 1 through 3 ranging from 4.0 ng/ml
to 9.5 ng/ml, from 9.5 ng/ml to 18.5 ng/ml, and from 18.5 ng/ml to 108.3 ng/ml, respectively.
Association of plasma omentin with cardiometabolic risk markers
Table 1 summarizes patient characteristics by tertiles of plasma omentin. No significant
associations between conventional cardiometabolic risk markers and plasma omentin were
observed.
Also when plasma omentin was used as a continuous variable, it did not significantly correlate
with age (r=0.113, p=0.052), BMI (r=-0.016, p=0.789),
waist circumference (r=0.030,
p=0.618), systolic or diastolic blood pressure (r=0.059, p=0.316 and r=-0.072, p=0.218,
respectively), LDL cholesterol (r=-0.03, p=0.955), HDL cholesterol (-0.011, p=0.857), or
CRP (-0.096, p=0.099). Furthermore, omentin did not differ significantly between men and
women (18.7±16.0 ng/ml vs. 16.0±12.0 ng/ml; p=0.361), between patients with and subjects
without diabetes (16.3±11.7 ng/ml vs. 17.7±15.1 ng/ml; p=0.728), between patients with and
subjects without hypertension (17.5±14.5 ng/ml vs. 16.8±13.7 ng/ml; p=0.600), or between
smokers and non-smokers (16.8±13.4 ng/ml vs. 18.1±15.4 ng/ml; p=0.301).
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8
Concordantly, in an ANCOVA model including age, gender, diabetes, smoking, hypertension,
BMI, LDL cholesterol, and HDL cholesterol, no parameter except age (F=3.98, p=0.047) was
a significant predictor of plasma omentin.
Association of plasma omentin with the coronary artery state
Plasma omentin did not significantly differ between patients with significant CAD and
subjects who did not have significant CAD (17.2±13.6 ng/ml vs. 17.5±15.1 ng/ml; p=0.783).
Moreover, there was no significant difference of plasma omentin between patients with any
visible lumen narrowing at angiography and those with normal coronary arteries (18.1±15.5
vs. 15.2±9.5 ng/ml, p=0.777). Also, omentin was not significantly correlated with the extent
of CAD (r=-0.046, p=0.428).
Omentin as a predictor of future cardiovascular events
During a mean (SD) follow-up time of 3.5±1.1 years we
recorded 72 vascular events in 52
patients; encompassing 17 cardiovascular deaths, 10 non-fatal myocardial infarctions, 11 non-
fatal ischemic strokes, 5 CABGs, 17 PCI’s, and 12 non-coronary revascularizations at the
carotid and peripheral arteries
. First vascular events occurred in 17.6% of the study
population, amounting to an annual event rate of 5.0%.
Figure 1 shows event free survival in tertiles of plasma omentin. Patients in the highest tertile
of omentin were at the highest cardiovascular event risk (29.5%), which was significantly
higher than both in tertiles 2 (13.8%; p=0.032) and 1 (12.1%; p=0.012); p
trend
for
cardiovascular event risk over tertiles of omentin was 0.003.
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In Cox regression analysis, omentin significantly predicted cardiovascular events univariately
(HR 1.41 [95% CI 1.17-1.69], p<0.001), after adjustment for age, gender, diabetes,
hypertension, smoking, BMI, LDL cholesterol, and HDL cholesterol (model 2; HR 1.41 [95%
CI 1.16-1.72], p<0.001), as well as after additional adjustment for the presence and extent of
baseline CAD (model 3; HR 1.59 [95% CI 1.29-1.97], p<0.001; Figure 2).
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Discussion
This is the first prospective evaluation showing an increased cardiovascular risk with high
plasma omentin levels. We demonstrate that this novel adipokine strongly predicts
cardiovascular events in angiographied coronary patients independently from standard
cardiovascular risk factors and from the baseline coronary artery state.
Some earlier studies had suggested negative correlations between omentin and BMI, waist
circumference, insulin sensitivity, and glucose tolerance as well as decreased omentin in
patients with T2DM
4;21-23
. Thus, a decreased omentin level had been suggested to be a
biomarker of metabolic disorders and potentially cardiovascular risk
24
. In a Japanese cohort
of heart failure patients high omentin appeared to be protective against cardiac events, which
in this study however were mainly related to readmissions for heart failure
25
. Other data
refuted some of these earlier observations regarding associations between omentin and
metabolic syndrome parameters and in addition did not suggest an anti-inflammatory action
of the adipokine
26
.
Also in our cohort of angiographied coronary patients, omentin was not associated with
stigmata of the metabolic syndrome. In addition, we did not find associations of omentin with
the presence or extent of angiographically determined stable CAD at baseline. One report
from China
27
suggested lower serum omentin concentrations in patients with acute coronary
syndromes or stable angina pectoris compared to healthy control subjects. The enrollment of
acute coronary syndrome patients, who have been excluded in our cohort, and perhaps also
ethnical differences may explain why these findings differ from ours; of note also another
report showed lower omentin in acute myocardial infarction patients when compared to
healthy controls
9
. Future investigations addressing omentin levels in acute coronary syn-
drome patients and in patient cohorts of non-Caucasian ethnicities appear necessary.
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It is known that omentin is expressed in epicardial adipose tissue
28
and acts antiangiogenic
29
,
but from a functional perspective, the biological roles of omentin are hardly understood.
Omentin recognizes galactofuranosyl residues in bacterial cell walls
30
and also works as a
lactoferrin receptor
31
; it thus may play a role in innate immunity and pathogen recognition
30
.
Due to elevated omentin levels in cancer patients, the adipokine has recently been suggested
to be involved in cancer development
32
. This, however does not explain its association with
cardiovascular event risk. Given the strong association of omentin with cardiovascular event
risk found in our study, intense research addressing the biological functions of omentin
appears worthwhile, with roles of the adipokine in inflammatory and thrombotic pathways as
potential candidates.
This study has strengths and limitations. We used a very well characterized study cohort in
which coronary angiography was performed at baseline. Further, we performed a prospective
study on angiographically characterized patients, which allowed us to study the power of
omentin to predict cardiovascular events independently from the baseline CAD state.
Additional strengths are the high follow-up rate and a sample size that is rather large for
cross-sectional analyses. Sample size of course is limited for the prospective evaluations.
However, even with a limited number of endpoints omentin proved significantly predictive of
cardiovascular events in our study, which points to a particularly strong association of this
adipokine with cardiovascular event risk. The results from the population of Caucasian
patients undergoing coronary angiography for the evaluation of established or suspected
stable CAD we choose to investigate are not necessarily applicable to the general population
or to populations of other ethnicities. Investigations on the power of omentin to predict
cardiovascular events in other populations therefore are warranted.
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In conclusion, this study for the first time demonstrates that the adipocytokine omentin
strongly predicts cardiovascular events in angiographied coronary patients independently
from standard cardiovascular risk factors and from the baseline coronary artery state.
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Acknowledgements
We thank the Jubiläumsfonds of the Austrian National Bank (Vienna, Austria), Dr. Karl Josef
Hier and the Peter Goop Stiftung (Vaduz, Liechtenstein), the Fachhochschule Dornbirn
(Dornbirn, Austria), and the Institute for Clinical Chemistry at the Academic Teaching
Hospital Feldkirch (Feldkirch, Austria) for providing us with generous research grants. We
further thank Dr. Nicole Stark and Dr. Simone Geller Rhomberg for performing ELISAs.
Funding sources
This work has been supported by the Jubiläumsfonds of the Austrian National Bank (project
number 14159).
Disclosures
All authors state that they have nothing to disclose.
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Reference List
1. Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC et al. Identification of omentin as
a novel depot-specific adipokine in human adipose tissue: possible role in modulating
insulin action. Am J Physiol Endocrinol Metab. 2006;290:E1253-E1261.
2. Xue Y, Jiang L, Cheng Q, Chen H, Yu Y, Lin Y et al. Adipokines in psoriatic arthritis
patients: the correlations with osteoclast precursors and bone erosions. PLoS One.
2012;7:e46740.
3. Schäffler A, Neumeier M, Herfarth H, Furst A, Scholmerich J, Buchler C. Genomic
structure of human omentin, a new adipocytokine expressed in omental adipose tissue.
Biochim Biophys Acta. 2005;1732:96-102.
4. Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J et al. Omentin plasma
levels and gene expression are decreased in obesity. Diabetes. 2007;56:1655-1661.
5. Saely CH, Aczel S, Marte T, Langer P, Hoefle G, Drexel H. The metabolic syndrome,
insulin resistance, and cardiovascular risk in diabetic and nondiabetic patients. J Clin
Endocrinol Metab. 2005;90:5698-5703.
6. Saely CH, Koch L, Schmid F, Marte T, Aczel S, Langer P et al. Adult Treatment Panel
III 2001 but not International Diabetes Federation 2005 criteria of the metabolic
syndrome predict clinical cardiovascular events in subjects who underwent coronary
angiography. Diabetes Care. 2006;29:901-907.
7. Saely CH, Rein P, Drexel H. The metabolic syndrome and risk of cardiovascular disease
and diabetes: experiences with the new diagnostic criteria from the International
Diabetes Federation. Horm Metab Res. 2007;39:642-650.
8. Mattu HS, Randeva HS. Role of adipokines in cardiovascular disease. J Endocrinol.
2013;216:T17-T36.
9. Kadoglou NP, Tahmatzidis DK, Giannakoulas C, Kapelouzou A, Gkontopoulos A,
Parissis J et al. Serum levels of novel adipokines, omentin-1 and chemerin, in patients
with acute myocardial infarction: KOZANI STUDY. J Cardiovasc Med (Hagerstown ).
2014.
10. Kadoglou NP, Lambadiari V, Gastounioti A, Gkekas C, Giannakopoulos TG, Koulia K
et al. The relationship of novel adipokines, RBP4 and omentin-1, with carotid
atherosclerosis severity and vulnerability. Atherosclerosis. 2014;235:606-612.
11. Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, Eagle KA et al.
ACC/AHA guidelines for coronary angiography. A report of the American College of
Cardiology/American Heart Association Task Force on practice guidelines (Committee
on Coronary Angiography). Developed in collaboration with the Society for Cardiac
Angiography and Interventions. J Am Coll Cardiol. 1999;33:1756-1824.
12. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and
its complications. Part 1: diagnosis and classification of diabetes mellitus provisional
report of a WHO consultation. Diabet Med. 1998;15:539-553.
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13. Expert Panel. Third Report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.
14. Vonbank A, Saely CH, Rein P, Drexel H. Insulin resistance is significantly associated
with the metabolic syndrome, but not with sonographically proven peripheral arterial
disease. Cardiovasc Diabetol. 2013;12:106.
15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting
plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419.
16. Drexel H, Amann FW, Rentsch K, Neuenschwander C, Luethy A, Khan SI et al.
Relation of the level of high-density lipoprotein subfractions to the presence and extent
of coronary artery disease. Am J Cardiol. 1992;70:436-440.
17. Drexel H, Amann FW, Beran J, Rentsch K, Candinas R, Muntwyler J et al. Plasma
triglycerides and three lipoprotein cholesterol fractions are independent predictors of the
extent of coronary atherosclerosis. Circulation. 1994;90:2230-2235.
18. Saely CH, Rein P, Vonbank A, Huber K, Drexel H. Type 2 diabetes and the progression
of visualized atherosclerosis to clinical cardiovascular events. Int J Cardiol. 2012.
19. Saely CH, Drexel H, Sourij H, Aczel S, Jahnel H, Zweiker R et al. Key role of
postchallenge hyperglycemia for the presence and extent of coronary atherosclerosis: an
angiographic study. Atherosclerosis. 2008;199:317-322.
20. Saely CH, Koch L, Schmid F, Marte T, Aczel S, Langer P et al. Lipoprotein(a), type 2
diabetes and vascular risk in coronary patients. Eur J Clin Invest. 2006;36:91-97.
21. Yoo HJ, Hwang SY, Hong HC, Choi HY, Yang SJ, Seo JA et al. Association of
circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes.
Cardiovasc Diabetol. 2011;10:103.
22. Yan P, Liu D, Long M, Ren Y, Pang J, Li R. Changes of serum omentin levels and
relationship between omentin and adiponectin concentrations in type 2 diabetes mellitus.
Exp Clin Endocrinol Diabetes. 2011;119:257-263.
23. Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in
patients with impaired glucose regulation and with newly diagnosed and untreated type
2 diabetes. Diabetes Res Clin Pract. 2010;88:29-33.
24. Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N et al. Omentin as a
novel biomarker of metabolic risk factors. Diabetol Metab Syndr. 2012;4:37.
25. Narumi T, Watanabe T, Kadowaki S, Kinoshita D, Yokoyama M, Honda Y et al. Impact
of serum omentin-1 levels on cardiac prognosis in patients with heart failure.
Cardiovasc Diabetol. 2014;13:84.
26. Sdralis E, Argentou M, Mead N, Kehagias I, Alexandridis T, Kalfarentzos F. A
prospective randomized study comparing patients with morbid obesity submitted to
sleeve gastrectomy with or without omentectomy. Obes Surg. 2013;23:965-971.
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16
27. Zhong X, Zhang HY, Tan H, Zhou Y, Liu FL, Chen FQ et al. Association of serum
omentin-1 levels with coronary artery disease. Acta Pharmacol Sin. 2011;32:873-878.
28. Fain JN, Sacks HS, Buehrer B, Bahouth SW, Garrett E, Wolf RY et al. Identification of
omentin mRNA in human epicardial adipose tissue: comparison to omentin in
subcutaneous, internal mammary artery periadventitial and visceral abdominal depots.
Int J Obes (Lond). 2008;32:810-815.
29. Tan BK, Adya R, Randeva HS. Omentin: a novel link between inflammation, diabesity,
and cardiovascular disease. Trends Cardiovasc Med. 2010;20:143-148.
30. Tsuji S, Yamashita M, Hoffman DR, Nishiyama A, Shinohara T, Ohtsu T et al. Capture
of heat-killed Mycobacterium bovis bacillus Calmette-Guerin by intelectin-1 deposited
on cell surfaces. Glycobiology. 2009;19:518-526.
31. Suzuki YA, Shin K, Lonnerdal B. Molecular cloning and functional expression of a
human intestinal lactoferrin receptor. Biochemistry. 2001;40:15771-15779.
32. Fazeli MS, Dashti H, Akbarzadeh S, Assadi M, Aminian A, Keramati MR et al.
Circulating levels of novel adipocytokines in patients with colorectal cancer. Cytokine.
2013;62:81-85.
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Figure Legends
Figure 1. Incidence of cardiovascular events by tertiles of omentin. The survival plot
indicates event-free survival according to tertiles of omentin concentration (p
trend
=0.003)
detected in patient plasma. Plasma omentin tertiles 1 through 3 range from 4.0 ng/ml to 9.5
ng/ml, from 9.5 ng/ml tp 18.5 ng/ml, and from 18.5 ng/ml to 108.3 ng/ml, respectively.
Figure 2. Omentin as a predictor of cardiovascular event risk: Results from Cox
regression analyses. Hazard ratios and 95% CI are for omentin as a continuous variable.
Model 1 represents univariate analysis; model 2 includes the covariates age, gender, BMI,
type 2 diabetes mellitus and hypertension, smoking, LDL cholesterol, and HDL cholesterol;
model 3 includes the parameters included in model 2 and in addition the presence and extent
of CAD.
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Tables
Table 1. Patient characteristics according to tertiles of plasma omentin
All patients
Omentin
tertile 1
Omentin
tertile 2
Omentin
tertile 3
p-value
Age (years)
66.5±10.7
64.5±10.4
67.1±11.7
67.8±9.8
0.075
Male gender (%)
52.5
56.1
41.4
60.2
0.568
BMI (kg/m²)
27.9±4.8
28.1±4.4
27.7±5.0
28.0±5.1
0.879
Waist circumference (cm)
99±12
99±13
99±12
100±12
0.930
MetS (%)
31.2±46.4
29.6±45.9
37.4±48.6
26.5±44.4
0.644
T2DM (%)
26.1±44.9
23.5±42.6
31.3±46.6
23.5±42.6
1.000
Hypertension (%)
67.3±42.6
72.4±44.9
76.8±42.4
79.6 ±40.5
0.241
Smoking (%)
56.3
59.2
59.6
50.0
0.196
Total cholesterol (mg/dl)
196±47
197±47
198±50
194±44
0.576
LDL cholesterol (mg/dl)
128±43
128±42
127±46
128±41
0.889
HDL cholesterol (mg/dl)
59±19
58±19
60±20
58 ±18
0.992
Triglycerides (mg/dl)
131±74
132±70
143±86
120±62
0.243
Fasting glucose (mg/dl)
106±32
102 ±21
111±38
105±35
0.970
HOMA insulin resistance
5.20±24.99
2.99±2.95
8.64±42.28
3.96±7.81
0.906
HbA1c (%)
6.1±0.9
6.0±0.7
6.1±1.0
6.1±0.9
0.624
CRP (mg/dl)
0.39±0.55
0.32±0.44
0.43±0.61
0.44±0.58
0.140
Fibrinogen (mg/dl)
332±75
330±71
333±73
334±81
0.614
Systolic BP (mmHg)
135±18
134±16
134±16
138±20
0.217
Diastolic BP (mmHg)
81±9
82±8
81±8
81±11
0.397
Aspirin (%)
63.4±48.3
68.4±46.7
65.7±47.7
56.1±49.9
0.174
Statins (%)
44.7±49.8
45.9±50.1
49.5±50.3
38.8±49.0
0.306
ACE inhibitors (%)
30.8±46.3
34.7±47.8
27.3±44.8
30.6±64.3
0.529
ARB (%)
9.5±29.4
6.1±24.1
10.1±30.3
12.2±32.9
0.332
Beta blockers (%)
54.9±49.8
54.1±50.1
56.6±49.8
54.1±50.1
0.921
Sign. CAD (%)
54.6±49.9
53.1±50.2
57.6±49.7
53.1±50.2
1.000
Any CAD (%)
75.9±42.8
77.6±41.9
71.7±45.3
78.6±41.2
0.478
Extent of CAD
1.3±1.7
1.3 ±1.7
1.4±1.6
1.3±1.7
0.801
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Tertiles 1 through 3 of plasma omentin range from 4.0 ng/ml to 9.5 ng/ml, from 9.5 ng/ml to
18.5 ng/ml, and from 18.5 ng/ml to 108.3 ng/ml, respectively. Data are means ± standard
deviations as indicated. BMI denotes body mass index, CAD coronary artery disease, MetS
metabolic syndrome, T2DM type 2 diabetes mellitus, LDL low density lipoprotein, HDL high
density lipoprotein, HbA1c haemoglobin A1c, HOMA insulin resistance homeostasis model
of insulin resistance, BP blood pressure, ACE angiotensin converting enzyme, ARB
angiotensin II receptor blockers. Significant CAD is defined as the presence of coronary
artery stenoses with lumen narrowing ≥50%. To convert values for fasting plasma glucose to
mmol/l multiply by 0.0555, to convert values for triglycerides to mmol/l multiply by 0.0113,
and to convert values for total cholesterol, LDL cholesterol, or HDL cholesterol to mmol/l
multiply by 0.0259.
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Figures
Figure 1. Incidence of cardiovascular events by tertiles of omentin
Figure 2. Omentin as a predictor of cardiovascular event risk: Results from Cox
regression analyses
