Monday, January 26, 2009

Influence of Life Course Socioeconomic Position on Older Women's Health Behaviors: Findings From the British Women's Heart and Health Study

Influence of Life Course Socioeconomic Position on Older Women's Health Behaviors: Findings From the British Women's Heart and Health Study
Abstract (Summary)

We examined the association between health behaviors and socioeconomic status (SES) in childhood and adult life. Self-reported diet, smoking, and physical activity were determined among 3523 women aged 60 to 79 years recruited from general practices in 23 British towns from 1999 through 2001. The most affluent women reported eating more fruit, vegetables, chicken, and fish and less red or processed meat than did less affluent women. Affluent women were less likely to smoke and more likely to exercise. Life course SES did not influence the types of fat, bread, and milk consumed. Adult SES predicted consumption of all foods considered and predicted smoking and physical activity habits independently of childhood SES. Childhood SES predicted fruit and vegetable consumption independently of adult SES and, to a lesser extent, predicted physical activity. Downward social mobility over the life course was associated with poorer diets and reduced physical activity. Among older women, healthful eating and physical activity were associated with both current and childhood SES. Interventions designed to improve social inequalities in health behaviors should be applied during both childhood and adult life.

[Headnote]
Objectives. We examined the association between health behaviors and socioeconomic status (SES) in childhood and adult life.
Methods. Self-reported diet, smoking, and physical activity were determined among 3523 women aged 60 to 79 years recruited from general practices in 23 British towns from 1999 through 2001.
Results. The most affluent women reported eating more fruit, vegetables, chicken, and fish and less red or processed meat than did less affluent women. Affluent women were less likely to smoke and more likely to exercise. Life course SES did not influence the types of fat, bread, and milk consumed. Adult SES predicted consumption of all foods considered and predicted smoking and physical activity habits independently of childhood SES. Childhood SES predicted fruit and vegetable consumption independently of adult SES and, to a lesser extent, predicted physical activity. Downward social mobility over the life course was associated with poorer diets and reduced physical activity.
Conclusions. Among older women, healthful eating and physical activity were associated with both current and childhood SES. Interventions designed to improve social inequalities in health behaviors should be applied during both childhood and adult life. (Am J Public Health. 2009;99:320-327. doi:10.2105/AJPH.2007.129288)


In 1977, the United Kingdom Department of Health commissioned an inquiry focusing on health inequalities in the country's population. The resulting report-the Black Report, published in 1980-highlighted the marked association between adult socioeconomic status (SES) and mortality rates.1 Such socioeconomic gradients inmortality rates persist today, tracking into old age.2

Inequalities in health are a result of clearly identifiable social and economic factors that could potentially be modified to improve people's quality and length of life. Employment, education, housing, transportation, environment, health care, and "lifestyle" (in particular smoking, exercise, and diet) all affect health and tend to be favorably distributed in advantaged groups.

In the United Kingdom, the introduction of the National Service Framework for Coronary Heart Disease in 2000 was intended to reduce the prevalence of and social inequalities in coronary risk factors in the country's population. 3 Achieving these aims requires equitable access to and use of preventive care irrespective of SES, age, and gender. Health promotion initiatives such the "5-a-day" fruit and vegetable diet plan,4 smoking cessation clinics, and structured exercise plans have all been part of the drive to reduce the prevalence of coronary risk factors.

Recent years have seen increased recognition of the potential implications of life course SES and a deeper understanding of the conceptual framework on which it is based.5,6 There is growing evidence that coronary heart disease (CHD) risk is associated with life course SES,7-10 with those in the most disadvantaged SES groups throughout life showing nearly 3 times greater risk than those in more advantaged groups.8 This raises the question of the extent to which behavioral CHD risk factors are similarly dependent on life course SES. We examined the effects of childhood and adulthood SES on various health behaviors (diet, smoking, and physical activity) of older British women.

METHODS

Study Design and Data Collection

We conducted a cross-sectional analysis of baseline data from participants in the British Women's Heart and Health Study. The methodology of that study has been fully reported elsewhere.11 Briefly, from 1999 through 2001, 4286 women aged 60 to 79 years were recruited from general practice lists in 23 representative British towns. Participants completed a questionnaire including items focusing on diet, smoking,12 and physical activity. As a means of gathering dietary data, women were asked how often (more than once a day, daily, most days, once or twice a week, less than weekly, or never) they ate fresh fruit, green vegetables, meat, and other foods.

Behavioral Data

Principal-component analyses were used to identify various food groups. Fruits, salads, green vegetables, fish, and poultry formed the first component; however, given the public health focus on fruits and vegetables, these foods were examined separately. Red and processed meat formed the second component; healthful bread (e.g., whole-meal bread), milk (e.g., skim milk), and fat (e.g., vegetable oil rather than animal fats, and low-fat margarine rather than butter) formed the third.

Participants were asked to indicate the number of hours each week during the winter and summer they engaged in a specified range of physical activities; they were also asked to rate their walking speeds.13 These measurements were used to calculate their weekly number of hours of moderate or vigorous physical activity. Activities considered moderate or vigorous included walking at a relatively brisk or fast pace, cycling, heavy gardening, and other physical exercise (e.g., aerobics, swimming).

Socioeconomic Status Data

Ten SES indicators8 were used to construct a life course SES score and childhood and adult subscores: longest-held occupation of the participant's father during her childhood; whether the participant's childhood home had a bathroom and a hot water supply; whether the participant had shared a bedroom as a child; whether, during the participant's childhood, her family had access to a car; the age at which the participant completed full-time education; the longest-held occupation of the participant and her spouse; the participant's current housing status (whether she lived in rented social housing or owner-occupied and private rented properties); and the participant's current automobile access and pension arrangements (state only or state in combination with other arrangements).

Participants' childhood social class was based on their fathers' longest-held occupation, and their adult social class was based on their husbands' longest-held occupation (or, in the case of single women, their own longest-held occupation). Adult and childhood social class categories, defined according to the UK registrar general's classification, ranged from I (nonmanual, professional occupations) to V (manual, unskilled occupations). Given that the life-course SES score denoted the number of socioeconomic hardships experienced by women, a score of 10 indicated the greatest level of hardship.

We assessed the effects of changes in SES over the life course on health behaviors by classifying upward social mobility as change from manual social class in childhood (defined according to father's occupation) to nonmanual social class in adulthood (defined according to husband's occupation or, among unmarried women, their own occupation); downward social mobility was classified as the reverse circumstance. All analyses were restricted to women without any evidence of CHD or stroke at baseline (n=3523; 83% of the cohort); 595 women (13%) were excluded from the analyses (with the exception of those involving multiple imputations) because they also had missing data on 1 or more SES indicator.

Statistical Analyses

Women were grouped according to SES score, and the percentage of women reporting adverse health behaviors in each SES group was calculated. We assessed differences in the percentages of women reporting high-risk behaviors by individual SES indicator variables. In addition, stratifying by town of recruitment, we conducted logistic regression analyses examining the relative importance of childhood SES and adult SES scores as predictors of health behaviors and the effects of upward and downward social mobility on health behaviors.

We used conditional logistic regression in most of our analyses because the sampling strategy produced data clustered according to town of residence. We used ordinal logistic regression, clustered by town, in analyses of smoking and diet because the behavioral data were collected in 3 ordered categories. This technique allowed us to avoid using multiple significance tests, which would have been required to compare each pair of categories in turn.

Our analyses were based on the assumption that missing data were missing completely at random; that is, women included in the analyses could be regarded as a random sample of the women who took part in the study. If this assumption proved to be false, our results could be biased.

We assessed the sensitivity of the results by examining the effects of missing data. We assumed that data were missing at random (rather than missing completely at random, where the probability of data being missing does not depend on observed or unobserved values) and in this situation the missing values depend on the values of variables measured in the study. The missing values can then be imparted from knowledge of other measured values. Multiple imputation allowed our analysis to be conducted under the missing-atrandom assumption; we used the multivariate chained equation method,14,15 including all of the health habit variables and childhood and adulthood SES scores in the imputation model.

Ten regression switching cycles were used with 20 imputed data sets. Use of Rubin's formulas for combining results from the separate imputed data sets ensured that any incomplete data were properly accommodated in the inferences. The results of these alternative analyses were very similar to the results of the analyses conducted with women who had complete data (i.e., the analyses described here). Stata version 9 (StataCorp, College Station, TX) was used in conducting all analyses.

RESULTS

Table 1 presents health behavior data by SES score, and Table 2 shows differences in the percentages of women reporting unhealthful behaviors according to individual SES indicator variables. Table 3 shows odds of unhealthful behaviors for each 1-unit increase in childhood and adulthood SES score (i.e., increasing deprivation), with adjustment of childhood associations for adult SES (and vice versa).

Diet

Only 10% of women reported eating 4 or 5 portions of fruits and vegetables daily (the UK government recommendation); half reported consuming less than 2 portions (Table 1). A majority of the women (55%) selected mostly healthful fat, milk, and bread options; 30% ate red or processed meat on most days.

Women in the most deprived groups (those with an SES score of 9 or 10) had poorer diets than did women in the less deprived groups, consuming fewer fruits and vegetables (61% consumed less than 2 portions per day) and more red or processed meats (41% ate these meats on most days; Table 1). Both childhood and adult indicators of low SES were associated with unhealthful diets (Table 2). Eleven percent (P<.001) more women raised in manual social class families than in nonmanual social class families ate fruits and vegetables less than twice a day. Similar differences of between 5% and11%in consumption of fruit and vegetables were seen for other childhood deprivation indicators (e.g., no hot water in the family home, no family access to a car).

Adult indicators of deprivation showed similar levels of strength; the strongest predictor was current residence in local authority (i.e., social) housing (13% more women living in local authority housing than women not living in such housing reported eating fruit and vegetables less than twice a day; P<.001). Both childhood (for each 1-unit increase in childhood SES score, odds ratio [OR]=1.13; 95% confidence interval [CI]=1.07, 1.19) and adult (for each 1-unit increase in adult SES score, OR=1.16; 95% CI=1.07, 1.25) SES scores were independent predictors of fruit and vegetable intake (Table 3).

Associations with the other dietary variables were less strong. Consumption of red or processed meat on most days was independently associated with adult SES (adjusted OR=1.15; 95% CI=1.06, 1.25) but not childhood SES (adjusted OR=1.03; 95% CI=0.97, 1.09) after mutual adjustment. Poultry and fish consumption showed a similar pattern of stronger association with adult SES (adjusted OR=1.17; 95% CI=1.08, 1.26) than childhood SES (adjusted OR=1.06; 95% CI=1.00, 1.12). Selection of mostly healthful fat, milk, and bread options was not significantly related to SES or any SES subcomponents.

Smoking

Most women (57%) had never smoked tobacco regularly, and only 11% currently smoked (Table 1). However, 62% of women in the lowest SES group had smoked regularly at some point in their life (and 18% of them continued to smoke), as compared with less than 50% of the women in all other SES groups. The median age of smoking initiation was 18 years (5th percentile=15 years, 95th percentile=35 years), and there were minimal differences according to SES. Among quitters, women in higher SES groups quit at a younger median age (45 years [5th percentile=24 years, 95th percentile=65 years] among women with SES scores of 0-3 and 51 years [5th percentile=22 years, 95th percentile=70 years] among women with SES scores of 7-10).

Smoking was associated with having grown up in a manual social class family but was not related to other childhood SES indicators (Table 2). All adverse adult SES indicators were associated with smoking. The strongest predictor was local authority housing tenancy; women living in such housing were 18% more likely to smoke. As can be seen in Table 3, adult SES, but not childhood SES, was independently associated with smoking (for each 1-unit increase in adult SES, adjusted OR=1.18; 95% CI=1.09, 1.27).

Physical Activity

Most women were inactive. Sixty-one percent reported less than 2 hours per week of moderate or vigorous exercise; however, more than one quarter (28%) engaged in more than the recommended minimum of 3 hours per week. Generally, more women in the most disadvantaged SES groups than in the less disadvantaged groups reported a sedentary lifestyle (P<.001).

Adverse individual childhood and adult SES indicators were each associated with an increase in physical inactivity of at least 5% (Table 2). The strongest association was with local authority housing tenancy in adulthood; 16% more women living in this type of housing than in other types of housing engaged in less than 2 hours of moderate or vigorous activity each day. Adult SES and childhood SES were both independently associated with physical activity, but the association with adult SES was stronger (for each 1-unit increase in childhood SES, adjusted OR=1.06; 95% CI=1.01, 1.12; for each 1-unit increase in adult SES, adjusted OR=1.22; 95% CI=1.13, 1.32).

Social Mobility

Table 4 shows the effects of social mobility, classified according to father's and husband's social class (or, in the case of unmarried women, their own social class), on women's health behaviors. Upwardly mobile women were less likely to report unhealthful behaviors than were women who remained in the manual group. For example, they were 37% less likely to consume small amounts of fruits and vegetables (OR= 0.73; 95% CI=0.61, 0.88) and 21% less likely to be inactive (OR=0.79; 95% CI=0.66, 0.94).

Downwardly mobile women adopted worse health behaviors than women remaining in the nonmanual social class. For example, they were 51% more likely to eat red or processed meat on most days (OR=1.51; 95% CI=1.04, 2.18) and 47% more likely to engage in less than 2 hours of exercise per week (OR=1.47; 95% CI=1.05, 2.06); surprisingly, however, they were 45% more likely to select mostly healthful fat, milk, and bread options (OR=1.45; 95% CI=1.03, 2.06). We found no effects of social mobility on smoking. Although downward social mobility adversely affected women's diet and physical activity behaviors, the effect was not as marked as that observed when women who had remained in the manual social class throughout their life were compared with those who had always been in the nonmanual class.

DISCUSSION

Women who had experienced socioeconomic adversity throughout their lives were less likely than women who had not to eat healthily and were more likely to have smoked regularly at some point in their lives, to currently smoke, and to be inactive. Our data suggest that both childhood and adult SES affect fruit and vegetable consumption in old age, with roughly an equal strength of association. However, it was primarily adult SES that influenced whether these women were more likely to eat meat or fish. Adult SES appeared to determine quantity and duration of smoking through the age of smoking cessation. Although exercise behaviors in old age were influenced by childhood SES, the effect of adult SES was greater. Upward social mobility and downward social mobility were, respectively, beneficial and detrimental with respect to health behaviors.

Diet

Elderly people come from a generation in which childhood diets were generally healthier in terms of lower saturated fat and calorie content than today. Indeed, it has been reported that older people continue to have better diets; however, deprivation, which may particularly affect elderly people, may partially counteract this trend.16 Other studies have shown that elderly people often have a poor diet that is low in energy and in the amounts of vitamins and minerals consumed. 17-19

Given that few people do so, it is not surprising that small numbers of women in this cohort reported eating the recommended 5 portions of fruits and vegetables per day. Our findings with respect to deprivation are consistent with those of other research.20 People in lower SES groups are more likely to live in areas lacking access to high-quality produce, especially if they do not have access to a car or suffer from poor personal mobility.21Access to social support (e.g., "meals on wheels" programs) may provide a partial solution for the most vulnerable groups.

Childhood SES indicator variables were associated with diet quality in adulthood; however, after adjustment for adult SES, the associations were weaker than the associations of adult SES variables adjusted for childhood SES. This finding suggests that some of the childhood risk factors assessed were mediated through adult SES. The direct effect of childhood SES on diet in old age may result from the tastes developed and the cooking skills and practices learned in childhood.22 This might explain some of the observed effect of childhood SES on adult CHD risk.

Childhood diet may also have a more direct effect on adult health, in that growth affects later disease risk. Leg length (indicative of prepubertal nutritional status) is positively associated with a reduced risk of cardiovascular disease in later life.23,24 Similarly, reduced energy intake in childhood is associated with reduced adult cancer risk.25,26 This direct effect on health may have unforeseen consequences for the increasing number of overweight children in our population.

Smoking

Women who experienced lifelong deprivation were more likely to have smoked in the past and to currently smoke. Among those who had quit, more deprived women generally had smoked for longer periods. These findings are consistent with those of other research on SES and smoking habits.27-29

Our analysis of individual SES indicators suggested that, consistent with other research, adult SES had a strong influence on smoking habits.30 If women perceive more immediate threats to their health (e.g., occupational hazards, street crime), they may downplay the health dangers of smoking and place less priority on stopping smoking.31,32 There is little evidence in our data that childhood SES was related to smoking. This may reflect the attitude toward smoking in the 1940s and 1950s; when these women were young, smoking was more acceptable.

Physical Activity

Most participants were inactive, which is a concern given the strong evidence linking activity with healthy survival in old age.33,34 However, the percentage of women who did exercise for more than 3 hours per week (28%) was higher than the percentages reported among other UK cohorts (e.g., 13% in the English Longitudinal Study of Ageing35). According to the Allied Dunbar National Fitness Survey, conducted in1990, 40%of women aged 65 to 74 years (comparable to the age range in our cohort) reported no physical activity in the previous 4 weeks, and the average was less than 3.5 hours during a 4-week period.36 However, that survey showed that neither education nor social class had an effect on women's exercise behavior.

Our data show that both adult SES and childhood SES were associated with exercise patterns. Few studies have examined the relationship between SES and physical activity across the life span.37 Participation in sports in adolescence is reportedly a predictor of adult physical activity,38 and teenagers in low-SES groups have been shown to be less likely to participate than teenagers in high-SES groups. Other studies have revealed little association between childhood SES and adult physical activity.39 In a separate study involving the present cohort,40 we also found an independent effect of area-level deprivation over and above individual SES, and this is a further and important dimension for consideration in developing health and social policy.

Adult SES affects exercise behavior both directly, as a result of factors such as financial costs (e.g., gym memberships), and indirectly, given that deprivation is associated with increased disability.41 Women without access to a car reported less physical activity than those who had a vehicle, suggesting that walking does not fully compensate for structured exercise opportunities.

Social Mobility

Our data suggest that socially mobile individuals adopt the eating and exercising habits of their new social group. Women whose SES improved over the course of their lives (i.e., women who became more affluent) were more likely than were women whose SES did not improve to eat fruit and vegetables and to exercise; however, they were not as likely to do so as those who had always been members of the nonmanual social class. Conversely, those who moved down the social scale were likely to adopt detrimental health behaviors, but these behaviors were not as harmful, in general, as those engaged in by women who had always been members of the manual social class.

Motivation for some of these behavioral changes may be financial; for example, processed meats are cheaper, and gym admissions and structured exercise programs are expensive. Moreover, many downwardly mobile women married men from poorer backgrounds who then influenced the family's health behaviors.

Strengths and Limitations

Previous studies have highlighted how the use of separate indicators for education, occupation, and family income during childhood adds uniquely to our understanding of how SES is related to behavior.5,6,8 Our work, which extends earlier findings in that we used a much wider range of SES indicators, demonstrates the various ways in which cumulative disadvantage influences health behaviors. Our use of several childhood and adult SES indicators is a strength of this study; it is common practice to use only 1 measure for each, often occupational social class. Adjusting for an individual's socioeconomic position either by conditional logistic regression adjusted for the10-point socioeconomic score, or by using each of the 10 socioeconomic variables as a binary indicator variable did not make any difference to the findings.

We acknowledge that SES measurement error may have influenced the accuracy of our results regarding the independent predictive effects of adulthood and childhood SES on women's health behaviors. However, the modest correlation of 0.33 between SES scores in childhood and adulthood, the differences in the independent predictive power of childhood and adult SES with respect to different health behaviors, and the use of multiple SES indicators at each study time point all suggest that our results are likely to have captured meaningful differences in the predictive power of childhood and adult SES.

Our results were derived from women who were all aged 60 to 79 years at the time of data collection. Without evidence to the contrary, it seems likely that today's children will also retain some of their dietary and exercise habits into adulthood, implying that our findings may have some relevance to the current population of children.

Some women without cardiovascular disease at baseline were excluded from the study because they had missing SES data; however, it is unlikely that exclusion of these women resulted in substantial bias in our analyses, as indicated by the very similar findings obtained in multivariate multiple imputation analyses (data available on request). Dietary data were derived from a simple selfreported food frequency questionnaire that allowed participants to answer questions relatively quickly and easily. The resulting food groups used to indicate a healthful diet were simple but were based on a principalcomponents analysis that produced interpretable groupings. However, our categories did not capture detailed differences in types of food; for example, fish and chicken can include very healthful oily fish and unhealthful fried chicken and fish.

Physical activity as assessed here was not purely a measure of exercise or sporting activities, but rather, included day-to-day activities such as walking and gardening, which are recommended as part of adult activity programs. These forms of physical activity were appropriate for women of the age of our study population and captured the activity level currently recommended by the UK government (30 minutes of moderate activity at least 5 days a week).42

Social desirability bias is a potential issue in all observational studies that collect selfreported behavioral data. However, such bias would tend to attenuate any associations and was unlikely to be sufficiently powerful to remove the widely reported differences in cardiovascular disease outcomes either between socioeconomic groups or by selfreported diet, exercise, or smoking behaviors. Whenever possible, we attempted to validate our risk factor data; for example, we found, in a repeated measures analysis of variance, a significant association between quantity of fruits and vegetables consumed and serum vitamin C levels (P<.001), suggesting that reported intake was a valid indicator (data available on request).

Implications

We have demonstrated that childhood SES, independently of adult SES, is associated with aspects of a healthful diet and physical activity. Our results emphasize the importance of establishing good habits during childhood. School meals in England, after strong criticism, 43 are currently being reformed through government programs. These reform efforts may improve the diets of today's generation of children as they mature.

Home economics classes in which children are taught about food preparation and healthful eating may also be helpful. Successfully educating adults to improve their diets will reduce not only their own CHD risk but that of their children. Targeted programs aimed at increasing physical activity in the poorest communities (where activity levels are lowest), through better provision of opportunities for activity in schools, may also help to increase adult activity levels in years to come.

A focus on the individuals who are currently at highest cardiovascular risk is also warranted. Seemingly the most direct way to improve older people's health behaviors would be to tackle their underlying deprivation. According to recent estimates, the minimum income for pensioners in the United Kingdom to maintain a healthful lifestyle is £122.70 ($236.00) per person per week, somewhat more than the minimum pension credit of £109.45 ($210.50) (including additional benefits such as winter fuel).44 One of the consequences of poverty is that dietary decisions are often financial,45 and members of low-SES groups typically choose unhealthful, cheaper foods. A healthful diet for a moderately active couple in which each partner is older than 65 years costs approximately £63.70 ($122.50) per week, yet average spending in the poorest 40% of couples in this age group is just £44.50 ($85.60) per week.44

The small increases in the UK basic pension instituted in the past 2 years have not been adequate to close these gaps. Older widowed women, previously dependent on their partner's income to raise their family, are particularly affected by today's inadequate pension provisions. Additional financial support for our growing elderly population is needed to ensure people's health in old age.

Conclusions

Our findings highlight the adverse effects of socioeconomic inequalities throughout life on behaviors that are known risk factors for cardiovascular disease and other life-threatening conditions. Improving socioeconomic inequalities in health behaviors and, ultimately, in disease outcomes will require development of better interventions, and these interventions will need to be applied across the life course and will need to focus on disadvantaged groups to provide the greatest benefit.

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41. Ebrahim S, Papacosta O, Wannamethee G, Adamson J. Social inequalities and disability in older men: prospective findings from the British Regional Heart Study. Soc Sci Med. 2004;59:2109-2120.
42. The National Service Framework for Older People. London, England: Dept of Health Publications; 2004.
43. Gould R, Russell J, Barker ME. School lunch menus and 11 to 12 year old children's food choice in three secondary schools in England-are the nutritional standards being met? Appetite. 2006;46:86-92.
44. Morris J, Dangour A, Deeming C, Fletcher A, Wilkinson P. Minimum Income for Healthy Living: Older People. London, England: Age Concern Reports; 2005.
45. Giskes K, Lenthe F, Brug HJ, Mackenbach J. Dietary intakes of adults in the Netherlands by childhood and adulthood socioeconomic position. Eur J Clin Nutr. 2004;58:871-880.

[Author Affiliation]
Hilary C. Watt, MSc, MA, Claire Carson, PhD, Debbie A. Lawlor, PhD, MBChB, MPH, FFPH, Rita Patel, MSc, and Shah Ebrahim, DM, MSc, BMedSci, FRCP, FFPHM

[Author Affiliation]
About the Authors
Hilary C. Watt, Claire Carson, and Shah Ebrahim are with the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England. Debbie A. Lawlor and Rita Patel are with the Department of Social Medicine, University of Bristol, Bristol, England.
Requests for reprints should be sent to Shah Ebrahim, BMedSci, MSc, DM, FRCP, FFPHM, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, England (e-mail: shah.ebrahim@lshtm.ac.uk).
This article was accepted May 1, 2008.
Contributors
H. C. Watt contributed to developing the study aims and writing the article and undertook and interpreted the statistical analysis. C. Carson contributed to developing the study aims, undertook the literature review, and made major contributions to the drafting of the article. D. A. Lawlor contributed to developing the study aims and design and contributed to the writing of the article. R. Patel contributed to the drafting of the article. S. Ebrahim supervised the writing of the article and contributed to developing the study aims.
Acknowledgments
The British Women's Heart and Health Study was funded by the Department of Health Policy Research Programme and the British Heart Foundation. Debbie A. Lawlor is funded by a UK Department of Health Career Scientist Award.
We thank Carol Bedford, Alison Emerton, Nicola Frecknall, Karen Jones, Mark Taylor, and Katherine Wornell for collecting and entering British Women's Heart and Health Study data.Wethank all of the general practitioners and their staff who supported collection of data for this study and the women who took part in the study.
Note. The views expressed in this article are those of the authors and not necessarily those of any funding agency. No funding agency influenced data analysis or interpretation.
Human Participant Protection
The British Women's Heart and Health Study received local research ethics committee approval from each of the 23 towns in the study and multicenter approval from the London Multi Region Ethics Committee. All participants provided informed consent.

References
Indexing (document details)
Subjects:Cardiovascular%20disease%22)">Cardiovascular disease, Womens health, Older people, Health behavior, Diet
Author(s):Hilary C Watt, Claire Carson, Debbie A Lawlor, Rita Patel, Shah Ebrahim
Author Affiliation:Hilary C. Watt, MSc, MA, Claire Carson, PhD, Debbie A. Lawlor, PhD, MBChB, MPH, FFPH, Rita Patel, MSc, and Shah Ebrahim, DM, MSc, BMedSci, FRCP, FFPHM

About the Authors
Hilary C. Watt, Claire Carson, and Shah Ebrahim are with the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England. Debbie A. Lawlor and Rita Patel are with the Department of Social Medicine, University of Bristol, Bristol, England.
Requests for reprints should be sent to Shah Ebrahim, BMedSci, MSc, DM, FRCP, FFPHM, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, England (e-mail: shah.ebrahim@lshtm.ac.uk).
This article was accepted May 1, 2008.
Contributors
H. C. Watt contributed to developing the study aims and writing the article and undertook and interpreted the statistical analysis. C. Carson contributed to developing the study aims, undertook the literature review, and made major contributions to the drafting of the article. D. A. Lawlor contributed to developing the study aims and design and contributed to the writing of the article. R. Patel contributed to the drafting of the article. S. Ebrahim supervised the writing of the article and contributed to developing the study aims.
Acknowledgments
The British Women's Heart and Health Study was funded by the Department of Health Policy Research Programme and the British Heart Foundation. Debbie A. Lawlor is funded by a UK Department of Health Career Scientist Award.
We thank Carol Bedford, Alison Emerton, Nicola Frecknall, Karen Jones, Mark Taylor, and Katherine Wornell for collecting and entering British Women's Heart and Health Study data.Wethank all of the general practitioners and their staff who supported collection of data for this study and the women who took part in the study.
Note. The views expressed in this article are those of the authors and not necessarily those of any funding agency. No funding agency influenced data analysis or interpretation.
Human Participant Protection
The British Women's Heart and Health Study received local research ethics committee approval from each of the 23 towns in the study and multicenter approval from the London Multi Region Ethics Committee. All participants provided informed consent.
Document types:Feature
Document features:Tables, References
Section:RESEARCH AND PRACTICE
Publication title:American Journal of Public Health. Washington: Feb 2009. Vol. 99, Iss. 2; pg. 320, 8 pgs
Source type:Periodical
ISSN:00900036
ProQuest document ID:1630875651
Text Word Count6054
Document URL:http://proquest.umi.com/pqdweb?did=1630875651&sid=1&Fmt=3&clientId=45625&RQT=309&VName=PQD


Thursday, January 15, 2009

Acute infections, vaccination and prevention of cardiovascular disease

Acute infections, vaccination and prevention of cardiovascular disease
Mohammad Madjid. Canadian Medical Association. Journal. Ottawa: Oct 7, 2008. Vol. 179, Iss. 8; pg. 749, 2 pgs
Abstract (Summary)

The study by [Lamontagne] and colleagues does not include data on the incidence of pneumonia and its relation to myocardial infarction in cases and controls. However, it is reasonable to hypothesize that pneumococcal vaccination may protect against cardiovascular events by preventing pneumonia, as the latter has been shown to trigger myocardial infarction. Musher and colleagues4 reviewed a series of 170 patients admitted to hospital with pneumococcal pneumonia over a 5- year period and found that about 7% of patients had a myocardial infarction while in hospital. They also report that about 20% of patients had either a myocardial infarction, atrial fibrillation, or new or worsening congestive heart failure while in hospital.4 Other studies have suggested that infections in the upper respiratory tract and urinary tract can trigger myocardial infarctions.5 Spodick and colleagues reported that, in the 2-week period before being admitted to hospital for a myocardial infarction, 28% of patients had acute respiratory symptoms.6 In an autopsy-based study, my group observed that influenza epidemics are associated with a sharp rise in the number of deaths caused by myocardial infarction and ischemic heart disease.7 In fact, during almost all influenza epidemics and pandemics (except for the 1918 Spanish influenza pandemic), about twice as many people die of cardiac causes as die of pneumonia.8 Myocardial infarction was also reported to be the cause of death in 2 of 5 fatal cases among 75 patients with severe acute respiratory syndrome.9

Multiple mechanisms could contribute to the cardioprotective effect of pneumococcal vaccination. A study in mice lacking the low-density lipoprotein (LDL) receptor suggested that the molecular mimicry between epitopes of Streptococcus pneumoniae and oxidized LDL may lead to increased anti-oxidized LDL immunoglobins following pneumococcal vaccination, which may lead to a decreased extent of atherosclerosis.10 However, production of such antibodies following pneumococcal vaccination in humans has not been confirmed.11 This interesting pathway requires further research. In addition, S. pneumoniae and other respiratory infections may exert many acute effects directly relevant to acute coronary syndromes. My colleagues and I have previously shown that influenza infection leads to excessive recruitment of inflammatory cells to atherosclerotic aortic plaques in mice lacking apolipoprotein E receptor.12 Similarly, compared with controls, the coronary arteries of patients who died of acute systemic infections show a higher number of macrophages and T cells in their adventitia and periadventitial fat, and more dendritic cells in the intima and media.13 In synergy with local cellular inflammation, there is an extensive systemic inflammation heralded by acute increase in systemic markers of inflammation.2 These acute inflammatory changes are paralleled by activation of the coagulation cascade and increased levels of coagulation factors. Finally, such acute infections are also associated with tachycardia, hemodynamic stress, fever, dehydration, increased plasma viscosity, release of endogenous cathecholamines, possible demand ischemia, severe endothelial dysfunction and qualitative pro-oxidant changes in high-density lipoprotein. Each of these can play an important role in acute coronary syndromes.2,14

Copyright Canadian Medical Association Oct 7, 2008

Extensive research in recent decades has established a critical role for cellular and humoral inflammation in the initiation and progression of atherosclerosis and its acute clinical presentations.1 Although atherosclerotic disease has a slow progression over many years, several intrinsic and extrinsic factors may trigger latent stable atherosclerotic plaques to become inflamed, unstable plaques that often rupture and start a cascade leading to thrombus formation and acute coronary syndromes or sudden cardiac death. Respiratory infections are among the known triggers for such acute cardiovascular events.

In the past 2 decades, many basic and epidemiologic studies have suggested a role for chronic indolent infections, such as Chlamydia pneumoniae, in the chronic progression of atherosclerotic lesions over years. Failure of clinical trials using antibiotics against C. pneumoniae to prevent cardiovascular events has led to a decreased interest in the role of infections in cardiovascular disease. However, in contrast to chronic infections, acute infections may cause acute coronary syndromes by triggering severe and abrupt inflammatory changes in high-risk coronary plaques over a few days or weeks. Prevention or treatment of these infections may offer new targets for coronary prevention.2

In this issue of CMAJ, Lamontagne and colleagues3 present their findings from a large hospital-based database study. The authors studied the incidence of myocardial infarctions among those who had or had not received a pneumococcal vaccine before admission to hospital. They include patients who were free of known atherosclerotic disease but who were at risk of myocardial infarction based on age (men aged 45 years or older, women aged 50 years or older) and who had at least 1 cardiovascular disease risk factor (hypertension, diabetes or hyperlipidemia). The authors report that people who had a myocardial infarction were less likely than those who did not have a myocardial infarction to have received a pneumococcal polysaccharide vaccine (7.1% v. 11.6%; adjusted odds ratio 0.53, 95% confidence interval 0.40-0.70).

The study by Lamontagne and colleagues does not include data on the incidence of pneumonia and its relation to myocardial infarction in cases and controls. However, it is reasonable to hypothesize that pneumococcal vaccination may protect against cardiovascular events by preventing pneumonia, as the latter has been shown to trigger myocardial infarction. Musher and colleagues4 reviewed a series of 170 patients admitted to hospital with pneumococcal pneumonia over a 5- year period and found that about 7% of patients had a myocardial infarction while in hospital. They also report that about 20% of patients had either a myocardial infarction, atrial fibrillation, or new or worsening congestive heart failure while in hospital.4 Other studies have suggested that infections in the upper respiratory tract and urinary tract can trigger myocardial infarctions.5 Spodick and colleagues reported that, in the 2-week period before being admitted to hospital for a myocardial infarction, 28% of patients had acute respiratory symptoms.6 In an autopsy-based study, my group observed that influenza epidemics are associated with a sharp rise in the number of deaths caused by myocardial infarction and ischemic heart disease.7 In fact, during almost all influenza epidemics and pandemics (except for the 1918 Spanish influenza pandemic), about twice as many people die of cardiac causes as die of pneumonia.8 Myocardial infarction was also reported to be the cause of death in 2 of 5 fatal cases among 75 patients with severe acute respiratory syndrome.9

Multiple mechanisms could contribute to the cardioprotective effect of pneumococcal vaccination. A study in mice lacking the low-density lipoprotein (LDL) receptor suggested that the molecular mimicry between epitopes of Streptococcus pneumoniae and oxidized LDL may lead to increased anti-oxidized LDL immunoglobins following pneumococcal vaccination, which may lead to a decreased extent of atherosclerosis.10 However, production of such antibodies following pneumococcal vaccination in humans has not been confirmed.11 This interesting pathway requires further research. In addition, S. pneumoniae and other respiratory infections may exert many acute effects directly relevant to acute coronary syndromes. My colleagues and I have previously shown that influenza infection leads to excessive recruitment of inflammatory cells to atherosclerotic aortic plaques in mice lacking apolipoprotein E receptor.12 Similarly, compared with controls, the coronary arteries of patients who died of acute systemic infections show a higher number of macrophages and T cells in their adventitia and periadventitial fat, and more dendritic cells in the intima and media.13 In synergy with local cellular inflammation, there is an extensive systemic inflammation heralded by acute increase in systemic markers of inflammation.2 These acute inflammatory changes are paralleled by activation of the coagulation cascade and increased levels of coagulation factors. Finally, such acute infections are also associated with tachycardia, hemodynamic stress, fever, dehydration, increased plasma viscosity, release of endogenous cathecholamines, possible demand ischemia, severe endothelial dysfunction and qualitative pro-oxidant changes in high-density lipoprotein. Each of these can play an important role in acute coronary syndromes.2,14

Given the pivotal role of inflammation and its relation to infection in the development of acute coronary syndromes, it would be prudent to test drugs that affect inflammatory mechanisms in clinical scenarios involving atherosclerosis. Statins are known to have such anti-inflammatory effects.1 There have been conflicting conclusions from studies examining the effect of statins on mortality of people admitted to hospital with community-acquired pneumonia. New well-designed studies of statins in the context of acute infection focused on cardiovascular outcomes are needed. Preliminary reports from my laboratory suggest that statins have a direct antiinfluenza effect,15 and they could be tested for similar effects against S. pneumoniae and other microbial agents. Hypothetically, in adults with respiratory infections, acetylsalicylic acid (ASA) could be useful not only for relief of respiratory symptoms but also for preventing coronary events, because ASA may help to reduce inflammation and inhibit platelet function during high-risk periods.2 Finally, further research is needed to assess whether the use of antimicrobials can prevent cardiovascular events if used in a timely manner when infections occur without or despite vaccination.

Multiple case-control, cohort and randomized clinical trials in different settings have shown that preventing influenza by vaccination can reduce the risk of recurrent myocardial infarction, sudden cardiac death, cardiac hospital admissions, need for revascularization and stroke.2,14 The current study by Lamontagne and colleagues suggests that pneumococcal vaccination could similarly be a safe and inexpensive tool to prevent cardiovascular events. However, results of case-control studies should be interpreted with caution. "Healthy user" bias is a possibility in case-control studies. Receipt of pneumococcal vaccine may be an indicator of better access to health care, healthier life style and better control of risk factors. The study findings were significant after adjustment for several confounders; however, statistical models may not completely overcome the complex interactions between confounders. Further prospective and randomized studies are needed to confirm these findings.

Until confirmatory studies are available, clinicians should comply with available guidelines by increasing current vaccination rates among patients at high risk. In the United States, rates of pneumococcal and influenza vaccination are well below the established goals, and the situation is worse in many other countries. In addition, clinicians should reduce the baseline risk of cardiovascular events in vulnerable patients by judicious use of antihypertensive, lipid-lowering drugs (preferably statins) and ASA.

Competing interests: Mohammad Madjid received an honorarium from Pfizer for participation in an advisory board meeting in 2007.

[Sidebar]
Key points
* Infections of the upper respiratory tract, including pneumonia and influenza, can trigger acute coronary syndromes.
* Prevention of these infections by vaccination may prevent cardiovascular events in people at high risk.
* Rates of pneumococcal and influenza vaccination are below the optimal level in most countries.
* Physicians need to improve vaccination rates by actively advocating vaccination following established guidelines.
* Special attention should be paid to symptoms and signs of cardiac events in patients at high risk for cardiovascular disease who have an upper respiratory tract infection.
From the Texas Heart Institute and the Baylor College of Medicine, Houston, USA

[Reference] » View reference page with links
REFERENCES
1. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation 2004;109(Suppl 1):II2-10.
2. Madjid M, Naghavi M, Litovsky S, et al. Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies. Circulation 2003;108:2730-6.
3. Lamontagne F, Garant MP, Carvalho JC, et al. Pneumococcal vaccination and risk of myocardial infarction. CMAJ 2008;179:773-7.
4. Musher DM, Rueda AM, Kaka AS, et al. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis 2007;45:158-65.
5. Smeeth L, Thomas SL, Hall AJ, et al. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004;351:2611-8.
6. Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol 1984;53:481-2.
7. Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects. Eur Heart J 2007;28:1205-10.
8. Madjid M, Casscells SW. Of birds and men: cardiologists' role in influenza pandemics. Lancet 2004;364:1309.
9. Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003;361:1767-72.
10. Binder CJ, Horkko S, Dewan A, et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between streptococcus pneumoniae and oxidized LDL. Nat Med 2003;9:736-43.
11. Nguyen JT, Myers N, Palaia J, et al. Humoral responses to oxidized low-density lipoprotein and related bacterial antigens after pneumococcal vaccine. Transl Res 2007;150:172-9.
12. Naghavi M, Wyde P, Litovsky S, et al. Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein e-deficient mice. Circulation 2003;107:762-8.
13. Madjid M, Vela D, Khalili-Tabrizi H, et al. Systemic infections cause exaggerated local inflammation in atherosclerotic coronary arteries: clues to the triggering effect of acute infections on acute coronary syndromes. Tex Heart Inst J 2007;34:11-8.
14. Madjid M, Aboshady I, Awan I, et al. Influenza and cardiovascular disease: Is there a causal relationship? Tex Heart Inst J 2004;31:4-13.
15. Haidari M, Ali M, Casscells W, et al. Statins block influenza infection by downregulating Rho/rho kinase pathway [abstract]. Circulation 2007;116:II_7.

[Author Affiliation]
Mohammad Madjid MD

[Author Affiliation]
Correspondence to: Dr. Mohammad Madjid, Texas Heart Institute, 6770 Bertner Ave., MC 2-255, Houston TX 77030, USA; fax 832 355-9595; mmadjid@gmail.com

Sunday, January 11, 2009

Impact of type 2 diabetes on manifestations and treatment outcome of pulmonary tuberculosis

Impact of type 2 diabetes on manifestations and treatment outcome of pulmonary tuberculosis
C S WANG, C J YANG, H C CHEN, S H CHUANG, et al. Epidemiology and Infection. Cambridge: Feb 2009. Vol. 137, Iss. 2; pg. 203, 8 pgs
Abstract (Summary)

SUMMARY

Diabetes mellitus (DM) is a known risk factor for pulmonary tuberculosis (PTB). This study aimed to determine if type 2 DM alters manifestations and treatment outcome of PTB. Records of 217 consecutive culture-proven PTB patients were analysed retrospectively. The manifestations and treatment outcomes of 74 patients with type 2 DM (PTB-DM group) were compared to 143 patients without DM (PTB group). PTB-DM patients showed higher frequencies of fever, haemoptysis, positive acid-fast bacilli sputum smears, and consolidation, cavity, and lower lung field lesions on chest radiographs, and higher mortality rate. Furthermore, type 2 DM, age [= or >, slanted]65 years, and extensive radiographic disease were factors independently associated with an unfavorable outcome. This study confirmed that clinical manifestations and chest radiographs of PTB patients associated with type 2 DM significantly depart from the typical presentation. Type 2 DM seems to have a negative effect on treatment outcome of PTB. [PUBLICATION ABSTRACT]
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Full Text (2829 words)
Copyright © 2008 Cambridge University Press

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INTRODUCTION

Although the prevalence rate of pulmonary tuberculosis (PTB) has declined significantly in western countries in the past few decades, PTB remains one of the most common infectious diseases in developing countries [1]. Diabetic patients are considered a high-risk population [2] and many studies have shown a 1·5-7·8 times higher prevalence of PTB among diabetics than non-diabetics [3-6]. With increasing life expectancy, there is also a current global increase in diabetic patients [7]. Thus, PTB in diabetic patients will become an increasingly important problem.

A high index of suspicion and prompt investigation of diabetic patients with clinical presentation of PTB may allow earlier diagnosis and treatment. Nonetheless, some previous reports have described an atypical presentation of PTB in diabetic patients [8-10]. When these differences are ignored, establishing a diagnosis may be delayed, leading to increased morbidity and mortality.

On the other hand, there is scarce information about the influence of type 2 diabetes mellitus (DM) on the treatment outcome of culture-proven PTB patients. The present study aimed to determine, in a developed Asian city with a sizable study sample and a high prevalence of PTB, if type 2 DM alters manifestations and treatment outcome of PTB.

METHODS

Subjects and study design

This study was conducted at the Kaohsiung Municipal Hsiao-Kang Hospital, a 500-bed, university-affiliated teaching hospital that serves as a tertiary referral centre and primary-care facility in southern Taiwan. From the retrospective review, 217 consecutive adult patients with PTB from 1 January 2003 to 31 December 2006 were selected and 21 patients were excluded because either the chest radiograph (CXR) done at the first presentation was missing or there was no clear data on bacteriology and history of DM, as radiographic and bacteriological findings were the main parameters that this study investigated in patients with and without DM. The study protocol was reviewed and approved by the hospital's human experiment and ethics committee.

Cases were identified from the hospital coding system and microbiology department records, and included both outpatients and in-patients. In this institution, the main criteria for hospital admission of tuberculous patients included sepsis, haemoptysis, respiratory failure, advanced malnutrition, and pleural effusion. However, about two-thirds of hospitalized tuberculous patients were admitted for treatment or diagnosis confirmation even in the absence of the above-mentioned criteria. Patients were excluded if one of the following was present: aged <18>126 mg/dl on a different day in an outpatient setting. Patients who did not have DM in the same period were chosen as the control group (PTB group). The characteristics of the 74 type 2 DM patients (PTB-DM group) were compared to those of the 143 non-diabetic patients (PTB group).

Clinical data collection

All of the patients had a medical chart, microbiology results, and standard posterior-anterior CXR. Although this was a retrospective study, the patients were interviewed by the same trained nurse-case manager using a structured questionnaire and the completed questionnaires were then reviewed by the physician investigator. Demographic information included age and sex. Risk factors for PTB infection were recorded, including previous TB disease, infectious TB contact history, alcoholism, illegal drug use, long-term glucosteroid use, immunosuppressive drug use, and other comorbidities associated with TB, such as DM, end-stage renal disease, cancer, human immunodeficiency virus infection, silicosis, and gastrectomy history.

Initial presenting symptoms prior to hospital consultation included the presence of cough, expectoration, fever, weight loss, dyspnoea, anorexia, haemoptysis, chest pain, fatigue, and night sweats, which were considered positive if these symptoms were present for [= or >, slanted]2 weeks. Less than this was coded as negative for the analysis. Weight loss was defined as positive if it was >10% of body weight within the last 6 months. Fever was defined as a body axillary temperature above 37·5°C. Haemoptysis was recorded as positive even if it occurred only once.

All of the sputum smears were concentrated and stained with Ziehl-Neelsen stain by trained technicians. Each sputum sample was prepared in Löwenstein-Jensen culture medium and Middlebrook 7H11 selective agar, and maintained for at least 8 weeks to detect the presence of growth.

Initial standard posterior-anterior CXR taken at the time of the patient's first hospital visit was independently reviewed by two external chest physicians, both of whom were unaware of the patient's clinical data. Differences were then resolved by consensus. CXR results were categorized by the involved field and pattern. An upper lung field lesion was defined as the presence of any lesion above an imaginary line across the hilum. Radiographic presentation was categorized as normal, consolidation, cavity, or pleural effusion [12]. 'Normal' pattern was defined as the absence of any abnormal lesion on CXR. 'Consolidation' pattern was defined as an essentially homogenous opacity in the lung characterized by little or no loss of volume, effacement of blood vessel shadows, and sometimes by the presence of an air bronchogram. 'Cavitary' pattern was defined as a lucent area within the lung that may or may not contain a fluid level and that is surrounded by a wall, usually of varied thickness. 'Pleural effusion' was defined as a uniform opacity extending upwards from the costophrenic angle in an erect film. Ultrasound was later used to confirm pleural effusion.

TB treatment consisted of a standard regimen of daily rifampicin, isoniazid, pyrazinamid, and ethambutol for 2 months and rifampicin, isoniazid, and ethambutol for another 4 months or daily rifampicin, isoniazid, and ethambutol for 9 months. Treatment outcomes after 1 year from the initiation of anti-TB treatment were extracted from the records. They were analysed and defined according to World Health Organization recommendations [13]. 'Cure' was defined as a patient who was sputum smear-negative in the last month of treatment and on at least one previous occasion. 'Treatment completed' was defined as a patient who had completed treatment but who did not meet the criteria to be classified as a cure or a failure. 'Treatment failure' was defined as a patient who was sputum smear-positive at 5 months or later during treatment. 'Died' was defined as a patient who died for any reason during the treatment course. 'Default' was a patient whose treatment was interrupted for two consecutive months or more, and 'Transfer out' was a patient who was transferred to another recording and reporting unit, with unknown outcome. A favourable outcome was defined as including cure and treatment completed. Any other outcome was classified as unfavourable. In subgroup analysis, 'PTB-related death' was defined as a patient who died due to PTB during the treatment course.

Statistical analysis

Univariate comparisons between the PTB-DM and PTB groups were performed using the [chi] 2 test except when expected values of <5>, slanted]0·10. All of the analyses were performed using a statistical software program (version 12.0, SPSS Inc., Chicago, IL, USA).

RESULTS

Demographic characteristics and sputum acid-fast bacilli (AFB) stain results

A total of 217 culture-positive PTB patients were enrolled in the study. There were no type 1 DM patients in this study. The demographic characteristics and sputum AFB stain results of the PTB-DM and PTB groups are presented in Table 1. There was no statistically significant difference between the two groups regarding age, sex, previous TB disease, infectious TB contact history, alcoholism, end-stage renal disease, and cancer. No patient had the following risk factors: illegal drug use, long-term glucosteroid or immunosuppressive drug use, human immunodeficiency virus infection, silicosis, and gastrectomy history. In the PTB-DM group, 68·9% of patients were AFB positive on sputum smear compared to 53·8% of the PTB group (OR 1·90, 95% CI 1·051-3·435).


Initial presenting symptoms

The initial presenting symptoms of the PTB-DM and PTB groups are described in Table 2. The PTB-DM group had higher frequencies of fever (OR 2·2, 95% CI 1·233-4·011) and haemoptysis (OR 2·6, 95% CI 1·238-5·297) than the PTB group. There were no statistically significant differences in terms of cough, expectoration, weight loss, dyspnoea, anorexia, chest pain, fatigue, and night sweats.


Initial presenting CXR findings

Initial presenting CXR findings of the PTB-DM and PTB groups are shown in Table 3. Isolated lower lung field lesions were significantly more common in the PTB-DM group than the PTB group (OR 2·04, 95% CI 1·027-4·042). The PTB-DM group also had significantly higher frequencies of consolidation (OR 2·23, 95% CI 1·040-4·798) and cavity (OR 1·91, 95% CI 1·072-3·412) in terms of lung lesions. There were no statistically significant differences between the two groups regarding radiographic features, including the prevalence of normal and pleural effusion.


Treatment outcome after 1 year from the initiation of anti-TB treatment

Treatment outcome after 1 year from the initiation of anti-TB treatment is shown in Table 4. Mortality for PTB-DM patients was 17·6%, in sharp contrast to 7·7% for PTB patients (OR 2·56, 95% CI 1·084-6·034). Univariate analysis shows that type 2 DM (OR 2·9, 95% CI 1·456-5·928), age [= or >, slanted]65 years (OR 8·5, 95% CI 3·970-18·352), and extensive radiographic disease that was defined as radiographic lesions involving both upper and lower lung field (OR 3·2, 95% CI 1·551-6·802) were all associated with an unfavourable outcome. On multiple logistic regression analysis after adjusting for age and sex, type 2 DM (OR 5·5, 95% CI 2·273-13·452), age [= or >, slanted]65 years (OR 10·8, 95% CI 4·402-26·251), and extensive radiographic disease (OR 2·40, 95% CI 1·027-5·617) remained as independent and significant risk factors (Table 5). In subgroup analysis, PTB-related death was significantly more common in the PTB-DM group than the PTB group (12·2% vs . 4·2%; OR 3·16, 95% CI 1·080-9·257). On multiple logistic regression analysis after adjusting for age and sex, type 2 DM (OR 7·6, 95% CI 1·976-29·083) still remained as an independent and significant risk factor for PTB-related death.



DISCUSSION

The increased incidence of DM among PTB patients is well known [3-6], but less is known about its possible effects on the manifestations and treatment outcome of PTB. Recent studies show that 10-30% of patients with PTB may also have DM [2-4, 14-18]. In this study, 34% of the total PTB patients had co-existing type 2 DM.

Recently, a number of studies compared disease presentation between diabetic and non-diabetic PTB patients. Studies in Saudi Arabia [16], Malaysia [19], and Turkey [20] did not find major differences in presenting symptoms. Similar to our findings, a recent large retrospective study involving the Texas-Mexico border region revealed a higher rate of fever and haemoptysis among diabetic PTB patients [14]. Whether the symptomatic differences of PTB patients with DM in the present study represent physiological or cultural differences (or both) remains unclear.

Comparative studies of PTB images in diabetics have yielded conflicting results. The impact of DM on the radiological presentation of PTB is important because misinterpretations may delay appropriate diagnostic tests and treatment, thus risking dissemination of M. tuberculosis to others. Some studies on the radiographic findings of PTB patients with DM report atypical localization patterns, namely an increased incidence of lower lung field involvement [8-10], which is confirmed in the present study. Other reports do not confirm these observations and find no difference in terms of the radiographic involvement of the lung fields [20, 21]. Possible explanations for these discrepancies are demographic characteristics and patient selection process.

Our study shows a significantly higher frequency of consolidation and cavitary lung lesions on CXR in the PTB-DM group. Some previous studies have also reported cavitary lesions as more common among diabetic patients [8-10, 14, 22]. Moreover, our sputum bacteriology results reveal that diabetics have a higher prevalence of AFB smear-positive cases compared to non-diabetic PTB patients. Our study also shows an interesting finding - increasing cavitation together with increased smear positivity in the diabetic group - which is the same as a previous study [23]. Cavitary disease is associated with a larger population of bacilli.

Immunosuppression induced by DM may be responsible for the atypical images and higher bacillary load in PTB patients with DM [24]. It is known that DM causes a decrement in lymphocyte activity and a diminution in the number of monocytes and macrophages, with abnormalities in their chemotactic and phagocytic activities [25, 26]. Moreover, DM also causes dysfunction of polymorphonuclear leukocytes, with a reduction in their bactericidal activity [27].

There are conflicting reports regarding the influence of associated DM on the treatment outcome of TB patients. One study has reported no effect of DM on the treatment outcome of TB patients [16], while another has reported a negative effect [18]. In the present study, the mortality rate for all patients at 12 months was 11·0%, accounting for 60% (24/40) of the patients with unfavourable outcome. There was also a sharp contrast in mortality rates (17·6% vs . 7·7%; OR 2·56, 95% CI 1·084-6·034) and PTB-related death (12·2% vs . 4·2%; OR 3·16, 95% CI 1·080-9·257) between PTB-DM and PTB patients. As more than one third of patients were diabetics with PTB, the higher mortality rate may have contributed to the overall low treatment completion rate.

Altered pharmacokinetics of anti-TB drugs may explain the adverse effect of DM on the treatment outcome of TB patients. One recent study has reported low plasma concentrations of rifampicin in diabetic patients with TB [28]. Several mechanisms have been postulated to explain the altered pharmacokinetics of anti-TB drugs in TB patients with DM. The absorption, distribution, metabolism, and excretion of drugs could all be changed in TB patients with DM [29]. Lower plasma concentrations of anti-TB drugs have been associated with clinical failure and acquired drug resistance [30]. If these findings are confirmed, higher fixed dosages of rifampicin may be warranted for TB patients with DM. If available, physicians may consider the assessment of plasma concentrations of rifampicin in patients with DM in order to individualize dosing.

The present study reveals on univariate analysis that type 2 DM, age [= or >, slanted]65 years, and extensive radiographic disease were all associated with an unfavourable outcome. Moreover, even after adjustment for age and sex, logistic regression analysis also showed that type 2 DM was an independent and significant risk factor associated with an unfavourable outcome. This suggests that clinicians must pay more attention to PTB patients with associated DM. A previous study has shown that the advent of effective anti-TB and anti-diabetic treatments has led to a decrease in the death rate of TB in patients with DM [31].

Our study had some methodological limitations. Twenty-one patients were excluded in the retrospective study because either the CXR that was done at the first presentation was missing or there was no clear data on bacteriology and history of DM. Part of the findings might result from missing patient records unrelated to DM status. Therefore, future prospective studies should formally evaluate the differences.

In summary, this study has shown that PTB patients with associated type 2 DM had higher frequencies of fever, haemoptysis, positive AFB sputum smears, and consolidation, cavity, and lower lung field lesions on CXR, and mortality rate. Furthermore, PTB-DM patients also have higher frequencies of unfavourable outcome. PTB should be included in the differential diagnosis when diabetic patients present with unusual findings, thus avoiding postponing the diagnosis and the start of treatment, and reducing the dissemination of M. tuberculosis to others and the mortality rate for PTB-DM patients.

DECLARATION OF INTEREST

None.
[Reference]
REFERENCES

[Author Affiliation]
1 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Indexing (document details)
Subjects: Diabetes, Tuberculosis, Epidemiology
Author(s): C S WANG, C J YANG, H C CHEN, S H CHUANG, I W CHONG, J J HWANG, M S HUANG
Author Affiliation: 1 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Document types: Feature
Publication title: Epidemiology and Infection. Cambridge: Feb 2009. Vol. 137, Iss. 2; pg. 203, 8 pgs
Source type: Periodical
ISSN: 09502688
ProQuest document ID: 1621810791
Text Word Count 2829
DOI: 10.1017/S0950268808000782
Document URL: http://proquest.umi.com/pqdweb?did=1621810791&sid=1&Fmt=3&clientId=45625&RQT=309&VName=PQD