Comorbidities in hereditary angioedema—A population‐based cohort study

Abstract

Background In hereditary angioedema (HAE), low levels (type 1) or defect in function (type 2) of the serine‐protease inhibitor C1 Inhibitor protein results in activation of the classical pathway of the complement system as well as the contact system. Here, we investigated the risk of comorbidities in HAE. Methods Individuals with HAE (n = 239; identified through a physician made diagnosis) and a control cohort from the general population (n = 2383; matched for age, gender, and county of residence) were compared with the Swedish inpatient, cause of death, cancer, and prescription registers. Conditional logistic regression was used to analyze the data. Results Increased risk of cardiovascular disease (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.32–2.54), including arterial (OR 6.74; 95% CI 1.89–24.06) and venous thromboembolic disease (OR 4.20; 95% CI 2.42–7.23) as well as hypertension (OR 1.64; 95% CI 1.12–2.39) was seen in HAE. There was also an increased number of individuals diagnosed with hyperlipidemia (OR 2.01; 95% CI 1.16–3.50) among HAE patients. Furthermore, the risk of autoimmune disease was increased (OR 1.65; 95% CI 1.15–2.35) being particularly pronounced for systemic lupus erythematosus (OR 71.87; 95% CI 8.80–586.7). The risk of having two or more autoimmune diseases was also higher among HAE patients (p = 0.017). In contrast, the risk of cancer was not increased. Data from the prescription register revealed higher prescription rates of drugs against hypertension, hypothyroidism, and hyperlipidemia among HAE patients. Conclusions The results warrant for awareness and prevention of comorbid conditions, in particular, thromboembolic and autoimmune diseases in HAE. Future prophylactic interventions may modify these risks.

Hereditary angioedema is associated with an increased risk of venous thromboembolism

“…3 This study demonstrated that patients with HAE had an increased risk of autoimmune disease and cardiovascular disease. 3 Of particular interest, HAE patients had a significant increased risk of ICD-based diagnoses of a subset of venous thromboembolic events (odds ratio [OR] 4.20, 95% confidence interval [CI] 2.47-7.19). 3 This category of venous thromboembolism (VTE) included ICD-10 based codings of thrombophlebitis, portal vein thrombosis, and other VTE and included deep vein thrombosis (DVT).…”

“…3 Individuals with HAE caused by low plasma levels of C1INH or impaired plasma C1INH function were recruited through contacting treating physicians and an age-, sex-, and country of residence-matched control cohort assembled. 3 Validated health records that provided International Classification of Diseases 10th revision (ICD-10)-coded annotations of inpatient and outpatient diagnoses were used to identify comorbidities in the case and control cohorts. 3 This study demonstrated that patients with HAE had an increased risk of autoimmune disease and cardiovascular disease.…”

“…3 Validated health records that provided International Classification of Diseases 10th revision (ICD-10)-coded annotations of inpatient and outpatient diagnoses were used to identify comorbidities in the case and control cohorts. 3 This study demonstrated that patients with HAE had an increased risk of autoimmune disease and cardiovascular disease. 3 Of particular interest, HAE patients had a significant increased risk of ICD-based diagnoses of a subset of venous thromboembolic events (odds ratio [OR] 4.20, 95% confidence interval [CI] 2.47-7.19).…”

“…3 Of particular interest, HAE patients had a significant increased risk of ICD-based diagnoses of a subset of venous thromboembolic events (odds ratio [OR] 4.20, 95% confidence interval [CI] 2.47-7.19). 3 This category of venous thromboembolism (VTE) included ICD-10 based codings of thrombophlebitis, portal vein thrombosis, and other VTE and included deep vein thrombosis (DVT). Trends toward increased ORs for DVT and pulmonary embolism (PE) were also observed.…”

Coagulation and complement: Key innate defense participants in a seamless web

“…Based on the genetic association of C1-INH deficiency with hereditary angioedema, C1-INH should most prominently be viewed as a strategic piece for controlling BK formation (212). Notably however, its physiologic contribution to regulating coagulation has recently been revealed, with evidence -contrary to previous claims -that C1-INH deficiency is in fact, associated with an increased risk of thrombosis (213).…”