Homocysteine levels alter the TyG index-CKD link in Chinese hypertensive patients

Homocysteine (Hcy) is an established non-traditional risk factor for chronic kidney disease (CKD). However, the association between the triglyceride-glucose (TyG) index and CKD, and how this association may be modified by Hcy levels, remains unclear. This study aimed to investigate whether the association between the TyG index and CKD in hypertensive patients is modified by Hcy levels and to examine this potential interaction. 26679 subjects were included in this multicenter observational study. The TyG index was calculated as ln [TG (mg/dL) × fasting triglycerides (mg/dL)/2]. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The association between the TyG index and CKD was analyzed using fitted smoothing curves and multivariable logistic regression. The overall prevalence of CKD was 7.0%. The association between the TyG index and CKD was modified by Hcy levels. A significant positive association was observed in participants with Hcy > 15 μmol/L (ORs per 1-unit increase: 1.37; 95% CI: 1.22, 1.54), but not in those with Hcy ≤15 μmol/L (ORs: 1.33; 95% CI: 0.99, 1.78). In quartile analyses, the association was stronger in the Hcy > 15 μmol/L group, with ORs (95% CI) of 1.38 (1.17, 1.63), 1.46 (1.22, 1.75), and 1.67 (1.37, 2.05) for Q2–Q4, respectively. In the Hcy ≤15 μmol/L group, the corresponding ORs were 1.38 (0.88, 2.15), 1.35 (0.84, 2.15), and 1.80 (1.09, 2.97). Moreover, after adjusting for confounding factors, a significant synergistic effect of high TyG index and Hcy on CKD risk was observed (OR = 11.47; 95% CI: 7.91, 16.65). Our study findings suggest that Hcy and the TyG index are independently associated with an increased risk of CKD among Chinese patients with hypertension. The TyG index was strongly and consistently associated with increased CKD risk in individuals with elevated Hcy (>15 μmol/L), but this association was attenuated in those with lower Hcy levels. The China H-type Hypertension Registry Study (CHHRS) was registered in ChiCTR1800017274 on. July 20, 2018.