Rapid Responses to:

PRIMARY CARE: Julia Hippisley-Cox, Carol Coupland, Mike Pringle, Nicola Crown, and Vicky Hammersley Married couples' risk of same disease: cross sectional study BMJ 2002; 325: 636 [Abstract] [Full text]

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Rapid Responses published:

Spouses and Pets

Thomas S SULLIVAN,D.C.   (21 September 2002)

Hidden time effects and secondary demand on health care

Grazyna T Adamiak   (23 September 2002)

'Environment' factors may depend on lifestyle

Regina B. Stroebele   (23 September 2002)

Infectious agents?

Adam Jacobs   (24 September 2002)

Re: Spouses and Pets

James C. Denning   (27 September 2002)

Spouse similarities for disease: Can assortative mating be excluded?

Gonneke Willemsen, Jacqueline M Vink, Dorret I. Boomsma   (18 October 2002)

Coeliac disease in a married couple

Alastair D Smith   (6 March 2003)

Spouses and Pets 21 September 2002
Thomas S SULLIVAN,D.C., private practice 1261 Furnace Brook Parkway, Suite 36, Quincy Massachusetts 02169-4721 Send response to journal: Re: Spouses and Pets	George, ("Sr.") and Barbara Bush, the 41st president and first lady of the United States were treated for Grave's disease and apparently their dog evidenced hyperthyroidism as well. It may well be prudent to add the presence of pets, any updates to ailments, in a history inventory. Such data if captured in patient databases may yield future researchable associations.
Hidden time effects and secondary demand on health care 23 September 2002
Grazyna T Adamiak, PhD Student Uppsala University, Dep. of Public Health and Caring Sciences, HSR Send response to journal: Re: Hidden time effects and secondary demand on health care	The study on married couples’ risk of same disease is of large interest as it adds important and otherwise scarce evidence on the impact of shared environmental exposures on the prevalence of common diseases. However, there are some limitations that not addressed by the Authors. One is the problem of the hidden time effects in the case of blood pressure measurements, which were performed only once. As Altman (1999:79) concludes, the blood pressure is a particularly variable measurement. It varies considerably between individuals but also over time for each individual. There is marked variation over 24 hours (circadian variation) as well day-to-day variation. It is also difficult to measure blood pressure. The method used in the study was not mentioned at all. There are new techniques to perform measurements via an indwelling catheter in the arm linked to a small tape recorder, which provides more accurate information. Observer bias might also affect the results of blood pressure measurements. Since the blood pressure has a strong circadian rhythm being highest in the morning the advice is commonly to take repeat measurements of blood pressure from the same subject at the same time of day (Altman 1999:148). The Authors did not provide this information and the conclusions on the increased risk of hypertension shared by couples might thus be biased. The problem of the hidden time effects is also present due to the impact of seasons on the utilisation of care due to asthma and chronic obstructive disease. Both individual and population data might vary by month of the year, e.g. levels of IgE are affected by the seasons. We might also expect that there are variations in the practice among the participating general practices such as various routines for follow-up visits, i.e. the way in which the secondary demand on health care is upcoming, which might contribute to various patterns of utilisation. The problem of utilisation was partly mentioned by the Authors who pointed to the fact that they did not use consultation data and could not adjust for the different frequencies at which some groups of patients consult they general practitioner. Such differences might also arise e.g. due to distance to the general practices from the patients place of residence, due to non-random environmental factors, i.e. geographical differences affecting availability. It would be of interest to examine if the same factors affect the married couples in Sweden, whether there might be systematic health care systems effects, i.e. the degree of coverage of travel costs by the health insurance system could contribute to the various utilisation patterns in the two countries which would affect the shared environmental risks of couples. Reference: Douglas G Altman (1999). Practical statistics for medical research. Chapman & Hall/CRC, USA (Originally published in London, 1991).
'Environment' factors may depend on lifestyle 23 September 2002
Regina B. Stroebele, Specialist in General Practice D - 81677 Munich / Germany Send response to journal: Re: 'Environment' factors may depend on lifestyle	It is well known that diabetes / hyperlipidemia and hypertension / ischemic heart disease / stroke can be influenced positively by changes in lifestyle, mainly by body exercise = making sports and using the feet instead of the car and the lift/elevator, and by avoiding obesity. Peptic ulcers are not only associated with blood cell surface antigens (blood group A), but also - strongly - with smoking or with helicobacter pylori infection (of which the latter may be transmitted by 'closely living together'). An ulcus duodeni without h.p. infection (plus) in a non -smoker is a rarity. "Asthma" in adults, in up to 80% (at least in Germany) is not an intrinsic asthma, but a chronic obstructive pulmonal disease (COPD), and in common, it is caused by long term smoking. Patients with mental diseases may often choose a "corresponding" partner. Concerning the rapid response from the U.S. mentioning the very interesting case of multiple Grave's diseases within a family, I suggest to assure that the hyperthyreoidisms both in human and in animal family members are due to this autoimmune disease, and not to a long term iodine deficient feeding, thus not being a Grave's disease but an autonomous adenoma/ goiter (or several adenomas within the thyroid gland) secondarily resulting from the "iodine avidity" of the gland.
Infectious agents? 24 September 2002
Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ Send response to journal: Re: Infectious agents?	The results presented by Hippisley-Cox et al [1] make me wonder whether infectious agents might be more important in causing the various diseases they mention than we have previously thought. After all, we have only understood relatively recently about the importance of H pylori in peptic ulcer disease. The role of C pneumoniae infection in heart disease is still not completely understood, but could turn out to be important [2]. Perhaps there are many more diseases out there with infectious aetiologies waiting to be discovered. This would certainly explain high concordance among married couples. 1. Hippisley-Cox J, Coupland C, Pringle M, Crown N, Hammersley V. Married couples' risk of same disease: cross sectional study. BMJ 2002; 325: 636 2. Leinonen M, Saikku P. Evidence for infectious agents in cardiovascular disease and atherosclerosis. Lancet Infect Dis 2002; 2: 11- 7
Re: Spouses and Pets 27 September 2002
James C. Denning, President Sleep Disorders Info Inc. PO Box 365 Holbrook Ma 02343 Send response to journal: Re: Re: Spouses and Pets	Listen, perhap the fact Apnea is responsible or some other factor like that. Which causes some condition like being over weight. That could be the reason the attraction was there. Thus couple could share the responsible condition. jim
Spouse similarities for disease: Can assortative mating be excluded? 18 October 2002
Gonneke Willemsen, lecturer Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, The Netherlands, Jacqueline M Vink, Dorret I. Boomsma Send response to journal: Re: Spouse similarities for disease: Can assortative mating be excluded?	Hippisley-Cox et al (1) observed significant spouse similarities for disease in a large sample of 8386 couples recruited through general practice. They suggest shared environmental factors may cause these similarities, but reject assortative mating as an explanation. In a sample of the Netherlands Twin Register (2), we could not replicate their spouse similarities for asthma, depression, diabetes and cardiovascular disease, possibly due to our smaller sample size of 2152 spouse pairs. However, when examining health behaviour in a larger sample we found good associations between spouses for smoking, alcohol problems and exercise behaviour, even after controlling for age and BMI of both spouses. Interestingly, the duration of the relationship influenced these associations between the spouses (see figure). Except for alcohol problems, spouse similarities in health behaviour decreased as the duration of the relationship increased. This would suggest that assortment for these factors is based on similarity at the time dating began (3) and highlights the importance of determining similarities in disease status at the time of dating, as suggested by Hippisley-Cox et al. Figure: Risk of smoking (current smoking and ever smoked), exercise (regular sport participation and cycling) and alcohol problems in women whose partner had the same lifestyle compared to those whose partner did not. The logistic regression analyses were adjusted for age and body mass index of both males and females. Assortative mating may further be based upon social factors and personality traits. Indeed, in our sample we found significant spouse correlations for educational attainment, an indicator of social economic status, which is also related to disease development. These spouse correlations increased as the duration of the relationship increased (r=.292, r=.356, r=587 for <5, >5 and > 15 yrs duration respectively), possibly due to convergence of phenotypes of the spouses or to a higher divorce rate in dissimilar pairs (3). Significant spouse correlations were also found for inhibition, a personality trait associated with increased risk behaviour, but these correlations were unaffected by duration of relationship (r=.386, r=.334, r=.373 for <5, >5 and > 15 yrs duration respectively). These results suggest different mechanisms underlie spouse similarities for health behaviour, social factors and personality traits. However, the fact that spouse similarities were found for this wide range of variables indicates that assortative mating should not be hastily dismissed as a cause for spouse similarities in disease. It should be noted that any association between spouses does not exclude genetic effects. Hippisley-Cox et al. (1) assume that because spouses are unrelated, genes do not influence the association. However, the similarity of spouses may be an example of an active genotype- environment correlation which occurs when a particular genotype is associated with the selection or creation of a particular environmental circumstance (4). Gonneke Willemsen. Lecturer, epidemiology. Jacqueline M. Vink. Researcher, genetic epidemiology. Dorret I. Boomsma. Professor, genetic epidemiology. Dept. of Biological Psychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands 1. Hippisley-Cox, J Coupland, C., Pringle, M., Crown, N., Hammersley, V. Married couples’ risk of same disease: Cross-sectional study. BMJ 2002: 325; 1-5. (21 Sept) 2. Boomsma, D.I., Vink, J.M., Beijsterveldt, C.E.M.v., Geus de, E.J.C., Beem, A.L., Mulder, E.J.C.M., Riese, H., Willemsen, A.H.M., Bartels, M., Berg van den, M., Derks, E.M., Graaff, S.C., Kupper, H.M., Polderman, J.C., Rietveld, M.J.H., Stubbe, J.H., Knol, L.I., Stroet, T. and Baal, G.C.M. (in press). “Netherlands Twin Register: a focus on longitudinal research.” Twin Research. 3. Price, R.A. and Vandenberg, S.G. (1980). “Spouse similarity in American and Swedish couples.” Behavior Genetics 10(1): 59-71. 4. Rowe, D.C. (2002). Assesing genotype-environment interactions and correlations in the postgenomic era. Behavioral Genetics in the postgenomic era. R. Plomin, Defries, J.C., Craig, I.W., McGuffin, P. Washington, American Psychological Association: 71-86.
Coeliac disease in a married couple 6 March 2003
Alastair D Smith, Consultant Physician and Gastroenterologist Eastbourne District General Hospital, Kings Drive, Eastbourne. BN21 2UD Send response to journal: Re: Coeliac disease in a married couple	EDITOR - The data presented recently by Hippisley-Cox and colleagues raises interesting points about disease development in married couples, aged 30-74.1 All of the conditions they found to be more prevalent are multifactorial. Coeliac disease (CD) is a relatively common disorder in northern Europe with a reported prevalence as high as 1:152.2 It is characterised by lifelong gluten intolerance, a preponderance for the HLA -DR3, -DQ2 haplotype, and is more common among first degree relatives of affected individuals. 3 However, to my knowledge it has not been reported in both husband and wife following marriage hitherto. A 31-year-old woman complained of life long loose stools, bloating, lower abdominal discomfort and failure to gain weight. As a teenager she was conscious that these symptoms were not associated with gluten-free food consumption. Her daughter, at this stage aged 5, had been diagnosed with CD 27 months previously. The mother became aware that gluten avoidance, whilst making her daughter better, improved her symptoms also. Although her endomysial antibody (EMA) result was negative, distal duodenal biopsy demonstrated a dense chronic inflammatory cell infiltrate in the lamina propria, marked increase in intraepithelial lymphocytes, and mild villous atrophy. After 12 months' strict gluten avoidance her symptoms resolved completely, her weight had increased and follow-up duodenal biopsies revealed normal appearances. Three months later during hospital outpatient appraisal of her 30-year-old husband, systematic review revealed difficulty in him maintaining weight. He had no other alimentary tract symptoms. Standard blood test results including serum B12, folate and ferritin concentrations were normal. However, his EMA result was positive, distal duodenal biopsies demonstrated appearances characteristic of CD, and a subsequent bone density scan revealed osteoporosis. Rigorous adherence to a gluten free diet resulted in modest weight gain, but he relocated from this area before follow-up biopsy could be undertaken. One of Coeliac UK’s (formerly Coeliac Society) medical directors has encountered a husband and wife who were diagnosed with CD after marriage (personal communication), but otherwise I can find no record of this in the literature. Although CD is not as common as asthma, 4 if its prevalence approaches 1:150 then approximately 1:22,500 unions may expect both partners to have CD. This will have important ramifications for them and their issue: not only did one of this couple’s children have CD, but another had a positive IgG anti-gliadin antibody test (he had selective IgA deficiency), albeit a normal duodenal biopsy then. 1. Hippisley-Cox J, Coupland C, Pringle M, Crown N, Hammersley V. Married couples’ risk of same disease: cross sectional study. BMJ 2002; 325: 1-5. 2. Johnston SD, Watson RGP, McMillan SA, McMaster D, Evans A. Preliminary results from follow-up of a large-scale population survey of antibodies to gliadin, reticulin and endomysium. Acta Paediatr 1996; Suppl 412: 61-4. 3. Maki M, Holm K, Lipsanen V, Hallstrom O, Viander M, Collin P et al. Lancet 1991; 338: 1350-53. 4. Tattersfield AE, Knox AJ, Britton JR, Hall IP. Asthma (Review). Lancet 2002; 360: 1313-22. Competing interests:   None declared Editorial comment The patients whose cases are described have given their signed informed consent to publication.