Elevated risk of AAAs among individuals suffering depression post-risk factor adjustment discovered in HUNT study

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Linn Åldstedt Nyrønning

People with depressive symptoms have a significantly higher risk of incident abdominal aortic aneurysms (AAAs) after adjustments for established risk factors, a study published in the Journal of the American Heart Association found.

“Symptoms of depression and risk of abdominal aortic aneurysm: A HUNT study” sought to probe the association of the condition with AAAs given its connection to cardiovascular diseases.

A team led by Linn Åldstedt Nyrønning, MD, of the department of vascular surgery at St. Olavs Hospital in Trondheim, Norway, conducted the study against a backdrop of scarce evidence of a link. The researchers considered the background of AAA. The potentially life‐threatening disease occurs in 1–3% of the adult population, and, left untreated, they said, ruptured AAAs are associated with almost 100% mortality. Smoking, age, heredity and male sex have been identified as risk factors for the disease, with strong associations having been found with conditions such as hypertension and hyperlipidemia. “The pathogenesis of AAA is not fully understood, and it is highly likely that unknown factors that have yet to be discovered may influence development of this disease.”

In a population-based prospective study, some 59,136 participants (52.4% women) aged 50 to 106 years from the HUNT (Norwegian Nord‐Trøndelag Health) study, staged in the northern European country, were mined in pursuit of the central aim of determining whether individuals with depressive symptoms have increased risk of AAA.

“Symptoms of depression were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS),” Nyrønning et al wrote. “During a median follow‐up of 13 years, there were 742 incident cases of AAA (201 women). A total of 6,401 individuals (12.3%) reported depressive symptoms (defined as HADS depression scale [HADS‐D] ≥8); (52.5% women).

“The annual incidence rate of AAA was 1 per 1,000 individuals. At all ages, the estimated proportion of individuals diagnosed with AAA was higher among those with depressive symptoms (log‐rank test, p<0.001). People with HADS‐D ≥8 were older than those with HADS‐D <8 (median 57.8 vs. 52.3 years, p<0.001) and a statistically significantly higher proportion of them (p<0.001) were smokers, overweight or obese, and reported a history of coronary heart disease [CHD], diabetes mellitus and hypertension. In a Cox proportional hazard regression model adjusted for these factors, individuals with depressive symptoms had a ≈30% higher risk of AAA than those without (HR 1.32; 95% confidence interval [CI] 1.08–1.61; p=0.007).”

Setting the scene, the authors noted: “To our knowledge, only one previous study has reported a possible association between depression and development of AAA. This study showed a weak but increased risk of AAA in a subgroup with a history of depression.”

The HUNT study is a large multiphase affair conducted in the county of Nord‐Trøndelag in central Norway. The overall response rate was 89.4% in HUNT1 (1984–1986), which involved 77,212 participants; 69.5% in HUNT2 (August 1995–1997), including 65,237 people; and 54.1% in HUNT3 (2006–2008), capturing 50,807 participants. The population of Nord‐Trøndelag County (n=127,000 during HUNT2) is representative of the Norwegian population as a whole, the researchers noted. Since, the population has been found to be relatively stable and homogeneous, making it suitable for epidemiological studies, they write.

The investigators continued: “The present study population includes 59,136 individuals who participated in HUNT2 and/or HUNT3 (53.8% participated in both), with no prior diagnosis of AAA, and who reached the age of 50 years before the study ended on Dec. 31, 2014.

“Among the 59,136 individuals (52.4% women), 742 incident (27.1% women) AAAs were detected (1.2%). Median age at initial HUNT participation was 53.7 years (range 31.6–101.4 years). For each HUNT survey, participants completed questionnaires regarding clinical and demographic parameters and underwent clinical examination. The date of AAA diagnosis was obtained from hospital medical records. The unique personal identification number was used to link data on AAA diagnoses and death with exposure data from the HUNT study.

“In total, 622 cases of AAA (166 women) were identified among the 50,657 (51.2% women) individuals with complete data on all risk factors.”

In discussion of their findings, the investigators noted that the number of individuals with
severe depressive symptoms was low in their study population, which they said might have resulted from a recruitment bias. Individuals with depression, particularly severe depression, tend to not attend screening programs or population‐ based studies upon invitation, they wrote. Only five of 622 AAA individuals had a HADS‐D score that was ≥15. “It is possible that this may have led to an underestimation of the association between depressive symptoms and AAA (selection bias).”

The authors considered that depression has been found to be more prevalent among patients diagnosed with AAA than in the general population. “To our knowledge,” they wrote, “only one previous study has shown that depression might be a risk factor for AAA. Thus, our study adds evidence supporting that a bidirectional relationship may also exist between depression and AAA.”

The authors weighed the strengths and limitations of their study. On one hand they highlighted the prospective design, the size of the study population, and the duration of follow‐up as making “it possible to address the association between depression and the risk of AAA, adjusted for a comprehensive range of potential confounding factors.”

The access to repeated measurements of risk factors made it possible to account for changes in the exposure levels during follow‐up, they added. “The numbers at risk within a particular risk group are then more correctly defined, thereby reducing potential bias in the risk estimates because of misclassification of the exposure variable.”

On the other hand, the evaluation of depression and other risk factors was largely based on self‐ reported questionnaires, potentially leading to information bias, the researchers admitted. “Symptoms of depression may vary over time, and we did not have repeated measures on all individuals in our cohort,” they wrote.

“Thus, potential misclassification might have occurred, despite the use of time‐dependent covariates. However, possible misclassification is likely to have been random, most probably resulting in an underestimation of relative risk estimates. There was no information about use of antidepressants, family history of AAA or physical activity, and unmeasured unknown confounding is always a limitation.”

The authors believe their work provides new support “to include assessment of depression in the evaluation of risk of AAA, which could potentially be especially important when screening subgroups at increased risk of this disease.”

In conclusion, Nyrønning et al were succinct in their analysis. “Depression has previously been linked to the risk of CHD and stroke,” the authors wrote. “In this large population‐based, prospective study, individuals with symptoms of depression had significantly higher risk of AAA, even after adjustment for established risk factors.”

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