Constanze Leineweber
email: constanze.leineweber@stressforskning.su.se

Hugo Westerlund

Töres Theorell

Mika Kivimäki

professor emeritus Peter Westerholm

Lars Alfredsson

Covert coping with unfair treatment at work and risk of incident myocardial infarction and cardiac death among men: Prospective cohort study

Keywords: Coping, myocardial infarction, prospective studies

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

Coping is defined as action-oriented and intra-psychic efforts to manage the demands created by stressful events, and various measures to assess coping in specific stressful situation have been developed. [START_REF] Lazarus | Stress, Appraisal, and Coping[END_REF][START_REF] Taylor | Coping resources, coping precesses, and mental health[END_REF][START_REF] Folkman | Coping: Pitfalls and Promise[END_REF] Coping responses can be divided into problem-focused coping, which involves addressing the problem that causes distress, and emotion-focused coping, which is aimed at ameliorating the negative emotions associated with the problem. [START_REF] Folkman | An analysis of coping in a middle-aged community sample[END_REF] Although there is a clear individual component to a preferred coping pattern, environmental factors also play an important role. For example, it has been shown that subjects with low job control at work more often used a covert, avoiding coping style. [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF] Avoidant coping responses have been operationalised by Harburg et al. [START_REF] Harburg | Socio-ecological stress, suppressed hostility, skin color, and Black-White male blood pressure: Detroit[END_REF] According to his definition, covert coping refers "to a strategy of walking away from the conflict dealing with it indirectly and introvertly". [START_REF] Nordin | Low social support and disturbed sleep. Epidemiological and psychological perspectives[END_REF] There is evidence to show that covert coping is related to signs of coronary heart disease, high blood pressure, high levels of Apo-lipoprotein A1, as well as increased rates of sickness absence. [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF][START_REF] Theorell | Coping with critical life events and lack of control--the exertion of control[END_REF][START_REF] Härenstam | Coping with anger-provoking situations, psychosocial working conditions, and ECG-detected signs of coronary heart disease[END_REF] However, the underlying mechanisms still remain largely unknown. An often stated hypothesis is that circumstances that frequently evoke anger may result in psychophysiological tension which, in turn, facilitates the development of hypertension and related illnesses, particularly when anger is not expressed. [START_REF] Theorell | Coping with critical life events and lack of control--the exertion of control[END_REF][START_REF] Knox | Emotional coping and the psychophysiological substrates of elevated blood pressure[END_REF] The basic idea is that arousal that 'boils under the surface' and is not allowed to be constructively dealt with will cause physiological reactions. Indeed, the perception of unfair treatment has been shown to be associated with risk factors for cardiovascular disease. [START_REF] Guyll | Discrimination and unfair treatment: relationship to cardiovascular reactivity among African American and European American women[END_REF][START_REF] Troxel | Chronic stress burden, discrimination, and subclinical carotid artery disease in African American and Caucasian women[END_REF][START_REF] Lewis | Chronic exposure to everyday discrimination and coronary artery calcification in African-American women: the SWAN Heart Study[END_REF] The aim of the present study was to explore whether covert coping is prospectively associated with risk of myocardial infarction (MI) and cardiac death among working men.

METHODS

Study population

Data were drawn from the WOLF (WOrk, Lipids, and Fibrinogen) Stockholm study; a prospective cohort study of employees initially aged 19 to 70 years, working in companies in the Stockholm area. [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF][START_REF]Statistical yearbook of Sweden 1997[END_REF] Twenty occupational health units carried out the baseline screening between November 1992 and June 1995. With 76% participation, 3,239 men and 2,459 women participated in a clinical examination and questionnaire survey. A more detailed description of the study has been given elsewhere. [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF][START_REF] Alfredsson | Job strain and major risk factors for coronary heart disease among employed males and females in a Swedish study on work, lipids and fibrinogen[END_REF] Records of hospital admissions and deaths by the end of 2003 were obtained from national registers and linked to the data. We restricted the analyses to men only, since the number of myocardial infarctions and cardiac deaths among women was too low (n = 7). We also excluded 466 men who lacked complete data on the studied variables and/or any of the adjustment variables and 18 men who had prevalent myocardial infarction at inclusion in the WOLF study, leaving 2,755 men in the studied population. Ethical approval for the WOLF Stockholm study was obtained from the regional ethics committee in Stockholm.

Assessment of Covert Coping

Coping with unfair treatment at work was measured by means of a questionnaire focusing on two different factors, 'covert' and 'open coping' with unfair treatment. This questionnaire is based on a Swedish version of a questionnaire originally developed for a U.S. study on high blood pressure and has been extensively tested. [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF][START_REF] Harburg | Socio-ecological stress, suppressed hostility, skin color, and Black-White male blood pressure: Detroit[END_REF][START_REF] Härenstam | Coping with anger-provoking situations, psychosocial working conditions, and ECG-detected signs of coronary heart disease[END_REF][START_REF] Theorell | The Stockholm MUSIC 1 Study Group. Validitetsprovning av psykosociala indexbildningar (Validity tests of psychosocial indexes)[END_REF] Here we focus on covert coping. After an opening question which asks how the subject usually reacts when treated in an unfair way or when getting into conflict with (a) a superior, or (b) a workmate, different sub-questions are given. Four sub-questions measure covert coping or the results thereof: 'Let things pass without saying anything', 'Go away', 'Feeling bad (headache, stomach aching etc.)' and 'Get into a bad temper at home'. The first two sub-questions concern the immediate reaction, whereas the last two questions are about possible consequences of covert coping. For each alternative, the subject should indicate on a 4-point scale to what degree it applies to them, from 1='never' to 4='always'. The same questions are asked regarding both superiors and workmates. Cronbach's alpha for the covert coping scale was 0.77 for the entire scale on covert coping; when excluding the questions addressing consequences of covert coping, Cronbach's alpha increased to 0.83. A sum score of covert coping ranging from 8 to 32 was calculated. For statistical analyses covert coping was, following our practice, categorised into low (lowest quartile, score 8-14), medium (second and third quartile, score 15-18) and high (upper quartile, score [START_REF] Drexler | The role of hyperlipidaemia in peripheral arterial acclusive disease[END_REF][START_REF] Kniepeiss | Dyslipidemia during sirolimus therapy in patients after liver transplantation[END_REF][START_REF] Ernst | Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature[END_REF][START_REF] Eriksen | The CODE: a revised battery for coping and defense and its relations to subjective health[END_REF][START_REF] Schreurs | De Utrechtse Coping Lijst: Handleiding[END_REF][START_REF] Haynes | The relationship of psychosocial factors to coronary heart disease in the Framingham Study. III. Eight-year incidence of coronary heart disease[END_REF][START_REF] Julius | Anger-coping types, blood pressure, and all-cause mortality: a follow-up in Tecumseh, Michigan (1971-1983)[END_REF][START_REF] Gallacher | Anger and incident heart disease in the caerphilly study[END_REF][START_REF] Engebretson | Relations between anger expression and cardiovascular reactivity: Reconciling inconsistent findings through a matching hypothesis[END_REF][START_REF] Bosma | Job control, personal characteristics, and heart disease[END_REF][START_REF] Theorell | Decision latitude, job strain, and myocardial infarction: A study of working men in Stockholm[END_REF][START_REF] Deanfield | Silent myocardial ischaemia due to mental stress[END_REF][START_REF] Kivimaki | Justice at work and reduced risk of coronary heart disease among employees: the Whitehall II Study[END_REF][START_REF] Elovainio | Justice at work and cardiovascular mortality: a prospective cohort study[END_REF]. [START_REF] Theorell | Coping with critical life events and lack of control--the exertion of control[END_REF] In a further step, we restricted calculations to the two items measuring the direct reaction and a sum score of covert coping ranging from 4 to 16, which also was categorised into low (score 4-7), medium (score 8-10) and high (score [START_REF] Guyll | Discrimination and unfair treatment: relationship to cardiovascular reactivity among African American and European American women[END_REF][START_REF] Troxel | Chronic stress burden, discrimination, and subclinical carotid artery disease in African American and Caucasian women[END_REF][START_REF] Lewis | Chronic exposure to everyday discrimination and coronary artery calcification in African-American women: the SWAN Heart Study[END_REF][START_REF]Statistical yearbook of Sweden 1997[END_REF][START_REF] Alfredsson | Job strain and major risk factors for coronary heart disease among employed males and females in a Swedish study on work, lipids and fibrinogen[END_REF][START_REF] Theorell | The Stockholm MUSIC 1 Study Group. Validitetsprovning av psykosociala indexbildningar (Validity tests of psychosocial indexes)[END_REF]. For calculating the effect of each one of the covert coping items on myocardial infarction risk we combined the response options 'seldom/never' for 'let things pass without saying anything' and 'often/sometimes' for the remaining questions. We chose this categorization due to a low number of cases in some cells.

Covariates

Education, smoking status (current smoker versus non-smoker), drinking problems, physical activity (from 1="sedentary" to 4="regular exercise"), diabetes, job demands, decision latitude, and conflicts at the workplace were self-reported. Education was categorised into low ( Fibrinogen in plasma (mmol/L) was determined by spectrometric test. Blood pressure, BMI, total cholesterol level and triglycerin were divided following the recommendations of the American Heart Association. [18] Systolic and diastolic blood pressure was divided into optimal (≤119 mmHg and ≤ 79 mmHg, respectively), pre-hypertensive (120-139 mmHg and 80-89 mmHg) and hypertensive (≥140 mmHg and ≥ 90 mmHg). BMI was divided into underweight and normal (<25), overweight (25-29.9) and obese (≥ 30). Total cholesterol was divided into desirable (≤5.19 mmol/L), borderline-high risk (5.20-6.25 mmol/L) and high risk (>6.25 mmol/L). Triglycerides were divided into normal (<1.7 mmol/L), borderline (1.7-2.2 mmol/L) and high (>2.2 mmol/L).

The quotient total/HDL was following the literature divided into low (<4.0) and high (≥4.0). [START_REF] Drexler | The role of hyperlipidaemia in peripheral arterial acclusive disease[END_REF][START_REF] Kniepeiss | Dyslipidemia during sirolimus therapy in patients after liver transplantation[END_REF] Fibrinogen was divided into low (≤3.0 mmol/L) and high (>3.0 mmol/L). [START_REF] Ernst | Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature[END_REF]

Follow-up

Hard endpoint outcome for acute myocardial infarction was defined as hospital admission with a Follow-up time for cases was defined as the difference between the year of inclusion in the study and the year of the first event. The range was between one and 11 years.

Statistical Analysis

Time to the event was defined as the number of days between baseline screening and the first

RESULTS

Sample characteristics by level of covert coping are shown in Table 1. The participants were on average 41.5 years old at baseline and most of them highly educated and non-smokers. About a quarter of the subjects had supervisory status. Around half of the participants or more had favourable values on physiological risk factors. Among the 2,755 men included in the study, a total of 47 incident MI or cardiac death occurred during the mean follow-up period of 9.8 ± 0.9 years. Table 4 shows the associations of covert coping with risk of acute myocardial infarction or cardiac death. A high score on covert coping was associated with more than double risk of acute myocardial infarction or cardiac death. The test for linear trend showed a tendency towards a significant effect, which however decreased with adjustments for covariates. Tables 2 and3 clearly show that only the two items measuring the immediate response to an unfair treatment were related to the outcome, or showed a clear tendency of doing so, but not those that concerned consequences of covert coping, i.e. 'Feeling bad' and 'Getting into a bad temper at home'. Thus, in a further step, we restricted our analyses to the two items corresponding to the immediate response (or 'avoidance and passive expectancy' according to the Utrecht coping scale), [START_REF] Eriksen | The CODE: a revised battery for coping and defense and its relations to subjective health[END_REF] and excluded the remaining items from the covert coping scale.

Subjects who often use covert coping according to this shortened scale had a more than [START_REF] Theorell | Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)[END_REF] Figure 1 provides the Kaplan-Meier survival curve for the cumulative hazard rates of MI or cardiac death by levels of covert coping. An increased risk of MI or cardiac death appears soon after baseline. The separation in cumulative rates between the groups widens throughout the follow-up period.

-----------------------------------------figure 1 in here --------------------------------------------

Figure1. Age-adjusted survival function of cumulative hazard rates of myocardial infarction or cardiac death by levels of covert coping (short scale) among men free of cardiac disease at baseline (n=2755).

DISCUSSION

In this cohort of Swedish men, covert coping was associated with increased risk of future acute myocardial infarction and cardiac death. Analyses of the original covert coping scale showed that men who have a pronouncedly covert coping style had approximately two times greater risk compared with men with low levels of covert coping. As this scale combines covert coping with consequences of such coping, we ran subsidiary analyses using data exclusively from the two items that most directly assess direct covert coping, i.e., ' 4).

We refined the covert coping scale after performing an item-based analysis; the results based on these post hoc modifications in the exposure measure should therefore be interpreted cautiously and replicated in independent data sets. We believe that the observed association is real rather than attributable to chance. The two items in the refined scale were conceptually relevant, capturing immediate response to unfair treatment rather than longer-term consequences. The two items are also included in the Utrecht coping list (UCL) and the CODE scale, which partly builds on the UCL. [START_REF] Eriksen | The CODE: a revised battery for coping and defense and its relations to subjective health[END_REF][START_REF] Schreurs | De Utrechtse Coping Lijst: Handleiding[END_REF] In the UCL these two items are part of the same subscale 'Avoidance and passive expectancy' and in CODE this scale loads negatively on the coping factor 'Instrumental mastery-orientated coping', which may indicate that these two items are distinct from the other two covert coping items. It is noteworthy that our findings are consistent with previous studies using slightly different measures. For example, in the Framingham Study men who exhibited suppressed hostility (i.e. not showing anger) were found to be at increased risk of developing CHD and in a study by Julius et al. higher risk of ischemic heart disease (IHD) was found for those who suppressed anger. [START_REF] Haynes | The relationship of psychosocial factors to coronary heart disease in the Framingham Study. III. Eight-year incidence of coronary heart disease[END_REF][START_REF] Julius | Anger-coping types, blood pressure, and all-cause mortality: a follow-up in Tecumseh, Michigan (1971-1983)[END_REF] In the Caerphilly study anger out and suppressed anger were both predictive of incident IHD over a 9 year follow-up period. The items of the covert coping scale do not specify whether the respondent had actually been exposed to conflicts and unfair treatment at work, or how frequently they used covert coping. Furthermore, the questions were framed to involve unfair treatment and a conflict at work, which is a relatively specific context for a measurement of coping and corresponds to that used in the Whitehall II study. [START_REF] Bosma | Job control, personal characteristics, and heart disease[END_REF] Unlike the Framingham scales for anger management, which includes more generally framed questions (e.g., "When really angry or annoyed do you keep it to yourself?"), the covert coping scale is not limited to anger episodes. Indeed, although anger is a common reaction to unfair treatment; a proportion of people might react in other ways, e.g. by getting upset, sad or feeling guilty.

Confounding is a possible explanation for any findings of associations in observational studies. Given that high levels of covert coping are associated with low decision latitude, which in turn has been shown to be related to increased risk of myocardial infarction, it is possible that the association between covert coping and risk of myocardial infarction is driven by low decision latitude. [START_REF] Theorell | Decision latitude, job strain, and myocardial infarction: A study of working men in Stockholm[END_REF] In the present study, however, this is unlikely because the association between covert coping and cardiac events remained after controlling for decision latitude and job demands. An alternative hypothesis regarding the association between covert coping and coronary events is that it may induce acute physiological reactions, such as a dramatic but momentary increase in blood pressure, which are harmless to the healthy person and leave no physiological traces, but which could act on an underlying or subclinical cardiovascular disease and trigger an MI. [START_REF] Deanfield | Silent myocardial ischaemia due to mental stress[END_REF] If covert coping patterns are relatively stable, this could explain the association.

If the association between covert coping and increased heart disease is indeed causal, then avoidance of covert coping may lead to health benefits and other studies additionally suggest that low exposure to unfair treatment may also reduce risk of coronary heart disease incidence and cardiovascular mortality. [START_REF] Kivimaki | Justice at work and reduced risk of coronary heart disease among employees: the Whitehall II Study[END_REF][START_REF] Elovainio | Justice at work and cardiovascular mortality: a prospective cohort study[END_REF]

7 to 10 years

 10 of education), intermediate (vocational school, 10 or 11 years of education), high (12 years or more), and other education. Drinking problems were measured by a single question: 'Have you sought help during the last 10 years because of drinking problems?' with response alternatives 'yes' and 'no'. Diabetes was recorded by means of the question 'Do you have diabetes?' with response options 'yes' and 'no'. Job demands (five-item scale) and decision latitude (six-item scale) were measured by the Swedish Demand-Control Questionnaire and dichotomised (lower 80 % vs. upper 20 %). [17] Conflicts at the workplace were measured by an opening question: 'During the past 12 months, have you experienced one of the following life events?' One of these is conflicts at the workplace. Response alternatives are 'yes' and 'no'. The gross salary of 1994 was derived from the Income and Tax Register (IoT) and divided into quartiles. Systolic and diastolic blood pressure (mmHg) was measured on the right arm in the supine position after 5 minutes rest twice with 1-minute intermission. Height and weight were measured to determine body mass index (BMI, kg/m 2 ). Blood samples were taken after an overnight fast and analyzed in the same laboratory (CALAB Medical Laboratories AB, Stockholm, Sweden) accredited by Swedish Board for Accreditation and Conforming Assessment. Total cholesterol (mmol/L) and high density lipoprotein (HDL) cholesterol (mmol/L) were measured enzymatically after precipitation with phospotungstic acid and magnesium chloride. Low density lipoprotein (LDL) cholesterol concentration was calculated by the Friedewald formula.

  main diagnosis registered as acute myocardial infarction (the International Classification of Diseases, version 9 [ICD-9] code 410 or version 10 [ICD-10] code I21); or death with a registered underlying cause of coronary disease (ICD-9: 410-414; ICD-10: I20-I25) or cardiac arrest (ICD-9: 427; ICD-10: I46). Records of hospital admissions and deaths were obtained from 14 March 1963 until 31 December 2003. Incident cases were defined as the first event occurring after the baseline screening (November 1992 to June 1995). Those with prevalent ischemic disease at baseline were determined by a registered hospital admission for myocardial infarction between 1963 and the baseline screening, and they were excluded from the analysis (18 men).

  diagnosis after baseline and before 31 December 2003. For subjects with no events, the end of follow-up was 31 December 2003, or the date of death if earlier. Outcome of the analyses was a composite measure of acute MI and cardiac death. Cox proportional hazard regression models adjusting for potential confounders were constructed. Hazard ratios (HRs) are presented with their 95 % confidence intervals (CIs). In a first step we controlled for age solely. In further successive steps we additionally controlled for (a) demographic and socioeconomic factors (i.e. education, supervisory status, and income); (b) behavioural risk factors (i.e. smoking, physical activity, and drinking problems; (c) job demands and decision latitude; and (d) biological risk factors (i.e. BMI, systolic and diastolic blood pressure, total cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, fibrinogen, and diabetes). The significance of the trend was assessed by using covert coping as a continuous variable in the regression model. Chisquare tests and analyses of variance were performed to evaluate the association between covert coping and control variables. All individuals with any missing data on exposure or any covariate were excluded from any analyses. We used SPSS for Windows version 17.0 for the statistical analyses.

  Let things pass without saying anything' and 'Going away'. Based on this refined scale, men who often used covert coping had a more than 5-fold risk of myocardial infarction or cardiac death. As an indication of dose-response, those with less consistent patterns of covert coping had also less pronounced excess risk and the trend across levels of covert coping reached statistical significance. Expected associations between conventional risk factors and risk of myocardial infarction or cardiac death, such as drinking problems (HR=4.10; 95 % CI: 1.06-15.82), elevated triglycerides (HR=2.32; 95 % CI: 1.12-4.84) and diabetes (HR=4.04; 95 % CI: 1.36-12.02) provide support for the validity of our findings (all multivariate adjusted as in model 5, table

[ 26 ]

 26 Engebretson et al. proposed a matching hypothesis whereby adaptive responses to anger-provocation would occur among people who could use their preferred mode of anger management. [27] A 'mismatch', in contrast, occurs, for instance, when people who habitually express anger are forced by circumstances, experimental manipulations or real-life social constraints, to suppress it.

  Our data provide no answer to the question what might be a particularly healthy coping strategy. In the questionnaire, open coping was assessed by items requesting whether the respondent would 'Protest directly', 'Talk to the person right away', 'Yell at the person right away', and 'Speak to the person

Table 1 .

 1 Sample Characteristics stratified

by Covert Coping, Short Index incl. only Behaviour

	(n = 2,755 men)
		Covert coping, short index (mean ± SD)
	Risk Factor at Baseline	low	intermediate	high
	Age, yrs*	40.9±10.6	41.4±10.6	42.4±11.7
	Mean income 1994, US$1000 per yr***	205±109	209±108	182±89
	Demands (scale 1-4)**	2.1±0.4	2.1±0.4	2.2±0.4
	Decision latitude (scale 1-4)***	1.9±0.6	1.9±0.5	2.0±0.6
			% (n)
	BMI
	Normal (<25 kg/m 2 )	50.6 (362)	51.1 (669)	51.4 (375)
	Overweight (25-29.9 kg/m 2 )	42.2 (302)	40.5 (531)	40.8 (398)
	Obese (≥ 30 kg/m 2 )	7.1 (51)	8.4 (110)	7.8 (57)
	Systolic blood pressure
	Optimal (≤ 119 mmHg)	37.5 (268)	38.2 (501)	36.6 (267)
	Pre-hypertensive (120-139 mmHg)	50.5 (361)	47.2 (619)	47.9 (350)
	Hypertensive (≥ 140 mmHg)	12.0 (86)	14.6 (191)	15.5 (113)
	Diastolic blood pressure
	Optimal (≤ 79 mmHg)	63.8 (456)	65.0 (852)	61.8 (451)
	Pre-hypertensive (80-89 mmHg)	28.5 (204)	26.4 (346)	28.1 (205)
	Hypertensive (≥ 90 mmHg)	7.7 (55)	8.5 (112)	10.1 (74)
	Total cholesterol
	Desirable (≤ 5.19 mmol/L)	41.4 (296)	41.2 (540)	40.5 (296)
	Borderline risk (5.20-6.25 mmol/L)	34.7 (248)	33.4 (437)	37.1 (271)
	High risk (>6.25 mmol/L)	23.9 (171)	25.4 (333)	22.3 (163)
	Total / HDL cholesterol ratio
	Normal (<4.0 mmol/L)	52.7 (377)	48.9 (640)	49.2 (359)
	High (≥ 4.0 mmol/L)	47.3 (338)	51.1 (670)	50.8 (371)
	Triglycerides
	Normal (<1.7 mmol/L)	75.9 (543)	75.0 (982)	71.9 (525)
	Borderline (1.7-2.2 mmol/L)	12.3 (88)	12.7 (166)	15.9 (116)
	High/very high (>2.2 mmol/L)	11.7(84)	12.4 (162)	12.2 (89)
	Fibrinogen
	Normal (≤ 3.0 mmol/L)	73.3 (524)	72.7 (953)	70.3 (513)
	High (> 3.0 mmol/L)	26.7 (191)	27.3 (357)	29.7 (217)
	Diabetes, yes	0.7 (6)	1.6 (21)	1.9 (14)
	Education***
	Low	17.8 (127)	15.1 (298)	21.1 (154)
	Intermediate	29.5 (211)	26.3 (345)	28.4 (207)
	High	52.7 (377)	58.5 (767)	50.5 (369)
	Supervisory status, yes***	27.8 (199)	26.5 (347)	14.1 (103)
	Sought help for drinking problems, yes	1.3 (9)	1.1 (15)	1.1 (8)
	Current smoker, yes	24.9 (178)	22.4 (294)	23.3 (170)
	*** p ≤.001; ** p ≤.01; * p≤.05
	Statistically significant differences between covert coping groups were found with regard to age,
	income, demands and decision latitude at work, education, and supervisory status.

Table

2

and 3 shows results on the associations between individual covert coping items and risk of acute myocardial infarction and cardiac death. Men who reported 'going away' when having a conflict with a workmate or a supervisor sometimes or often had a more than tripled risk for MI or cardiac death compared with those who never go away. Showing this behaviour seldom when having a conflict with a workmate

also increased the risk noticeably. Those who 'Let things pass without saying anything' sometimes or often compared with those seldom or never let this happen had an increased risk for MI or cardiac death, although this did not reach statistical significance

  . 'Feeling bad' and 'getting into a bad temper at home' were not associated with an increased risk of acute myocardial infarction or cardiac death.

Table 2 .

 2 Age-adjusted Associations of Covert Coping When Treated Unfairly by a Boss with Hard

	End Point Myocardial Infarction or Cardiac Death among Men free of Myocardial Infarction at
	Baseline (n=2755).
			Acute MI or Cardiac Death*
		No. of	No. of	Hazard Ratio (95%
		Men	(Events)	CI)
	…with a boss?
	Let things pass without saying
	anything
	Seldom or never	1406	17	1
	Sometimes	954	20	1.76 (0.92-3.56)
	Often	348	10	2.09 (0.95-4.60)
	Go away
	Never	779	6	1
	Seldom	1123	20	2.38 (0.95-5.92)
	Sometimes or often	806	21	3.05 (1.23-7.58)
	Feel bad (head or stomach ache etc)
	Never	1035	16	1
	Seldom	1028	19	1.06 (0.54-2.206)
	Sometimes or often	645	12	1.05 (0.49-2.22)
	Get into a bad temper at home
	Never	761	15	1
	Seldom	1114	16	0.72 (0.36-1.46)
	Sometimes or often	833	16	1.03 (0.51-2.09)
	*Includes acute MI (ICD-10: I21) necessitating hospitalization or death from ischemic heart disease (ICD-
	10:I20-level)

How do you usually react if you are unjustly treated or become involved in a conflict...

Table 3 .

 3 Age-adjusted Associations of Covert Coping When Treated Unfairly by a Workmate with Hard End Point Myocardial Infarction or Cardiac Death among Men free of MyocardialInfarction at Baseline (n=2755).

	How

do you usually react if you are unjustly treated or become involved in a conflict... Acute MI or Cardiac Death* No. of Men

			No. of	Hazard Ratio (95%
			(Events)	CI)
	...with a workmate?
	Let things pass without saying
	anything
	Seldom or never	1514	18	1
	Sometimes	919	20	1.75 (0.92-3.31)
	Often	275	9	2.10 (0.94-4.73)
	Go away
	Never	788	4	1
	Seldom	1123	23	4.08 (1.41-11.80)
	Sometimes or often	797	20	4.45 (1.52-13.04)
	Feel bad (head or stomach ache etc)
	Never	1077	17	1
	Seldom	1070	21	1.12 (0.59-2.13)
	Sometimes or often	5861	9	0.90 (0.40-2.02)
	Get into a bad temper at home
	Never	829	17	1
	Seldom	1147	16	0.76 (0.39-1.47)
	Sometimes or often	732	12	0.86 (0.41-1.81)
	*Includes acute MI (ICD-10: I21) necessitating hospitalization or death from ischemic heart disease (ICD-
	10:I20-level)

Table 4 .

 4 Associations of Covert Coping (long scale) when Treated Unfairly with Hard End Point Acute Myocardial Infarction (MI) or Cardiac Death Among Men Free of Apparent MI at Baseline after Adjustment for Different Risk Factors at Baseline (n=2755).

	Model 1	Model 2	Model 3	Model 4	Model 5

a adjusted for age, b adjusted for age and demographic and socioeconomic factors; c adjusted for the

same variables as in model 2 and behavioural

risk factors; d adjusted for the same variables as in model 3 and decision latitude and demand at work; e adjusted for the

same variables as in model 4 and biological risk factors

table 4 ). Controlling for conflict at the workplace did not change the results substantially (HR=4.20; 95 % CI: 1.25 to 14.14 and HR=5.94; 95 % CI: 1.75 to 20.19).

 4

	-fold

MK is supported by the Academy of Finland (projects 117614, 124322 and 124271). CL, TT, and HW are financed by a research program grant from the Swedish Council for Working Life and Social Research (FAS, grant no. 2004-2021). The WOLF study was originally funded by the Swedish Council for Working Life and Social Research (FAS, grant no. 2001-0163). All authors are independent from their funders.

later when things have calmed down' when experiencing unfair treatment or facing with a conflict. However, there was no association between such active ("open") coping strategies and myocardial infarction or cardiac death.

Our study has several major strengths. Our data is based on a longitudinal study and loss to follow-up was minimal and comprised only those individuals who emigrated during the study period. The outcomes we used, myocardial infarction and cardiac death, were based on objective criteria (e.g. electrocardiography and enzymes) and are not self-reported. However, despite the longitudinal nature of our study, we cannot draw definite conclusions about causation. On the basis of this present dataset it is not possible to attribute with any certainty the association observed to coping behaviour; other factors could also operate as risk determinants, such as a personality trait or some other personal characteristic underlying the coping pattern.

Furthermore, the measure of covert coping we used may capture subjection to unfair treatment rather than a pure coping style. However, the term "covert coping" has been used earlier and we decided to follow this tradition. Because of an insufficient number of cardiac events among women, only men were included in the analyses. Analyses with the total cohort combining men and women yielded nearly identical results to the one reported here (results not shown) but do not justify conclusions regarding the effects of covert coping on myocardial infarction and cardiac death risk among women.

In sum, these data raise an interesting hypothesis which needs to be confirmed or refuted by future studies. Important directions into the future include a closer investigation of the concept of covert coping, including testing of its psychometric properties. Ultimately, further research should examine whether interventions designed to reduce covert coping would alter risk of myocardial infarction and cardiac death.

COMPETING INTEREST

All authors declare that the answer to the questions on your competing interest form are all No and therefore have nothing to declare FUNDING


Patrícia Padrão

Carla Silva-Matos

Albertino Damasceno

Nuno Lunet
email: nlunet@med.up.pt

Association between tobacco consumption and alcohol, vegetable and fruit intake across urban and rural areas in Mozambique

Keywords: Smoking, Smokeless tobacco, Alcohol drinking, Fruit, Vegetable, Mozambique

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

of alcoholic beverages and a lower intake of vegetables and fruit. Evidence from developing countries, at the early phases of the tobacco epidemics and with markedly different cultures, lifestyles and forms of tobacco use, was scarce.

• This manuscript is the first that addresses this topic in an African country, adding knowledge on the discrimination of different types of tobacco use when evaluating the association between those forms of tobacco exposure and the consumption of alcoholic beverages (according to type), fruit and vegetable. Our results show that the use of distinct types of tobacco is associated with different dietary choices. Positive associations were found between tobacco use and alcohol drinking, regardless of type of tobacco consumed, but differences were observed according to the main type of alcoholic beverage consumed, with the smoking of hand rolled cigarettes and the consumption of smokeless tobacco being negatively associated with beer drinking. Manufactured cigarette smokers exhibited a less frequent intake of fruit, but a consistently negative association between smoking of manufactured cigarettes and vegetable intake was observed only in women. Conversely, smokeless tobacco consumption and hand-rolled cigarette smoking were not inversely related to fruit and vegetables intake.

BACKGROUND

The leading causes of death in Sub-Saharan African countries at the earliest stage of the epidemiologic transition, [START_REF] Yusuf | Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization[END_REF] are HIV/AIDS, malaria and diarrhoeal diseases.[2] Nevertheless, morbidity and mortality from cardiovascular disease, cancer and chronic respiratory disease, all associated with smoking, are now responsible for a "double burden" on low income countries. [START_REF]Preventing chronic diseases : a vital investment : WHO global report[END_REF] Cardiovascular disease accounts for 10% of all deaths, [START_REF] Yusuf | Global Burden of Cardiovascular Diseases: Part II: Variations in Cardiovascular Disease by Specific Ethnic Groups and Geographic Regions and Prevention Strategies[END_REF] and cancer for 4%. [START_REF] Sitas | Disease and Mortality in Sub-Saharan Africa[END_REF] The patterns of tobacco consumption are shaped by demographic, economic, and cultural determinants, [START_REF] Ezzati | Estimates of global mortality attributable to smoking in 2000[END_REF] as well as by other specific factors operating at different phases of the smoking epidemic, such as the tobacco industry pressure and politics for controlling tobacco exposure. [START_REF] Lunet | Tobacco advertising in Maputo, Mozambique: how will they keep pressing?[END_REF][START_REF] Eriksen | The Diffusion and Impact of Clean Indoor Air Laws[END_REF][START_REF] Gallus | Price and cigarette consumption in Europe[END_REF][START_REF] Lopez | A descriptive model of the cigarette epidemic in developed countries[END_REF] In the African setting, oppositely to most high income societies, hand-rolled cigarettes and smokeless tobacco are commonly consumed, in addition to manufactured cigarettes. However, with urbanization those traditional forms of tobacco use are shifting to manufactured cigarettes' smoking and the prevalence of smoking is also expected to increase, [START_REF] Townsend | A systematic literature review of tobacco use among adults 15 years and older in sub-Saharan Africa[END_REF] Urbanization is also associated with an increase in the consumption of energy rich foods and a reduction in physical activity. Global influences (via advertising or increased availability of processed and animal-source food) contribute to changes in the types of food consumed in both urban and rural areas. [START_REF] Yusuf | Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization[END_REF][START_REF] Popkin | Global nutrition dynamics: the world is shifting rapidly toward a diet linked with noncommunicable diseases[END_REF]13] Smoking, alcohol consumption and unhealthy diet tend to cluster and are all major modifiable contributors to the burden of chronic disease. [START_REF] Yach | Global Chronic Diseases[END_REF] Tobacco consumers have a higher consumption of alcoholic beverages, [START_REF] Fisher | The relation of drinking and smoking habits to diet: the Lipid Research Clinics Prevalence Study[END_REF][START_REF] Ramos | Diet and smoking in Spain and Portugal: a comment[END_REF][START_REF] Laaksonen | Associations among health-related behaviours: sociodemographic variation in Finland[END_REF][START_REF] Rust | Relationship between dietary intake, antioxidant status and smoking habits in female Austrian smokers[END_REF][START_REF] Majem | Food consumption and nutrient intake in relation to smoking (article in Spanish)[END_REF][START_REF] Morabia | Effects of smoking and smoking cessation on dietary habits of a Swiss urban population[END_REF][START_REF] Morabia | Dietary habits of smokers, people who never smoked, and exsmokers[END_REF][START_REF] Dallongeville | Cigarette smoking is associated with unhealthy patterns of nutrient intake: a Meta-analysis[END_REF] and a lower intake of vegetable and fruit. [START_REF] Morabia | Effects of smoking and smoking cessation on dietary habits of a Swiss urban population[END_REF][START_REF] Morabia | Dietary habits of smokers, people who never smoked, and exsmokers[END_REF][START_REF] Dallongeville | Cigarette smoking is associated with unhealthy patterns of nutrient intake: a Meta-analysis[END_REF][START_REF] Marangon | Diet, antioxidant status, and smoking habits in French men[END_REF][START_REF] Palaniappan | Fruit and vegetable consumption is lower and saturated fat intake is higher among Canadians reporting smoking[END_REF][START_REF] Hebert | Differences in dietary intake associated with smoking status[END_REF][START_REF] Margetts | Interations between people's diet and their smoking habits:the dietary and nutritional survey of British adults[END_REF][START_REF] Woo | Dietary habit of smokers in a Chinese population[END_REF][START_REF] Padrao | Smoking, alcohol, and dietary choices: evidence from the Portuguese National Health Survey[END_REF][START_REF] Osler | Does the association between smoking status and selected healthy foods depend on gender? A population-based study of 54 417 middle-aged Danes[END_REF][START_REF] Billson | Variation in fruit and vegetable consumption among adults in Britain. An analysis from the dietary and nutritional survey of British adults[END_REF][START_REF] Pollard | Lifestyle factors affecting fruit and vegetable consumption in the UK Women's Cohort Study[END_REF][START_REF] Koh | Middle-Aged and Older Chinese Men and Women in Singapore Who Smoke Have Less Healthy Diets and Lifestyles than Nonsmokers[END_REF][START_REF] Wilson | Differences in food intake and exercise by smoking status in adolescents[END_REF][START_REF] Oshaug | Tobacco smoking, an independent determinant for unhealthy diet? A cross-sectional study of Norwegian workers on platforms in the North Sea[END_REF][START_REF] Vecchia | Differences in dietary intake with smoking, alcohol, and education[END_REF] However, most studies evaluating the association between smoking and diet come from Western societies in an advanced phase of the smoking epidemic and where manufactured cigarettes are the main type of tobacco consumed. Evidence from developing countries with markedly different cultures and lifestyles and where several types of tobacco exposure co-exist is scarce. [START_REF] Faruque | Relationship between smoking and antioxidant nutrient status[END_REF] We aimed to quantify the association between tobacco consumption and alcohol, fruit and vegetable intake, according to place of residence (urban/rural), in a representative sample of the Mozambican general population.

METHODS

In a community-based cross-sectional study 12 902 subjects aged 25 to 64 years were evaluated, between September and December 2003. The homeless and the population living in collective residential institutions (e.g. hotels, hospitals, military facilities) were not eligible, and only the population living in households was selected. The sampling procedure was designed to yield samples representative at the country and province levels and, at a national level, according to place of residence (urban-rural). Using the sampling frame of the 1997 census, [START_REF]II Recenseamento Geral de População e Habitação[END_REF] 604 geographical clusters were selected and within each area 24 households were randomly selected and visited. All eligible subjects in the same household were invited for the study, according to the sampling protocol. In the Demographic and Health Survey the proportion of participating women was 93.5% in rural and 87.7% in urban areas and among men the participation was 85.6% and 75.2% respectively in rural and urban settings.

Trained interviewers conducted face-to-face interviews in each household. Given the ethnic and linguistic diversity in Mozambique, all the interviewers were from the provinces in which they were going to do the interviews and were able to speak correctly the predominant languages from each region. A questionnaire-based assessment of sociodemographic and behavioral factors was conducted using standardized methods.

Regarding tobacco consumption participants were asked about the use of any tobacco product, including manufactured cigarettes, hand-rolled cigarettes and smokeless tobacco, anytime in their lives and currently. Current users were asked about the type of tobacco most usually consumed.

Manufactured cigarette smokers were asked about the number of cigarettes smoked in the previous 24 hours. Subjects reporting current consumption of any tobacco product were classified as consumers and grouped according type of tobacco most usually consumed (hand rolled cigarettes, smokeless tobacco or manufactured cigarettes). Manufactured cigarettes smokers were further grouped according to the frequency of consumption (<5 and ≥5 cigarettes/day). The relatively low cutoff used to distinguish smokers in two groups reflects the low frequency of consumption in this population (table 1).

Participants were asked about the intake of any type of alcoholic beverage, including beer, wine, spirits, traditional (including sura, chicaju, tontonto, mal-coado, chicanhu) or other beverages, anytime in their lives and currently. Current drinkers were asked about the beverage most usually consumed and the frequency of consumption (number of days per week in which alcoholic beverages were consumed). Subjects having consumed alcoholic beverages before, but not currently, were classified as ex-drinkers and those reporting current consumption were grouped according to the frequency of weekly consumption of any type of beverage (<1 day, 1-2 days, 3-7 days), to allow the distinction between those drinking less than daily and almost every day, and according to the beverage most usually consumed (beer, traditional beverages, other beverages).

Fruit and vegetable consumption was assessed separately by asking the number of days per week in which these foods were consumed. Participants were grouped according to the weekly consumption of fruit (<1 day, 1 day, 2 days, 3-7 days) and vegetable (<3 days, 3-4 days, 5-6 days, 7 days). The cutoffs were chosen to allow the distribution of participants by groups of similar size, and are different for fruit and vegetable, reflecting distinct patterns of consumption.

Education was registered as the highest education level attained and participants grouped in four categories (<1 year, 1-5 years, 6-7 years, ≥8 years).

The classification of the place of residence as urban (in any of the 23 cities and 68 towns) or rural (outside cities or towns), and the definition of categories for the highest level of education attained were done in accordance with the 1997 census. [START_REF]II Recenseamento Geral de População e Habitação[END_REF] Information on the consumption of tobacco and socio-demographic variables were available for 12 614 subjects, used in the present analysis. Multinomial logistic regression models were fitted separately for men and women, and for urban and rural areas, to compute age-and education-adjusted odds ratios (OR) and respective 95% confidence intervals (95%CI) for the association between tobacco consumption (independent variable, with non consumers as reference) and frequency of alcohol drinking (baseline outcome: non-drinkers), main type of alcoholic beverage consumed (baseline outcome: non-drinkers), fruit consumption (baseline outcome: <1 day/week) and vegetable consumption (baseline outcome: <3 days/week).

Since the sample was stratified, including a similar number of participants across provinces with unequal population size, each participant contributed to the analyses with a weight inversely proportional to the number of inhabitants per province in order to produce estimates representative of the Mozambican population. All the analyses were conducted considering the sampling weights and adjusting for strata and clustering at primary sampling unit level using STATA, version 9.2.

The study protocol was approved by the National Mozambican Ethics Committee and written informed consent was obtained from all participants.

RESULTS

The population under study is predominantly rural (three quarters), most subjects are aged less than 45 years (two thirds) and less than 15% have more than 54 years, and about half of women and one quarter of men have less than one year of formal education. Nearly 20% of women and 40% of men were tobacco consumers, and current alcohol drinking, mostly traditional beverages, was reported by about 25% of women and 50% of men. Approximately one third of the participants consumed fruit at least every two days and vegetable daily (Table 1).

Table 1. Socio-demographic characteristics, tobacco consumption (main type of tobacco product consumed), alcohol main type of alcoholic beverage consumed, fruit (weekly frequency) and vegetable (weekly frequency) intake of the participants. * within each variable the sum of the proportions may not be 100% due to rounding.

Tobacco consumption was strongly associated with drinking of alcoholic beverages (Table 2).

The odds favoring smoking tended to increase with increasing drinking amount categories, regardless of the type of tobacco consumed, gender or place of residence. When comparing consumers of different types of tobacco with non consumers, the ORs for 3-7 days/week drinking, were: 9.19 (95%CI: 5.70-14.8) in men, for manufactured cigarette smokers (≥ 5 cigarettes/day), and 2.13 (95%CI: 1.01-4.50) in women, for manufactured cigarette smokers; 5.17 (95%CI: 3).

Beer drinking was positively associated with manufactured cigarette smoking in men regardless of place of residence and in urban women, but inversely related with hand-rolled cigarette smoking in men and with smokeless tobacco consumption in women, especially urban. When comparing manufactured-cigarette smokers with non-tobacco consumers, the OR for beer drinking were 7.32 (95%CI: 4.76-11.3) in men (≥ 5 cigarettes/day) and 2.45 (95%CI: 1.44-4.18) in women.

Comparing hand-rolled cigarette smokers with non-tobacco consumers, the OR for beer drinking was 0.21 (95%CI: 0.03-1.62) in urban and 0.13 (95%CI: 0.02-0.90) in rural men. In women the OR for beer drinking (smokeless tobacco consumers vs. non-tobacco consumers) was 0.94 (95%CI: 0.40-2.20) in urban and 0.14 (95%CI: 0.02-1.03) in rural areas (Table 3). of smokeless tobacco consumers among men from urban areas was too small (n=13) and no estimates are provided for this group; † the number of women smoking ≥5 manufactured cigarettes per day was too small in both urban (n=25) and rural (n=6) areas and the estimates are provided for smoking, regardless of the number of cigarettes consumed. number of smokeless tobacco consumers among men from urban areas was too small (n=13) and no estimates are provided for this group; † the number of women smoking ≥5 manufactured cigarettes per day was too small in both urban (n=25) and rural (n=6) areas and the estimates are provided for smoking, regardless of the number of cigarettes consumed.

13

Regarding the association between tobacco and fruit consumption the OR for fruit intake (3-7 times/week) were 0.60 (95%CI: 0.42-0.86) in men (≥5 cigarettes/day) and 0.61 (95%CI: 0.35-1.04) in women, for manufactured cigarettes smokers compared to non-consumers, with similar point estimates for urban and rural areas. However, in men, this association only remained statistically significant in rural areas (Table 4). Among women, the manufactured cigarette smoking was positively associated with fruit intake once a week (OR=1.62; 95%CI: 0.92-2.85), though statistically significant only in urban areas (urban: OR=2.26; 95%CI: 1.05-4.87; rural: OR=1.36; 95%CI: 0.63-2.93). Smokeless tobacco consumption was positively associated with fruit intake (once weekly) in both genders (men: OR=2.53, 95%CI: 1.40-4.59; women: OR=1.51, 95%CI: 1.07-2.14), but no estimates could be computed for urban men due to the small number of smokeless tobacco consumers among the males in this setting. No significant associations between hand-rolled cigarettes smoking and fruit intake were observed in either gender (Table 4). * the number of smokeless tobacco consumers among men from urban areas was too small (n=13) and no estimates are provided for this group; † the number of women in smoking ≥5 manufactured cigarettes per day was too small in both urban (n=25) and rural (n=6) areas and the estimates are provided for smoking, regardless of the number of cigarettes consumed. * the number of smokeless tobacco consumers among men from urban areas was too small (n=13) and no estimates are provided for this group; † the number of women in smoking ≥5 manufactured cigarettes per day was too small in both urban (n=25) and rural (n=6) areas and the estimates are provided for smoking, regardless of the number of cigarettes consumed.

DISCUSSION

Our results from a country under epidemiologic transition, in the earlier phases of the tobacco epidemic, show that the use of distinct types of tobacco is associated with different dietary choices.

Positive associations were found between tobacco use and alcohol drinking, regardless of type of tobacco consumed, but differences were observed according to the main type of alcoholic beverage consumed, with the smoking of hand rolled cigarettes and the consumption of smokeless tobacco being negatively associated with beer drinking. Manufactured cigarette smokers exhibited a less frequent intake of fruit, but a consistently negative association between smoking of manufactured cigarettes and vegetable intake was observed only in women. Conversely, smokeless tobacco consumption and hand-rolled cigarette smoking were not inversely related to fruit and vegetable intake. This pattern was relatively consistent across urban and rural areas, with the observed differences being explained either by random variation or heterogeneity in the tobacco consumption patterns across urban and rural areas.

To our knowledge this is the first report addressing this topic in an African country, based on a large representative sample of the Mozambican population, but some limitations need to be pointed.

Unfortunately no validation of the method used for assessing fruit and vegetable intake could be accomplished. The recall of the frequency of usual consumption depends on the participants' memory although compared to methods referring to more recent periods, such as a 24-hour recall, it is expected to minimize the effects of the daily or weekly variability [START_REF] Willett | Nutritional Epidemiology[END_REF]. The questionnaire employed the generic terms "vegetable" and "fruit", rather than specific varieties of these food groups which may contribute for inaccurate reporting. Although misclassification is expectedly non-differential, probably driving the associations conservatively towards the null, we cannot dismiss the possibility that it may differ across the urban and rural settings or dependent on the main type of tobacco consumed. The latter, however, could hardly be responsible for a bias responsible for the differences observed across settings or types of tobacco consumed. Either way, it is unlikely the validity of our conclusions is compromised by such misclassification. Also, as for alcoholic beverages intake, only the frequency of consumption was assessed and it was not possible to estimate the quantity consumed.

The frequency of consumption, however, is likely to reflect the quantity consumed and our results clearly show that the magnitude of the association between tobacco consumption and alcoholic beverages increased with increasing drinking frequency. In our study, the frequency of consumption was recorded only for the more usual type of alcoholic beverage consumed, but this option is not expected to compromise our conclusions, given the consistency of the associations for different types of beverages.

The association between manufactured cigarette smoking and dietary intake may be confounded by other factors such as prohibitive costs of vegetable and fruits, recent migration to urban places or loss of livelihood or stress or staying away from family or socio-economic condition.

Unfortunately, no data on the family income, specific indicators of socioeconomic position or migration to urban areas were available for the present analysis. These aspects were partially accounted by including education in the multivariate models, and by conducting stratified analyses according to gender and place of residence. The analyses were also conducted for specific types of tobacco consumption, which have different frequencies across urban and rural areas.

Our findings confirm a well-known relationship between smoking and alcohol consumption, [START_REF] Fisher | The relation of drinking and smoking habits to diet: the Lipid Research Clinics Prevalence Study[END_REF][START_REF] Ramos | Diet and smoking in Spain and Portugal: a comment[END_REF][START_REF] Laaksonen | Associations among health-related behaviours: sociodemographic variation in Finland[END_REF][START_REF] Rust | Relationship between dietary intake, antioxidant status and smoking habits in female Austrian smokers[END_REF][START_REF] Majem | Food consumption and nutrient intake in relation to smoking (article in Spanish)[END_REF][START_REF] Morabia | Effects of smoking and smoking cessation on dietary habits of a Swiss urban population[END_REF][START_REF] Morabia | Dietary habits of smokers, people who never smoked, and exsmokers[END_REF][START_REF] Dallongeville | Cigarette smoking is associated with unhealthy patterns of nutrient intake: a Meta-analysis[END_REF][START_REF] Accortt | Need to educate primary caregivers about the risk factor profile of smokeless tobacco users[END_REF] but also enable further discussions on this subject as they add to the previous studies information on the type of tobacco used and the discrimination of alcoholic beverage consumed. Manufactured cigarette smoking tends to cluster with all different types of alcoholic beverages analysed while the pattern of the association between other types of tobacco use and each type of alcoholic beverage was clearly different. While traditional beverages drinking was associated with all different types of tobacco consumed, beer drinking was inversely related with hand-rolled cigarette smoking in men and with smokeless tobacco consumption in women. This is probably due to the fact that both hand-rolled cigarette smoking and smokeless tobacco are the traditional forms of tobacco use, more frequent in rural regions where the access to manufactured cigarettes and beer drinking, expected to increase with urbanization, is probably more difficult and the determinants of its use may differ in urban and rural areas. Another possible reason is the extreme poverty of the majority of the rural population that could contribute to the pattern of alcohol and tobacco consumption, since manufactured cigarettes and beer are more expensive and less accessible to this population. Although no such data is available in the dataset made available for our analysis, a recent STEPS survey conducted in Mozambique showed that approximately two thirds of the adult Mozambican population has an annual family income lower than 400 United States dollars (data not shown).

Unfortunately, our study quantifies the association between the most frequent forms of tobacco consumption and alcohol, fruit and vegetable intake, but no conclusions can be drawn regarding the consumption of more than one type of tobacco simultaneously. However, our genderspecific estimates are consistent across urban and rural areas, and we may assume that different forms of tobacco use do not coexist frequently or to a large extent and that there is an association between consumption patterns and gender and place of residence. [START_REF] Townsend | A systematic literature review of tobacco use among adults 15 years and older in sub-Saharan Africa[END_REF] Smoking manufactured cigarettes was inversely related with the frequency of fruit and vegetable intake in both genders. Several studies have reported that compared to smokers, nonsmokers are more likely to consume fruit and vegetable, [20-35, 40, 41] items rich in fibre, antioxidants, and phytochemicals. [START_REF] Manach | Polyphenols: food sources and bioavailability[END_REF][START_REF] Holland | McCance and Widdowson's The Composition of Foods London: Ministry of Agriculture, Fisheries and Food and The Royal Society of Chemistry The Royal Society of Chemists[END_REF] These results are also consistent with those obtained when nutrients, instead of food items, were analysed. Several studies have found that non-smokers had higher intakes of vitamins, antioxidants, and fibre, [START_REF] Dallongeville | Cigarette smoking is associated with unhealthy patterns of nutrient intake: a Meta-analysis[END_REF][START_REF] Koh | Middle-Aged and Older Chinese Men and Women in Singapore Who Smoke Have Less Healthy Diets and Lifestyles than Nonsmokers[END_REF][START_REF] Vardavas | Smoking status in relation to serum folate and dietary vitamin intake[END_REF][START_REF] Tonstad | Under-reporting of dietary intake by smoking and non-smoking subjects counselled for hypercholesterolaemia[END_REF][START_REF] Trobs | Nutrition, antioxidants, and risck factor profile of nonsmokers, passive smokers and smokers of the Prevention Education Program (PEP) in Nuremberg, Germany[END_REF] which are found in vegetable and fruit. However, despite the well documented inverse association between manufactured cigarette smoking and fruit and vegetable consumption, in our study smokeless tobacco use was positively associated with fruit intake. This result is consistent with those obtained by Stegmayr et al in Sweden, who showed that plasma levels of antioxidant vitamins are not reduced in snuff dippers as they are in smokers, possibly due to the combined result of higher intake and lower expenditure of ascorbate and tocopherols in those who use smokeless tobacco. [START_REF] Stegmayr | The decline of smoking in northern Sweden[END_REF] However, it is not possible to determine the extent to which the higher levels of plasma antioxidants in consumers of smokeless tobacco compared to smokers can be attributed to higher consumption of fruit and vegetable or lower expenditure of nutrients contained in those food items. Inversely, Accort et al. [START_REF] Accortt | Need to educate primary caregivers about the risk factor profile of smokeless tobacco users[END_REF] and Giraud et al, [START_REF] Giraud | Plasma and dietary vitamin C and E levels of tobacco chewers, smokers, and nonusers[END_REF] in the United States, showed that smokeless was associated with low fruit and vegetable intake. However, all the previous studies come from high income countries in an advanced phase of smoking epidemic, with high level of urbanization, western culture and where the determinants of the consumption of each type of tobacco are probably distinct from those from low income countries.

20

In Mozambique, manufactured cigarette smokers have a lower intake of fruit and vegetable and a higher alcohol intake, consistently with the tendency for health behavior to cluster. [START_REF] Berrigan | Patterns of health behavior in U.S. adults[END_REF][START_REF] Galan | Clustering of behavioural risk factors and compliance with clinical preventive recommendations in Spain[END_REF] However this association was not consistent across other types of tobacco consumed. Hand-rolled cigarette smokers and smokeless tobacco consumers showed, in general, a healthier diet, especially in rural areas. We may speculate about the existence of a construct that joins different aspects of a less urban lifestyle such as eating healthier (namely more fruit and vegetable), being physically more active (inherent to a more rural environment), drinking traditional food and beverages (including traditional alcoholic beverages) and using non-manufactured ways of tobacco use (such as hand-rolled and smokeless). The urban construct, on the other hand, may aggregate unhealthier choices. Our results suggest that lifestyles are culturally determined and that the pattern of association of lifestyle behaviours also differs across societies.

Although this epidemiological study was not specifically designed to assess the role of social aspects on the association between smoking and other health-related behaviors, we agree that socioeconomic exposures and urban-rural migrations should be accounted in future investigations.

This study adds to previous research on this subject a greater knowledge on the association between different forms of tobacco exposure and the consumption of alcoholic beverages (including traditional beverages), fruit and vegetable. These findings suggest the importance of knowing, in depth, how health behaviors are distributed and how they cluster in Mozambique, namely for etiological research and design of health promotion programs.

  3.82-6.98) in men and 1.94 (95%CI: 1.02-3.69) in women, for hand-rolled cigarette smokers; 2.30 (95%CI: 1.15-4.58) in men and 3.69 (95%CI: 2.56-5.33) in women, for smokeless tobacco consumers. In the analysis stratified by place of residence the results remained similar, with the largest differences being

observed for the association between 3-7 days/week drinking and manufactured cigarette smoking in women, which was positive only in urban women (urban: OR=5.69, 95%CI: 2.65-12.19; rural: OR=0.44, 95%CI: 0.08-2.40).

Tobacco exposure was associated with traditional beverages drinking, regardless of the type of tobacco consumed. When comparing hand-rolled cigarette smokers with non-tobacco consumers, the ORs for traditional beverages drinking was 6.44 (95%CI: 4.97-8.35) in men and 4.05 (95%CI: 2.86-5.75) in women. Associations of a similar magnitude were observed for smoking manufactured cigarettes (men, ≥5 cigarettes/day: OR=4.19, 95%CI: 2.67-6.56; women: OR=2.25, 95%CI: 1.27-4.01) or consumption of smokeless tobacco (men: OR=2.77, 95%CI: 1.70-4.51; women: OR=3.68, 95%CI: 2.92-4.64). In general those associations were stronger in urban than in rural areas, in both genders (Table

Table 2 .

 2 Odds ratios for alcoholic beverages intake, according to tobacco consumption status, adjusted for age and education.

	Frequency of consumption

(urban areas) Non-tobacco consumers Tobacco consumers Hand rolled cigarettes Smokeless Manufactured cigarettes †

		92.5	93.1	1	[reference]	89.9	1	[reference]	79.0	1	[reference]	68.5	1	[reference]
		0.4	0.8	2.44	0.59-10.19	2.2	7.58	2.28-25.21	3.1	11.67	4.86-28.04	1.4	3.64	0.59-22.36
		4.6	3.7	0.98	0.42-2.24	3.5	1.21	0.40-3.65	11.7	4.46	2.62-7.59	19.3	4.14	1.62-10.60
		2.5	2.3	0.99	0.31-3.23	4.4	2.14	0.79-5.81	6.3	3.31	1.30-8.43	10.8	5.69	2.65-12.19
								Women (rural areas)
	Non-tobacco consumers	85.0	76.7	1	[reference]	70.4	1	[reference]	60.4	1	[reference]	57.7	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	4.5	8.4	1.65	0.89-3.07	13.2	2.96	1.36-6.44	13.7	3.40	2.29-5.07	9.6	1.92	0.94-3.88
	Smokeless	8.3	12.7	1.37	0.75-2.50	14.2	1.74	0.95-3.19	22.2	3.07	2.33-4.03	31.8	3.68	2.45-5.53
	Manufactured cigarettes †	2.1	2.2	0.97	0.30-3.10	2.2	1.16	0.37-3.67	3.7	2.18	1.00-4.72	0.8	0.44	0.08-2.40
	* the number

Table 3 .

 3 Odds ratios for alcoholic beverages intake (type), according to tobacco consumption status, adjusted for age and education.

	Type of beverage more frequently consumed

(urban areas) Non-tobacco consumers Tobacco consumers Hand rolled cigarettes Smokeless Manufactured cigarettes †

		92.5	93.1	1	[reference]	90.6	1	[reference]	64.1	1	[reference]	95.3	1	[reference]
		0.4	0.8	2.30	0.55-9.63	0.0	-	-	6.1	19.24	7.48-49.51	0.0	-	-
		4.6	3.7	0.94	0.41-2.17	2.3	0.94	0.40-2.20	22.4	6.28	3.45-11.44	1.7	0.46	0.05-3.82
		2.5	2.3	1.00	0.31-3.20	7.1	3.59	1.55-8.34	7.4	4.15	1.92-9.00	3.0	1.33	0.38-4.68
								Women (rural areas)
	Non-tobacco consumers	85.0	76.7	1	[reference]	97.5	1	[reference]	58.5	1	[reference]	85.1	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	4.5	8.4	1.65	0.89-3.07	0.0	-	-	13.8	3.30	2.26-4.81	11.3	1.98	0.23-17.23
	Smokeless	8.3	12.7	1.36	0.74-2.49	1.2	0.14	0.02-1.03	24.5	3.28	2.55-4.22	3.5	0.34	0.05-2.51
	Manufactured cigarettes †	2.1	2.2	0.97	0.30-3.10	1.3	0.59	0.08-4.59	3.1	1.83	0.86-3.92	0.0	-	-
	* the

Table 4 .

 4 Odds ratios for fruit intake according to tobacco consumption status, adjusted for age and education.

					Frequency of consumption
		<1day/week		1 day/week		2 days/week		3-7 days/week
		%	%	OR	95% CI	%	OR	95% CI	%	OR	95% CI
					Men (urban and rural areas)
	Non-tobacco consumers	58.3	57.5	1	[reference]	61.7	1	[reference]	63.3	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	19.0	20.0	1.15	0.84-1.56	18.1	0.99	0.71-1.37	17.8	1.06	0.79-1.43
	Smokeless	2.8	5.9	2.53	1.40-4.59	4.2	1.72	0.97-3.06	2.9	1.31	0.74-2.33
	Manufactured cigarettes
	<5 cig/day	11.9	11.0	0.90	0.61-1.32	11.8	0.87	0.60-1.26	10.0	0.72	0.49-1.05
	≥5 cig/day	8.0	5.6	0.67	0.43-1.06	4.2	0.47	0.31-0.70	6.0	0.60	0.42-0.86
						Men (urban areas)
	Non-tobacco consumers	64.8	69.8	1	[reference]	74.8	1	[reference]	73.6	1	[reference]
	Tobacco consumers *
	Hand rolled cigarettes	2.8	6.6	2.56	0.86-7.64	5.2	2.38	0.95-5.97	3.4	1.59	0.64-3.95
	Manufactured cigarettes
	<5 cig/day	16.8	13.3	0.74	0.34-1.58	11.2	0.54	0.28-1.04	10.6	0.56	0.31-1.00
	≥5 cig/day	15.6	10.3	0.63	0.35-1.13	8.7	0.47	0.26-0.84	12.3	0.73	0.44-1.20
						Men (rural areas)
	Non-tobacco consumers	55.9	54.4	1	[reference]	58.4	1	[reference]	59.5	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	25.3	24.3	1.04	0.75-1.44	21.6	0.86	0.62-1.21	23.6	0.96	0.70-1.32
	Smokeless	3.7	6.6	2.15	1.14-4.04	5.0	1.50	0.82-2.71	3.7	1.16	0.63-2.12
	Manufactured cigarettes
	<5 cig/day	10.0	10.4	0.99	0.65-1.52	12.0	1.05	0.68-1.62	9.7	0.81	0.51-1.29
	≥5 cig/day	5.0	4.2	0.80	0.42-1-.50	3.0	0.53	0.30-0.96	3.5	0.57	0.33-0.97
					Women (urban and rural areas)
	Non-tobacco consumers	81.3	77.4	1	[reference]	81.8	1	[reference]	85.6	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	6.1	5.8	1.11	0.72-1.71	5.6	1.09	0.73-1.61	3.3	0.66	0.42-1.05
	Smokeless	9.8	12.6	1.51	1.07-2.14	10.3	1.25	0.92-1.71	9.2	1.15	0.83-1.57
	Manufactured cigarettes †	2.8	4.3	1.62	0.92-2.85	2.3	0.83	0.44-1.58	1.8	0.61	0.35-1.04

Women (urban areas) Non-tobacco consumers Tobacco consumers Hand rolled cigarettes

		87.9	82.9	1	[reference]	92.4	1	[reference]	92.2	1	[reference]
		1.5	0.9	0.69	0.16-3.01	1.1	0.83	0.25-2.78	0.5	0.42	0.11-1.63
	Smokeless	7.1	8.6	1.42	0.81-2.49	4.4	0.77	0.42-1.42	4.9	1.06	0.56-2.03
	Manufactured cigarettes †	3.5	7.6	2.26	1.05-4.87	2.1	0.60	0.25-1.46	2.4	0.71	0.34-1.49
					Women (rural areas)
	Non-tobacco consumers	78.4	75.6	1	[reference]	78.0	1	[reference]	82.5	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	8.1	7.3	1.07	0.68-1.69	7.2	1.05	0.69-1.61	4.6	0.65	0.39-1.06
	Smokeless	11.0	13.8	1.48	0.98-2.23	12.5	1.33	0.93-1.90	11.4	1.15	0.79-1.66
	Manufactured cigarettes †	2.6	3.2	1.36	0.63-2.93	2.3	0.99	0.44-2.23	1.5	0.61	0.29-1.27

Table 5 .

 5 Odds ratios for vegetable intake according to tobacco consumption status, adjusted for age and education.

					Frequency of consumption
		<3 days/week		3-4 days/week		5-6 days/week		7 days/week
		%	%	OR	95% CI	%	OR	95% CI	%	OR	95% CI
					Men (urban and rural areas)
	Non-tobacco consumers	63.3	63.1	1	[reference]	55.7	1	[reference]	56.7	1	[reference]
	Tobacco consumers
	Hand rolled cigarettes	11.5	17.5	1.58	1.21-2.08	24.6	2.27	1.66-3.10	24.3	2.24	1.71-2.94
	Smokeless	3.7	4.6	1.28	0.74-2.21	4.1	1.15	0.64-2.04	2.5	0.70	0.38-1.26
	Manufactured cigarettes
	<5 cig/day	15.0	8.6	0.58	0.42-0.81	9.4	0.70	0.48-1.02	11.0	0.83	0.62-1.10
	≥5 cig/day	6.4	6.1	0.92	0.60-1.41	6.2	1.13	0.68-1.90	5.5	0.97	0.63-1.51
						Men (urban areas)
	Non-tobacco consumers	72.7	74.1	1	[reference]	61.2	1	[reference]	65.6	1	[reference]
	Tobacco consumers *
	Hand rolled cigarettes	2.8	4.4	1.65	0.69-3.92	4.2	1.99	0.68-5.82	5.7	2.33	1.00-5.42
	Manufactured cigarettes
	<5 cig/day	14.3	9.8	0.69	0.40-1.22	15.1	1.40	0.76-2.57	15.7	1.31	0.88-1.95
	≥5 cig/day	10.3	11.6	1.16	0.61-2.19	19.4	2.29	1.09-4.81	13.0	1.44	0.78-2.65
						Men (rural areas)
	Non-tobacco consumers	59.8
	Tobacco consumers
	Hand rolled cigarettes
	Smokeless
	Manufactured cigarettes
	<5 cig/day
	≥5 cig/day

FUNDING

This work was supported by the Mozambican Ministry of Health and by the World Health Organization.

COPYRIGHT LICENCE STATEMENT

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COMPETING INTERESTS

The authors declare that they have no competing interests.


G David Batty

Martin J Shipley

David Gunnell

George Davey Smith

Jane E Ferrie

Robert Clarke

Michael G Marmot

Mika Kivimaki

George Davey

David Batty
email: david-b@sphsu.mrc.ac.uk

Height loss and future coronary heart disease in London: the Whitehall II study

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Abstract

Background. While several plausible biological mechanisms have been advanced for the association between greater physical stature and lower coronary heart disease (CHD) risk in prospective cohort studies, the importance of one of the principal artifactual explanations -reverse causality due to shrinkage -remains unresolved. To explore this issue, studies with repeat measurements of height are required, however, to date, such data have been lacking.

Methods. We analysed data from the Whitehall II prospective cohort study of 3802 men and 1615 women who participated in a physical examination in 1985/88, had their height re-measured in 1997/99, and were then followed for fatal and non-fatal CHD.

Results. A mean follow-up of 7.4 years after the second height measurement gave rise to 69 CHD events in men (18 in women). After adjustment for baseline CHD risk factors, greater loss of physical stature between survey and resurvey was associated with an increased risk of CHD in men (hazard ratio; 95% CI for a one SD increase: 1.24; 1.00, 1.53) but not women (0.93; 0.58, 1.50).

Conclusions. It is possible that reverse causality due to shrinkage may contribute to the inverse association between a single measurement of height and later CHD in other studies.

Background

A series of prospective cohort studies have shown that people who are shorter in middle-and older-age experience an increased risk of future coronary heart disease (CHD). [START_REF] Batty | Height, wealth, and health: an overview with new data from three longitudinal studies[END_REF] While several biologically plausible mechanisms for this effect have been advanced, the importance of one of the principal artifactual explanations -reverse causality due to shrinkage -remains largely unresolved. [START_REF] Batty | Height, wealth, and health: an overview with new data from three longitudinal studies[END_REF] That is, the early stages of disease, which are undetectable at study entry, could lead to reductions in height and increase risk of coronary heart disease, thus generating the observed inverse stature-CHD associations.

Three observations provide mixed support for the reverse causality explanation. First, if reverse causality is generating the inverse relation between height with CHD in cohort studies, the magnitude of any height-CHD gradient should diminish over time. This is because individuals with sub-clinical disease at study entry would be expected to die in the earlier stages of follow-up, so contributing a declining proportion of person years to the risk set. In reports from studies with between 20 [START_REF] Yao | Anthropometric predictors of coronary heart disease and total mortality: findings from the US Railroad Study[END_REF] and 36 [START_REF] Kannam | Short stature and risk for mortality and cardiovascular disease events. The Framingham Heart Study[END_REF] years of follow-up, the absence of a height-CHD effect provides some support for reverse causality. In a second approach, student populations who had their height assessed at University enrolment in early adulthood, when this measurement can largely be regarded as being pre-morbid and therefore pre-shrinkage, were followed for mortality experience. These studies, in contrast, showed greater height was associated with reduced CHD risk [START_REF] Mccarron | Height in Young Adulthood and Risk of Death from Cardiorespiratory Disease: A Prospective Study of Male Former Students of Glasgow University, Scotland[END_REF][START_REF] Paffenbarger | Chronic disease in former college students. X. The effects of single and multiple characteristics on risk of fatal coronary heart disease[END_REF] so failing to support the reverse causality explanation.

The third observation comes from studies that have examined the relation between components of height -trunk and leg length -and future CHD. [START_REF] Gunnell | Childhood leg length and adult mortality: follow up of the Carnegie (Boyd Orr) Survey of Diet and Health in Pre-war Britain[END_REF][START_REF] Smith | Leg length, insulin resistance, and coronary heart disease risk: the Caerphilly Study[END_REF] With the trunk, but not the leg length, being subject to shrinkage due to osteoporotic vertical collapse, an inverse association of the former but not the latter with CHD would be anticipated if reverse causality was a likely explanation for the inverse overall height-CHD association. The finding that leg length was, in fact, the component of height that showed the strongest inverse relation with CHD provides evidence against the reverse causality explanation, [START_REF] Gunnell | Childhood leg length and adult mortality: follow up of the Carnegie (Boyd Orr) Survey of Diet and Health in Pre-war Britain[END_REF][START_REF] Smith | Leg length, insulin resistance, and coronary heart disease risk: the Caerphilly Study[END_REF] although this is not a universal finding. [START_REF] Ferrie | Birth weight, components of height and coronary heart disease: evidence from the Whitehall II study[END_REF] With height measured on only one occasion in these published analyses, none of the three approaches directly explores, nor quantifies, reverse causality due to shrinkage. In the only study of which we are aware to examine the relation of height loss between two time points and subsequent CHD, there was a suggestion of increased risk in older men undergoing the greatest degree of shrinkage. [START_REF] Wannamethee | Height loss in older men: associations with total mortality and incidence of cardiovascular disease[END_REF] We further examine the relation of height loss with later CHD in participants in a prospective cohort study who had their height measured on two occasions. In doing so, we provide the first examination of CHD and height loss in women who typically experience a greater degree of decline in physical stature over time than men. [START_REF] Sorkin | Longitudinal change in height of men and women: implications for interpretation of the body mass index: the Baltimore Longitudinal Study of Aging[END_REF]

Methods

Details of the ongoing Whitehall II prospective cohort study have been reported previously. [START_REF] Marmot | Cohort Profile: the Whitehall II study[END_REF] In brief, the baseline survey took place in 1985/88 (Phase 1) when 6895 men and 3413 women aged 35-55 (mean 44.4 years) entered the study. All odd-numbered Phases include a clinical examination in addition to a self-completion questionnaire. In the present analyses, we utilise data from Phases 1 and 5, the latter of which took place in 1997/99 (participants aged 45-69; mean 55.7 years). The University College London ethics committee reviewed and approved the study, and written informed consent was obtained from each participant.

At baseline and Phase 5, height was measured in bare feet to the nearest 1 mm using a stadiometer with the participant standing erect with head in the Frankfort plane. CHD risk factors at baseline were measured using standard protocols and included socioeconomic position (high, intermediate, low -as derived from civil service employment grade), current smoking (yes, no), systolic blood pressure (mmHg), total cholesterol (mmol/L), diabetes (self-reported) and, in women, menopausal status (selfreported). Body mass index (BMI; kg/m 2 ) was computed using the usual formulae (weight[kg]/height [m] 2 ).

Ascertainment of CHD

CHD was based on CHD death or non-fatal myocardial infarction. The records of all study members were traced and flagged using the procedures of the National Health Service Central Registry which led to a notification of death. Potential cases of definite, non-fatal myocardial infarction were ascertained by questionnaire items on chest pain and/or doctor's diagnosis of heart attack, an approach we have used elsewhere. [START_REF] Ferrie | Birth weight, components of height and coronary heart disease: evidence from the Whitehall II study[END_REF] Details of physician diagnosis and investigation results were sought from clinical records for all potential cases of myocardial infarction. Twelve-lead resting electrocardiograms were performed at phases 5 and 7 (Siemens Mingorec) and assigned Minnesota codes. Based on these data, non-fatal myocardial infarction was defined according to MONICA criteria. [START_REF] Tunstall-Pedoe | Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents[END_REF]

Statistical analyses

Analyses were restricted to study members who provided complete data at Phases 1 and 5, and whose for whom CHD status at follow-up after Phase 5 could be ascertained (3802 men and 1615 women).

Using the baseline characteristics, relative to those excluded from the analysis (n=4891), participants included in the analytical sample were younger (44.1 years vs. 44.8 years), more likely to be men (70.2% vs. 63.2%), less likely to be from low SES groups (16.5% vs. 29.5%), and taller (average height 172.6 cm vs. 170.6 cm) (p-value for differences all <0.0001).

In the analyses, the exposures of interest were height at baseline, height at Phase 5, average height loss per decade between these two time points (calculated as: (absolute difference in height[cm] / duration of follow-up[yr.]) * 10 yr.), and the proportional height loss per decade between these two time points (calculated as: (height loss[cm] / height at baseline[cm]) * 100% * (10 yr. / duration of follow-up[yr.]).

Results

As expected, on average, women (163.0 [SD=6.5] cm) were shorter than men (176.6 [SD=6.7] cm) at baseline examination, and the rate of height loss per decade was also greater in women (mean absolute loss 0.52 cm [SD 0.90]) than men (mean height loss 0.35 [SD 0.80] cm; p=value for difference<0.0001). Proportional loss in height per decade was 0.3% (SD=0.6) in women and 0.2% (SD=0.5) in men (p-value for difference<0.0001).

In table 1 we present the associations of absolute height loss between baseline and resurvey with baseline CHD risk factors. As anticipated, age was strongly associated with height loss such that men and women who were older at baseline experienced a greater reduction in stature. Height loss was socially patterned in men -but not women -whereby the more disadvantaged based on their employment grade had a greater height loss. Study members of both sexes who smoked, those with diabetes (men only), and those who were overweight experienced greater height loss. Height loss was not associated with menopausal status in women. A mean follow-up of 7.4 years in 3802 Whitehall II men gave rise to 69 CHD events, while in the 1615 women there were 18 such cases (table 2). In women, but not men, there was a negative association between height at both baseline and resurvey with later CHD in age-adjusted analyses (p for sex interaction=0.05 for the height-CHD association for height at both baseline and at resurvey), although this association was attenuated when other covariates were added to the multivariable model.

Conversely, height loss between these two time points was associated with CHD in men but not women (p for sex interaction 0.85). The height loss-CHD gradient was essentially unchanged after multiple adjustment, and when height loss was modeled for proportional rather than absolute change. a Age at resurvey. b Adjusted for baseline measures of socio-economic status, smoking, total cholesterol, systolic blood pressure, body mass index and diabetes. c Units are cm per decade; comparison is 1 SD increase. d Units are percent reduction in height per decade; comparison is 1 SD increase. e Cox proportional hazards regression was used to compute these hazard ratios with accompanying 95% confidence intervals.

Conclusion

In the present analyses, there was some evidence that loss of physical stature between survey and resurvey around a decade later was associated with an increased risk of CHD in men. This provides some support for the suggestion that height loss associated with pre-existing morbidity may contribute to the inverse relationship between a single measurement of height and later CHD reported in a number of studies. [START_REF] Smith | Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality[END_REF][START_REF] Langenberg | Adult socioeconomic position and the association between height and coronary heart disease mortality: findings from 33 years of follow-up in the whitehall study[END_REF][START_REF] Lee | Adult height and the risks of cardiovascular disease and major causes of death in the Asia-Pacific region: 21 000 deaths in 510 000 men and women[END_REF] We did not, however, make the same observations in women. This may be due to the low number of CHD events in this group. This notwithstanding, there were negative relationships of both baseline and resurvey height with incident CHD.

Results from the present cohort are consistent with those from the British Regional Heart Study of older men, [START_REF] Wannamethee | Height loss in older men: associations with total mortality and incidence of cardiovascular disease[END_REF] the only other study of which we are aware to have examined height loss and future CHD risk. Our findings also accord with a related literature on osteoporosis, a condition which has recently been postulated to have a shared aetiology with cardiovascular disease. [START_REF] Mcfarlane | Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?[END_REF] Thus, as well as having an unfavorable level of traditional risk factors for CHD (raised blood cholesterol, blood pressure and blood glucose, smoking), people with evidence of osteoporosis also experience higher rates of cardiovascular disease events than those with normal bone mineral density. However, given that the average absolute height loss in the Whitehall II study over a decade (0.52 cm in women, 0.35 cm in men) is much less pronounced than that seen in osteoporosis (>6 cm), [START_REF] Siminoski | The accuracy of historical height loss for the detection of vertebral fractures in postmenopausal women[END_REF] this is unlikely to be the sole explanation for the elevated CHD risk. That the rate of height loss is low in this population is likely to be due to the occupational nature of the cohort which, by definition, contains a greater proportion of healthy individuals than the general population (the so called 'healthy worker' effect). Of further mechanisms worthy of exploration, given the suggested association of vitamin D with both CHD [START_REF] Pittas | Systematic review: Vitamin D and cardiometabolic outcomes[END_REF] and loss of physical stature, [START_REF] Fang | Vitamin D receptor gene haplotype is associated with body height and bone size[END_REF] it is plausible that vitamin D levels mediate the height loss-CHD link.

In conclusion, our findings suggest that it is possible that reverse causality due to shrinkage may have contributed to the inverse association between a single measurement of height and later CHD.

What this paper adds 'box'

What is already known on this subject?

• While several plausible biological mechanisms have been advanced for the association between greater physical stature and lower CHD risk in prospective cohort studies, the importance of one of the principal artifactual explanations -reverse causality due to shrinkage -remains unresolved.

• To explore this issue, studies with repeat measurements of height are required, however, to date, such data have been lacking.

What does this study add?

• This is the first examination of CHD and height loss in women who typically experience a greater degree of decline in physical stature over time than men.

• Greater loss of physical stature between survey and resurvey was associated with an increased risk of CHD in men but not women

• These results suggest that reverse causality due to shrinkage may contribute to the inverse association between a single measurement of height and later CHD in other studies.

Table 1 . The association of baseline characteristics with rate of height loss between baseline and resurvey: the Whitehall II study a

 1

	Baseline characteristic	Overall	Height loss (95% CI) a , cm	P-value
		(mean [SD] or N [%])
	Men (N=3802)
	Age, yr	44.0 (6.0)
	35-39	1107 (29.1)	Ref.
	40-44	1069 (28.1)	0.24	(0.18, 0.30)	<0.0001
	45-49	721 (19.0)	0.46	(0.39, 0.53)	<0.0001
	50-55	905 (23.8)	0.80	(0.73, 0.87)	<0.0001
	Systolic blood pressure, mm Hg	124 (14)	-0.00	(-0.03, 0.02)	0.79
	BMI, kg/m 2 b	24.5 (2.9)	0.02	(0.00, 0.05)	0.04
	Total cholesterol, mmol/l	5.9 (1.1)	0.01	(-0.02, 0.03)	0.50
	SES, %
	High	1560 (41.0)	Ref.
	Medium	2004 (52.7)	0.08	(0.03, 0.13)
	Low	238 (6.3)	0.18	(0.08, 0.28)	<0.0001
	Diabetes
	No	3780 (99.4)	Ref.
	Yes	22 (0.6)	0.34	(0.03, 0.66)	0.03
	Current smoking, %
	No	3301 (86.8)	Ref.
	Yes	501 (13.2)	0.09	(0.02, 0.16)	0.01
	Women (N=1615)
	Age, yr	44.6 (6.0)			<0.0001
	35-39	432 (26.7)	Ref.
	40-44	410 (25.4)	0.24	(0.13, 0.35)	<0.0001
	45-49	342 (21.2)	0.54	(0.42, 0.65)	<0.0001
	50-55	431 (26.7)	0.88	(0.76, 0.99)	<0.0001
	Systolic blood pressure, mm Hg	119 (15)	0.02	(-0.02, 0.06)	0.29
	BMI, kg/m 2	24.3 (4.0)	0.06	(0.02, 0.10)	0.004
	Total cholesterol, mmol/l	5.8 (1.1)	0.01	(-0.03, 0.06)	0.54
	SES, % b
	High	246 (15.2)	Ref.
	Medium	712 (44.1)	-0.05	(-0.17, 0.07)
	Low	657 (40.7)	-0.06	(-0.18, 0.07)	0.43
	Diabetes, %
	No	1605 (99.4)	Ref.
	Yes	10 (0.6)	-0.19	(-0.71, 0.32)	0.46
	Current smoking, %
	No	1329 (82.3)	Ref.
	Yes	286 (17.7)	0.02	(-0.09, 0.13)	0.70
	Post menopause, %
	No	1409 (69.7)	Ref.
	Yes	456 (30.3)	0.06	(-0.11, 0.13)	0.87

a Age-adjusted rate of absolute height loss in cm per decade for 1 SD increase in continuous risk factors (systolic blood pressure, BMI and total cholesterol), and age-adjusted difference in height loss per decade from reference group for categorical risk factors (age group [not age-adjusted], socio-economic status, diabetes, smoking, and menopausal status [women only]). Analyses are based on linear regression models.

Table 2 . Hazard ratios e (95% CI) for the relationship of a 1 SD increase in height and height loss with future CHD: the Whitehall II study

 2

	Age-adjusted a	Age-+ baseline
		risk factor b -
		adjusted

The Whitehall II study has been supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (HL36310), US; and the National Institute on Ageing (AG13196), US; and the Agency for Health Care Policy Research (HS06516). David Batty is a Wellcome Trust Fellow; Michael Marmot is a UK Medical Research Council Research Professor. Martin Shipley is supported by the British Heart Foundation, Jane Ferrie by the MRC (Grant number G8802774) and Mika Kivimaki by the Academy of Finland. We are also very grateful to all participating Civil Service departments and their welfare, personnel, and establishment officers; the Occupational Health and Safety Agency; the Council of Civil Service Unions; all participating civil servants in the Whitehall II study; and all members of the Whitehall II study team. The Medical Research Council (MRC) Social and Public Health Sciences Unit receives funding from the UK MRC and the Chief Scientist Office at the Scottish Government Health Directorates. Licence for Publication Statement: The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive