CVD has been a worldwide healthcare burden for a long time, and medical providers are always interested in finding reliable biomarkers for CVD and CVD risk factors. In this community-based study, we investigated homocysteine levels in association with high CVD risk in middle-aged and elderly people in northern Taiwan. Looking at three homocysteine tertiles (Table 1), there was a rising proportion of males, HTN, smoking status, and SBP as the homocysteine level increased. These results correspond with previous studies,     but HDL had an inverse relationship with homocysteine, which was also noted in a previous study . According to the Framingham risk score, male sex, HTN, smoking status, and SBP are risk factors for CVD, but HDL serve as a protective factor against CVD.  Meanwhile, an increase in plasma homocysteine is directly associated with increases in Framingham CVD risk. In Fig. 3, the prevalence of high CVD risk was significantly greater in the higher tertiles of homocysteine. These findings led us to speculate that an association exists between homocysteine levels and Framingham CVD risk.
In Table 2, we found a positive correlation between homocysteine levels and Framingham CVD risk, along with other traditional CVD risk factors such as BMI and waist circumference. All the correlations reached statistical significance even after adjustment for age. The Pearson’s correlation between homocysteine and CVD risk was 0.360 with a p value < 0.001, which corresponds with a previous study that homocysteine can be a risk factor for CVD  . All the previous results raise the question of whether homocysteine can be an important risk factor for predicting high CVD risk. Hence, we wanted to know whether homocysteine can be an independent risk factor for high CVD risk or not.
In the logistic regression models (Table 3), the middle and high homocysteine groups were compared with the low homocysteine group, and the prevalence of high CVD risk increased as homocysteine increased. After adjusting for age, sex, smoking, DM, HTN, hyperlipidemia, and BMI, the odds ratio (OR) and 95% confidence interval for high CVD risk was 2.851 (1.402 to 5.801) in the high homocysteine group compared with the low homocysteine group. This result confirmed that homocysteine was an independent risk factor for high CVD risk. Figure 2 shows the ROC curve for homocysteine as a biomarker for high CVD risk. The AUC was 0.667. The optimized cut-off value for homocysteine was 12.15 µmol/L with a sensitivity of 0.75 and a specificity of 0.51.
There are many possible explanations for the relationship between homocysteine and CVD. Homocysteine is a sulfur-containing amino acid that is a metabolic precursor of methionine and cystathionine . Elevated homocysteine levels are not only considered a risk factor for cardiovascular disease    but are also linked to various diseases, such as chronic kidney disease . A previous animal study with cell culture showed that high homocysteine levels had toxic effects on the vasculature, with manifestations of medial remodeling, adventitial inflammation, and endothelial injury. The mechanisms include abnormal protein metabolism  and the production of reactive oxidative species  . Homocysteine specifically damages the endothelial, medial and adventitial layers of the vessel wall , than vessel damage leads to atherosclerosis , hypertension , stroke , coronary artery disease , peripheral arterial disease , and aneurysm .
Many studies have pointed out the positive relationship between homocysteine and CVD, but most of them did not consider the influence of other traditional CVD risk factors on the relationship between homocysteine and CVD. In our study, we considered traditional CVD risk factors and other parameters, and the results revealed that homocysteine level may be an important independent predictor of high CVD risk. Our findings may have an impact on health screening among middle-aged and elderly populations. In addition to those traditional parameters of CVD, homocysteine level should be considered an important biomarker in health screening, and people with elevated homocysteine should be warned of higher CVD risk.