Family History, Comorbidity and Risk of Thoracic Aortic Disease
Family History, Comorbidity and Risk of Thoracic Aortic Disease
Swedish citizens are issued a 12-digit unique personal identification number at birth, and so are permanent residents, allowing their identification in registries. The National Hospital Discharge Registry (HDR) and the Cause of Death Registry (CODR), maintained by The National Board of Health and Welfare, were used to identify all cases of thoracic aortic aneurysm (including thoracoabdominal, but excluding abdominal aneurysms) or dissection based on the relevant diagnostic codes in the Swedish adaptations of the 9–10th revisions of The International Classification of Diseases (ICD-9, ICD-10), Table 1. Aneurysms of non-specified locations were not included. When adequately coded (Table 1), traumatic aortic injuries, mycotic aneurysms and inflammatory aortic disease (ie, TAD without family history implications) were not included. Controls were randomly selected from the Total Population Registry (Statistics Sweden). The family history of the index cases and controls was obtained by identifying all first-degree relatives in the Multigeneration Registry (Statistics Sweden)—a registry including first-degree relatives (parents, children, siblings and half-siblings) of subjects born 1932 or later—and identifying diagnoses of thoracic or AAA in these subjects, if any. Besides age and sex, atherosclerosis, hypertension and smoking are implied risk factors for TAD. Their influence on the risk of TAD was assessed in terms of occurrence of correlated clinical conditions identifiable in discharge records; ischaemic heart disease, congestive heart failure, hypertension and chronic obstructive pulmonary disease. To minimise the chance of simple coexistence of conditions, the putative risk factors had to present prior (up to 5 years) to the initial TAD diagnosis. The study was approved by the regional research ethics committee, waiving individual informed consent.
Index cases (n=2436) were individuals with TAD according to ICD-10 and defined as a first occurrence in the HDR or as cause of death (direct or contributing or underlying) in the CODR during the period 2000–2005. To each index case, five subjects, alive and without known TAD at the index date of the corresponding case, were randomly selected. Controls (n=12 152) were matched to have the same sex and age as the index case, and to being residents of the same geographic area, forming a total study population of 14 588.
The matched case-control model was analysed with conditional logistic regression analyses. Results are presented as ORs with Wald 95% CIs. The risk of TAD was assessed in relation to family history of TAD categorised according to the number of affected first-degree relatives, family history of AAA (yes/no), and presence of the studied comorbid conditions (yes/no for each condition, as outlined above). Deviation from multiplicative effects of family history of TAD and other risk factors was assessed through introducing appropriate interaction terms into the model. Heterogeneity of the risk related to family history of TAD was assessed by Wald's testing. In assessing interactions, family history of TAD and comorbid conditions, respectively, were dichotomised. To display effects of combinations of different risk factors, compound variables were created from the dichotomised risk factor variables. The prevalence of risk factors among cases and controls was compared using χ test, and p values<0.05 were considered statistically significant. Statistical analyses were performed using SAS V.9.2 (SAS Institute, Cary, North Carolina, USA).
Methods
Swedish citizens are issued a 12-digit unique personal identification number at birth, and so are permanent residents, allowing their identification in registries. The National Hospital Discharge Registry (HDR) and the Cause of Death Registry (CODR), maintained by The National Board of Health and Welfare, were used to identify all cases of thoracic aortic aneurysm (including thoracoabdominal, but excluding abdominal aneurysms) or dissection based on the relevant diagnostic codes in the Swedish adaptations of the 9–10th revisions of The International Classification of Diseases (ICD-9, ICD-10), Table 1. Aneurysms of non-specified locations were not included. When adequately coded (Table 1), traumatic aortic injuries, mycotic aneurysms and inflammatory aortic disease (ie, TAD without family history implications) were not included. Controls were randomly selected from the Total Population Registry (Statistics Sweden). The family history of the index cases and controls was obtained by identifying all first-degree relatives in the Multigeneration Registry (Statistics Sweden)—a registry including first-degree relatives (parents, children, siblings and half-siblings) of subjects born 1932 or later—and identifying diagnoses of thoracic or AAA in these subjects, if any. Besides age and sex, atherosclerosis, hypertension and smoking are implied risk factors for TAD. Their influence on the risk of TAD was assessed in terms of occurrence of correlated clinical conditions identifiable in discharge records; ischaemic heart disease, congestive heart failure, hypertension and chronic obstructive pulmonary disease. To minimise the chance of simple coexistence of conditions, the putative risk factors had to present prior (up to 5 years) to the initial TAD diagnosis. The study was approved by the regional research ethics committee, waiving individual informed consent.
Study Population
Index cases (n=2436) were individuals with TAD according to ICD-10 and defined as a first occurrence in the HDR or as cause of death (direct or contributing or underlying) in the CODR during the period 2000–2005. To each index case, five subjects, alive and without known TAD at the index date of the corresponding case, were randomly selected. Controls (n=12 152) were matched to have the same sex and age as the index case, and to being residents of the same geographic area, forming a total study population of 14 588.
Statistical Analysis
The matched case-control model was analysed with conditional logistic regression analyses. Results are presented as ORs with Wald 95% CIs. The risk of TAD was assessed in relation to family history of TAD categorised according to the number of affected first-degree relatives, family history of AAA (yes/no), and presence of the studied comorbid conditions (yes/no for each condition, as outlined above). Deviation from multiplicative effects of family history of TAD and other risk factors was assessed through introducing appropriate interaction terms into the model. Heterogeneity of the risk related to family history of TAD was assessed by Wald's testing. In assessing interactions, family history of TAD and comorbid conditions, respectively, were dichotomised. To display effects of combinations of different risk factors, compound variables were created from the dichotomised risk factor variables. The prevalence of risk factors among cases and controls was compared using χ test, and p values<0.05 were considered statistically significant. Statistical analyses were performed using SAS V.9.2 (SAS Institute, Cary, North Carolina, USA).
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