4-pyridoxic acid

Abstract

Background: Vascular diseases are multifactorial and several risk factors may have synergetic effect on the global vascular risk. Among patients with diabetes, we investigated whether vitamin B6 species differ according to global cardiovascular risk. Methods: The present observational study included 122 patients with type 2 diabetes (mean (SD) age = 69.9 (9.1) years; 50% men). Concentrations of vitamin B6 vitamers were measured. Classical blood biomarkers and risk factors were used to compute a multivariate risk score. Results: Plasma concentrations of 4-pyridoxic acid were higher in patients with high risk versus those with low risk scores (48.2 (63.7) vs. 31.9 (15.0) nmol/L; p = 0.031). Plasma pyridoxine was significantly lowered in patients at high risk (2.8 (28.4) vs. 38.1 (127.8) nmol/L; p = 0.003). PAr index (4-pyridoxic acid/pyridoxal + pyridoxal 5′-phosphate) (1.05 (0.07) vs. 0.84 (0.06); p = 0.017) and the ratio of 4-pyridoxic acid/pyridoxine (7.0 (4.8) vs. 3.9 (3.2); p < 0.001) were higher in patients at high risk. After adjustment for cystatin C and C-reactive protein, only pyridoxine and 4-pyridoxic acid/pyridoxine ratio remained significantly different according to vascular risk scores. 4-Pyridoxic acid/pyridoxine ratio was the best marker to discriminate between patients according to their risk scores—area under the curve (AUC) (95% confidence intervals (CI)) = 0.72 (0.62–0.81). 4-Pyridoxic acid/pyridoxine ratio was directly related to plasma levels of soluble vascular cell adhesion molecule 1. Conclusion: Vitamin B6 metabolism was shifted in patients with multiple vascular risk factors. The catabolism to 4-pyridoxic acid was enhanced, whereas the catabolism to pyridoxine was lowered. High 4-Pyridoxic acid/pyridoxine ratio is independently associated with global cardiovascular risk.

2.2. Exposure Definition

The main exposure in the current study is a multivariate cardiovascular risk score that has been developed and validated in patients with diabetes []. This score is computed from common clinical measurements available in primary care settings, such as age, sex, BMI, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), systolic blood pressure, diastolic blood pressure, and HbA1c (, ). The score estimates the two-year risk of hospitalization due to a cardiovascular event in patients with type 2 diabetes []. The present observational study used already established global risk scores and it was not planned to be prospective or to prove if subjects would attain the outcome predicted by the risk scores in the future.

3.2. Plasma Vitamin B6 Species in Patients with Type 2 Diabetes According to Cardiovascular Hospitalization Risk

The plasma concentrations of vitamin B6 forms are shown in in the whole group and in subgroups according to risk scores. 4-Pyridoxic acid was higher in patients in the high-risk group compared to those in the low-risk group (mean = 48.2 vs. 31.9 nmol/L: p = 0.031). The differences in concentrations of 4-pyridoxic acid was not significant between the two risk categories after adjusting for serum cystatin C (p = 0.168) or for cystatin C and CRP (p = 0.166). The percentage of plasma 4-pyridoxic acid of total vitamin B6 (i.e., the sum of vitamin B6 forms) was higher in the high-risk group, even after adjustment for cystatin C and CRP (p = 0.005). Plasma concentration of pyridoxine was significantly lower in the high-risk group compared to that in the low-risk group (12.8 vs. 38.1 nmol/L; p = 0.003). This difference remained significant after adjustment for cystatin C (p = 0.007) or for cystatin C and CRP (p = 0.010). Plasma concentrations of pyridoxal, PLP, pyridoxamine, and pyridoxamine phosphate, or the sum of all vitamin B6 forms did not differ significantly between the risk categories. Thus, 4-pyridoxic acid (elevated by 51%) and pyridoxine (lowered by 66%) were the vitamin B6 forms with marked changes in patients with high vascular risk scores compared to those with low risk scores.