P

A

BPbptmP(Pipi©

K

R

CldaddéL3vl

X

0

Disponible en ligne sur

ScienceDirectwww.sciencedirect.com

Annales d’Endocrinologie 75 (2014) 159–164

Original article

-wave dispersion and maximum duration are independently associated withinsulin resistance in metabolic syndrome

La dispersion et la durée maximum de l’onde P sont indépendamment associées à la résistance àl’insuline dans le syndrome métabolique

Weiwei Wang , Feilong Zhang , Jianhua Xhen , Xuehai Chen , Fayuan Fu ,Mirong Tang , Lianglong Chen ∗

Union Hospital, Union Clinic Medical College, Fujian Medical University, Fuzhou, People’s Republic of China

bstract

ackground. – Metabolic syndrome (MS) is an important risk factor for atrial fibrillation. P-wave indices, including P-wave dispersion (PWD) and-wave duration, can be used as non-invasive markers of heterogeneous atrial conduction. The aim of our study was to evaluate the relationshipetween P-wave indices and insulin resistance in patients with MS. Methods. – Seventy-four patients with MS (44 men, 30 women) and 81atients without MS (48 men, 33 women) were enrolled in the study. A diagnosis of MS was made as defined by the Adult Treatment Panel III ofhe National Cholesterol Education Program. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. P-wave

aximum duration (Pmax) and P-wave minimum duration (Pmin) were calculated on a 12-lead electrocardiogram, and the difference between themax and the Pmin was defined as PWD. Results. – Patients with MS had a longer PWD and a higher Pmax compared with patients without MSPWD, 35.65 ± 4.36 vs. 26.27 ± 4.04, P < 0.001; Pmax, 117.12 ± 10.77 vs. 105.98 ± 9.02, P < 0.001), whereas no difference was found betweenmin values from MS patients and controls (81.47 ± 9.54 vs. 79.70 ± 8.76, P = 0.231). Stepwise multivariate analysis revealed only the HOMA

ndex to be an independent predictor of PWD (� = 3.115, P < 0.001) and Pmax (� = 7.175, P < 0.001). Conclusion. – This study suggests thatatients with MS have a prolonged PWD and Pmax. The increase in these parameters may be an indicator for identification of patients at anncreased risk for atrial fibrillation.

2014 Published by Elsevier Masson SAS.

eywords: Metabolic syndrome; P-wave dispersion; Insulin resistance; Atrial conduction

ésumé

ontexte. – Le syndrome métabolique (SM) est un facteur de risque important pour la fibrillation auriculaire. Les indices des ondes P, à savoireurs dispersion et durée, peuvent être utilisés comme marqueurs non invasifs de la conduction auriculaire hétérogène. Le but de notre étude était’évaluer la relation entre les indices des ondes P et la résistance à l’insuline chez les patients atteints de SM. Méthodes. – Soixante-quatre patientstteints de SM (44 hommes, 30 femmes) et 81 patients non atteints (48 hommes, 33 femmes), ont été inclus dans l’étude. Le diagnostic de MS était

éfini par le Adult Treatment Panel III du National Cholesterol Education Program. La résistance à l’insuline était estimée au moyen du modèle’évaluation de l’homéostasie (HOMA). La durée maximale de l’onde P (Pmax) ainsi que sa durée minimale (Pmin) ont été calculées sur unlectrocardiogramme à 12 dérivations, et la différence entre la Pmax et la Pmin a été définie comme dispersion de l’onde P (DOP). Résultats. –es patients atteints de SM ont une vitesse de dispersion de l’onde P supérieure et une Pmax plus élevée par rapport aux patients sans SM (DOP,5,65 ± 4,36 vs 26,27 ± 4,04, p < 0,001 ; Pmax, 117,12 ± 10,77 vs 105,98 ± 9,02, p < 0,001), alors qu’aucune différence n’a été observée entre les

vs 8,76 ± 79,70, p = 0,231). L’analyse multivariée pas à pas a révélé que

aleurs Pmin de patients atteints de SM et les témoins (81,47 ± 9,54 ’indice HOMA était un facteur prédictif indépendant de la DOP (� = 3,115, p < 0,001) et de la Pmax (� = 7,175, p < 0,001).

∗ Corresponding author at: Union Hospital, Union Clinic Medical College, Fujian Medical University, Department of Coronary Artery Disease, 29,in-Quan Road, Fuzhou 350001, People’s Republic of China.

E-mail address: lianglongchenxhyy@126.com (L. Chen).

http://dx.doi.org/10.1016/j.ando.2014.05.004003-4266/© 2014 Published by Elsevier Masson SAS.

1

Cp©

M

1

sagctttaesl[

mr[wsnpa

2

2

8OwITa

•

••

•

•

60 W. Wang et al. / Annales d’Endocrinologie 75 (2014) 159–164

onclusion. – Cette étude suggère que les patients atteints de sclérose en plaques ont un PH et Pmax prolongés. L’augmentation de ces paramètreseut être un indicateur pour l’identification de patients à un risque accru de fibrillation auriculaire.

2014 Publié par Elsevier Masson SAS.

suline

maiCtiscafs6dvsaa

oow

2

elubPlDUsH(

2

ert

ots clés : Syndrome métabolique ; Dispersion des ondes P ; Résistance à l’in

. Introduction

Metabolic syndrome (MS), defined as the clustering ofeveral cardiovascular risk factors in an individual includingbdominal obesity, dyslipidemia, elevated blood pressure, andlucose intolerance, is associated with a 2-fold increase inardiovascular events and a 1.5-fold increase in all-cause mor-ality [1]. Recent studies have shown that MS can increasehe risk for the development of atrial fibrillation (AF) [2,3],he most common cardiac arrhythmia. The potential mech-nism for the increased risk of AF by MS may concernlectrical and structural remodeling of the atria. It has beenuggested that insulin resistance (IR), a common patho-ogic condition observed in MS, can trigger atrial remodeling4,5].

P-wave indices such as P-wave dispersion (PWD) and P-waveaximum duration (Pmax) serve as intermediate phenotypes

eflecting alterations in atrial electrophysiology and morphology6]. A prolonged PWD and an increase in Pmax are associatedith an increased risk for AF [7,8]. Recently, a cross-sectional

tudy of 14,433 subjects reported that P-wave indices are sig-ificantly associated with MS [9]. Accordingly, the goal of theresent study was to investigate the associations among MS, IRnd indices of P-wave duration and dispersion.

. Methods

.1. Study population

We selected 74 consecutive hospitalized patients with MS and1 control subjects without MS who visited our hospital fromctober 2011 to December 2012 to participate in the study. MSas diagnosed according to the Adult Treatment Panel (ATP)

II criteria of the National Cholesterol Education Program [10].he presence of MS was defined as patients with three or morebnormal components as follows:

abdominal obesity (waist circumference ≥ 90 cm in menand ≥ 80 cm in women);a high triglyceride level (≥ 150 mg/dL);a low HDL cholesterol level (< 40 mg/dL for menand < 50 mg/dL for women);high blood pressure (systolic ≥ 130 mmHg or dias-tolic ≥ 85 mmHg) or were taking an antihypertensive

medication;a high fasting plasma glucose concentration (≥ 100 mg/dL)or a clinical history of diabetes mellitus.

scst

; Conduction auriculaire

Metabolic scores were calculated as the number of abnor-al items in the ATP III criteria, with a score of 0 representing

bsence of any abnormal metabolic components and 5 represent-ng an individual with all five abnormal metabolic components.ases with a history of myocardial infarction or angina pec-

oris, AF, previous implantation of a pacemaker, or overt renalnsufficiency (creatinine > 2.5 mg/dL) were not included in thetudy. In addition, patients were excluded if they had left ventri-ular ejection fraction (LVEF) < 50%, pre-excitation syndrome,trioventricular conduction abnormalities, abnormal thyroidunction or serum electrolytes, more severe pulmonary hyperten-ion (defined as systolic pulmonary arterial pressure higher than0 mmHg), chronic lung disease, existence of congenital heartisease on echocardiography, known prior cardiac surgery, oralvular heart disease. In addition, patients using antihyperten-ive drugs thought to improve atrial electrical remodeling, suchs beta-blockers, angiotensin-converting enzyme inhibitors orngiotensin receptor blockers, were excluded from the study.

The study protocol was approved by the Ethics Committeef Fujian Medical University and conformed to the principlesutlined in the Declaration of Helsinki. Signed informed consentas obtained from all participants.

.2. Lab data acquisition

Fasting blood glucose, insulin, total cholesterol, triglyc-ride, low-density lipoprotein (LDL) cholesterol, high-densityipoprotein (HDL) cholesterol and N-terminal pro-brain natri-retic peptide (NT-proBNP) values were measured from venouslood collected from the subjects after fasting for eight hours.lasma insulin concentrations were analyzed using chemi-

uminescent immunoassays on a Beckman Coulter UnicellxI 800 immunoassay analyzer (Beckman Coulter Inc., CA,SA). Insulin resistance was calculated by the homeosta-

is model assessment insulin resistance (HOMA-IR) method:OMA index = fasting glucose (mmol/L) × fasting insulin

�U/mL)/22.5.

.3. Electrocardiographic analysis

The 12-lead electrocardiogram (ECG) was recorded forach subject at a paper speed of 50 mm/s and 20 mm/mV. Allecordings were performed in the same quiet room during spon-aneous breathing, following 15 minutes of adjustment in the

upine position. P-wave duration was measured manually usingalipers by two investigators who were blinded to the clinicaltatus of the patients. The onset of the P-wave was defined ashe junction between the isoelectric line and the beginning of the

W. Wang et al. / Annales d’Endocrinologie 75 (2014) 159–164 161

Table 1Clinical characteristics of the study population.

MS group(n = 74) Control group(n = 81) P value

Age (years) 54.73 ± 6.51 55.00 ± 7.21 0.807

Male (%) 44 (59.46) 48 (59.26) 0.980

Clinical featuresSmoker (%) 18 (24.32) 19 (23.46) 0.899Body mass index (kg/m2) 27.33 ± 2.72 23.79 ± 2.92 < 0.001Waist circumference (cm) 90.97 ± 7.00 84.31 ± 7.79 < 0.001Elevated BP or hypertension (%) 55 (74.32) 8 (9.88) < 0.001Systolic blood pressure (mmHg) 137.22 ± 11.04 117.25 ± 10.20 < 0.001Diastolic blood pressure (mmHg) 82.32 ± 6.12 69.70 ± 6.36 < 0.001Heart rate (beat/min) 75.69 ± 11.01 76.17 ± 10.40 0.779Diabetes mellitus (%) 18 (24.32) 9 (11.11) 0.030Fasting glucose (mg/dL) 101.70 ± 17.82 92.88 ± 14.04 0.001Total cholesterol (mg/dL) 201.54 ± 30.20 189.30 ± 26.53 0.008LDL cholesterol (mg/dL) 115.67 ± 26.25 112.78 ± 26.93 0.500Triglycerides (mg/dL) 209.31 ± 71.51 133.14 ± 42.47 < 0.001HDL (mg/dL) 44.01 ± 8.70 49.90 ± 10.05 < 0.001NT-proBNP (pmol/L) 199.65 ± 62.09 197.47 ± 55.78 0.818Metabolic score, [median (interquartile range)] 3 (3–4) 1 (0–2) < 0.001Insulin (�IU/mL) 8.94 ± 2.83 6.65 ± 3.09 < 0.001HOMA index 2.24 ± 0.81 1.53 ± 0.75 < 0.001

Transthoracic echocardiogramLeft atrial diameter (mm) 33.38 ± 3.89 30.35 ± 3.41 < 0.001LV end-diastolic diameter (mm) 45.52 ± 2.50 44.87 ± 2.18 0.087LV end-systolic diameter (mm) 27.15 ± 2.74 26.30 ± 2.68 0.053LV ejection fraction (%) 65.65 ± 3.60 65.79 ± 3.33 0.800LV septal thickness (mm) 101.01 ± 10.90 97.02 ± 11.50 0.029LV posterior wall thickness (mm) 100.55 ± 10.74 96.22 ± 12.13 0.020E (cm/s) 77.30 ± 23.58 81.19 ± 19.54 0.264A (cm/s) 82.09 ± 14.19 77.33 ± 14.74 0.043E/A ratio 0.94 ± 0.22 1.06 ± 0.18 < 0.001

MS: metabolic syndrome; BP: blood pressure; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol; NT-proBNP: N-terminal pro-brainn E: mit

PjPufwIdtar

2

i(d(ate

Lvvidr

2

aSCtuwlation tests were used to determine the correlations between

atriuretic peptide; HOMA: homeostasis model assessment; LV: left ventricle;

-wave deflection. The offset of the P-wave was defined as theunction between the end of the P-wave and the isoelectric line.max in any of the 12-lead surface ECGs was calculated andsed as a marker of prolonged atrial conduction time. The dif-erence between Pmax and P-wave minimum (Pmin) durationsas defined as the P-wave dispersion (PWD = Pmax − Pmin).

ntra- and inter-observer coefficients of variation (the standardeviation of differences between two observations divided byhe mean value and expressed as a percent) were found to be 3.2nd 3.7% for P-wave dispersion, and 3.1 and 3.4% for Pmax,espectively.

.4. Echocardiographic study

Transthoracic echocardiography was performed using a dig-tal imaging system equipped with a 2.5- to 3.5-MHz transducerVivid-7, GE healthcare, USA) for all patients. All images wereigitally recorded for cardiac function assessment. Left atrium

LA) diameter was measured in the parasternal long axis viewt end systole, and the left ventricle (LV) diameter in end dias-ole. Interventricular septum and LV posterior wall thickness innd diastole were measured from the M-mode readings. The

PaPs

ral early diastolic velocity; A: mitral late diastolic velocity.

V ejection fraction was estimated by the use of a modifiedersion of Simpson’s biplane method. Pulse wave mitral flowelocities were measured from the apical 4-chamber view bynserting a sample volume to mitral leaflet tips. Mitral earlyiastolic velocity (E), late diastolic velocity (A), and the E/Aatio were determined.

.5. Statistical analysis

Continuous variables are presented as mean ± standard devi-tion (SD). Categorical variables are presented as percentages.kewed data are presented as medians and interquartile ranges.omparisons of categorical and continuous variables between

he two groups were performed by the chi-square and annpaired t-test, respectively. The Mann-Whitney rank-sum testas used for the analysis of skewed variables. Pearson corre-

WD and Pmax and clinical parameters. Stepwise multiple vari-ble linear regressions were used to determine the variables forWD and Pmax. A P value < 0.05 was considered as statisticallyignificant.

162 W. Wang et al. / Annales d’Endocrinologie 75 (2014) 159–164

Table 2P-wave parameters of the study population.

MS group(n = 74)

Control group(n = 81)

P value

Pmax (ms) 117.12 ± 10.77 105.98 ± 9.02 < 0.001

Pmin (ms) 81.47 ± 9.54 79.70 ± 8.76 0.231

PWD (ms) 35.65 ± 4.36 26.27 ± 4.04 < 0.001

PP

3

twa5sagbwwpacawdbdmv(sg

a3vb7

wiwclH(

4

pf

Table 3Univariate and stepwise multivariate linear regression analyses of Pmax forclinical parameters in patients with MS.

Pmax

Univariate Multivariate

r P � P

Body mass index 0.386 < 0.001 NI

Waist circumference 0.310 0.007 NI

Insulin 0.496 < 0.001 NI

HOMA index 0.538 < 0.001 7.175 < 0.001

NT-proBNP 0.232 0.047 NI

Pmax: P-wave maximum duration; MS: metabolic syndrome; HOMA: homeo-stasis model assessment; NT-proBNP: N-terminal pro-brain natriuretic peptide;NI: indicates not included in multivariate analysis.

Table 4Univariate and stepwise multivariate linear regression analyses of PWD forclinical parameters in patients with MS.

PWD

Univariate Multivariate

r P � P

Waist circumference 0.237 0.042 NI

Fasting glucose 0.255 0.029 NI

Insulin 0.512 < 0.001 NI

HOMA index 0.578 < 0.001 3.115 < 0.001

Metabolic score 0.286 0.014 NI

E/A ratio −0.263 0.023 NI

PWD: P-wave dispersion; MS: metabolic syndrome; HOMA: homeostasismi

•

•

tPtatttip

max: P-wave maximum duration; Pmin: P-wave minimum duration; PWD:-wave dispersion; MS: metabolic syndrome.

. Results

The clinical characteristics of the cases in the MS group andhe control group are shown in Table 1. Seventy-four patientsith MS (44 men, 30 women; mean age, 54.73 ± 6.51 years)

nd 81 patients without MS (48 men, 33 women; mean age,5.00 ± 7.21 years) participated in our study. There were noignificant differences between the two groups with regard toge, gender and number of smokers. Compared with the controlroup, there was a higher prevalence of hypertension and dia-etes mellitus in the MS group. Additionally, body mass index,aist circumference, and systolic and diastolic blood pressuresere significantly increased in the MS group. The level of fastinglasma glucose, total cholesterol, triglyceride, LDL cholesterolnd NT-proBNP levels were significantly higher, while HDLholesterol levels were significantly lower in the MS group. Inddition, the insulin levels, HOMA indices and metabolic scoresere increased in the MS group. Among transthoracic echocar-iogram parameters, no significant differences were presentetween the two groups when considering LV end-diastoliciameter, LV end-systolic diameter, LV ejection fraction anditral early diastolic velocity (E velocity). However, LA, left

entricular wall thicknesses and mitral late diastolic velocityA velocity) were significantly higher, and the E/A ratio wasignificantly lower in the MS group compared with the controlroup.

P-wave measurements are given in Table 2. Although PWDnd Pmax were significantly higher in MS patients (PWD,5.65 ± 4.36 vs. 26.27 ± 4.04, P < 0.001; Pmax, 117.12 ± 10.77s. 105.98 ± 9.02, P < 0.001), no difference was determinedetween Pmin of MS cases and controls (81.47 ± 9.54 vs.9.70 ± 8.76, P = 0.231).

In univariate analyses with Pearson’s correlations, PWDas associated with waist circumference, fasting glucose level,

nsulin level, HOMA index, metabolic score and E/A ratio,hile Pmax was associated with body mass index, waist

ircumference, insulin level, HOMA index and NT-proBNPevel. However, stepwise multivariate analysis revealed only theOMA index to be an independent predictor of PWD and Pmax

Tables 3 and 4).

. Discussion

In this study, we investigated the associations among P-wavearameters, insulin resistance and MS. Our main findings are asollows:

hnac

odel assessment; E/A: mitral early diastolic velocity/mitral late diastolic veloc-ty; NI: indicates not included in multivariate analysis.

Pmax and PWD were increased in patients with MS comparedwith the control subjects without MS;PWD was independently associated with insulin resistance,but not other factors such as waist circumference, body massindex, blood pressure, LA size and left ventricular diastolicfunction.

There are several studies confirming the roles of P-wave dura-ion and dispersion as non-invasive markers associated with AF.-wave durations and PWD are markers of intra- and intera-

rial conduction disorders of sinus impulses and heterogeneousnd discontinuous atrial conduction [11], providing a substratehat favors reentry mechanisms [12]. P-wave durations longerhan 110 ms suggest interatrial block, which is associated withhe development of atrial fibrillation [13]. Prolonged Pmax andncreased PWD have been suggested to represent independentredictors for AF in patients with hypertrophic cardiomyopathy,yperthyroidism, secundum atrial septal defect, isolated coro-

ary artery ectasia, rheumatic mitral stenosis, obstructive sleeppnea, and in those after cardioversion or after radiofrequencyatheter ablation for overt pre-excitation [14].

ndocr

dilmfcalrigh[

asiiotmboiat

iaadtr

d[HPt

•

•

•

•

•

(eooacr

5

sMSLtpmii

6

iap

D

c

R

of increasing importance. J Am Coll Cardiol 2010;55(21):2328–9.[5] Dublin S, Glazer NL, Smith NL, Psaty BM, Lumley T, Wiggins KL, et al.

W. Wang et al. / Annales d’E

MS represents a cluster of cardiovascular and metabolicerangements (i.e., increased blood pressure, abdominal obesity,nsulin resistance, and dyslipidemia), which deteriorate vascu-ar function and cause subclinical damage in a variety of organs,

ore than individual traditional risk factors [15]. MS was alsoound to be an independent predictor of AF recurrence afteratheter ablation [16,17]. AF is certainly the most prevalentrrhythmia in everyday clinical practice, and its increased preva-ence parallels MS frequency. Each of the MS components iselated to an increased risk for AF occurrence. The vast major-ty of epidemiological and observational studies conducted ineneral population samples have shown that subjects with MSave a greater likelihood of AF than their non-MS counterparts18–21].

Structural and electrophysiological remodeling of the atriumre critical for AF to perpetuate. Furthermore, animal and humantudies have shown that MS is associated with remodeling,ncluding an increased LA size and decreased conduction veloc-ty [22,23]. A recent study [24] also showed that the reductionf AF recurrence and severity in patients with MS is associatedo the decrease of PWD, which may be related to the improve-

ent in atrial fibrosis and electrical remodeling. The associationetween atrial remodeling and MS was confirmed by the resultsf this study, which shows that Pmax and PWD are increasedn patients with MS. The association between atrial remodelingnd MS was confirmed by the results of this study, which showshat Pmax and PWD are increased in patients with MS.

A stepwise multivariate analysis revealed that the HOMAndex was the only independent predictor of this prolonged PWDnd Pmax. A previous study that had reported increases in Pmaxnd PWD in patients with MS found that PWD was indepen-ently correlated only with the triglyceride level [25]. However,he relationship between triglyceride level and AF occurrenceemains controversial.

A growing body of evidence indicates that IR is the fun-amental pathophysiology responsible for metabolic syndrome26], for which this condition was originally classified [27].owever, the exact mechanism by which IR results in prolongedWD and Pmax is still not well understood. IR may contribute

o atrial electro-structural remodeling in the following ways:

IR causes an intra-atrial conduction abnormality by worsen-ing diastolic function and increasing atrial size [28]. A recentstudy also reported that a greater HOMA index was stronglyassociated with echocardiographic LA size in patients withHCM [29];it has been shown that IR is correlated with endothelial dys-function [30]. The impairment in the vascular endothelium ofatrial tissue might be a trigger for remodeling in the atriumand cause atrial conduction abnormalities and arrhythmia;IR can result in the activation of many proinflammatory tran-scription factors [31] and induce the generation of reactive

oxygen species [26,32]. Inflammation and oxidative stresshave been proposed as common etiological factors in thepathogenesis of AF [33–35];

inologie 75 (2014) 159–164 163

the sympathetic nervous system is overactive in insulin-resistant states [36], which results in a significant prolongationof P-wave duration and PWD [37,38];finally, angiotensin II receptor expression is upregulated in IRpatients [39].

The activation of the renin-angiotensin-aldosterone systemRAAS) causes atrial fibrosis, cardiomyocyte apoptosis, andlicits reactive oxygen species generation [40]. The inhibitionf RAAS by candesartan has been shown to prevent shorteningf the atrial effective refractive period and preserve the rate ofdaptation during rapid atrial pacing in dogs [41]. This indi-ates RAAS may be involved in the early process of electricalemodeling in AF.

. Study limitations

There are several limitations of the present study. First, thistudy was of a cross-sectional design. Therefore, patients withS were not followed prospectively for arrhythmic episodes.

econd, some precise echocardiographic parameters of LA andV diastolic dysfunction, such as LA volume, LA ejection frac-ion, isovolumetric relaxation time and deceleration time of earlyhase of mitral valve flow, were not available. Finally, inflam-ation markers, such as C-reactive protein, were not measured

n the study. Accordingly, the association between the P-wavendices and inflammation in MS deserves further investigation.

. Conclusion

Our study shows that PWD and Pmax are prolonged in MS,ndicating that patients with MS already have atrial electricalnd structural remodeling. Additionally, insulin resistance maylay a key role in the changes of atrial conduction.

isclosure of interest

The authors declare that they have no conflicts of interestoncerning this article.

eferences

[1] Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. Themetabolic syndrome and cardiovascular risk: a systematic review and meta-analysis. J Am Coll Cardiol 2010;56(14):1113–32.

[2] Watanabe H, Tanabe N, Watanabe T, Darbar D, Roden DM, Sasaki S,et al. Metabolic syndrome and risk of development of atrial fibrillation: theNiigata preventive medicine study. Circulation 2008;117(10):1255–60.

[3] Nicolaou VN, Papadakis JE, Karatzis EN, Dermitzaki SI, Tsakiris AK,Skoufas PD. Impact of the metabolic syndrome on atrial size in patientswith new-onset atrial fibrillation. Angiology 2007;58(1):21–5.

[4] Dagres N, Anastasiou-Nana M. Atrial fibrillation and obesity an association

Diabetes mellitus, glycemic control, and risk of atrial fibrillation. J GenIntern Med 2010;25(8):853–8.

[6] Hazen MS, Marwick TH, Underwood DA. Diagnostic accuracy ofthe resting electrocardiogram in detection and estimation of left atrial

1 ndocr

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

64 W. Wang et al. / Annales d’E

enlargement: an echocardiographic correlation in 551 patients. Am HeartJ 1991;122(3 Pt 1):823–8.

[7] Koz C, Uzun M, Yokusoglu M, Ulas UH, Baysan O, Genc C,et al. Echocardiographic, electrocardiographic, and clinical correlates ofrecurrent transient ischemic attacks: a follow-up study. South Med J2008;101(3):246–51.

[8] Magnani JW, Johnson VM, Sullivan LM, Gorodeski EZ, Schnabel RB,Lubitz SA, et al. P-wave duration and risk of longitudinal atrial fibrillation inpersons ≥ 60 years old (from the Framingham Heart Study). Am J Cardiol2011;107(6):917–21.

[9] Magnani JW, Lopez FL, Soliman EZ, Maclehose RF, Crow RS, Alonso A.P-wave indices, obesity, and the metabolic syndrome: the atherosclerosisrisk in communities study. Obesity 2012;20(3):666–72.

10] Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA,et al. Diagnosis and management of the metabolic syndrome. An Ameri-can Heart Association/National Heart, Lung, and Blood Institute ScientificStatement. Executive summary. Cardiol Rev 2005;13(6):322–7.

11] Centurion OA. Clinical implications of the P-wave duration and dis-persion: relationship between atrial conduction defects and abnormallyprolonged and fractionated atrial endocardial electrograms. Int J Cardiol2009;134(1):6–8.

12] Koide Y, Yotsukura M, Sakata K, Yoshino H, Ishikawa K. Investigation ofthe predictors of transition to persistent atrial fibrillation in patients withparoxysmal atrial fibrillation. Clin Cardiol 2002;25(2):69–75.

13] Agarwal YK, Aronow WS, Levy JA, Spodick DH. Association of interatrialblock with development of atrial fibrillation. Am J Cardiol 2003;91(7):882.

14] Turgut O, Tandogan I, Yilmaz MB, Yalta K, Aydin O. Association ofP-wave duration and dispersion with the risk for atrial fibrillation: prac-tical considerations in the setting of coronary artery disease. Int J Cardiol2010;144(2):322–4.

15] Cuspidi C, Sala C, Zanchetti A. Metabolic syndrome and target organ dam-age: role of blood pressure. Expert Rev Cardiovasc Ther 2008;6(5):731–43.

16] Tang RB, Dong JZ, Liu XP, Long DY, Yu RH, Kalifa J, et al. Metabolicsyndrome and risk of recurrence of atrial fibrillation after catheter ablation.Circ J 2009;73(3):438–43.

17] Chang SL, Tuan TC, Tai CT, Lin YJ, Lo LW, Hu YF, et al. Comparisonof outcome in catheter ablation of atrial fibrillation in patients with versuswithout the metabolic syndrome. Am J Cardiol 2009;103(1):67–72.

18] Tanner RM, Baber U, Carson AP, Voeks J, Brown TM, Soliman EZ, et al.Association of the metabolic syndrome with atrial fibrillation among UnitedStates adults (from the REasons for Geographic and Racial Differences inStroke [REGARDS] Study). Am J Cardiol 2011;108(2):227–32.

19] Chamberlain AM, Agarwal SK, Ambrose M, Folsom AR, Soliman EZ,Alonso A. Metabolic syndrome and incidence of atrial fibrillation amongblacks and whites in the Atherosclerosis Risk in Communities (ARIC)Study. Am Heart J 2010;159(5):850–6.

20] Liu HL, Lu XL, Guo ZP, Lin JX. Association between metabolic syndromeand incidence of atrial fibrillation in essential hypertensive patients withoutleft ventricular hypertrophy [in Chinese]. Zhonghua Xin Xue Guan BingZa Zhi 2010;38(1):15–9.

21] Umetani K, Kodama Y, Nakamura T, Mende A, Kitta Y, Kawabata K,et al. High prevalence of paroxysmal atrial fibrillation and/or atrial flutterin metabolic syndrome. Circ J 2007;71(2):252–5.

22] Abed HS, Samuel CS, Lau DH, Kelly DJ, Royce SG, Alasady M, et al.Obesity results in progressive atrial structural and electrical remodeling:implications for atrial fibrillation. Heart Rhythm 2013;10(1):90–100.

23] Munger TM, Dong YX, Masaki M, Oh JK, Mankad SV, Borlaug BA,et al. Electrophysiological and hemodynamic characteristics associated

with obesity in patients with atrial fibrillation. J Am Coll Cardiol2012;60(9):851–60.

24] Fogari R, Mugellini A, Zoppi A, Preti P, Destro M, Lazzari P, et al. Effectof telmisartan and ramipril on atrial fibrillation recurrence and severity in

[

inologie 75 (2014) 159–164

hypertensive patients with metabolic syndrome and recurrent symptomaticparoxysmal and persistent atrial fibrillation. J Cardiovasc Pharmacol Ther2012;17(1):34–43.

25] Yasar AS, Bilen E, Bilge M, Ipek G, Ipek E, Kirbas O. P-wave duration anddispersion in patients with metabolic syndrome. Pacing Clin Electrophysiol2009;32(9):1168–72.

26] Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syn-drome: a comprehensive perspective based on interactions between obesity,diabetes, and inflammation. Circulation 2005;111(11):1448–54.

27] Reaven GM. Banting lecture 1988. Role of insulin resistance in humandisease. Diabetes 1988;37(12):1595–607.

28] Dinh W, Lankisch M, Nickl W, Scheyer D, Scheffold T, Kramer F, et al.Insulin resistance and glycemic abnormalities are associated with dete-rioration of left ventricular diastolic function: a cross-sectional study.Cardiovasc Diabetol 2010;9:63.

29] Shigematsu Y, Hamada M, Nagai T, Nishimura K, Inoue K, Suzuki J, et al.Risk for atrial fibrillation in patients with hypertrophic cardiomyopathy:association with insulin resistance. J Cardiol 2011;58(1):18–25.

30] Kravariti M, Naka KK, Kalantaridou SN, Kazakos N, Katsouras CS,Makrigiannakis A, et al. Predictors of endothelial dysfunction in youngwomen with polycystic ovary syndrome. J Clin Endocrinol Metab2005;90(9):5088–95.

31] Aljada A, Ghanim H, Mohanty P, Kapur N, Dandona P. Insulin inhibits theproinflammatory transcription factor early growth response gene-1 (Egr)-1expression in mononuclear cells (MNC) and reduces plasma tissue factor(TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. J ClinEndocrinol Metab 2002;87(3):1419–22.

32] Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, et al.Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaBin mononuclear cells in obese subjects: evidence for an anti-inflammatoryeffect? J Clin Endocrinol Metab 2001;86(7):3257–65.

33] Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, CarnesCA, et al. C-reactive protein elevation in patients with atrial arrhythmias:inflammatory mechanisms and persistence of atrial fibrillation. Circulation2001;104(24):2886–91.

34] Mihm MJ, Yu F, Carnes CA, Reiser PJ, McCarthy PM, Van Wagoner DR,et al. Impaired myofibrillar energetics and oxidative injury during humanatrial fibrillation. Circulation 2001;104(2):174–80.

35] Kim YH, Lim DS, Lee JH, Shim WJ, Ro YM, Park GH, et al. Gene expres-sion profiling of oxidative stress on atrial fibrillation in humans. Exp MolMed 2003;35(5):336–49.

36] Grassi G, Dell’Oro R, Quarti-Trevano F, Scopelliti F, Seravalle G, Paleari F,et al. Neuroadrenergic and reflex abnormalities in patients with metabolicsyndrome. Diabetologia 2005;48(7):1359–65.

37] Cheema AN, Ahmed MW, Kadish AH, Goldberger JJ. Effects of autonomicstimulation and blockade on signal-averaged P-wave duration. J Am CollCardiol 1995;26(2):497–502.

38] Tükek T, Akkaya V, Demirel S, Sözen AB, Kudat H, Atilgan D, et al.Effect of Valsalva maneuver on surface electrocardiographic P-wavedispersion in paroxysmal atrial fibrillation. Am J Cardiol 2000;85(7):896–9.

39] Yamagishi SI, Matsui T, Nakamura K. Possible molecular mechanisms bywhich angiotensin II type 1 receptor blockers (ARBs) prevent the devel-opment of atrial fibrillation in insulin-resistant patients. Horm Metab Res2008;40(9):640–4.

40] Singh VP, Le B, Khode R, Baker KM, Kumar R. Intracellular angiotensinII production in diabetic rats is correlated with cardiomyocyte apo-ptosis, oxidative stress, and cardiac fibrosis. Diabetes 2008;57(12):

3297–306.

41] Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K.Angiotensin II antagonist prevents electrical remodeling in atrial fibrilla-tion. Circulation 2000;101(22):2612–7.