Background

Aorta dilation is a common problem in clinical practice, and the subsequent aortic aneurysm is a significant cause of adult death. The pathogenesis of aortic dilation is characterized by aortic wall inflammation, induction of smooth muscle cell apoptosis, extracellular matrix degradation, plaque formation, oxidative stress and vascular remodeling [1]. Potential biological mechanisms still need to be explored.

Aortic diameter is a critical parameter for the diagnosis of aortic aneurysms. The risk of rupture increases as the diameter of the aneurysm increases. Increased baseline diameter of infrarenal aorta is an independent risk factor for abdominal aortic aneurysm (AAA) in a population-based follow-up study [2]. Increased aortic aneurysm diameter is associated with a significantly increased risk of future cardiovascular events and all-cause mortality [3], while previous follow-up research holds the same view for the whole range of diameter values [4]. Therefore, exploring the risk factors for aortic dilation has great significance in predicting, preventing and treating cardiovascular disease.

Currently, research on the epidemiology of aortic diameter is gradually emerging. Many studies pointed out that aortic diameter and cardiovascular diseases shared common influencing factors. Age, sex, race, body surface area (BSA), smoking status, alcohol consumption, and lipid profile, hypertension and diabetes mellitus (DM) are all known major traditional cardiovascular risk factors which have effects on aortic diameter [5,6,22]. One epidemiological study indicates that smoking history is the strongest factor associated with AAA progression [23]. Mechanistic research report that smoking promotes the degradation of collagen and elastin and consequent weakening of the arterial wall by highly expressed matrix metalloproteinase in aortic wall, finally leading to aortic aneurysm formation [24]. Although we observed that smoking had a robust association with the diameter of almost all segments apart from ascending aorta in the unadjusted model, the strength of this association could not be further demonstrated by fully adjusted analysis. Only the annulus diameter showed its independent association with smoking. The lack of association with abdominal aorta diameter was consistent with previous studies [7, 25]. Contrarily, some studies indicated that incremental widening of the abdominal and ascending aorta was independently related to smoking [6, 20]. Smoking cessation may have a certain effect on alleviating the dilation of the aorta.

In an unadjusted model, serum lipids were not relevant to aorta diameter of any segment. Surprisingly, HDL-C were an independent determinant of the diameters of ascending and abdominal aorta. Although previous studies on the relation among AAAs, abdominal aortic diameters and serum lipid levels were contradictory [7, 25]. Dyslipidemia has grown in importance among well-established risk factors for AAAs. A prospective study cohort for AAA patients found that HDL-C predicted the growth rate of aneurysms for its inverse association with AAA size [26]. Wang et al. [7] found that LDL-C and ratios of TC/HDL-C and LDL-C/HDL-C were independent negative determinants of infrarenal aortic diameter, and infrarenal aortic diameter was significantly positively associated with HDL-C (r = 0.139, P = 0.006) independent of age, sex, and height. The current research held the consistent view. Based on the results, we could speculate that HDL-C may have an effect on the increase in the diameter of the ascending aorta and abdominal aorta. The use of statins and the small research samples may affect the accuracy of the outcome. The effect of serum lipids on aortic dilation needs further study.

In contrast, diabetes mellitus plays a protective role in dilated aortic diseases [8, 27], characterized by the accumulation of collagen in the aortic wall and subsequent increases in matrix volume [28]. Interestingly, a rat study found that the total count of elastic fibers, fragmentation of the elastic lamina, pericellular matrix deposition, and cell loss/substitution in the tunica media were higher in the diabetic + smoker group (DSG) aorta than those in the smoker group (SG) aorta [24].The negative relationship between the presence of DM and aortic diameter was supported by a few other reports [8, 15]. However, we found only that DM was inversely related with the diameters of annulus, mid and distal arch in univariate analysis. Consistently, there was an independent negative correlation between the use of hypoglycemic drugs and the aorta diameter of some segments. The effect of blood sugar control on the diameter of the aorta needs further investigation.

Atherosclerosis represents an important independent risk factor for AAA formation [9]. In the Tromsø Study [20], as the measures of subclinical atherosclerosis, coronary artery calcium burden but not CIMT were independently associated with larger aortic diameter, which was supported by a population-based follow-up study [11]. In the current unadjusted analysis, CIMT was only positively associated with descending and abdominal aorta diameter, but was not an independent indicator of any segment. Carotid atherosclerosis, carotid artery stenosis and aortic sclerosis represented no association to all segments' diameters. Differently, coronary artery disease represented a significant independent relationship with the diameter of transverse arch and abdominal aorta in the current multivariate analysis. However, whether this association between atherosclerosis and aortic aneurysm is causal or a result of common shared risk profiles remains unknown. Johnsen et al. [29] indicated that no dose–response relationship between abdominal aortic diameter and atherosclerosis burden assessed as carotid total plaque area, common femoral lumen diameter, and self-reported coronary heart disease, suggested that atherosclerosis may not be a causal event in AAA, but occurred concurrently with aneurysm expansion or secondary to aneurysm expansion.

The segmental inconsistency may be ascribed to distinct structural, genetic, and biochemical factors [1, 30]. Specific segments of the thoracic and abdominal aorta have differences in vascular mechanics, atherosclerotic plaque deposition, MMPs distribution, and cell signaling pathways, which may lead to differences in each segment's susceptibility to risk factors [30].

Limitation

First, the current study was an observational study in which potential confounders and selection bias could not be fully adjusted. Second, potential misunderstanding due to missing data on use of over-the-counter medication has to be taken into account. Third, the sample size was not large enough and all individuals were included non-randomly resulting in reduced power of the test. Lastly, the current research was biased toward patients with cardiovascular diseases so that some findings may have limited generalizability to non-cardiovascular diseases patients with cardiovascular risk factors. The listed limitations need to be solved by well-designed large observational cohort studies.

Conclusion

In conclusion, different segments of aortic diameter may have different independent related factors. Aortic segmental diameters were associated with DBP, HDL-C, atherosclerosis and other traditional cardiovascular risk factors. These findings may provide new information for understanding the potential mechanism of the early stages of aortic dilation. Additionally, the methods of exploring novel biomarkers for the risk prediction, prevention and early diagnosis of aortic dilation diseases should take segment specificity into consideration. The well-designed studies including cohort studies and molecular level research need further development.