The current study investigated any relationship between the leptin, adiponectin and L/A ratio and the extent or severity of coronary artery disease based on the number of involved vessels and GS, and this was the first study in this field. In fact, several studies have reported the association between leptin or adiponectin and CAD separately; however, there is no study to show any correlation between the L/A ratio and angiographic findings. Our study findings showed that the serum adiponectin level among case group was significantly lower than that among healthy individuals. Additionally, a significant and inverse relationship between serum adiponectin levels and the extent of CAD, according to number of involved vessels, was revealed among patients. According to this finding, hypoadiponectinemia was identified as an independent risk factor for the extent of CAD and this finding was in accordance with previous reports [
22]. Some studies have shown that hypoadiponectinemia was associated with CAD, particularly in the content of obesity, hyperinsulinemia, diabetes type 2, and dyslipidemia [
23,
24]. Another study reported that hypoadiponectinemia could increase the risk of atherosclerosis and acute coronary syndrome [
25]. Different mechanisms exist regarding the protective role of adiponectin in the control of atherosclerosis, but its anti-atherogenic role is not clear [
25]; nevertheless, some studies reported that the anti-atherogenic effect of adiponectin was mediated through the inhibition of neointimal formation [
26]. In vitro studies have shown a progressive neointimal damage and proliferation of smooth muscle in damaged arteries among mice without adiponectin [
27,
28]. Furthermore, some studies have shown that the accumulation of adiponectin in the sub-endothelial spaces of damaged arteries causes an inhibition of genes related to inflammation, such as tumor necrosis factor-α (TNF-α), and markers related to endothelial malfunction, such as VCAM-1 and ICAM-1. With these effects, adiponectin may inhibit the adhesion of monocytes to the endothelial of cells, which is the first step in arteriogenesis, and their migration to the sub-endothelial spaces, as well as impose anti-atherogenic effects. The adiponectin-based inhibition of lipid accumulation in macrophages and increasing blood flow, resulted from vasodilator effects through nitric oxide (NO) production, are other beneficial effects of adiponectin in the inhibition of atherosclerosis [
29,
30]. Our study showed that adiponectin has an inverse but insignificant relationship with the GS, namely an increase in the GS was associated to a reduction of adiponectin level among CAD patients. A study by Fukuta et al. reported that lower level of adiponectin was associated with LV diastolic dysfunction, among patients with CAD [
31]. Another study reported that leptin was associated with increased atherogenic processes [
32]. The results of our study indicated that serum levels of leptin were significantly higher among CAD patients than in healthy control subjects and leptin was also directly related to the extent of coronary artery disease, based on number of involved vessels. Unlike adiponectin, leptin significantly increased with increasing the numbers of involved vessels in CAD patients. Previous studies have shown a harmful effect of leptin in the pathogenesis of atherosclerosis and demonstrated that leptin was an independent risk factor for CAD [
33]. It has been shown that leptin can increase the risk of CAD more than other risk factors for cardiovascular diseases such as sex, race, smoking, and body mass index [
34]. A study reported that after excluding other risk factors, the odds ratio for increased disease severity among patients with high leptin levels was preserved [
31]. The atherogenic mechanisms of leptin have not been clearly identified but its beneficial effects, such as increasing NO production, improving coronary blood flow [
35] and its role in the process of angiogenesis have been reported [
36]. On the other hand, some adverse effects of leptin have such as direct contact with the components of metabolic syndrome and impaired fibrinolysis have been reported [
37]. Based on different reports, leptin can have other effects, such as obesity-related hypertension as well as pro-thrombotic properties, in the cardiovascular system [
38‐
40]. Though the current study showed an higher significant serum level of Leptin among CAD patients than the healthy individuals, but it’s correlation with GS and CAD severity was not significant. The difference between our findings about relationship between leptin and severity of CAD with other reports is not clear but it may bay associated with the performance of coronary angiography and its interpretation by interventional cardiologists and score estimation or even a lower number of evaluated patients in the current study.
An important result of the current study was a significantly higher L/A ratio in patients with CAD in comparison with healthy individuals. This study also revealed that the L/A ratio was directly correlated with the extent but not severity of coronary artery disease. Additionally, the L/A ratio showed a direct correlation with the number of involved coronary vessels, indicating that patients with three-vessel coronary artery involvement had a higher serum L/A ratio than patients with two or one coronary artery involvement. A few studies have investigated the effects of serum L/A ratio on CAD. Kappelle and colleagues showed that the serum L/A ratio could be a useful marker for predicting the risk of the first cardiovascular event in men [
46]. The advantage of our study was the investigation of serum L/A ratio in CAD patients compared with healthy subjects and its association with the numbers of involved coronary arteries and GS. Though the predictor effects of either serum leptin or adiponectin for the severity and extent of coronary artery disease has been reported previously [
13], and our findings were almost in consistence with these reports; however, the current study revealed that the serum L/A ratio was another predictor rather than either leptin or adiponectin for CAD separately. This study was limited to compare the factors related to endothelial dysfunction or cardiac anatomic findings with the serum leptin, or adiponectin levels and/or the serum L/A ratio. A future cohort study, examining the relationship between the serum L/A ratio and patient’s prognosis would be helpful.
In the current study, serum levels of leptin were associated with incident of CAD and it was also directly related to the extent of coronary artery disease. As the number of involved vessels was higher, the serum level of leptin was higher too and this association could be shown as an increasing trend, so that leptin values in patients with one involved vessel compared to controls and those with two involved vessels compared to one and those with three involved vessels compared to two involved vessels were higher. A similar trend was revealed for the L/A ratio and the number of involved vessels in CAD patients but with an insignificant difference between 3 vessels compared to two vessels; however, in case of serum level of adiponectin, a negative relationship with involved vessels was appeared. Based on these results two concepts could be considered. Firstly, the serum level of both leption and L/A ratio are related to the increase in coronary atherosclerotic load. Secondly, at the start and during the progression of coronary atherosclerosis, the release of proaterogenic adipocytokines is increased, may be due to increased inflammatory process, and after a primary inflammation, this phenomenon declines and the serum level of leptin does not increase as markedly.