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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Background

Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors.

Aim

To characterise IHD according to CD status.

Methods

Data on duodenal or jejunal biopsies were collected in 2006–2008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals.

Results

We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P < 0.001) and cholesterol values (P < 0.001) and were less likely to be active smokers (OR = 0.74; 95% CI = 0.56–0.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR = 0.80; 95% CI = 0.66–0.97; three-vessel disease: OR = 0.73; 95% CI = 0.57–0.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, = 0.766).

Conclusion

Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Coeliac disease (CD) occurs in about 1% in the European and North American population.[1] Cardiovascular disease is one of the leading causes of death in CD.[2] Several studies have reported statistically significant increased risks of ischaemic heart disease (IHD) (incident or death) in CD,[2-4] whereas two British studies suggested nonsignificant negative associations with IHD.[5, 6] The increased risk of IHD in CD cannot be fully explained by traditional cardiovascular risk factors because CD patients have a lower average body mass index (BMI),[7] less often suffer from hypertension (HT),[6] and in some studies are reported to be less likely to be daily smokers[8] (while smoking is not associated with CD in other populations[9, 10]). To our knowledge, no study has examined the prevalence of traditional cardiovascular risk factors or clinical presentation and phenotype of IHD in CD patients and general population reference individuals. The aim of this nationwide population-based study was therefore to characterise the risk-factor profiles and phenotype of IHD in CD.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Study design

In this study we conducted a case-only comparison. We compared the clinical presentation of IHD (hospitalised myocardial infarction or death from MI) and IHD risk-factor profiles in patients with biopsy-verified CD to reference individuals from the general population at time of their first myocardial infarction.

Setting

In Sweden, small-intestinal biopsy is routine clinical practice for the diagnosis of CD. In fact, 96–100% of Swedish gastroenterologists and paediatricians[11] perform a biopsy before assigning a diagnosis of CD. There is universal access to publicly funded health care, including in-patient care, for all residents. Through the unique national personal identity number issued to all Swedish residents,[12] data from national and virtually complete administrative or clinical registers on demographics, morbidity and mortality can be linked.

CD patients

In this study, we used a previously identified and defined population-based cohort of CD patients.[11] To put this cohort together data on all pathology reports performed from 1969 to 2008 of small-intestinal biopsies with a morphology code indicating villous atrophy were gathered from all of Sweden's 28 regional pathology departments. A validation study of a subset of these pathology reports (n = 114) was performed using information on clinical CD diagnosis from patient charts as gold standard. The validation study indicated that 95% of all individuals with a pathology report indicating villous atrophy also had CD.[11] Based on this high validity, all individuals with a pathology report from a small-intestinal biopsy indicating villous atrophy (Marsh stage 3) (for a detailed list of relevant morphology codes, see the Appendix) were included in the CD cohort. Positive CD serology was not required to be classified as having CD, but serology was positive at diagnosis in 88% of the CD patients.[11] Detailed information on the CD cohort and the validation study has been published previously.[11] In total, we identified 29 096 individuals with biopsy-verified CD. Each individual entered the study at the date of CD diagnosis.

Reference population

For each patient with CD, we randomly selected five individuals with no previous record of small-intestinal biopsy from the Total Population Register (which includes all Swedish residents). Each reference individual was matched for age, gender, county and calendar year. In all, 144 522 reference individuals were identified and all entered the study at the date of CD diagnosis of their matched CD patient.

Data sources

Using the personal identity number, we linked the CD patients and their matched reference individuals to the following data sources for which data were available through 31 December 2008: The Swedish Patient Register, the Total Population Register, the Cause of Death Register and SWEDEHEART. The Swedish Patient Register contains information on in-patient care since 1964, with nationwide 100% coverage since 1987.[13] The register lists date of admission, date of discharge and the discharge diagnosis (primary and secondary diagnoses) as set by the discharging physician and classified according to the calendar year-specific ICD. The Total Population Register includes information on deaths, emigration and immigration for the entire Swedish population.[14] The Cause of Death Register has complete coverage of all deaths occurring and includes information on all causes of death. It was initiated in 1951, is updated yearly and is based on death certificates.[15] The Swedish cardiac care register SWEDEHEART was formed by a merger of earlier quality registers: the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKSHIA), the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), the Swedish Heart Surgery Registry, the Thoracic Surgery Registry and the National Registry of Secondary Prevention (SEPHIA).[16] SWEDEHEART has a 100% coverage of coronary care units and virtually 100% coverage of all coronary angiographies performed in Sweden.[16] It contains information on traditional cardiovascular risk factors and treatment at the time of admission, laboratory values such as total cholesterol, haemoglobin (Hb) levels, creatinine levels and CRP at admission, as well as presenting symptoms of IHD and other clinical characteristics, indication for angiography, findings from the procedure and what treatment decisions are made based on the findings. There is also information on traditional cardiovascular risk factors and information on previous coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI). Coronaries were classified as significantly stenosed if a >50% stenosis could be detected and considered clinically important or if the fractional flow reserve was <75%. For detailed information on SWEDEHEART, please be referred to previously published studies.[16, 17]

By linking the CD patients and their matched reference individuals to these registers, we identified all admissions listing myocardial infarction or angina pectoris, all individuals included in SWEDEHEART, all deaths from IHD and all emigrations from Sweden during follow-up.

Study population

All CD patients and their matched reference individuals with an IHD diagnosis before study entry were excluded from the analyses and only first-time myocardial infarctions registered in RIKSHIA after study entry were eligible. After excluding all patients with a prior event, 1075 CD patients and 4142 reference individuals with an ICD code of IHD in the Swedish Patient Register or the Cause of Death Register and who had a record in SWEDEHEART during follow-up (i.e. two independent records of IHD) were identified. Figure 1 presents a flow chart of exclusions. Calendar-specific ICD codes used to define IHD are found in the Appendix.

image

Figure 1. Flow chart of study population. CD, coeliac disease; MI, myocardial infarction; PCI, percutaneous coronary intervention; PR, Patient Register (Swedish National). # Patients with a history of prior MI were excluded since we were only interested in individuals with their first MI.

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Number of patients in the subgroup analyses

Of the 1075 CD patients and 4142 reference individuals identified, 430 CD patients and 1988 reference individuals had a record of first myocardial infarction in SWEDEHEART. Data were available from angiographies in 742 CD patients and 2901 reference individuals (Figure 1).

Statistical analyses

We used logistic regression adjusted for age group (0–59, 60–69, 70–79, 80–95) and gender to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for binary outcome variables. We tested statistical significance for continuous variables with the Mann–Whitney U-test as well as unianova, adjusted for age at SWEDEHEART admission, calendar period and gender. In all our analyses the comparison was made between CD patients with MI/coronary angiography vs. reference individuals with MI/coronary angiography. The statistical analyses were nonstratified and we did not consider any time frame in the analyses since the purpose of this study was to describe the clinical presentation of first MI in CD patients compared with reference individuals at the time of the first infarction. In a sensitivity analysis we restricted our data to patients with an IHD indication for angiography because angiographic evaluation may be undertaken for non-ischaemic reasons. We also excluded individuals with earlier PCI or CABG. This analysis was based on 292 CD patients and 1107 reference individuals with primary angiography that was due to strictly ischaemic indication. In post hoc analyses we evaluated the angiographic findings of 251 CD patients and 1180 reference individuals with an angiography performed within 10 days before and up to 30 days after their first SWEDEHEART admission. In a separate analysis we also examined the proportion of coeliac patients (and MI) who had persistent villous atrophy on second biopsy (0.5–5 years after the first biopsy). Persistent villous atrophy may correlate with chronic inflammation and could potentially contribute to IHD. We defined statistical significance as 95% CIs for risk estimates not including 1.0. We used spss version 20.0 (SPSS Inc, Chicago, IL, USA) for all analyses.

Ethics and role of funding source

This study was approved by the Research Ethics Committee of Karolinska Institutet. The funding sources did not influence the study's design, conduct and reporting.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Some 3.7% (1075/28 833) of all CD patients and 2.9% (4142/143 729) of all reference individuals were registered in the Swedish Patient Register or the Cause of Death Register and also had a record in SWEDEHEART (P < 0.001, Figure 1). Some 430 (2.1%) of the CD patients and 1988 (1.8%) of the reference individuals were recorded in SWEDEHEART with a myocardial infarction (P < 0.001). In total 57 CD patients and 327 reference individuals were registered to have suffered ischaemic death without being entered in SWEDEHEART.

Patients with a first episode of myocardial infarction registered in SWEDEHEART

Age, gender and prior medication

Gender and age distributions were similar in CD patients and reference individuals with myocardial infarction (Table 1). The use of Ca-blockers prior to first MI was less common in CD patients than in reference individuals (Table 2).

Table 1. Patient characteristics
Myocardial infarction P-value
Reference individuals, N (%)Coeliac disease patients, N (%)
Total1988430
Gender0.98
Men1231 (61.9)266 (61.9)
Women757 (38.1)164 (38.1)
Age group at first diagnosis of myocardial infarction/angina pectoris (years)0.85
30–59399 (20.1)89 (20.7)
60–69568 (28.6)130 (30.2)
70–79644 (32.4)132 (30.7)
80–95377 (19.0)79 (18.4)
Median age (range), years70, 30–9569, 39–93
Calendar year of SWEDEHEART entry0.54
1991–1996165 (8.3)35 (8.1)
1997–2002748 (37.6)174 (40.5)
2003–20081075 (54.1)221 (51.4)
Table 2. Clinical parameters
Reference individuals, N (%)Coeliac disease patients, N (%) P-value
  1. ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ASA, acetylsalicylic acid; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention.

  2. a

     Data missing for most patients because of later onset of registration of ARB medication.

  3. b

     P-value <0.05.

Hypertension715 (36.3)133 (31.3)0.05
Diabetes (any)334 (16.9)77 (18.0)0.80
History of prior PCI38 (1.9)4 (0.9)0.16
Cardiogenic shock on arrival to the hospital99 (5.3)27 (6.6)0.28
Biochemical indication of myocardial infarction755 (91.5)154 (92.2)0.77
Smoking0.04
Non smoking856 (46.5)214 (53.5)
Ex smoker528 (28.7)104 (26.0)
Smoking456 (24.8)82 (20.5)
LVEF0.049
Normal451 (50.5)107 (60.1)
40–49%218 (24.4)40 (22.5)
30–39%155 (17.4)25 (14.0)
<30%69 (7.7)6 (3.4)
Pharmacological therapy at arrival
ACE-I257 (13.1)60 (14.1)0.59
ARB82 (9.9)a 20 (11.9)a 0.44
Anticoagulation77 (3.9)12 (2.8)0.28
ASA516 (26.2)126 (29.5)0.16
B-Blockers507 (25.8)107 (25.1)0.75
Ca-blockers323 (16.4)b 46 (10.8)b 0.004
Insulin126 (6.6)38 (9.2)0.06
Oral diabetic treatment176 (9.2)30 (7.2)0.20
Digitalis74 (3.8)20 (4.7)0.37
Diuretics419 (21.3)83 (19.5)0.40
Statins227 (11.6)39 (9.1)0.15
Nitroglycerin (long duration)154 (7.8)36 (8.5)0.67
Hypertension, diabetes, smoking and BMI

Coeliac disease patients were less likely to be active smokers (OR = 0.74; 95% CI = 0.56–0.98) and more likely never smokers compared with ever smokers (OR = 1.38; 95% CI = 1.10–1.72) (Figure 2). BMI was significantly lower in CD patients than in reference individuals (24.6 vs. 26.1, P < 0.001) (Figure 2). Coeliac disease patients were less likely to suffer from HT (OR = 0.80; 95% CI = 0.64–1.00) (Figure 2), but this negative association failed to attain statistical significance (P = 0.054). The prevalence of any diabetes was similar in CD patients and reference individuals (OR = 1.08; 95% CI = 0.82–1.43) however, insulin-dependent diabetes was significantly more common in CD patients (OR = 1.50; 95% CI = 1.03–2.17) whereas diabetes with oral treatment was less common (OR = 0.64; 95% CI = 0.41–1.01).

image

Figure 2. Odds ratios for a number of cardiovascular risk factors in patients with coeliac disease and ischaemic heart disease. Patients with coeliac disease and myocardial infarction (*) or coeliac disease and angiography (§) that is due to ischaemic heart disease. For example, the odds ratio of 0.80 for hypertension in patients with coeliac disease and myocardial infarction means that these coeliac patients were at a lower risk of having hypertension at time of infarction compared with reference individuals with myocardial infarction.

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Laboratory values

The unadjusted median levels of haemoglobin and cholesterol were lower in CD patients, but CRP and creatinine levels were not (Table 3). However, the mean level of CRP was higher in CD patients than in reference individuals (30 vs. 26). CD patients had 5.35 units lower haemoglobin (g/L) (95% CI = 1.34–9.37) (unianova - normal scale). Using a logarithmic scale because of the skewed distribution of laboratory values, the unianova, adjusted for gender, age and calendar year, revealed that CD patients overall had a 7% statistically significantly lower total cholesterol level at first myocardial infarction. We found no statistically significant differences for CRP or creatinine between CD patients and reference individuals.

Table 3. Laboratory values and anthropometry on first hospital admission with myocardial infarction
Reference individuals Median (Range)Coeliac disease patients Median (Range) P-value
  1. BMI, body mass index; Hb, haemoglobin.

  2. Statistical significance was tested using the Mann–Whitney U-test. Missing values ranged from 48.4% for cholesterol levels to 75.1% for Hb.

Cholesterol Total (mmol/L)5.1 (1.7–10.3)4.7 (2.0–8.2)<0.001
CRP (mg/L)8 (0–416)7.5 (0–321)0.958
Creatinine (μmol/L)85 (34–743)83 (41–522)0.247
Hb (g/L)139 (70–180)136 (83–161)0.019
Systolic blood pressure145 (60–260)140 (80–224)0.23
Diastolic blood pressure80 (30–145)80 (40–130)0.20
BMI (kg/m2)26.1 (13.9–49.4)24.6 (14.2–38.4)<0.001
Clinical presentation and presenting symptoms

Patients with CD tended to present at hospital with dyspnoea (OR = 1.30; 95% CI = 0.74–2.31) more commonly than reference individuals, whereas chest pain (OR = 0.76; 95% CI = 0.56–1.04) and cardiac arrest (OR = 0.34; 95% CI = 0.04–2.62) were less common. Cardiogenic shock on arrival to the hospital occurred more often in CD patients (Table 2). Biochemical indication of infarction (See Appendix for included biochemical markers) was present in 92.2% of the CD patients and in 91.5% of the reference individuals (Table 2).

Heart function

Left ventricular function, as defined by left ventricular ejection fraction (LVEF), was significantly better in CD patients (P = 0.049) (Table 2).

Patients with information on angiography

For patients undergoing angiography, we observed a negative association between CD and daily smoking (OR = 0.69; 95% CI = 0.52–0.92) and HT (OR = 0.76; 95% CI = 0.62–0.93) (Figure 2). Prevalence of self-reported any diabetes on admission was similar, however (16.5% in CD patients vs. 17.5% in reference individuals, corresponding to an OR of 0.94; 95% CI = 0.72–1.22, Supplementary Table S4). Having a prior myocardial infarction or CABG and cardiogenic shock on arrival to the hospital were more common in CD patients (Supplementary Table S4). Indication for angiography did not differ between CD patients and reference individuals. Unstable angina pectoris, however, was slightly more common in CD patients, whereas ST elevation myocardial infarction was more common in reference individuals (Supplementary Table S4). Any stenosis (OR = 0.80; 95% CI = 0.66–0.97) and three-vessel disease [significantly so for three-vessel disease not affecting the left main stem (‘LMS’), OR = 0.73; 95% CI = 0.57–0.94] were less common in CD patients. Complementary, not statistically significant results on coronary angiography are available in Supplementary Table S7.

Sensitivity analysis

The sensitivity analyses were restricted to angiography because of IHD. We found a negative association between CD and HT (OR = 0.65; 95% CI = 0.49–0.86) and daily smoking (OR = 0.60; 95% CI = 0.42–0.87). CD patients had more often undergone angiography because of unstable angina pectoris and nonspecific chest pain but less often because of ST elevation myocardial infarction. Angiographic findings that were due to IHD were similar to those seen in any angiography (stenosis: OR = 0.60; three-vessel disease: OR = 0.62) (Supplementary Table S6).

Post hoc analyses

In a subset of patients undergoing angiography <10 days prior to or <30 days after SWEDEHEART admission we evaluated the following biochemical markers: infarction, heart function, LVEF and angiographic findings. This evaluation revealed no significant differences in angiographic findings (Supplementary Table S8). Elevated biochemical markers were similar in both groups (Supplementary Table S8). Out of 430 coeliac patients with MI, 74 had a recorded second biopsy. Of these, 41 (55.4%) had persistent VA.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

The most important finding of this study is a more favourable IHD risk-factor profile in patients with CD, with the exception of high levels of biochemical markers in both CD patients and reference individuals. Hence, traditional IHD risk factors are unlikely to explain our previous observations of an increased risk of IHD in CD.[4]

Comparison with the literature

Some studies have found an increased risk of IHD in CD[2-4] and others have not.[5, 6, 18] Most evidence suggests that CD patients have a cholesterol profile that, from a IHD risk perspective, is more beneficial[19] and that the introduction of a gluten-free diet does not alter cholesterol levels.[20] Worth mentioning is also that CD patients received statins to the same extent as reference individuals, despite having lower cholesterol levels. Moreover, BMI seems to be lower in CD patients,[7, 21, 22] with most studies indicating that smoking is less common in CD.[8, 19, 21, 23] In that way the findings of our study are consistent with previous data. Furthermore, West et al. reported less HT in individuals with undiagnosed CD.[6] Concerning the use of antihypertensive drugs, the evidence is less clear.[3, 22] In the current study CD patients seem to have similar levels of antihypertensive treatment (apart from Ca-blockers) but fewer CD patients had a record of HT. However, all these studies, except for Lewis et al., [20] examined cardiovascular risk factors in the general CD population and did not in detail examine characteristics of CD patients with IHD. Concerning the evidence of heart failure and better left ventricular ejection fraction seen in this study, this confirms similar findings including a different risk-factor profile and better ejection fraction seen in patients with other inflammatory or autoimmune conditions such as rheumatoid arthritis.[24]

Potential mechanisms

Systemic inflammation may be one explanation for the increased risk of IHD in CD.[4] CRP in our study was 12% higher in CD patients with myocardial infarction than in reference individuals with myocardial infarction, but the difference was not statistically significant. The lack of substantial difference in CRP levels either implies that systemic inflammation is not important for IHD risk in CD or (more likely) that CRP is not an optimal marker of systemic inflammation in CD. Studies have shown elevated levels of various interleukins and tumour necrosis factor[25] in active CD, but elevated CRP has not been associated with CD in the few published studies on this topic.[26, 27] Another autoimmune disease, systemic lupus erythematosus (SLE), has similarly been linked to an increased risk of atherosclerosis potentially due to chronic inflammation in SLE as these patients lack traditional IHD risk factors.[28] Assessments of carotid plaques have shown that atherosclerosis is both more common and positively associated with disease duration in both SLE and rheumatoid arthritis.[29] As of today we are not aware of any study examining disease severity in CD and cardiovascular pathology but one case report has described a patient with refractory CD whose cerebellum autopsy showed small vessel angiopathy, potentially due to circulating neoplastic clones of activated T-cells. In this patient the lymphocytes surrounding and infiltrating the vessel walls had the same phenotype as the intraepithelial lymphocytes.[30] Given that CD is an autoimmune disease (like SLE and RA) chronic inflammation may explain the adverse cardiovascular outcome seen in Swedish patients with CD. Some 55.4% of patients with both CD and MI had persistent villous atrophy implicating that chronic inflammation may be involved in the pathogenesis since this percentage is considerably higher than the overall percentage (43%) of coeliac patients with persistent VA at their second biopsy.[31]

Another potential explanation for the excess risk of IHD in CD is ascertainment bias (patients with CD may, to a larger extent than reference individuals, be investigated for any symptom, including cardiovascular symptoms). However, such systematic bias is unlikely for two reasons. First, CD patients with myocardial infarction had even higher rates of elevated biochemical markers of infarction, which argues that their myocardial infarctions were not diagnosed differently to myocardial infarctions in the average population. Second, in a previous study we found that patients with CD were at a 22% increased risk of death from IHD (95% CI = 1.06–1.40),[4] a finding that cannot be explained by ascertainment bias. Although the proportion of coeliac patients with any diabetes was similar to that in reference individuals, patients with CD had more type 1 diabetes suggesting a longer duration of diabetes since type 1 often has its onset in childhood. Also hyperhomocysteinaemia found to be associated to CD through vitamin deficiencies is a risk factor for cardiovascular disease[32] and might therefore contribute to the increased risk of MI in patients with CD.

Myocardial infarction with angiographically normal coronary arteries has lately attracted more attention.[33] Several mechanisms for the development of myocardial infarction in the absence of stenosis have been suggested, including inflammation.[33, 34] Myocardial infarction with angiographically normal coronary arteries and stress-induced cardiomyopathy also seem to be more common than previously recognised. In fact, a recent study found that this subtype of myocardial infarction constitutes 7% of all myocardial infarction.[35] Myocardial infarction without stenosis is more prevalent in women[34, 35] and may have other risk factors than stenotic coronary artery disease. Our study found that CD patients have elevated biochemical markers when diagnosed with myocardial infarction but more often a beneficial classical risk-factor profile and better results on coronary angiography. We therefore speculate that CD may be a risk factor specifically for myocardial infarction with less extensive coronary disease.

Strengths and limitations

The major strength of this nationwide study is the large number of patients and its use of detailed clinical data through SWEDEHEART. All diagnoses and angiographies performed were standard procedures and therefore not subject to any particular study or inclusion bias. We required two independent records of IHD for study inclusion (national registers and the SWEDEHEART record) and individuals with CD were identified through small-intestinal biopsy yielding a high specificity.

A limitation is our lack of individual-based data on dietary adherence of CD patients. Earlier validation has shown that 17% of CD patients have signs of low dietary adherence according to patient charts.[11] Although our study was nationwide it was limited to Swedish patients with CD. We cannot rule out that CD patients in countries where no link between CD and cardiovascular disease has been shown have a different cardiac risk profile even in the presence of IHD.

Conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

IHD is more common in CD patients than in reference individuals; however, CD patients with IHD have a more favourable classic cardiac risk profile (e.g. HT, smoking, and BMI) compared with reference individuals with IHD.

Authorship

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Guarantor of the article: Louise Emilsson.

Author contributions: LE: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis. RC: critical revision of the manuscript for important intellectual content. MH: analysis and interpretation of data; critical revision of the manuscript for important intellectual content. SJ: analysis and interpretation of data; critical revision of the manuscript for important intellectual content. JFL: study concept and design; acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; statistical analysis; funding; study supervision. All authors approved the final version of the manuscript.

Acknowledgement

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

This project (2006/633-31/4) was approved by the Research Ethics Committee of the Karolinska Institute, Sweden on 14 June 2006.

Declaration of personal interests: None.

Declaration of funding interests: LE was supported by a grant from Värmland County. JFL was supported by a grant from The Swedish Society of Medicine, the Swedish Research Council, the \xD6rebro Society of Medicine and the Swedish Celiac Society. None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information

Supporting Information

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Authorship
  9. Acknowledgement
  10. References
  11. Supporting Information
FilenameFormatSizeDescription
apt12271-sup-0001-Appendix.docWord document172K

Table S1. Small-intestinal histopathology classifications – a comparison.

Table S2. Classification of myocardial infarction.

Table S3. Cardiovascular characteristics and in-patient complications in myocardial infarction.

Table S4. Patient characteristics in individuals undergoing angiography for any reason.

Table S5. Sensitivity analysis - angiography that is due to ischaemic heart disease, IHD, indication with no earlier CABG*, or PCI*.

Table S6. Angiographic findings and primary decision within sensitivity analysis.

Table S7. Angiographic findings and primary decision.

Table S8. Characteristics of coeliac disease patients with a diagnosis of any ischaemic disease* undergoing angiography ≤10 days prior to or ≤30 days after SWEDEHEART admission.

Appendix S1. Relevant ICD codes for ischaemic heart disease.

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.