Homocysteine (Hcy), an endogenous amino acid, which can be metabolised enzymatically to either be converted into cysteine or to be remethylated back into methionine (1). Since McCully’s (2) groundbreaking discovery in 1969 highlighted the role of Hcy in altering cases of atherosclerosis, Hcy has emerged as a recognized biomarker and an independent associated with various diseases. Its association with conditions such as coronary artery disease, cardiovascular disease, cerebrovascula disease (3–7), neurocognitive impairment (8, 9), depression, and osteoporotic fractures in the older adult (10, 11) has attracted significant attention from researchers and clinicians. However, to date, the majority of Hcy researches have focused on the correlation between Hcy concentration and diseases, with limited emphasis on epidemiological investigations. Therefore, the prevalence of HHcy in routine health examinations conducted in Hebei, were assessed, with an aim to elucidate the correlation between HHcy and diseases. The associations of Hcy with gender, age, carotid ultrasound, BP, BMI, serum levels of TC, TG, LDL-C, HDL-C, ALT, AST, RBC, Cr, urea, UA, FBG, and GHb concentration were investigated. These findings provide valuable evidence for the prevention and management of HHcy and its associated diseases.

Screen out 10,511 individuals who underwent health check-ups at the Second Hospital of Hebei Medical University from 2021 to 2022 were included in this study. The data collected for these individuals included gender, age,carotid ultrasound, BP,BMI,serum levels of Hcy, TC, TG, LDL-C, HDL-C, ALT, AST, RBC, Cr, urea, UA, FBG, and GHb concentration. Exclusion criteria for individuals affecting Hcy results included recent use of lipid-lowering drugs, folic acid, B-vitamins, and other relevant factors. The study population excluded individuals with severe cardiovascular and cerebrovascular diseases, kidney diseases, thyroid diseases, malignant tumors, as well as those with incomplete information or test results. This study was approved by the Ethics Committee of the Second Hospital of Hebei Medical University. The informed consent to participate was waived by the Ethics Committee of the Second Hospital of Hebei Medical University. All methods were carried out according to relevant guidelines and regulations.

Studies have demonstrated a significant association between Hcy levels and the occurrence of cardiovascular and cerebrovascular diseases, as well as the severity of cognitive impairment. In the Framingham study, there was a positive correlation observed between Hcy levels and both overall mortality and cardiovascular mortality among older adult individuals. Furthermore, a dose-dependent relationship exists between Hcy levels and the development of CSVD, with elevated homocysteine concentrations being linked with cognitive dysfunction (12, 13). That is, for every 3umol/L increase in plasma Hcy, the incidence of ischemic heart disease increases by 11% (14), and for every 2.5umol/L increase in plasma Hcy concentration, the risk of stroke increases by approximately 20% (15). For every 5umol/L increase in Hcy, a patient’s risk of AD increases by 40%, and individuals with Hcy levels higher than 14umol/L are twice as likely to develop AD 8 years later (16). With the aging problem in China, the older adult are facing great threat of aging-related chronic diseases. Therefore, the investigation of Hcy metabolism in Hebei is bound to play a very important role in the prevention and treatment of cardiovascular and cerebrovascular diseases in middle-aged and older adult people.

In this study, a total of 10,511 individuals who participated in the health examination in the Hebei area were included. The overall prevalence of HHcy in the healthy population was found to be 22.0% (18.1% among men and 3.9% among women). Previous reports have indicated that HHcy incidence in China ranges from 10% to 68% (17, 18,) with higher rates observed among older adult individuals and males, which is consistent with our findings. Gender differences may be attributed to variations in muscle mass, estrogen status, lifestyle factors, and vitamin levels (19). Furthermore, it has been established that homocysteine production is associated with creatinine-creatinine synthesis (20). Males generally exhibit a higher muscle mass, leading to an increasing demand for creatine biosynthesis and subsequently resulting in elevated Hcy production (21). Hormonal disparities between genders may also contribute to sex-related differences. Furthermore, compared to females, Chinese men have a higher prevalence of alcohol consumption and smoking habits, both of which are positively correlated with Hcy concentration (22). Alternatively, discrepancies in folate, vitamin B12, and vitamin B6 status between the sexes could partially account for the observed gender difference (19).

Age is a associated with HHcy; Xu (23) et al.’s study confirmed its effect on the prevalence of HHcy while our study demonstrated that men had significantly higher rates of HHcy than women across different age groups.The plasma levels of Hcy exhibited a pattern of initial decline followed by an increase in both males and females. Bivariate unconditional logistic regression analysis revealed that age was a associated with HHcy. This could potentially be attributed to altered renal function, decreased vitamin levels, and impaired renal metabolism of Hcy (24–27).

Furthermore, Hcy has been found to interfere with hepatic lipid metabolism leading to disorders in lipid metabolism. Liao (28) et al.’s study demonstrated that CBS-/-/apoE-/- mice with hyperhomocysteinemia exhibited an increased incidence of atherosclerosis along with reduced HDL levels. In this study, the analysis of the biochemical results revealed that the HHcy group exhibited lower levels of HDL-C compared to the normal group, and a negative correlation was observed between HHcy and HDL-C. Consistent with these findings, each unit increase in HDL-C was associated with a 0.697 times decrease in the risk of HHcy, indicating that HDL-C serves as “good cholesterol” in blood lipids and its reduction is negatively correlated with the risk of atherosclerosis. UA and Cr are crucial indicators for assessing renal function. This study identified UA and Cr as risk factors for HHcy. Malinow et al. (29) proposed that the metabolic product of Hcy was the precursor of UA synthesis. It may be related to the effect of Hcy on renal function and its metabolic pathway and oxidative stress function (30). Xu Shan (31) et al. found that there was a certain correlation between the production and metabolism of plasma Hcy and blood uric acid in the study of the prevalence of hyperuricemia in patients with H-type hypertension. At the same time, because the kidney is also involved in the filtration and metabolism of Hcy, the damage of kidney function will also lead to the increase of Hcy, and there is an interaction between kidney function and Hcy level, which is consistent with the results of this study. Li et al. (32) reported that a high serum UA concentration can acgtivate proinflammatory factors,damage vascular endothelial function,increase oxidative stress,and lead to renal inadequacy.They also reported that Hcy accumulation in the plasma strengthens lipid peroxidation,which further influences kidney function,and Hcy and UA show synergistic effects.

Erythrocytes are the site of homocysteine production. This study found that for each unit increase in red blood cells, the risk of HHcy decreased by 0.820 times, and the mechanism is not clear. Previous research has confirmed a positive correlation between CIMT and plasma Hcy levels (33, 34), with the mechanism involving endothelial injury, oxidative stress, and alterations in lipid metabolism (35). The results of this study are consistent with those findings. Clinical studies have found that the number of individuals with elevated plasma Hcy levels is 2.8 times higher in hypertensive patients compared to the normal population, and high Hcy hyperhomocysteinemia is a associated with hypertension (36). Wilcken’s (37) research also suggests a link between hypertension and gene mutations in MTHFR. In this experiment, a close relationship was found between a history of hypertension and Hcy levels, with both hypertensive cerebrovascular disease patients and the control group exhibiting higher plasma Hcy levels than those without a history of hypertension. Multiple linear regression analysis revealed that hypertension is a associated with HHcy. Simultaneously, a plethora of evidence indicates that hyperhomocysteinemia and hypertension are both crucial and modifiable risk factors for cardiovascular and cerebrovascular events, particularly stroke. The coexistence of these two conditions exponentially increases the risk of cardiovascular and cerebrovascular events. Effectively controlling plasma homocysteine levels in hypertensive individuals may be a pivotal strategy to address the high incidence of stroke.

Li Y, et al.’s study found a close association between HHcy and blood glucose levels as well as transaminase levels (38–41). However, significant differences in blood glucose, glycated hemoglobin, and transaminase between the two population groups have not been detected in this study. This may be due to the uneven distribution in the stratified sampling of subjects or the insignificant impact of blood glucose, glycated hemoglobin, and transaminase on Hcy levels.

In summary, the prevalence of HHcy was high in Hebei province, China. Male, above 65 years old age, hypertension, carotid artery abnormalities, elevated Cr, UA, decreased HDL-C and RBC constitute high-risk factors for HHcy. Adopting a rational lifestyle, timely blood pressure reduction and weight management, and implementing effective intervention measures can contribute to lowering HCY levels and thereby reducing the incidence of older adult-related diseases.