To explore the risk factors associated with AAD has important clinical significance. This study was the first time to found that exposure to famine in childhood may significantly increase the risk of AAD in adulthood, and this effect will not be modified by other cardiovascular risk factors, such as smoking, hypertension and diabetes.
AAD often appears asymptomatic, but once ruptured it often lead to serious outcomes. In this study, famine exposure during childhood was found to be an independent risk factor for AAD in adulthood after some potential confounding factors were adjusted. Famine exposure was usually accompanied by a lack of nutrient intake, such as protein, vitamins, and trace elements. Demir, et al[22] found that vitamin D deficiency was an independent factor for aortic dilatation. Adam and his team discovered the concentration of Copper and Zinc was significant associated with the size of the aneurysmal enlargement in the wall of the abdominal aortic aneurysm[23]. In addition, although there was no research has specifically evaluated the relationship between Chinese early life famine exposure and AAD in adulthood, we further found that there was a stronger risk of AAD in female, BMI ≥ 24 kg/m2, smokers, hypertensive patients, and this effect has not been adjusted by the above traditional risk factors for AAD. This suggested that prevention of AAD should pay attention to nutrition status run through the entire life process from early life, and different population may need different nutritional support.
The mechanisms of the relationship between famine exposure and AAD remain unclear, but there have been several possibilities. First of all, subjects who survived from famine may develop compensatory nutrition or nutritional catch-up growth, which may lead to over- nutrition, and further lead to overweight or obesity. It has been found that obesity was independently related to AAD[24]. Second, the Dutch famine study revealed that those exposed to famine in early gestation could increase stress responsiveness[25]. AAD was considered as a disorder of oxidative stress, and basic research indicated that oxidative stress played an important role in thoracic aortic aneurysms[26]. Third, exposure to famine during early life was associated with increased risks of obesity in adulthood[27], and obesity was significantly linked with increased visceral, perivascular, and epicardial adipose tissue[28]. A previous study demonstrated that increased epicardial adipose tissue thickness was correlated with AAD[29]. Fourth, AAD was a chronic inflammatory disorder disease; its main feature was the local weakening and dilatation of the aortic wall[1]. Destructive remodeling of the extracellular matrix and endothelial dysfunction played a vital in AAD[30, 31]. Based on animal and human studies, low birth-weight babies and nutrient deficiency were likely to have endothelial dysfunction, less vascular elastin, increased sympathetic tone and liver-derived dyslipidemias[32, 33].In addition, increased sympathetic tone was commonly associated with hypertension in animal models of both under nutritional and over nutritional states[34]. It was now generally accepted that exposure to famine in early life was closely related to adult hypertension[35], and that hypertension was an independent risk factor for AAD[36]. The mechanism of AAD is unclear. Therefore, further research is required to investigate the correlation between famine exposure and AAD.
The present study has several strengths. First, to our best knowledge, it was the first study to investigate the relationship between famine exposure in early life and AAD in adulthood among Chinese population. Second, this study adjusted as many as possible risk factors related to the occurrence of AAD. However, some potential limitations should also be noted. First, this study did not collect birth weight and the severity of famine. These confounding factors have a certain impact on the results of the study. Second, it was a cross-sectional study, and the study population cannot represent the entire Chinese population. Third, some baseline variables, such as disease history and medication history come from self-reporting, so there may be a recall bias. Fourth, since children with poor health when exposed to famine during early life may have partially died, and the present study was to analyze the population that was still alive, so the impact of famine may be underestimated. In addition, the specific start and end time of famine in China was not clear, so the grouping according to the date of birth may be different from the actual famine exposure. Finally, although the study group based on birth data, and the birth data was related to age, the possibility of residual confounding due to age differences could not be completely excluded.