Leukocytes in peripheral blood are one of the most crucial elements for diagnosing and assessing disease [52]. Samples of patients’ peripheral blood smears are analyzed by pathologists for clinical diagnosis. This examination is predicated mostly on the morphological properties of leukocytes and their nuclei and cytoplasm, such as their form, size, color, texture, maturity, and staining [53]. Leukocytes are closely associated with blood diseases and various other disorders. Recently, computer-aided diagnosis technology has developed rapidly in the field of digital hematology, which is related to the detection of leukocytes and their nuclei and cytoplasm, as well as segmentation and classification technology. These technologies continue to play a crucial role in digital hematological image analysis by delivering traceable clinical data and decreasing human intervention [54].

It has been suggested that serum proteins contribute to every aspect of life. Moreover, it has been reported that the human serum proteome is under strong genetic control [55]. Additionally, it was discovered that serum proteins are part of the regulatory group of network modules, which includes members synthesized in all parts of the body. The underlined finding suggests that thousands of proteins in the blood play a significant role in mediating coordination or homeostasis at the system level [56]. Importantly, deep serum and plasma proteomes are associated with a variety of diseases, human life spans, and the ability to predict how well individuals would respond to treatment [55, 57, 58, 59, 60, 61, 62, 63]. Recent research has linked genetics, protein levels, and diseases as well as highlighted the potential causative link between proteins and complex disorders [64, 65].

Zinc ions influence the body’s metabolism of a variety of proteins, lipids, and carbohydrates as well as a variety of other cellular metabolic activities [77, 78]. More than 70 enzymes depend on zinc, including glutathione peroxidase and superoxide dismutase. By serving as a cofactor of Cu-Zn superoxide dismutase (Cu, Zn-SOD), zinc can have an impact on CHD (coronary heart disease). According to the reported studies, zinc supplementation decreases Cu-Zn superoxide dismutase activity because copper absorption and increased zinc consumption have an antagonistic relationship [79]. Moreover, zinc also has anti-inflammatory and antioxidant effects [80, 81]. With the increase in zinc concentration, cells are better able to act as antioxidants, and normal endothelium function is maintained. The role of zinc in enzymes, humoral mediators, and mitosis is crucial for the function of the immune system [82]. Zinc deficiency can lead to an increase in oxidative stress sensitivity, as well as interleukin-1 and tumor necrosis factor $\alpha$ increase of factors. The expression is connected to endothelial cells’ enhanced apoptosis.

The zinc ion concentration of female patients with coronary heart disease was low, according to our study of 3541 cases [83]. Further grade analysis revealed a connection between the decline in menopausal hormones in women and the decline in zinc ion concentration. It was discovered that the zinc ion concentration of female smokers over 50 years of age was different, using the age of 50 as the cutoff threshold for hormone secretion drop [83]. It, therefore, makes sense to speculate the association between the decrease in hormone secretion during female menopause, the concentration of zinc, and the occurrence of coronary heart disease in menopausal women.

Iron holds critical importance for a variety of physiological processes. Proteins and enzymes that contain iron are crucial components of cell metabolism. These enzymes and proteins are necessary for mitochondrial function, DNA synthesis, DNA repair, cell death, and cell proliferation [84, 85, 86]. Additionally, the generation of red blood cells (RBCs) and the transportation of oxygen both depend on iron, which is the primary component of hemoglobin. Due to its propensity to form reactive oxygen species (ROS) and its ability to catalyze the Fenton reaction, which produces hydroxyl radicals, iron may also be toxic at high doses [87]. In addition, it is essential for determining the amount of bacterial toxicity [88].

The disease may also result from irregular iron intake or output. Initially, iron was linked to the onset of coronary atherosclerosis [87, 89]. LDL oxidation can be hastened by free iron [90]. Due to the absorption of low-density lipoprotein by macrophage LDL receptors, foam cells congregate. The two primary steps in the development of coronary atherosclerosis are the development of a necrotic core and the invasion of foam cells [91]. Numerous macrophage subtypes have been identified in atherosclerotic plaques [92]. Macrophages are crucial to the development of coronary atherosclerosis. The primary cause of M1 macrophage activation in plaques is lipid absorption, which can result in foam cell formation and the generation of inflammatory cytokines [93]. It is postulated that M1 macrophages produce coronary atherosclerosis through media-induced paracrine stimulation of MSC (mesenchymal stem cells) migration and proliferation in the intima.

Plaque instability may result from the M1 cells’ production of a fibrous cap after the hydrolysis of collagen fibers [94]. Additionally, M2 macrophages are stimulated by Th2 cytokines including IL-4, IL-10, and IL-13 to create anti-inflammatory cytokines. The inflammatory response is balanced by M2 macrophages, which also aid in tissue healing and inflammation reduction. The M1/M2 model provides a concise framework for comprehending macrophage behavior in a damaged environment. Although M2 macrophages can export and metabolize iron, M1 macrophages have an advantage in iron accumulation due to their high ferritin level. Changes in the iron turnover between M1 and M2 macrophages may contribute to coronary atherosclerosis. The association between peripheral blood iron concentration and coronary atherosclerosis was validated by a cross-sectional study encompassing more than 4000 individuals [95]. A biomarker for the prediction of coronary atherosclerosis is the decrease of iron ions in peripheral blood [95].

Copper is the most abundant element in the human brain [96, 97, 98] and is involved in a variety of biological functions. Its abnormal changes have been linked to numerous neurological diseases [99, 100]. In biological systems, copper ions usually have coexisting oxidation states. On the other hand, copper has various complexes, including distribution, storage, and transportation. Therefore, in a diseased condition [101], the dynamic change in copper concentration results in abnormal accumulation or uncontrollable oxidation-reduction reactions [102], which then disturb the natural balance or start a chain of events that eventually result in neurodegenerative diseases like Alzheimer’s and Parkinson’s [103]. To understand how copper changes over time, we need to make more copper detection tools, especially ones that can accurately separate copper ions without damaging samples.

With the development of a large number of Cu${}^{2+}$ detection methods [104, 105], fluorescent probe methods have received widespread attention due to their probe characteristics, such as visible fluorescent signals and immediate response to targets [106, 107, 108]. In particular, the rhodamine spiral CT (computed tomography) Cu${}^{2+}$ probe, its significant copper ion evaluation, and the specific color change accompanying the recognition process are particularly prominent. Efforts are being made to improve the probe’s sensitivity and selectivity to Cu${}^{2+}$ in complex environments or biological systems [109, 110, 111], the probe’s long-wavelength excitation and emission characteristics [112], thereby avoiding biological interference and the probe’s solubility and affinity [113].

Manganese (Mn), an essential component of the human body, is mostly obtained through food and water. Mn enters the body via the digestive system and is then transported to tissues with a high concentration of mitochondria, such as the pituitary, liver, and pancreas, where it is rapidly accumulated [114, 115]. The synthesis and activation of numerous enzymes, including oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases, as well as glucose and lipid metabolism, the accelerated synthesis of protein, vitamin C, and vitamin B, the catalysis of hematopoiesis, the regulation of the endocrine system, and the enhancement of immune function, are all facilitated by Mn [116, 117]. Other Mn metalloenzymes, such as arginase, glutamine synthetase, phosphoenolpyruvate decarboxylase, and manganese superoxide dismutase (MnSOD), also help with these metabolic processes and lessen the oxidative stress on free radicals.

In recent years, there has been a marked rise in the incidence of metabolic illnesses like type 2 diabetes (T2DM), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis [118]. Metabolic syndrome is typically what causes these metabolic illnesses (MetS). MetS criteria must be met if three of the five markers are present: abdominal obesity, impaired glucose metabolism, hypertension, and dyslipidemia, which includes higher triglyceride levels and reduced high-density lipoprotein (HDL) levels [119]. Additionally, several studies [120, 121, 122, 123, 124, 125, 126] have demonstrated a connection between oxidative stress and inflammation, and metabolic disorders. Mn is a component or activator of various enzymes, primarily antioxidants, and it is crucial for maintaining appropriate insulin production and secretion as well as glucose and lipid metabolism. As a result, manganese may prevent the development of MetS [127].

It’s important to note that Mn is required for MnSOD (Manganese Superoxide Dismutase) to lower mitochondrial oxidative stress. ROS are produced mostly by mitochondria in both healthy and diseased cells. Various neuropathological illnesses are associated with the increased production of glucocorticoids, which are crucial in controlling the biosynthesis and metabolism of proteins, lipids, and carbohydrates. Excessive ROS inappropriately accumulates and causes oxidative damage [128]. MnSOD is a significant antioxidant that can also remove superoxide produced in mitochondria and guard against oxidative stress [129, 130]. If mitochondria are damaged or dysfunctional, the production of ROS and oxidative stress are exacerbated [131].

According to a reported study, central obesity, increased triglycerides, decreased high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose is the five factors that often define MetS [132]. The existence of MetS aids in the identification of high-risk people who have T2DM and cardiovascular disease (CVD) [132]. A frequent risk factor for MetS components is oxidative stress. In MetS patients, persistent low-level inflammation and oxidative stress state are typically regarded as second-level abnormalities, while insulin resistance is typically regarded as the first level of metabolic alterations [133]. All individual MetS components and the incidence of cardiovascular problems in MetS participants are linked to oxidative stress [133, 134, 135, 136].

One of the key elements used to gauge air quality is nickel. About 20% of people have an allergy to nickel ions, and there are more female patients than male patients. Nickel is the most frequently sensitizing metal. Nickel ions can enter the skin through pores and sebaceous glands and cause skin allergy and inflammation, which are clinically seen as dermatitis and eczema when in touch with the human body [137]. Nickel allergy frequently lasts forever once sensitization takes place. Humidity, pressure, sweat, and friction can exacerbate nickel allergy symptoms. Nickel-allergic dermatitis manifests clinically as itchy, papular, or vesicular dermatitis with mossing [138]. In nickel deficiency, the activity of six dehydrogenases decreases, including glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and isocitrate dehydrogenase. These enzymes are essential for the tricarboxylic acid cycle, anaerobic glycolysis, the synthesis of NADH (nicotinamide adenine dinucleotide), and the release of nitrogen from amino acids. Nickel deficiency was also found to change the structure of hepatocytes and mitochondria, especially with an irregular endoplasmic reticulum and a drop in oxidative activity [139].

In a study on the Chinese population, the link between several chemical elements, pollution sources for ambient fine particles (PM2.5), and oxidative stress indicators in healthy college students was examined. Participants in the study underwent 12 additional blood draws before and after transferring from suburban to urban campuses in Beijing, China, which had significant levels of air pollution. The 95% confidence interval (CI) of ox LDL is thought to widen with each quartile point rise in nickel (2.5 ng/m${}^3$) and with the duration of exposure to polluted air [140, 141, 142].

Selenium (SE) is a crucial part of selenoprotein and an essential element for antioxidant defense. The involvement of selenium in antioxidant defense, which is mediated by the glutathione peroxidase (GPX) family, supports the nutrient’s preventive action against dyslipidemia and cardiovascular disease (CVD). In this case, GPX slows or stops atherosclerosis by lowering the production of hydroperoxides of phospholipids and cholesterol esters and stopping the buildup of oxidized low-density lipoprotein (LDL) in arteries [143, 144, 145].

Low activity of this enzyme will harm the body’s antioxidant defense system because of insufficient selenium intake and the presence of GPX1 gene polymorphism [146]. According to several studies, single nucleotide polymorphisms (SNPs) of the GPX gene have been linked to a higher risk of metabolic syndrome and cardiovascular disease [147, 148]. Due to the lack of extensive studies, the cardioprotective effects of selenium are currently debatable [149].

Recent research has demonstrated that patients with CVID (common variable immunodeficiency) had considerably lower levels of plasma selenium and GPX activity than healthy controls [150]. Se level, apolipoprotein A-1 concentration, and the main proteins that make up the high-density lipoprotein cholesterol component all showed a substantial positive association. Numerous bacteria are capable of producing selenocysteine, suggesting that selenoproteins may be important for bacterial physiology [151]. Moreover, dietary selenium impacts the composition of the host microbiota. Therefore, pathogenic bacteria, microbiota, and host immune cells may dispute the limited availability of selenium, which is especially critical in CVID patients [151, 152, 153]. Se and apoA-1 concentrations are significantly correlated in the literature. In predicting the risk of cardiovascular disease, apolipoprotein A-1 and other HDL-C functional markers outperform HDL-C concentration [154].

In previously reported studies [155], anatomical imaging models used to measure atherosclerosis usually focused on non-localization characteristics. The degree of luminal stenosis can be examined using conventional ultrasound and angiography methods, and coronary calcium scores can be generated using cardiac CT to measure coronary artery calcification. However, alternative techniques have started to be used with the explicit aim of identifying plaque components, such as multi-detector CT coronary angiography, MRI, intravascular ultrasound (IVUS), and optical coherence tomography [155, 156]. Since these patterns are based on anatomy and don’t have the sensitivity and chemical specificity of early detection, they are best suited for revealing late structural changes or calcifications in the vessel wall [157].

In contrast to anatomical imaging, molecular imaging mode can identify minute processes like microcalcification and inflammation. These chemical alterations take place before the aforementioned morphological changes during the early stages of the disease process. The most well-known of these molecular technologies is positron emission tomography (PET), which uses the radiotracer 18F fluorodeoxyglucose (18F-FDG), a radiolabeled glucose analog that is used as a marker of metabolic activity and, in turn, for inflammation. In contrast, 18F sodium fluoride (18F NaF), a particular marker of bone mineralization, has lately been utilized to diagnose vascular calcification after being traditionally used to diagnose metastatic bone malignancy.

One of the initial molecular markers used to assess atherosclerosis was 18F-FDG, which is currently the most widely used PET radiotracer and may also be the most thoroughly researched. Early research supported the use of 18F-FDG as a diagnostic tool by demonstrating a relationship between the vascular system’s 18F-FDG activity and atherosclerosis and cardiovascular risk factors [158, 159, 160, 161]. More concrete proof of the connection between 18F-FDG uptake and atherosclerotic disease was found in later investigations. 18F-FDG activity is higher in 58–85% of carotid lesions, according to studies on patients with a history of cerebrovascular accidents [162, 163]. Before endarterectomy, Tawakol et al. [164] used PET scanning on patients with severe carotid stenosis and discovered a strong relationship between the uptake of 18F-FDG in carotid plaques and the staining of macrophages on comparable pathological specimens. Rudd et al. [165] utilized autoradiography to show in a related investigation that 18F-FDG avid lesions in individuals with symptomatic carotid stenosis were associated with macrophage-rich plaque regions in endarterectomy specimens. Additionally, the researchers discovered that symptomatic carotid lesion uptake of 18F-FDG was 27% higher than ipsilateral asymptomatic lesions [165].

The use of 18F-FDG PET imaging to evaluate plaque vulnerability and the risk of associated ischemia episodes has been supported by some evidence from other research [166]. Plaques with high-risk morphological characteristics on CT and histology exhibit a much higher affinity for 18F-FDG, according to Figueroa et al. [167]. Patients with elevated arterial 18F-FDG uptake have been observed to be more prone to experiencing ischemic cardiovascular events or cerebrovascular events [168, 169].

Iodine is commonly found in food, water, and iatrogenic sources, and excessive intake can result in disorders such as goiter [170, 171]. Iatrogenic iodine excess is the most prevalent adverse pharmaceutical effect, with amiodarone serving as a typical example [172]. Goiter, hyperthyroidism, hypothyroidism, and autoimmune thyroid disorders can all result from excessive iodine intake in humans [173, 174]. Additionally, some investigations have revealed that too much iodine can harm intellectual growth [175]. Furthermore, the effects of iodine excess on the cardiovascular system are still largely unknown.

According to an epidemiological analysis, individuals in the high-water iodine area had a greater incidence rate and more severe carotid atherosclerosis than adults in lower-water iodine locations [176]. Excessive iodine may harm rat aortic endothelial cells, according to cell tests [177]. The carotid artery is the area of atherosclerosis that is most susceptible and is a sensitive sign of vascular disorders. Carotid intima-media thickness (IMT) is a predictor of cardiovascular events [178] and a marker of atherosclerosis in coronary arteries and other blood vessels [179, 180, 181].