Niza Samsuddin 1, KG Rampal 2, Noor Hassim Ismail 3, Nur Zamzila Abdullah 4, Jamalludin Ab Rahman 1

Transcription

1 Niza Samsuddin 1, KG Rampal 2, Noor Hassim Ismail 3, Nur Zamzila Abdullah 4, Jamalludin Ab Rahman 1 Department of Community Medicine, International Islamic University Malaysia 1 Perdana University School Graduate of Medicine 2 Department of Community Health, National University Malaysia 3 Department of Basic Medical Sciences, International Islamic University Malaysia 4

2 Health Effects of Organophosphates (OP) Pesticides : Cholinergic Syndrome, Intermediate Syndrome, COIDP, Neurobehavioural, Psychiatric changes Growing evidence that OP pesticides exposure possibly pose a greater risk of atherosclerosis: OPs exposure Low PON1 activity level among OPs exposed workers (Sozmen et.al, 2002; Hernandez et. al., 2003; Mackness et al.,2000). High oxidized-ldl in animal study

3 OPs Metabolism and Toxicity O R-O R-O P OH + OH-AChE R-O R-O O P O X + OH- AChE phosphorilated AChE R-O 1 R-O - O R-O O P O P O O 2 3 spontaneous reactivation of AChE AChE AChE + X negatively charge phosphorilated AChE + R

4 OPs Metabolism and Toxicity O R O P O X R O In animal tissues (Abraham Mazur 1946) Human and mammalian sera (Aldriedge 1953) Human study detoxifying process(li et al. 1995; Davies et. al., 1996, Mackness et. al., 2003; Costa et. al., 2003), limits toxicity OP (Himbergen et. al., 2004, James, 2006)

5 LOW PON1 ENZYMES PROMOTE OXIDATIVE MODIFICATION PON1 hydrolyze and decrease lipid peroxides (Mackness, 1991) PON1 prevent oxidative modification of LDL (Mackness & Durrington, 1995; Wilkins & Leake 1994,) PON1 deficient mice high oxidized-ldl (Shih et al, 1998) PON1 LIPID Lipid peroxidation (Oxidized-LDL)

6 ATHEROSCLEROSIS FORMATION Lipid peroxidation and inflammatory reaction in the vascular wall is the hypothesis of atherosclerosis formation. PON1 LIPID Lipid peroxidation (Oxidized-LDL) Oxidized-LDL stimulate the inflammatory changes in the endothelial vascular Inflammatory response of vascular wall Atherosclerosis

7 CONCEPTUAL FRAMEWORK LDL OP Pesticide exposure PON1 Oxidized-LDL CHE Inflammatory response of vascular wall Atherosclerosis Arterial segment stiffness Changes in CVS haemodynamic parameters SyphgmoCor System:

8 Genetic factors PON1 Lipid (LDL) Genetic factors Many established risk factors of atherosclerosis Age Sex BMI Oxidized-LDL Inflammatory response of vascular wall Atherosclerosis Obesity Hypertension Diabetes Smoking Infection Family history of CVDs MOA induces different cell activation (Alexander, 1995, Basta et al 2004;Kaori Fukuhama-Takaki, 2005) inflammatory process atherosclerosis (Libby P, 2002)

9 RESEARCH QUESTION Does OP pesticides exposed group of workers has the difference in cardiovascular haemodynamic parameters compared to nonexposed group of workers? RESEARCH HYPOTHESIS OP pesticides exposed group of workers is difference in terms of cardiovascular haemodynamic parameters compared to nonexposed group of workers.

10 RESEARCH OBJECTIVES General Objective: To establish whether OP pesticides exposed group of workers is difference in terms of cardiovascular haemodynamic parameters compared to non-exposed group of workers. Specific objective 1. To measure plasma pseudo-che activity level among OPs pesticide exposed and non-exposed group of workers the 2. To measure and compare CVS Haemodynamic parameters among OPs pesticide exposed and non-exposed group of workers namely: Peripheral Parameters - Brachial Blood Pressure - Mean Pulse Pressure - Pulse Pressure Central Parameters -Aortic Blood Pressure -Central Blood Pressure -Augmentation Pressure -Augmentation Index -Pulse Wave Velocity

11 Study design: cross sectional study (comparative study) Target population: The target population was workers who were exposed to OPs pesticide. Study population: The study population was the male vector unit, MOH workers who were exposed to OPs pesticide. Comparative population: Non-exposed pesticides workers that match to the study group in terms of age, sex, and income bracket. Sampling technique: Purposive sampling Calculated sample size: 400 (200 in each group)

12 Inclusion criteria: OP pesticides must be the main chemicals used in the spraying preparation. Working as pesticide sprayers for more than 1.5 years (Quinn, 2005; Terry et al 2007) Age between 20 to 55 years old (CPG, 2004)

13 Exclusion criteria Tachycardia (Heart more than 100 bpm) Irregular rhythm (Ectopic beats, drop beats) Smoking or drinking caffeinated drinks 4 hrs before the 2 nd appointment for CVS assessment.

14 SYPHGMOCOR

15 By measuring radial pulse wave the general transfer function in the system will extrapolate the aortic pulse wave and pressure and later the central CVS haemodynamic parameters.

16 PWV values derived from carotid-femoral measurements (Im J-A, Lee J-W et al. 2007). Each detects the onset of the pressure wave form, in relation to an electrocardiogram time point. The distance along the arterial tree is measured and the velocity is calculated

17 Portable, convenient for screening Good inter and intra-operator reproducibility (Wilkinson et al 1998, Liang YL et al, 1998) Minimum training (Davies and Struthers, 2003) Powerful diagnostic instrument (Orlova et al 2008) High positive and negative predictive values (Benczur et al 2007, Davies and Struthers, 2003)

18 RESULTS 345 workers handling OP pesticides at work, identified in selected district health departments. 119 workers were excluded from the study 226 workers were included in the study 9- female workers 27- no exposure 20- age more than exposed less than 1.5 years 16 workers refused to participate 210 workers gave written consent to participate and gave blood samples

19 210 workers gave written consent to participate and gave blood samples 15 workers failed to attend SyphmoCor test (Nonrespond) 195 had undergone SypgmoCor test 3 workers failed to come for blood sample collection 6 had abnormal heart rhythm and 3 failed to get acceptable quality of report 186 data on PWA were acceptable for data analyses Pulse Wave Velocity Another 6 failed to get acceptable quality of PWV report, 180 data on PWV were acceptable for data analyses

20 NON-EXPOSED GROUP 200 workers that meet inclusion criteria were identified and gave their written consent 186 workers attended SyphmoCor test (14-Nonresponded) 2 had abnormal heart rhythm 5 workers failed to come for blood sample collection Pulse Wave Analyses Pulse Wave Velocity 14 failed to get acceptable quality of report, 184 data on PWA were acceptable for data analyses Another 16 failed to get acceptable quality of report, 168 data on PWV were acceptable for data analyses

21 Exposed group Non-exposed group Study place N(%) Study place N(%) DHO, Hulu Terengganu 15(8.1) JKR Kuantan 35(19.0) DHO, Kuala Terengganu 20(10.8) JKR Pekan 42(22.8) DHO, Besut 19(10.2) IIUM 26(14.1) DHO, Setiu 14(7.5) Kuantan Local Authority 81(44.0) DHO, Dungun 15(8.1) DHO, Kemaman 13(7.0) DHO, Kuantan 51(27.4) DHO, Pekan 28(15.1) DHO, Maran 11(5.9) Total 186(100) 184(100) DHO= District Health Office

22 Exposed group Non-exposed group N(%) N(%) General worker 74(9.8) 61(33.2) Public health assistant 62(33.3) 4(2.2) Driver 41(22.0) 54(29.3) Environmental health officer 9(4.8) 2(1.1) Technician - 28(15.2) Mechanic - 5(2.7) Security - 6(3.3) Office worker - 8(4.3) Enforcement officer - 16(8.7) Total 186(100) 184(100)

23 Exposed group N(%) Non-exposed group N(%) P value Age (year) 38±8 42±9 <0.001* Income(RM) ± ± <0.001* Education level Primary 20(10.8) 20(10.4) Secondary 157(84.4) 143(77.7) Tertiary 9(4.8) 21(11.4) Smoking Never 72(38.7) 81(44.0) Current 93(50.0) 76(41.3) Former 21(11.3) 27(14.7)

24 Exposed group (n=186) Non-exposed group (n=184) P value Weight(kg) 69.9± ± * Height(m) 166.5± ± BMI(kg/m 2 ) 25.2± ±5.1 <0.001* Family history of sudden death or heart attack Current Health Problems 16(8.6) 20(8.9) Diabetes Mellitus 9(4.8) 13(7.1) Hypertension 19(10.2) 25(13.6) Heart disease 2(1.1) 3(1.6) Kidney disease 4(2.2) 0(0) 0.045* Respiratory disease 11(5.9) 15(8.2) 0.40 Pseudo-cholinesterase (U/L) ± ±

25 Environmental Health Officer N=9 Driver N=41 Public Health Assistant N=62 General Worker N=74 P value Age(year) 36±6 40±8 40±8 36± * Salary(RM) ± ± ± ± <0.001* Education Primary 0(0) 7(17.1) 0(0) 13(17.6) 0.008* Secondary 1(11.1) 34(82.9) 61(98.4) 61(82.4) Tertiary 8(88.9) 0(0) 1(1.6) 0(0) Smoking Never 3(33.3) 15(36.6) 26(41.9) 28(37.8) Current 4(44.4) 20(48.8) 28(45.2) 41(55.4) Former 2(22.2) 6(14.6) 8(12.9) 5(6.8) Statistical test: one way of anova EHO is excluded from the statistical analysis due to small number of respondent in the group

26 Environmental Health Officer N=9 Driver N=41 Public Health Assistant N=62 General Worker N=74 P value Weight(kg) 71.7± ± ± ± * Height(m) 165.9± ± ± ± BMI(kg/m 2 ) 25.8± ± ± ± * FH of sudden death or 1(11.1) 5(12.2) 7(11.3) 3(4.1) heart attack Current Health Problems Diabetes Mellitus 0(0) 3(7.3) 3(4.8) 3(4.1) Hypertension 1(11.1) 6(14.6) 8(12.9) 4(5.4) Heart disease 1(11.1) 0(0) 1(1.6) 0(0) Kidney disease 0(0) 1(2.4) 1(1.6) 2(2.7) Respiratory disease 1(11.1) 4(9.8) 4(6.5) 2(2.7) Pseudo-cholinesterase (U/L) ± ± ± ± Statistical test: one way anova EHO is excluded from the statistical analysis due to small number of respondent in the group

27 EHO N=9 N(%) Driver N=41 N(%) PHA N=62 N(%) Gen.Worker N=74 N(%) P value Duration of working (months) 85.6± ± ± ±56.8 <0.001* Duration of working (day/week) 2.6± ± ± ± Duration of working (hour/day) 2.22± ± ± ± Had training on chemical 8(88.9) 18(43.9) 55(88.7) 63(85.1) <0.001* handling technique Had training on PPE 8(88.9) 7(17.1) 53(85.5) 57(77.0) <0.001* Used of PPE Goggle 3(33.3) 12(29.3) 33(53.2) 59(79.7) <0.001* Respirator 7(77.8) 30(73.2) 60(96.8) 72(97.3) <0.001* Plastic gloves 2(22.2) 13(31.7) 38(61.3) 58(78.4) <0.001* Plastic apron 1(11.1) 7(17.1) 10(16.1) 23(31.1) Safety boot 6(66.7) 28(68.3) 49(79.0) 65(87.8) 0.040* Ear plug 5(55.6) 17(41.5) 56(90.3) 71(95.9) <0.001* Statistical test: one way of anova EHO is excluded from the statistical analysis due to small number of respondent in the group

28 Exposed group Non-exposed P value N=186 group N=184 Heart Rate (bpm) 70±13 66± * Brachial Systolic BP (mmhg) 124±19 122± Brachial Diastolic BP (mmhg) 79±14 75± * Brachial Pulse Pressure (mmhg) 46±10 48± Peripheral Pulse Pressure (mmhg) 94±15 91± Aortic Systolic BP (mmhg) 112±16 111± Aortic Diastolic BP (mmhg) 79±15 76± * Central Pulse Pressure (mmhg) 32.17± ± * Aortic Augmentation Pressure (mmhg) 6.08± ± * Aortic Augmentation Index 15.46± ± Pulse Wave Velocity (m/s) 7.08± ± Statistical test: independent t-test Significant level at p=0.05

29 Group Age BMI Effect size p value Effect size p value Effect size p value Heart rate (b/m) <0.001* <0.001* Brachial SBP * <0.001* <0.001* (mmhg) Brachial DBP 0.07 <0.001* <0.001* <0.001* (mmhg) Mean PP (mmhg) <0.001* <0.001* <0.001* PPP (mmhg) * * Aortic SBP * <0.001* <0.001* (mmhg) Aortic DBP <0.001* <0.001* <0.001* (mmhg) CPP (mmhg) <0.001* AP (mmhg) <0.001* * AIx (%) * <0.001* PWV(m/s) < <0.001* Effect size is determine by partial eta 2

30 EHO N=9 Driver N=41 PHA N=62 Gen.Worker N=74 Heart Rate (bpm) 66±10 71±12 70±14 70± P value Brachial SBP (mmhg) 121±9 133±22 123±14 120±16 <0.001* Brachial DBP (mmhg) 76±4 84±17 78±11 76± * Brachial Mean PP (mmhg) 91±6 100±21 94±11 91± * Peripheral PP (mmhg) 45±9 51±12 45±10 44± * Aortic SBP (mmhg) 108±10 121±21 111±13 108±15 <0.001* Aortic DBP (mmhg) 77±4 85±17 77±16 77± * CPP (mmhg) 30±8 35±9 32±8 31± * AP (mmhg) 4.56± ± ± ± Aix (%) 10.22± ± ± ± PWV (m/s) 7.46± ± ± ± Statistical test: one way anova EHO is excluded from the statistical analysis due to small number of respondent in the group

31 Group Age BMI Effect size p value Effect size p value Effect size p value Heart rate (b/m) <0.001* Brachial SBP (mmhg) * <0.001* <0.001* Brachial DBP (mmhg) * <0.001* Mean PP (mmhg) * <0.001* PPP (mmhg) * * * Aortic SBP (mmhg) * <0.001* <0.001* Aortic DBP (mmhg) * <0.001* CPP (mmhg) * <0.001* AP (mmhg) <0.001* * AIx (%) <0.001* PWV(m/s) <0.001 * <0.001* Effect size is determined by partial eta 2

32 Failed to show depressed pseudo-che activity level Some other research findings showed significantly lower plasma CHE levels among the pesticide exposed group [Clerk E.E.K et al 1997, Ciesielski et. Al 1994, Sirivarasai J. et. Al. 2007] but some failed to establish the significant difference between the pesticides exposed and non-exposed group [Inayat-Hussain, 2007]. The possible reasons for inconsistent findings were different degree of pesticides exposure, body adaptation in producing more CHE in chronic exposure [Hayes W. J. 1982]

33 This study showed statistically higher heart rate, brachial BP, mean Arterial Pressure, Aortic BP and AIx among the OP pesticides exposed workers compared with the non-exposed group of workers, however the effect size is small. Higher brachial BP is associated with higher risk of cardiovascular disease (Lewington S., Clarke R. et al, 2002, Mac Mohan S, Peto R, 1990) Mean and Pulse Pressure are predictors of cardiovascular disease (Franklin SS, Lopez VA, 2009) Aortic BP has been shown to be an independent predictor of incident cardiovascular disease, independent of brachial systolic blood pressure (Roman, Kizer JR et al. 2005). The AIx has also been shown to be independently correlates with the extent of coronary artery disease (Weber T, Auer J et al. 2004), maximal aortic intima-media thickness (Qureshi G, Brown R et al. 2007), cardiovascular risk (Nürnberger J, Keflioglu-Scheiber A et al. 2002) and all-cause mortality (London GM, Blacher J et al. 2001).

34 The drivers were having higher BMI and had poor pesticides handling practices compared with the General Workers and PHA. Being the driver they had significant increase in terms of brachial and systolic blood pressure, pulse pressure and central BP. However the effect size is small. The obvious findings were age gives significant and strong effects in the changes of Central Pulse Pressure, AIx and PWV BMI gives significant and strong effects in the changes of PWV

35 The study concluded that OP pesticides exposure may contribute to the increase in cardiovascular risk through the changes in CVS haemodynamic parameters. Future study should explore on The genetic and phenotype of PON1 among the OP pesticides exposed workers in association with CVS haemodynamic parameters.

36 Express of thank you to: Director General of Ministry of Health IIUM and PPUKM Staff of Department of Community Health, HUKM Staff of Department of Community Medicine, IIUM and Kulliyyah of Medicine Research assistants