Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community

Abstract

Background: Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families. Methods: We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least one parent did so in the Framingham Heart Study (FHS) cohorts, and estimated the incidence rates and hazards ratio of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, as compared with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries. Results: In FHS, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ~3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68,939 individuals (mean age 42 years) had a first-degree relative with aortic aneurysm and 7,209 persons (mean age 39 years) had a firstdegree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazards ratio of 6.70 (95% CI 5.96-7.52) for developing aortic aneurysm and 9.24 (95% CI 5.53-15.44) for dissection, compared to matched controls. These estimates remained unchanged upon adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11-13 (aortic aneurysm) and 2-3 (aortic dissections) per 100,000 person-years among controls. Conclusions: Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach that of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.

Reply: Future prospects for thoracic aortic prediction

“…It is becoming abundantly clear that once a family member dissects, the risk of dissection for other family members increases dramatically. We saw this in our studies (2.7-fold increase compared with aneurysm families without dissection), 6 and it was seen by Raunsø and colleagues 7 and Chen and colleagues 8 (nearly 9-fold and 6.3-fold increase compared with the general population, respectively). Accordingly, we see no reason to wait for the nearly inevitable dissection event in an aneurysm-bearing (almost any size) family member of a known dissector.…”

Hereditary thoracic aortic disease: How to save lives

“…The importance of family history in determining the risk for aortic aneurysm and dissection, and hence genetic predisposition, is reinforced by 2 recent simultaneous publications that provide population-based estimates of dissection risk when a first-degree relative has suffered an aortic dissection. 2,3 The Taiwan study 2 was based on data from its National Health Insurance Program that covers over 99% of the population. Almost 24,000 incident dissections occurred between 2000 and 2015.…”

“…The Danish study, performed in another country with universal health care, used registries to identify individuals with aortic aneurysms and dissections. 3 Over an average 7-year follow-up, first-degree relatives of these individuals had a hazard ratio (HR) of 6.7 for aneurysm and 9.24 for dissection compared with matched controls. Findings remained significant after exclusion of individuals with Marfan syndrome, bicuspid aortic valve, or hypertension.…”

“…The risk of an aortic diameter falling in the highest quartile in an offspring was increased by 2-to 3-fold, depending on the aortic level, if at least one parent had such a finding. 3 The strength of both studies lies in the use of robust population-based data to quantify rates of aortic dissection, although individuals who die before hospitalization obviously are not captured. Unfortunately, neither study subdivided dissection according to location.…”

Commentary: Thoracic aortic disease: One step closer to precision medicine

“…In the current issue of the Journal, Roman and De Backer 9 highlight the importance of family history in HTAD and advocated for cascade screening to allow for timely referral for elective aortic surgery to save lives. Their premise is based on 2 recent large population-based estimates of dissection risks in first-degree relatives who have sustained an aortic dissection, 10,11 showing that their overall relative risks are extremely high.…”