Aortic Dissection Runs in the Family

Family history was an important risk factor for aortic dissection, a large cross-sectional study of the Taiwanese national data registry found.

History of aortic dissection in first-degree relatives was linked to increased risk for aortic dissection (RR 6.82, 95% CI 5.12-9.07), reported Pao-Hsien Chu, MD, of the Chang Gung Memorial Hospital in Taiwan, and coauthors, in the Journal of the American College of Cardiology.

Excluding patients with Marfan syndrome or bicuspid aortic valve, family history of aortic dissection was associated with an RR of 6.56 (95% CI 4.92-8.77) for aortic dissection. Heritability of aortic dissection was estimated as 57% for genetic factors, 3% for shared environmental factors, and 40% for non-shared environmental factors.

Follow-up analysis comparing late outcomes of propensity-matched aortic dissection patients with and without family history of aortic dissection patients showed patients with family history had a higher risk of later aortic surgery (sub-distribution HR 1.40; 95% CI 1.12-1.76).

“A family history was a strong risk factor for aortic dissection, with or without syndromes related to aortic disease, and both genetic and environmental factors contributed to the overall risk of aortic dissection,” Chu and colleagues wrote. “Furthermore, a family history of aortic dissection in the patients with aortic dissection was associated with a higher risk of later aortic surgery.”

“We recommend routine imaging and genetic screening of individuals with a family history of aortic dissection,” they added. “Close surveillance and aggressive control of risk factors or even preventive aortic replacement in high-risk populations may decrease the frequency of dissection and possibly reduce mortality through an earlier preclinical diagnosis in affected families.”

In an accompanying editorial, John Elefteriades, MD, and Bulat Ziganshin, MD, PhD, both of Yale University, wrote, “The thrust of the study, like that of our earlier work, is that families with dissection manifest a much higher virulence of the aneurysmal disease.

“The [present study] found a 6.7-fold increase in prevalence of aortic dissection in families with a history of aortic dissection, much greater than the 2.7-fold increased risk in our study,” they continued. “The Taiwanese study compared dissection incidence to that of the general population, whereas our study compared to incidence in aneurysm families without a history of dissection. Thus, it makes sense that the comparison of incidence of aortic dissection would be much stronger with the general population as the comparator, rather than our already enriched comparison group.”

The editorialists also highlighted study findings that showed the prevalence of aortic dissection increased with advancing age, and that familial aortic dissection occurred at a younger age than non-familial dissection.

Genetic disorders including Marfan syndrome, Ehlers-Danlos syndrome, and bicuspid aortic valve, along with arterial hypertension, smoking, and vascular inflammation are known risk factors for aortic dissection. Aortic aneurysm and aortic dissection are usually asymptomatic until rupture with high mortality, so identifying risk factors, close surveillance, risk factor management — and in some high-risk cases, preventive ascending aortic replacement — are important.

A 2017 study of 100 aortic dissection patients found that those with a positive family history (at least one other family member with aortic dissection in addition to the index case) had higher annual probability of dissection, a shorter time before dissection occurred, and a lower age at the time of dissection.

In their study, Chu and colleagues analyzed data for patients with aortic dissection between 2000 and 2015 from the Taiwanese National Health Insurance Administration, a government-run universal single payer system covering 99% of Taiwan’s population. They conducted a cross-sectional study on 23,868 patients for those with aortic dissection diagnosis in 2015, including additive genetic and environmental factor analysis.

Average age was about 39 to 40 across women and men, for both the general population and those with one or more first degree relative with aortic dissection.

Aortic dissection incidence increased between 2001 and 2015 from 5.2 to 8.5 events per 100,000 person years. Those with an affected relative had higher prevalence of aortic dissection compared with the general population (0.21% versus 0.03% in women; 0.41% versus 0.08% in men).

Adjusted risk ratios for family members were significant for:

• Parents: RR 5.32, 95% CI 3.85-7.36.
• Offspring: RR 8.48, 95% CI 5.85-12.29.
• Siblings: RR 18.83, 95% CI 8.64-41.07.

Familial aggregation of aortic dissection was not seen in those who had affected spouses (RR 1.23, 95% CI 0.59-2.55).

“The relative risk of dissection increased according to closeness of the genetic link—rising from parents, to offspring, to siblings,” the editorialists observed.

Those with first-degree relatives with aortic dissection also had increased risk for Marfan disease (RR 31.92, 95% CI 26.19-38.90), bicuspid aortic valve (RR 5.88, 95% CI 3.62-9.53), and hypertension (RR 1.19, 95% CI 1.14-1.24), but no increased risk of Turner’s syndrome or Ehlers-Danlos syndrome.

Limitations include lack of anatomic imaging data, including CT scans. Severity and aortic dissection subtype were not analyzed separately. As a population-based study in Asia, generalizability to other groups may be limited.

1. Family history was a strong risk factor for aortic dissection, but both genetic and environmental factors contributed to overall risk.

2. In patients with aortic dissection, family history was associated with a higher risk of later aortic surgery.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Cat ID: 6

Topic ID: 74,6,730,6,914,192,916