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Exposure To Metal Welding Fume Particles and Risk For Cardiovascular Disease in Denmark: A Prospective Cohort Study
Exposure To Metal Welding Fume Particles and Risk For Cardiovascular Disease in Denmark: A Prospective Cohort Study
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Original article
Original article
to CVD,13e17 whereas others have shown no effect.18 19 Previous to 19 codes for additional diagnoses. Information on outpatients
studies of welders and CVD lacked detailed exposure measure- was added on 1 January 1994. Until the end of 1993, diagnoses
ments (eg, duration, mass or number of particles inhaled), were coded according to an extended Danish version of the
combined all diagnoses of cardiovascular or ischaemic heart International Classification of Diseases, Revision 8 (ICD-8), and
disease, or recorded only mortality from CVD, and few studies after that date according to ICD-10. We defined the first occur-
included adjustment for confounding by, for example, tobacco rence of CVD as the date of first hospitalisation with CVD as
smoking. In the study reported here, we estimated lifelong a main diagnosis after 1 January 1987; if a similar diagnosis had
exposure to welding fume particles, analysed doseeresponse been made earlier as a secondary diagnosis, however, we used this
relationships for different diagnoses of cardiovascular diseases to define the time of diagnosis. We excluded 236 welders’ hospi-
and attempted to adjust for individual lifestyle risk factors. talisations with CVD diagnoses (main or secondary) that had
occurred between 1977 and the start of follow-up.
METHODS We considered nine main disease outcomes from ICD-8 and
Study population ICD-10: acute myocardial infarct (AMI) (410, I21), angina
Potential study participants were selected from a cohort of 10 pectoris (413, I20), other acute ischaemic heart diseases (411,
059 male production workers that was established in 1986 with I24), chronic ischaemic heart disease (CHD) (412, I25), cardiac
the aim of studying associations between metal welding and arrythmias (427, I48 and I49), cardiac arrest (none, I46), heart
lung cancer. The various steps of the construction of the cohort failure (none, I50), cerebral infarct (433 and 434, I63) and arterial
have been described in detail elsewhere20 and are only embolism and thrombosis (444, I74).
summarised here. In 1982, employees of 79 companies in
Denmark with metal welding activities were identified in Assessment of exposure to welding fumes
a survey. After exclusion of shipyards, because of possible The questionnaire elicited information on the welding material
exposure to asbestos, 75 companies remained, employing about used (stainless or mild steel), welding process (manual metal arc,
60% of all Danish stainless-steel welders; five of the larger tungsten inert gas, metal inert gas, metal active gas, spot or gas
companies had substantial numbers of mild-steel welders. All welding), first year of welding, number of years welding in
men born before 1964 and employed by one of these companies various decades, use of exhaust ventilation and welding in
in the period April 1964eDecember 1984 for a minimum of confined spaces. In an attempt to cover any exposure to welding
1 year were then identified from the computerised files of the fumes after the baseline in 1986 and thereby obtain more
nationwide Danish Pension Fund.20 This pension scheme, with complete information about lifelong welding, we included data
compulsory membership for all wage earners aged 16e66 years, from the National Pension Fund register on duration of
contains the person’s name, the dates of the start and end of employment in welding companies after 1986.
each employment at company level (a unique company identi- To estimate total accumulated exposure to welding fume
fication number is assigned for tax purposes) and the unique particles before baseline, we used an exposure matrix based on
personal identification number assigned by the Central Popula- more than 1000 measurements of ambient air particles in the
tion Registry to all residents of Denmark.21 These two registers workplace between 1971 and 1985 made by the Danish Welding
are regarded as both accurate and complete.21 In order to iden- Institute and the National Institute of Occupational Health. Air
tify workers potentially exposed to welding, all the companies samples were collected on filters placed in the breathing zone
were visited in 1986, and employees in departments with behind welding helmets. Filters used were pore size 0.8 mm, so
welding activities were identified from independent information particles smaller than this did not contribute to the mass
in company records, foremen, long-term workers and other measurements. Earlier exposures were estimated by extrapola-
sources. Information on emigration, disappearance and death for tion, on the assumption of a declining trend in exposure in all
each worker identified, was retrieved from the files of the welding processes during 1971e1985. The database provided
Central Population Registry, which was established in 1968. In geometric mean values (mg/m3) for exposure to particulates in
autumn 1986, all the workers (or spouses or long-term each welding process.23
colleagues of deceased or emigrated workers) were sent ques- By linking the exposure matrix to data from the question-
tionnaires eliciting information on lifetime exposure to welding naires on decade, type of steel, welding process, frequency,
and other exposures such as tobacco smoking, use of medica- exhaust ventilation and welding in confined spaces, we were
tions and alcohol consumption. Non-respondents were able to compute the total of number of years that each man had
contacted up to three times. Responses were received from 8376 spent in welding and the particulate concentration in each
workers (83.3%). Of these, 6162 (74.6%) had ever welded at decade and for all decades. This gave a summary measure of
baseline according to the questionnaire. We did not use men who total exposure to welding fumes (mg/m33years) before baseline.
had never welded as an internal comparison group, as this group To obtain a measure of total lifelong exposure before and after
was small and heterogeneous. We excluded three welders with baseline, we calculated an average exposure for 1980e1986 (the
inconsistent personal identification numbers, eight welders who last interval of the questionnaire data) and multiplied it by
immigrated to Greenland and 285 welders who had died before 1 number of years in the welding industry after baseline. Total
January 1987, leaving 5866 men for the analyses. exposure was calculated from data for 3499 welders for whom
consistent information on welding was available from the
Disease experience questionnaire, and especially details on years, processes, etc, for
Information on the occurrence of CVD in this population was the period 1980e1986.
retrieved by linkage to the Danish National Patient Registry by
personal identification numbers. The welders were followed up Statistical analysis
from the start of 1987 until the end of 2006. This computerised The risk for CVD was calculated from 1 January 1987, and
register, with high validity,22 stores information on all persons follow-up ended on the date of hospitalisation for CVD, death,
hospitalised in Denmark since 1 January 1977 and includes dates emigration from Denmark or 31 December 2006, whichever
of admission and discharge, codes for the primary diagnosis and up came first.
Original article
Original article
Table 2 Standardised incidence ratios (SIRs) and 95% CIs for selected cardiovascular diseases among
5866 male Danish welders followed up from 1986 to 2006 and compared with the general male
population
Cumulative particulate exposure
Cardiovascular disease (mg/m33years) Observed Expected SIR 95% CI
Acute myocardial infarct All 377 337.4 1.12 1.01 to 1.24
0e10 11 8.7 1.26 0.63 to 2.26
10e50 40 42.7 0.94 0.94 to 1.28
50e100 80 63.3 1.26 1.00 to 1.57
>100 76 77.3 0.98 0.77 to 1.23
Missing data* 170 145.4 1.17 1.00 to 1.36
Angina pectoris All 437 394.5 1.11 1.01 to 1.22
0e10 9 11.3 0.80 0.36 to 1.52
10e50 65 57.6 1.13 0.87 to 1.44
50e100 87 82.1 1.06 0.85 to 1.31
>100 101 90.4 1.12 0.91 to 1.36
Missing data* 175 153.1 1.14 0.98 to 1.33
Chronic ischaemic heart disease All 326 277.6 1.17 1.05 to 1.31
0e10 5 7.3 0.68 0.22 to 1.59
10e50 42 36.7 1.14 0.82 to 1.55
50e100 68 55.3 1.23 0.95 to 1.56
>100 65 65.3 1.00 0.77 to 1.27
Missing data* 146 15.2 1.29 1.09 to 1.52
Cerebral infarct All 169 136.5 1.24 1.06 to 1.44
0e10 2 3.4 0.58 0.07 to 2.10
10e50 21 16.7 1.26 0.78 to 1.92
50e100 30 25.6 1.17 0.79 to 1.67
>100 46 32.1 1.43 1.05 to 1.91
Missing data* 70 58.7 1.19 0.93 to 1.51
Other acute ischaemic heart disease All 14 13.02 1.08 0.59 to 1.80
Cardiac arrythmias All 237 233.5 1.01 0.89 to 1.15
Cardiac arrest All 32 33.7 0.95 0.65 to 1.34
Heart failure All 157 148.8 1.05 0.90 to 1.23
Arterial embolism and thrombosis All 11 15.3 0.72 0.36 to 1.29
*Welders for whom we had either incomplete information on duration of welding or no information on welding in the period 1980e86
for calculation of cumulative particulate exposure after baseline (from 1 January 1987).
pectoris and CHD than the groups with intermediate exposure The major strengths of our study are the large cohort of
when compared with the reference. It is possible that the group relatively young welders, detailed, prospectively obtained infor-
with the highest exposure were selected ‘healthy workers’. mation about welding processes and the long follow-up of
When we excluded welders who had started work before 1960 in nearly 30 years. In Denmark, all residents have equal, free
order to reduce this possible selection bias, the risk for the group admission to hospital, and, through the Danish National Patient
with the highest exposure increased but was still not signifi- Registry, we were able to obtain information on all relevant
cantly higher than that of the group with the lowest exposure. diseases that required hospitalisation. One limitation of the
This may indicate that there is a threshold of exposure to study is that we did not have information on men with
particles, a ‘healthy worker’ survivor effect or misclassification cardiovascular disorders who were not admitted to hospital; for
of exposure. instance, angina pectoris is sometimes treated by general prac-
One limitation is that particles less than 0.8 mm in size were titioners. As it is unlikely that welders are admitted more or less
not included in the job-exposure matrix. Another is that the often to hospital for a particular disease than the general
effect of specific compounds involved in the welding processes is population, we consider that this limitation does not reduce the
not represented in the jobeexposure matrix algorithms used. In validity of the study. Furthermore, we considered disease
particular, carbon monoxide and ozone generated from shielding outcomes that are usually treated in hospital.
gases used in various welding processes are toxic to the respi- Information on exposure to welding fumes before baseline
ratory system, organs and blood. Carbon monoxide may have an was obtained from self-reports by welders up to 40 years later.
acute effect because of the formation of carboxyhaemoglobin Therefore, the details of welding processes, time spent welding
and have long-term effects via a possible atherogenic mecha- and working conditions might not be totally accurate for the
nism.26 Ozone has been shown to affect levels of the cytokine oldest group. Calculation of cumulative exposure to particulates
interleukin-6 in the bronchoalveolar lavage, which might with the jobeexposure matrix and responses to a questionnaire
increase concentrations of plasma fibrinogen and thereby the is not as precise as individual measurements of inhaled particles
risk for ischaemic heart disease.16 Even though the questionnaire for each welder. Therefore, some differential misclassification of
provided information on specific welding processes and mate- exposure might have occurred, resulting in underestimation of
rials, it was not possible to construct ‘clean’ groups by type of the risk for CVD among the most heavily exposed men.27 28
welding (eg, manual metal arc or metal active gas) or by expo- The addition of information on estimated duration of welding
sure to specific compounds, since the majority of the welders after baseline to the data from the questionnaire strengthens the
worked with different methods over the years. association of exposure during welding and CVD. The compulsory
Original article
Table 3 Adjusted HRRs and 95% CIs for cardiovascular disease among 3499 welders according to
accumulated exposure to particles
Cumulative particulate
Cardiovascular disease exposure (mg/m33years) N* No. of cases HRRy 95% CI
Acute myocardial infarct 0e10 (reference) 37991 17 1 e
10e50 163075 67 1.11 0.65 to 1.89
50e100 184292 96 1.43 0.85 to 2.41
>100 150199 80 1.03 0.61 to 1.74
Log-rank test, c2¼5.95, p¼0.114
Test for trend, c2¼0.00, p¼0.969
routine registration of employment in the Danish Pension Fund have stayed the same over the years for this group of people. The
register ensures that there is no selection of individuals or missing number of welders using hypertension or ‘heart’ medicine is
or incorrect reporting of employment. One limitation in the likely to increase as the cohort grows older, but is only relevant
calculation of cumulative exposure after baseline was the lack of for a smaller group and can be an intermediate step before
information on whether the work specifically included welding experiencing a CVD diagnosis. We had no information on other
and whether the welders continued to have the same hours and risk factors for CVD, such as obesity, high intake of fatty foods,
processes reported in 1986. Also, we assumed that there was no low vegetable intake and low physical activity.29 As we found an
change in exposure after 1980e1986. The semi-quantitative esti- approximate doseeresponse relationship between exposure to
mate of exposure to particulates is therefore an approximate welding particles and CVD, the increased risk is unlikely to be
measure of the true lifelong exposure. We consider, however, that it due only to other, unknown confounders.
is a more informative, complete measure than measures based on Few other studies have investigated the risk for CVD in
total number of years welding (used in other studies) or cumula- welders, and half of them addressed only mortality from such
tive exposure calculated only from data before baseline. causes. One Danish cross-sectional study of AMI and three
True risk can be underestimated when the morbidity rates of cohort studies of mortality due to ischaemic heart disease found
welders are compared with those of the total population (given positive associations with welding, the results being: OR 2.1
no confounding from other exposures), because the general (95% CI 1.05 to 4.30) only for welders with blood type O,
population includes sick and disabled people who are unable to unadjusted17; standardised mortality ratio (SMR) 1.06 (1.02 to
work.16 In our internal analysis, we were able to lessen this 1.11) in the 1970 census and SMR 1.35 (1.10 to 1.64) in the 1990
possible bias and potential confounding by including tobacco census, unadjusted16; SMR 1.51 (1.00 to 2.18) and SMR 1.79
smoking, alcohol consumption and use of hypertension or (p<0.05) for welders who had worked $20 years, adjusted for
‘heart’ medicines. These exposures had, however, only smoking14; and SMR 1.30 (1.04 to 1.56), unadjusted.15 A cohort
a marginal influence on the results. Data on these lifestyle study of 236 workers showed increased risks adjusted for
factors were only collected at one time point and we had no smoking for angina pectoris and chest pain, with prevalence
information about changes over time. Smoking exposure is likely ratios of 2.61 (1.2 to 5.7) and 2.27 (1.5 to 4.9), respectively, and
to have decreased since 1986, and if so our results of welding a non-significant effect for AMI (prevalence ratio 1.37, 0.7 to
effect may be underestimated. Alcohol consumption is likely to 2.8).13 The risk estimate for AMI observed in our study is within
Original article
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Acknowledgements We are indebted to Klaus S Hansen for providing access to
cohort study analysis (WHO/IARC internal report no 89/006). Lyon: WHO/IARC, 1989.
the data on the cohort of welders, to Andrea Meersohn for help with data 25. Stata Corporation. Stata Statistical Software, release 9. College Station, Texas:
processing and to Kirsten Frederiksen for statistical assistance. Stata Corporation, 2006.
Funding This study was supported by a grant from the Danish Working Environment 26. Steenland K. Epidemiology of occupation and coronary heart disease: research
Research Fund. The funding source had no role in the design or analysis of the study or agenda. Am J Ind Med 1996;30:495e9.
in the decision to submit the manuscript for publication. 27. Birkett NJ. Effect of nondifferential misclassification on estimates of odds ratios
with multiple levels of exposure. Am J Epidemiol 1992;136:356e62.
Competing interests None. 28. Dosemeci M, Wacholder S, Lubin JH. Does nondifferential misclassification of
exposure always bias a true effect toward the null value? Am J Epidemiol
Contributors JH and JPB designed and planned the study and developed the 1990;132:746e8.
protocol. EI and AM carried out the statistical analyses. EI, JH and JBP interpreted the 29. Ignarro LJ, Balestrieri ML, Napoli C. Nutrition, physical activity, and cardiovascular
final data analyses and wrote the manuscript. disease: an update. Cardiovasc Res 2007;73:326e40.
Provenance and peer review Not commissioned; externally peer reviewed. 30. Magari SR, Hauser R, Schwartz J, et al. Association of heart rate variability with
occupational and environmental exposure to particulate air pollution. Circulation
2001;104:986e91.
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Occup Environ Med 2010 67: 772-777 originally published online June
27, 2010
doi: 10.1136/oem.2009.051086
These include:
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Notes