Risk of Morbidity in Contemporary Celiac Disease

Nina R Lewis; Geoffrey KT Holmes

Disclosures

Expert Rev Gastroenterol Hepatol. 2010;4(6):767-780. 

In This Article

Vascular Disease

Like in the general population, vascular disease is the most important single cause of mortality in celiac disease, accounting for 39% of all deaths.[51] However, the possibility that celiac disease might afford some protection from vascular disease mortality was first raised by Whorwell et al. in 1976, who observed a reduced risk of death from ischemic heart disease in men (but not women) with diagnosed celiac disease,[52] and this was further supported by studies in Scotland and Italy.[4,53] However, Peters et al., using data from the Swedish In-Patient Registry, observed that patients with celiac disease (n = 10,032) had a 50% increased mortality risk from ischemic heart disease (standardized mortality ratio [SMR]: 1.5 [95% CI: 1.3–1.8]) and 40% increased mortality risk from cerebrovascular disease (standardized mortality ratio: 1.4 [95% CI: 1.1–1.9]) in comparison with the Swedish general population.[51] On examining the risk of cardiovascular mortality in the presence of villous atrophy within the Swedish In-Patient Registry celiac cohort, a 19% (HR: 1.19 [95% CI: 1.11–1.28]) increased risk of death was observed compared with general population controls.[54]

Recent studies have found some evidence of a favorable vascular-risk profile in celiac disease. Adults newly diagnosed with celiac disease have lower total cholesterol levels than the general population, with a greater reduction in men (21%; -1.09 mmol/l [95% CI: -0.97 to -1.21]) than in women (9%; -0.46 mmol/l [95% CI: -0.24 to -0.68]).[8] While no increase in total cholesterol following a year's treatment with a gluten-free diet was observed, there was a significant increase in high-density lipoprotein cholesterol.[8] In a cross-sectional population screening study, people with positive endomysial antibodies, and thus undetected celiac disease, had an 8% (0.5 mmol/l) reduction in total cholesterol and a 2.4 mmHg lower diastolic blood pressure in comparison with antibody-negative controls.[1] Adults with treated celiac disease are reported to be less likely to have a diagnosis of hypertension (OR: 0.68 [95% CI: 0.60–0.76]) and have a lower reported antihypertensive medication use in comparison with age- and sex-matched general population controls.[55] Celiac disease appears to be associated with nonsmoking, although it is unclear whether or not this is a causal association.[56–58] However, smoking was more common in women with diagnosed celiac disease than those without celiac disease using data combined from national birth registers and the Swedish In-Patient Registry.[59] Homocysteine concentrations were significantly higher in newly diagnosed adult celiacs than in controls although the concentrations were not measured again in these 35 celiacs to determine if there was any change with exposure to a gluten-free diet.[60]

Despite this apparent favorable vascular risk profile and reduced risk of vascular-related mortality in comparison with the general population, not all studies have observed that celiac disease has a protective effect upon vascular disease events. A Swedish hospital-based cohort study of 13,358 people with celiac disease observed that people with celiac disease were at increased risk of myocardial infarction (HR: 1.27 [95% CI: 1.09–1.48]) and angina pectoris (HR: 1.46 [95% CI: 1.25–1.70]).[61] By contrast, no differences were observed in the risk of neither myocardial infarction (HR: 0.85 [95% CI: 0.63–1.13]) nor stroke (HR: 1.29 [95% CI: 0.98–1.70]) in people with treated celiac disease in comparison with general population controls in a population-based cohort study.[55] A total of 367 celiac patients identified by the presence of positive celiac serology or characteristic changes on small bowel histology had no increased risk of cardiovascular disease events such as myocardial infarction (unadjusted HR: 1.10 [95% CI: 0.62–1.92] in comparison with 5537 controls who had negative celiac serology.[62] Reasons for the observed lack of protection against vascular disease events in diagnosed celiac disease are unclear, but possible explanations include an altering, attenuating effect on the vascular risk profile by treatment with a gluten-free diet, or that other processes particular to people with celiac disease mediate the increased risk.[63]

Although suggested by Fonager using the Danish National Registry,[64] no association between celiac disease and cardiomyopathy nor myocarditis or pericarditis were observed in the Swedish hospital-based cohort of celiacs compared with controls.[65]

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