Hypertension and cystatin C account for sex differences in serum homocysteine levels in acute coronary syndrome subjects with normal serum creatinine

BACKGROUND: Hyperhomocysteinemia is one of cardiovascular disease risk factors and fasting homocysteine levels are significantly elevated in male compared to female acute coronary syndrome (ACS) patients with normal renal function. However, it is not known the sex related determinants of plasma homocysteine levels in ACS subjects without renal dysfunction. METHODS: A total of 165 ACS participants with normal plasma creatinine who underwent coronary angiography were included in the present study. Clinical parameters, homocysteine, fasting glucose and lipid profile, hemoglobin, white blood cell, platelets, creatinine, cystatin C, blood urea nitrogen, uric acid (UA), and albumin were measured. Multivariate linear regression analyses were used to recognize the predictive factors for homocysteine. RESULTS: The levels of plasma homocysteine were significantly higher in men than in women (P < 0.0001). In males, homocysteine (log10) was positively associated with hypertension (r = 0.569, P < 0.001), creatinine (r = 0.367, P < 0.001) and cystatin C (log10) (r = 0.333, P = 0.001). In females, homocysteine (log10) was positively correlated with age (r = 0.307, P = 0.107), hypertension (r = 0.456, P < 0.001), creatinine (r = 0.341, P = 0.008), cystatin C (log10) (r = 0.429, P = 0.001) and UA (r = 0.569, P < 0.001) whereas was negatively associated with LDL-C (r = − 0.298, P = 0.021) and ApoB (r = − 0.273, P = 0.033). Parameters up to statistical significance in males or females were incorporated into the stepwise linear regression models. In men, hypertension (P < 0.001) and creatinine (P = 0.031) were independently related to homocysteine. Most of the variability of homocysteine levels in males were only determined by hypertension. In women, cystatin C (log10) (P = 0.004) and hypertension (P = 0.005) were independently related to homocysteine (log10). Plasma cystatin C had a higher explanatory value than hypertension in females. CONCLUSIONS: Hypertension and cystatin C could explain most of the sex differences in serum homocysteine levels in ACS subjects with normal serum creatinine. This finding suggested the importance of making different strategies in males and females to manage hyperhomocysteinemia effectively in ACS subjects without renal dysfunction.