ACS is a generic term for all kinds of clinical syndromes caused by acute or subacute myocardial ischemia. The main pathophysiological basis is thrombus formation secondary to coronary artery spasm or rupture of atherosclerotic plaque in coronary arteries [21–23]. Traditional risk factors of CHD include age, hypertension, DM, hyperlipidemia, and smoking , and as a major risk factor, DM has been widely concerned by many scholars. Studies have shown that long-term hyperglycemia leads to increased vascular endothelial permeability, abnormal expression of inflammatory factors, and thus causes the body to be in a state of high inflammatory response . In addition, the hyperglycemia leads to excessive production of reactive oxygen species and decreases the activity of antioxidant enzymes, and thus causes the body to be in a state of oxidative stress . All of these factors contribute to the development of coronary atherosclerosis, which ultimately leads to the occurrence of CHD. Studies illustrate that as an independent risk factor of CHD, DM has a high predictive value for the occurrence of CHD . The most common type of DM is Type 2 DM. In this study, we selected elderly ACS patients with Type 2 DM as the research object, which has a good application prospect. We analyzed the general conditions and prognostic indicators of both DM and NDM patients. In the very old patients with ACS included in our study, the proportion of DM was more than one third, which was higher than 20% of the previously reported values .
Uric acid is the final metabolite of various purines in the body and the uric acid level of the body is affected by a variety of factors: excessive purine intake, reduced excretion, metabolic disorders, and gene mutations and so on may increase the uric acid level [29, 30]. Gertler et al firstly proposed the association between baseline serum uric acid level and CHD in 1951. Since then, multiple epidemiological studies and meta-analyses shown that hyperuricemia is an independent risk factor for CHD and increases the risk of CHD. Baseline serum uric acid level is positively correlated with the incidence and severity of CHD, and for each 1 mg/dl increase in uric acid level, the patient's all-cause mortality increases by approximately 12% [32–34]. However, there is no clear report on the indicators of long-term prognosis in very old ACS patients with DM by uric acid as evaluation factor.
This study prospectively collected the clinical information of 718 very old patients with suspected ACS who were admitted due to chest tightness and chest pain, and performed 10 years follow-up. Our objective was to analyze the relationship between baseline serum uric acid level and long-term prognosis including all-cause mortality, cardiovascular death, and MACE, and the emphasis was placed on the long-term prognosis of patients with DM. The main findings of our study are as follows: 1) uric acid is a predictor of all-cause mortality and MACE in very old ACS patients with DM. 2) The ability of uric acid to predict the prognosis of these patients increases with the uric acid level rise. 3) With the extension of follow-up time, the effect of uric acid on the prognosis of these patients becomes more significant. 4) the predict power of UA was stronger in DM patients than NDM patients. In addition, we also found that in the study group, with the increase of uric acid level, Gensini score of the patients did not present significant difference, which was inconsistent with the previous reports [35, 36]. It may be related to the significant increase in the scores of coronary artery lesions in all elderly patients enrolled in this study. By comparison and analysis of all-cause mortality and MACE rate in the study group, we found that only the results of DM and NDM patients in Group 2 were different, while there was no difference in Group 3 with high uric acid. However, the long-term prognosis indicators of both DM and NDM patients in Group 3 were significantly worse than that of the other three groups. These results suggest that the impact of elevated uric acid level on the long-term prognosis of elderly ACS patients may be higher than that of diabetes.
Our results also showed that the uric acid cutoff value of elderly ACS patients with DM was 353.6 µmol/L (sensitivity: 67.4%; specificity: 65.7%). Cox regression results showed that, after adjusting for other factors, uric acid was found to be an independent risk factor for all-cause mortality (OR = 2.106, P = 0.006) and MACE (OR = 1.752, P = 0.026) in elderly ACS patients with DM. Therefore, in clinical practice, we should not only pay attention to the traditional risk factors of CHD such as age, hypertension, hyperlipidemia, smoking, drinking, etc., but also to the uric acid level of patients, and physicians should consider the effect of drugs on uric acid metabolism of patients when prescribe.
Previous research indicated that the hyperuricemic state in the body mainly promotes the development of CHD via the following aspects: 1) Activates platelets, promotes thrombosis, and activates inflammatory mediators to reduce plaque stability [37–39]; 2) Stimulates NADPH oxidase, leading to the abnormal structure and function of vascular endotheliocytes and affects the production of ATP, resulting in the dysfunction of vascular endotheliocytes[40–43]; 3) leads to the precipitation of urate crystals and excessive generation of oxygen free radicals, reduces the stability of plaques [44–46]. Yuichi Saito  et al pointed out that elevated uric acid level was closely related to vascular endothelial dysfunction in ACS patients, which may further cause poor prognosis. In addition, uric acid reduces the ability of endotheliocytes utilizing NO, activates the oxidative stress response of mitochondria and renin-angiotensin-aldosterone system (RAAS), thus increasing the incidence of cardiovascular diseases. In terms of the interaction between uric acid and DM, inflammation and oxidative stress induced by high UA may further reduce insulin sensitivity and affect the expression of insulin gene in patients . Uric acid increases intracellular ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1), thereby directly inhibiting the insulin signaling pathway at the receptor level . In ACS patients with DM, uric acid causes insulin dysfunction and abnormal glucose metabolism, promoting oxidative stress, and ultimately aggravates the damage caused by the hyperglycemia itself to cardiovascular.
In summary, with the aggravation of global aging and the increasing incidence of CHD, the population with CHD complicated with DM is increasing year by year. With developing diagnostic techniques and treatment methods, it is necessary to find appropriate commonly used predictors to evaluate the prognosis of these patients. At present, there are relatively few studies on the predictor of prognosis for the very old ACS patients with DM. This study selected large samples, performed an up-to-10-year follow-up study, and finally confirmed that uric acid was an independent risk factor for evaluating the prognosis of such patients. What’s more, the uric acid test process is simple and inexpensive. Therefore, it can be used as a clinical promotion of the detection index, having a good clinical application value.