SEM allows for multiple linear equations, including direct and indirect effects, and latent variables, features not allowed by traditional regression methods[22, 23]. Our data derived common factors contained cluster of dietary observed variables, in this case, SEM was a proper way to incorporate integrated variables.
To our knowledge, the present study presented the first examination of the direct and indirect effects of modifiable risk factors on ED using SEM. The appropriate fit required the original hypothesized model to undergo changes. After the elimination of factors that made no contribution, only TG and prudent dietary pattern were directly associated with RHI. Furthermore, RHI had an indirect association with prudent dietary pattern via TG. In the field of health management, risk prevention and management of cardiovascular disease are vital important study topics, especially learning risk factors when diseases were detected at the earliest stage. Another more widely-applied macro-vascular ED measurement is flow-mediated dilation (FMD), which is estimated as the percent change of brachial artery diameter at maximal dilation during hyperemia, when compared with the baseline value. ED in the conduit arteries might be more important in subjects with existing atherosclerosis, while that in resistance small vessels might be an early indicator of arteriosclerosis risk[24, 25]. However, there was no correlation found between FMD and RHI when the two parameters were simultaneously measured[26]. Thus, the risk factors of RHI-measured ED, as an early marker of vascular impairment, are still worth digging in relatively healthy populations when undergoing health checkups.
It turned out that only TG in the metabolic syndrome cluster was associated with micro-vascular ED in the present health-checkup population, which was inconsistent with part of the previous reports listed in the introduction section. The observed strength of each metabolic risk factor significantly varied in several populations reported in previous studies and the present study. According to the heterogeneous strength of RHI-related risk factors, the investigators analyzed the potential causality as follows: (1) the estimated ED burden originated from cardio-metabolic risk factors should be affected by intrinsic characteristics of specific population in the magnitudes of their effects. Indeed, the sensitivity of endothelial function to risk injury varied owing to the differentiation of population age, gender, race, region and disease category [27–29]. The first four stratifications that referred to genetic background or physiological properties were complex and non-modifiable. Concerning disease background, most previous studies revealed subjects with cardio-metabolic disease or autoimmune disease as mentioned in the introduction. When comparing to subjects with diseases, the health-checkup population possessed relatively narrow range of abnormal risk factor levels, which were supposed to be below their counterpart under the pathological state. Thus, the SEM revealed such correlation eliminating the strength of blood pressure, blood glucose and other lipid index. Furthermore, unlike the present SEM with multiple regression pathways, most previous evaluations were univariate analyses without adequate adjustment, which might lead to inflated effect sizes. In addition, an interesting phenomenon was found: lowering BP and blood glucose using anti-hypertensive and anti-diabetic medications for weeks does not improve the RHI-measured ED[30–33], but a short-term use of fenofibrate lowering TG could achieve the efficacy[34]. It signifies that high TG might be a sensitive index imposing a greater effect on the endothelium for a certain amount of time.
Regarding the life-style behavior concerning diet, physical activity and sleep quality, this is the first study that explored the effect of diet pattern on micro-vascular ED. It was observed that prudent diet pattern consisted of recognized healthy food indirectly ameliorated the impairment of ED through lowering TG, meanwhile, a direct beneficial effect on ED was also found. The underlying mechanism for this advantage of prudent diet might be the high levels of contained vitamins, since it has been proven that vitamin C, D and E restored the macro- or micro-vascular ED[35–37]. With regard to specific food, the intake of blueberry acutely improved the peripheral arterial dysfunction, and the fruit contained polyphenol metabolites that might account for this advantage[38]. It remains unknown whether protein-contained milk, egg and legume are involved in ED improvement, and more exploration are needed. Indeed, in south of China, although a traditional dinner party generally tends to consume all kinds of alcoholic beverage and plenty of meat, no previous data revealed the effect of alcohol and meat on RHI-measured micro-vascular ED. However, several studies that evaluate the alcohol effect on the FMD index were controversial: chronic moderate to heavy alcohol consumption caused macro-vascular endothelial dysfunction in Asian men[39, 40], even more, FMD was significantly impaired in light alcohol drinkers[41]. Conversely, the consumption of moderate and high alcoholic beverages was independently associated with better FMD, when compared to no alcohol consumption[42, 43], especially when consuming red wine[44]. In general, the high dietary intake of food rich in antioxidants, such as specific fruits, vegetables and red wine, has a positive effect in improving FMD and endothelial function[45]. Thus, the diet pattern should be taken into account, and the food type should be further subdivided if possible. Aerobic exercise provides cardiovascular benefits without doubt. A previous study reported that physical activity improves micro-vascular ED[6, 46]. Furthermore, the present study suggested that this advantage might be mediated by TG reduction. However, other mediated factors should be further explored.
The limitations of the present study are, as follows: (1) The data was cross-sectional. Therefore, the present hypothesized pathway did not reflect the timing dimension and causality. (2) The self-reported life-style behavior data may also be subjectively affected by social desirability bias. That is, the participants are likely to over-report the "healthy" behaviors. (3) When conducting the factor analysis, the accepted value of factor loading, the reliability and validity of CFA in latent construct were not as desirable as the standard threshold should be. This was due to the wide variations of food major items and the diet was divided into broad categories, thus, the close inter-correlation or -aggregation between these measured variables was hard to achieve. A similarly low variance could be found in all of the factor analysis concerning food category[47–49].