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Serum myeloperoxidase level is increased in heavy smokers

January 2013
Open Journal of Clinical Diagnostics 03(01):5-8

DOI:10.4236/ojcd.2013.31002

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Serum level of IL-8. The results are mean and SEM (n = 34). # Statistically significant (Student t-test, p < 0.001).

…

. Peripheral blood leucocytes.

…

Serum level of MPO. The results are mean and SEM (n = 34). # Statistically significant (Student t-test, p < 0.001).

…

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Open Journal of Clinical Diagnostics, 2013, 3, 5-8 OJCD

http://dx.doi.org/10.4236/ojcd.2013.31002 Published Online March 2013 (http://www.scirp.org/journal/ojcd/)

Serum myeloperoxidase level is increased in heavy smokers

André B. Martins1, Valdecir F. Ximenes2, Luiz Marcos da Fonseca1

1Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Araraquara, Brasil

2Departamento de Química, Faculdade de Ciências, Universidade Estadual Paulista-UNESP, Bauru, Brasil

Email: fonseclm@fcfar.unesp.br

Received 18 January 2013; revised 28 February 2013; accepted 8 March 2013

ABSTRACT

Raised myeloperoxidase (MPO) serum levels are as-

sociated with endothelial dysfunction and cigarette

smoking is a risk factor for cardiovascular diseases.

Since myocardial infarction is associated with leuko-

cytosis and smokers present increased levels of neu-

trophils, here we hypothesized that the levels of se-

rum MPO in smokers could be also raised. We car-

ried out a study on sixty eight adult healthy volun-

teers. The control group consisted of thirty four non-

smokers and the test group was thirty four heavy

smokers. The hemogram, interleukin-8 (IL-8) and

MPO serum levels were measured. Neutrophil, mo-

nocyte and lymphocyte counts were higher (p < 0.05)

and the serum levels of interleukin-8 (IL-8) and MPO

were fourfold higher in smokers than in non-smokers

(n = 34, p < 0.05). This result correlated perfectly

with the increased neutrophil count and IL-8 serum

level that characterize smoking subjects. We propose

that the high level of serum MPO could be directly

involved in the higher prevalence of coronary artery

diseases among heavy smokers.

Keywords: Smokers; Neutrophils; IL-8;

Myeloperoxidase; Hypochlorous Acid; Atherosclerosis

1. INTRODUCTION

Myeloperoxidase (MPO) is a heme enzyme abundantly

expressed by neutrophils. It is the catalyst responsible for

production of the microbicide hypochlorous acid (HOCl)

by the oxidation of chloride (Cl–) by hydrogen peroxide

(H2O2) [1].This enzymatic pathway is a fundamental part

of the innate immune response and is triggered when

these cells are activated by noxious stimuli [2]. However,

HOCl can also take part in deleterious oxidative proc-

esses associated with chronic inflammatory diseases, in-

cluding atherosclerosis [3,4]. In addition to that, there is

substantial evidence that MPO plays an important role in

the pathogenesis of cardiovascular diseases [5-7]. The

discovery that the blood serum level of MPO is a bio-

marker for the prognosis of coronary artery diseases has

opened up a new area of research with immediate utility

in clinical practice [8-11].

It is well established, scientifically and clinically, that

smokers are significantly more susceptible to a variety of

diseases, including coronary artery diseases [12]. Smok-

ers also have increased blood counts of neutrophils and

monocytes [13], which are the main endogenous sources

of MPO. Moreover, chronic exposure to cigarette smoke

causes increased production and secretion of metallopro-

teinase by macrophages and proteolytic enzymes by neu-

trophils [14]. Hence, we hypothesized that the blood se-

rum level of MPO in tobacco smokers might also be ele-

vated and could be involved in their susceptibility to car-

diovascular diseases.

2. MATERIALS AND METHODS

Blood donors: The study included sixty eight adult healthy

volunteers (aged 20 to 67 years). The control group con-

sisted of thirty four non-smokers (15 women and 19 men)

and the study group was thirty four heavy smokers (more

than two packs/day, 16 women and 18 men). None of the

volunteers reported the use of medication. All subjects

gave written informed consent for examinations and par-

ticipation in the study. The study was approved by the

Faculty research ethics committee (Comite de Etica em

Pesquisa FCFAR/UNESP n˚ 24/ 2009).

Blood samples, hematological and biochemical analy-

sis: Blood samples (totaling 8 mL) were obtained by

venipuncture. The first 4 mL was collected in an EDTA

tube and used for hematological analysis. The Other 4

mL was collected without anticoagulant and used to de-

termine serum MPO and interleukin-8. The complete he-

mogram was performed in a Coulter STKS hematologi-

cal autoanalyzer (Miami, USA). Blood serum was sepa-

rated by centrifugation at 400 ×g for 20 minutes and

stored at –80˚C until analysis. The serum level of MPO

was measured by MPO-EIA (InnoZyme Calbiochem,

Merck KgaA, Darmstadt, Germany) and serum IL-8 was

measured by ELISA (RayBiotech, Norcross GA, USA)

following the manufacturer’s instructions. The blood sam-

OPEN ACCESS

A. B. Martins et al. / Open Journal of Clinical Diagnostics 3 (2013) 5-8

ples were assayed in duplicate and the results averaged.

3. RESULTS AND DISCUSSIONS

Leukocytosis is the main immune alteration observed in

the blood system of smokers and a common feature is the

increased number of neutrophils in blood, sputum and

bronchial biopsies [14]. The number of peripheral blood

neutrophils correlated with the smoking status. Thus, a

high smoking rate was associated with appreciable in-

creases counts; former smokers, with less than 5 years

abstinence, still demonstrated elevated counts and those

who had abstained for more than 5 years had counts com-

parable to those in people who had never smoked [15]. In

corroboration, we found in this study that neutrophil,

monocyte and lymphocyte counts are higher in smokers

than in non-smokers (Table 1).

The cause of the neutrophilia has not yet been totally

clarified, but nicotine has been implicated in the stimu-

lation of neutrophils to produce interleukin-8 (IL-8),

which is a potent neutrophil chemo-attractant and acti-

vator. IL-8 causes mild to moderate neutrophilia and its

blood level is positively correlated with the degree of ci-

garette smoking [16]. The pathway for nicotine-stimu-

lated production of IL-8 has been linked to nicotinic ace-

tylcholine receptors (nAChRs) via the generation of per-

oxynitrite and subsequent NF-kappaB activation [16]. In

addition, it has recently been demonstrated that dendritic

cells exposed to cigarette smoke extract release IL-8 [17].

Chronic cigarette smoking also stimulates the bone mar-

row, increases the size of the mitotic and postmitotic

pools of neutrophils and reduces the time that neutrophils

spend in the postmitotic pool in the marrow [18]. Cor-

roborating these findings, here we found that the serum

level of IL-8 was about 4-fold higher in smokers than in

non-smokers (Figure 1).

MPO, which constitutes up to 5% of the dry weight of

neutrophils [19], may play a pivotal role in atherogenesis

[5-7]. Hypochlorous acid, the endogenous product of

MPO-catalyzed oxidation of the chloride anion, has been

implicated as one of the major reactive intermediates in-

Table 1. Peripheral blood leucocytes.

Leucocytes (Cells/L)

Smokers (n = 34) Non-Smokers (n = 34)

Neutrophils 6002 ± 291# 3731 ± 144

Monocytes 639 ± 44# 481 ± 29

Lymphocytes 2281 ± 92# 2023 ± 86

Eosinophils 206 ± 25 191 ± 24

Basophils 58 ± 9 55 ± 8

Data are mean and SEM. #Statistically significant (Student t-test, p < 0.05).

volved in the oxidation of low-density lipoproteins (LDL),

which is an early event in atherosclerosis [3,4]. The es-

sential reverse cholesterol transport by high density lipo-

protein (HDL) might also be compromised, since this

lipoprotein is an in vivo target for MPO-catalyzed oxida-

tion, impairing its cardioprotective and anti-inflamma-

tory capacity [5,20,21]. MPO also impairs the ATP-bind-

ing cassette transporter AI (ABCA1)-dependent choles-

terol efflux by promoting methionine oxidation and site-

specific tyrosine chlorination of apolipoprotein A-I [22].

Moreover, elevated MPO levels are associated with en-

dothelial dysfunction [23] and acute myocardial infarc-

tion is frequently associated with leukocytosis and raised

peripheral neutrophil counts [24]. The influence of to-

bacco smoke on human health is still an important prob-

lem worldwide. Here, for the first time, it has been dem-

onstrated that smokers exhibit an increased level of

blood serum MPO (Figure 2). This result correlates per-

fectly with the increased in neutrophil count and IL-8

serum level that characterize smoking subjects.

4. CONCLUSION

Taking into account the widely-accept deleterious role of

MPO in atherosclerosis [5-7] and the raised values of

MPO serum level [8-11] and neutrophil counts [24-26]

as predictive factors for cardiovascular events, we pro-

pose that the high level of serum MPO could be directly

Smokers Non-Smokers

15 #

IL-8 (ng/L)

Figure 1. Serum level of IL-8. The results

are mean and SEM (n = 34). #Statistically

significant (Student t-test, p < 0.001).

100

Non-Smokers

Smokers

MPO (g/L)

Figure 2. Serum level of MPO. The results

are mean and SEM (n = 34). #Statistically

significant (Student t-test, p < 0.001).

A. B. Martins et al. / Open Journal of Clinical Diagnostics 3 (2013) 5-8 7

Scheme 1. Proposal for the corre-

lation among smoking, increased

neutrophil counts, augmented MPO

serum level and increased coronary

diseases in smokers subjects.

involved in the higher prevalence of coronary artery di-

seases among smokers [27,28]. Scheme 1 presents our

proposal for the correlation among smoking, increased

neutrophil counts, augmented MPO serum level and in-

creased coronary diseases in smokers.

5. ACKNOWLEDGEMENTS

This study was supported by Fundação de Amparo a Pesquisa do

Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvi-

mento Científico e Tecnológico (CNPq), Brazil.

REFERENCES

[1] Shepherd, V.L. (1986) The role of the respiratory burst of

phagocytes in host defense. Seminars in Respiratory In-

fections, 1, 99-106.

[2] Klebanoff, S.J. (2005) Myeloperoxidase: Friend and foe.

Journal Leukocytes Biology, 77, 598-625.

doi:10.1189/jlb.1204697

[3] Spickett, C.M. (2007) Chlorinated lipids and fatty acids:

An emerging role in pathology. Pharmacology Therapy,

115, 400-409. doi:10.1016/j.pharmthera.2007.06.002

[4] Lau, D. and Baldus, S. (2006) Myeloperoxidase and its

contributory role in inflammatory vascular disease. Phar-

macology Therapy, 111, 16-26.

doi:10.1016/j.pharmthera.2005.06.023

[5] Shao, B., Oda, M.N., Oram, J.F. and Heinecke, J.W.

(2010) Myeloperoxidase: An oxidative pathway for gen-

erating dysfunctional high-density lipoprotein. Chemical

Research Toxicology, 23, 447-454.

doi:10.1021/tx9003775

[6] Chantepie, S., Malle E., Sattler, W., Chapman, M.J. and

Kontush, A. (2009) Distinct HDL subclasses present

similar intrinsic susceptibility to oxidation by HOCl. Ar-

chives Biochemistry Biophysics, 487, 28-35.

doi:10.1016/j.abb.2009.05.005

[7] Van der Veen, B.S., de Winther, M.P. and Heeringa, P.

(2009) Myeloperoxidase: Molecular mechanisms of ac-

tion and their relevance to human health and disease. An-

tioxidant Redox Signaling, 11, 2899-2937.

doi:10.1089/ars.2009.2538

[8] Baldus, S., Heeschen, C., Meinertz, T., Zeiher, M., Eis-

erich, J.P., Münzel T., Simoons M.L. and Hamm, C.W.

(2003) Myeloperoxidase serum levels predict risk in pa-

tients with acute coronary syndromes. Circulation, 108,

1440-1445. doi:10.1161/01.CIR.0000090690.67322.51

[9] Roman, R.M., Camargo, P.V., Borges, F.K., Rossini, A.P.

and Polanczyk, C.A. (2010) Prognostic value of myelop-

eroxidase in coronary artery disease: Comparison of un-

stable and stable angina patients. Coronary Artery Dis-

ease, 21, 129-136. doi:10.1097/MCA.0b013e328333f50d

[10] Pawlus, J., Hołub, M., Kożuch, M., Dąbrowska, M. and

Dobrzycki, S. (2010) Serum myeloperoxidase levels and

platelet activation parameters as diagnostic and prognos-

tic markers in the course of coronary disease. Interna-

tional Journal Laboratory Hematology, 32, 320-328.

doi :1 0.1111/j.1751- 553X.2009.01203.x

[11] Wong, N.D., Gransar, H., Narula, J., Shaw, L., Moon,

J.H., Miranda-Peats, R., Rozanski, A., Hayes, S.W.,

Thomson, L.E., Friedman, J.D. and Berman, D.S. (2009)

Myeloperoxidase, subclinical atherosclerosis, and cardio-

vascular disease events. JACC Cardiovascular Imaging,

2, 1093-1099. doi:10.1016/j.jcmg.2009.05.012

[12] Doll, R. and Peto, R. (1976) Mortality in relation to

smoking: 20 years observation on male British doctors.

British Medical Journal, 2, 1525-1561.

doi:10.1136/bmj.2.6051.1525

[13] Bridges, R.B., Wyatt, R.J. and Rehm, S.R. (1885) Effect

of smoking on peripheral blood leucocytes. European

Journal Respiratory Diseases, 661, 24-33.

[14] Gorska, K., Krenke, R., Domagala-Kulawik, J., Korczyn-

ski, P., Nejman-Gryz, P., Kosciuch, J., Hildebrand, K.

and Chazan, R. (2008) Comparison of cellular and bio-

chemical markers of airway inflammation in patients with

mild-to-moderate asthma and chronic obstructive pulmo-

nary disease: An induced sputum and bronchoalveolar la-

vage fluid study. Journal Physiology Pharmacology, 59,

271-283.

[15] Parry, H., Cohens, S. and Schlarb, J.E. (1997) Smoking,

alcohol consumption and leucocytes counts. American

Journal Clinical Pathology, 107, 64-67.

[16] Iho, S., Tanaka, Y., Takauji, R., Kobayashi, C., Mura-

matsu, I., Iwasaki, H., Nakamura, K., Sasaki, Y., Nakao,

K. and Takahashi, T. (2003) Nicotine induces human

neutrophils to produce IL-8 through the generation of

peroxynitrite and subsequent activation of NF-kappaB.

Journal Leukocytes Biology, 74, 942-951.

A. B. Martins et al. / Open Journal of Clinical Diagnostics 3 (2013) 5-8

OPEN ACCESS

doi:10.1189/jlb.1202626

[17] Vassallo, R., Kroening, P.R., Parambil, J. and Kita, H.

(2008) Nicotine and oxidative cigarette smoke constitu-

ents induce immune-modulatory and pro-inflammatory

dendritic cell responses. Molecular Immunology, 45, 3321-

3329. doi:10.1016/j.molimm.2008.04.014

[18] Terashima, T., Wiggs, B., English, D., Hogg, J.C. and

Van Eeden, S.F. (1997) The effect of cigarette smoking

on the bone marrow. American Journal Respiratory

Critical Care Medicine, 155, 1021-1026.

[19] Schultz, J. and Kaminker, K. (1962) Myeloperoxidase of

leukocyte of normal blood content and localization. Ar-

chives Biochemistry Biophysics, 98, 465-471.

doi:10.1016/0003-9861(62)90321-1

[20] Undurti, A., Huang, Y., Lupica, J.A., Smith, J.D., DiDo-

nato, J.A. and Hazen, S.L. (2009) Modification of high

density lipoprotein by myeloperoxidase generates a pro-

inflammatory particle. Journal Biological Chemistry, 284,

30825-30835. doi:10.1074/jbc.M109.047605

[21] Malle, E., Marsche, G., Panzenboeck, U. and Sattler, W.

(2006) Myeloperoxidase-mediated oxidation of high-den-

sity lipoproteins: Fingerprints of newly recognized poten-

tial proatherogenic lipoproteins. Archives Biochemistry

Biophysics, 445, 245-255. doi:10.1016/j.abb.2005.08.008

[22] Shao, B., Oda, M.N., Bergt, C., Fu, X., Green, P.S., Brot,

N., Oram, J.F. and Heinecke, J.W. (2006) Myeloperoxi-

dase impairs ABCA1-dependent cholesterol efflux through

methionine oxidation and site-specific tyrosine chlorina-

tion of apolipoprotein A-I. Journal Biological Chemistry,

281, 9001-9004. doi:10.1074/jbc.C600011200

[23] Vita, J.A., Brennan, M.L., Gokce, N., Mann, S.A., Goor-

mastic, M., Shishehbor, M.H., Penn, M.S., Keaney, J.F.

and Hazen, S.L. (2004) Serum myeloperoxidase levels

independently predict endothelial dysfunction in humans.

Circulation, 110, 1134-1139.

doi:10.1161/01.CIR.0000140262.20831.8F

[24] Green, S.M., Vowels, J., Waterman, B., Rothrock, S.G.,

and Kuniyoshi, G. (1996) Leukocytosis: A new look at an

old marker for acute myocardial infarction. Academy

Emergence Medicine, 3, 1034-1041.

doi :1 0.1111/j.1553- 2712.1996.tb03350.x

[25] Angeli, F., Angeli, E., Ambrosio, G., Mazzotta, G., Re-

boldi, G. and Verdecchia, P. (2010) Neutrophil count for

the identification of postmenopausal hypertensive women

at increased cardiovascular risk. Obstetric Gynecology,

115, 695-703. doi:10.1097/AOG.0b013e3181d53df6

[26] Gibson, P.H., Cuthbertson, B.H., Croal, B.L., Rae, D.,

El-Shafei, H., Gibson, G., Jeffrey, R.R., Buchan, K.G.

and Hillis, G.S. (2010) Usefulness of neutrophil/lympho-

cyte ratio as predictor of new-onset atrial fibrillation after

coronary artery bypass grafting. American Journal Car-

diology, 105, 186-191.

doi:10.1016/j.amjcard.2009.09.007

[27] Nicita-Mauro, V., Maltese, G., Nicita-Mauro, C., Lasco,

A. and Basile, G. (2010) Non smoking for successful ag-

ing: Therapeutic perspectives. Current Pharmaceutical De-

sign, 16, 775-782. doi:10.2174/138161210790883552

[28] Luo, Y., Li, X., Li, J., Wang, X., Qiao, Y., Hu, D., Mer-

riam, P.A. and Ma, Y. (2010) Combined effects of smok-

ing and peripheral arterial disease on all-cause and car-

diovascular disease mortality in a Chinese male cohort.

Journal Vascular Surgery, 51, 673-678.

doi:10.1016/j.jvs.2009.09.024

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Article

Apr 1962

The myeloperoxidase content of the normal human leucocyte has been established as greater than 5% of the dry weight, which is contrary to the often quoted value of 1–2%. The conditions for the preparation of a new cellular particulate in which the peroxidase activity is localized is described; it is heavier than mitochondria, and contains at least 10–30 times more peroxidase than the particulate fractions carrying the cytochrome oxidase activity.

Non Smoking for Successful Aging: Therapeutic Perspectives

Article

Mar 2010
CURR PHARM DESIGN

The smoke of cigarettes represents an important accelerator of the aging process, and there is no doubt that smoke is an important risk factor for many diseases, in particular for cardiovascular, neoplastic and respiratory diseases. Smoking plays an important role also in the development of other pathological conditions being particularly frequent in geriatric ages, such as dementia, osteoporosis, diabetes, erectile dysfunction, senile macular degeneration, nuclear cataract and alterations of skin. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autonomy. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. The first requirement of stopping smoking certainly is the motivation of the smoker himself to do this, since without this motivation any attempt is futile. Today numerous quitting strategies exist, either of pharmacological or non-pharmacological type, which are also advantageous for the elderly person. Approved pharmacological treatments include nicotine replacement therapies, bupropion, drugs targeting cannabinoid receptors and newer pharmacological approaches including the selective nicotinic partial agonists. Varenicline, an alpha4 beta2 nicotinic acetylcoline receptor partial agonist, is the most recently agent approved for smoking cessation. This drug works by reducing the strength of the smoker's urge to smoke and by relieving withdrawal symptoms. The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates.

Neutrophil Count for the Identification of Postmenopausal Hypertensive Women at Increased Cardiovascular Risk

Article

Apr 2010

High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women. We examined 298 initially untreated postmenopausal women with essential hypertension who were part of Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA). Mean duration of follow-up was 8 years (range 1-20 years). Treatment was tailored to each individual. Mean age at entry was 59 years. Diabetic women comprised 9.1% of the group, and current smokers comprised 17.5% of the group. During follow-up, 31 new major cardiovascular events occurred. In univariable analyses, age, diabetes, serum creatinine, blood pressure, left ventricular hypertrophy, and neutrophil count showed an association with the risk of events (all P<.05). In a multivariable Cox analysis, after adjustment for traditional cardiovascular risk factors, for each 1.25x10 (1 standard deviation) increase in neutrophil count there was a 67% higher risk of cardiovascular events (hazard ratio 1.67, 95% confidence interval 1.32-2.07; P<.001). Furthermore, neutrophil count showed robust incremental predictive value for cardiovascular events, in addition to traditional risk factors. Total white blood cell count did not show any association with cardiovascular events. A high peripheral neutrophil count identifies postmenopausal hypertensive women at increased risk of cardiovascular disease. Such relation appears to be independent of traditional risk factors. III.

Prognostic value of myeloperoxidase in coronary artery disease: Comparison of unstable and stable angina patients

Article

Mar 2010

Atherosclerosis is a chronic inflammatory process, and myeloperoxidase (MPO) seems to contribute directly to the pathogenesis of acute coronary syndrome (ACS). To compare MPO levels among the patients with stable and unstable ischemic heart disease and to evaluate their independent prognostic value for cardiovascular events. MPO and C-reactive protein (CRP) were assessed in two cohorts of coronary artery disease patients, including 178 patients with stable angina and 130 patients with ACS evaluated at the emergency department. MPO and CRP levels were significantly higher among patients with ACS [MPO 93 (54-127) vs. 9.9 pmol/l (5-21) and high sensitivity-CRP 11 (3-27) vs. 2.6 mg/l (1-5)]. Among patients with stable angina, high sensitivity-CRP levels greater than 3 mg/l were associated with a three-fold risk of further cardiovascular events during a mean follow-up period of 13+/-4 months, although there was no significant association between MPO levels and outcomes. Among patients with ACS, baseline MPO level was an independent predictor of major adverse cardiac events during hospitalization, odds ratio of 3.8 (95% confidence interval: 1.2-12) for the combined endpoint (death, recurrent angina, heart failure, and arrhythmia). CRP levels were associated with hospital mortality in patients with ACS, but were not independently related to cardiovascular events. Elevated MPO levels among the ACS patients suggest that this marker may participate in plaque vulnerability and instability process, whereas higher CRP levels were predictive of cardiac events only among the stable angina patients. These findings suggest distinct role of the inflammatory markers studied in the pathophysiology of coronary artery disease.

Combined effects of smoking and peripheral arterial disease on all-cause and cardiovascular disease mortality in a Chinese male cohort

Article

Mar 2010

Smoking is a major risk factor for peripheral arterial disease (PAD), and PAD is associated with all-cause and cardiovascular disease (CVD) mortality. The objective of this study was to determine the combined effects of smoking and PAD on all-cause and CVD mortality. A total of 1979 males 35 years of age or older were enrolled from eight university-affiliated hospitals in Beijing and Shanghai in 2004, with both smoking status and PAD diagnosis obtained, 1712 of them had complete follow-up data. Mortality data were obtained from all participants between December 2007 and February 2008. Cox proportional hazards models were used to evaluate relative risks (RRs) of all-cause mortality and CVD mortality among different groups. At baseline, the average age of participants was 66.98-years-old (SD = 11.57), prevalence of PAD was 24.0% and 65.4% smoked cigarettes. During the 3-year follow-up, all-cause cumulative mortality rates were 27.9% (PAD/smoker), 26.3% (PAD/nonsmoker), 14.1% (no PAD/smoker), and 14.4% (no PAD/nonsmoker) (P < .001), and CVD cumulative mortality rates were 17.8%, 14.9%, 8.1%, and 7.3%, respectively (P < .001). Compared with the no PAD/nonsmoker subjects, adjusted RR from all-cause mortality in the groups of both PAD/smoker, PAD/nonsmoker, and no PAD/smoker were 1.88 (95% confidence interval [CI], 1.34-2.64), 1.37 (95% CI, 0.85-2.23), and 1.08 (95% CI, 0.79-1.49), respectively. The adjusted RR from CVD mortality was 2.12 (95% CI, 1.37-3.28), 1.55 (95% CI, 0.84-2.86), and 1.13 (95% CI, 0.74-1.71), respectively. PAD is a major determinant of mortality. Smoking did not contribute to mortality in this study. Further research is needed.

Serum myeloperoxidase levels and platelet activation parameters as diagnostic and prognostic markers in the course of coronary disease

Article

Feb 2010

Early prediction of coronary artery disease complications is vital for the prevention and effective treatment of patients with coronary cardiac disease. It has been reported that inflammatory markers play a key role in the progression of cardiovascular diseases. Platelet count and platelet morphological parameters were analyzed on a fully-automated hematological analyzer ADVIA 2120 (Siemens). Serum myeloperoxidase (MPO) level was determined with an enzyme immunoassay (BioCheck). The measuring range of this assay is between 0 and 40 ng/ml. We demonstrate that serum MPO concentration and platelet activation increase systematically with the advancement of coronary artery disease. Moreover, MPO level is significantly higher in patients with unstable coronary artery disease and myocardial infarction compared with healthy subjects and patients with stable angina. The diagnostic sensitivity of these parameters was higher than of TnI (cardiac troponin I), CK-MB (creatine kinase-heart type), CRP (C-reactive protein), and fibrinogen and DD (D-dimers). MPO, L-PLT (large platelet), MPV (mean platelet volume), and MPC (mean platelet component concentration) may serve as attractive diagnostic and prognostic markers in the assessment of the risk for unstable atheroma in the course of coronary artery disease.

Usefulness of Neutrophil/Lymphocyte Ratio As Predictor of New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting

Article

Jan 2010

The neutrophil/lymphocyte (N/L) ratio integrates information on the inflammatory milieu and physiologic stress. It is an emerging marker of prognosis in patients with cardiovascular disease. We investigated the relation between the N/L ratio and postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting. In a prospective cohort study, 275 patients undergoing nonemergency coronary artery bypass grafting were recruited. Patients with previous atrial arrhythmia or requiring concomitant valve surgery were excluded. The N/L ratio was determined preoperatively and on postoperative day 2. The study end point was AF lasting >30 seconds. Patients who developed AF (n = 107, 39%) had had a greater preoperative N/L ratio (median 3.0 vs 2.4, p = 0.001), but no differences were found in the other white blood cell parameters or C-reactive protein. The postoperative N/L ratio was greater in patients with AF (day 2, median 9.2 vs 7.2, p <0.001), and in multivariate models, a greater postoperative N/L ratio was independently associated with a greater incidence of AF (odds ratio 1.10 per unit increase, p = 0.003: odds ratio for N/L ratio >10.14 [optimal postoperative cutoff in our cohort], 2.83 per unit, p <0.001). Elevated pre- and postoperative N/L ratios were associated with an increased occurrence of AF after coronary artery bypass grafting. In conclusion, these results support an inflammatory etiology in postoperative AF but suggest that other factors are also important.

Serum myeloperoxidase level is increased in heavy smokers

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