Synergistic interaction of hypertension and hyperhomocysteinemia on chronic kidney disease: Findings from the National Health and Nutrition Examination Survey 1999‐2006

Hypertension and hyperhomocysteinemia are two independent risk factors of chronic kidney disease (CKD). Our study aimed to evaluate whether hypertension and hyperhomocysteinemia act synergistically toward renal injury. Our analysis included 13 693 subjects from the National Health and Nutritional Survey (NHANES) 1999-2006. Association was assessed by multivariate logistic regressions. The interaction was investigated on both additive and multiplicative scales. CKD had a prevalence of 17.62% in the NHANES population. After adjusting for age, sex, race, education, physical activity, drinking frequency, current smoking status, poverty-to-income ratio, Total cholesterol, high-density lipoprotein cholesterol, serum folate, vitamin B12, body mass index, waist circumference, and diabetes mellitus, patients with both hypertension and hyperhomocysteinemia had a 5.072 (3.967-6.486) times risk of CKD than their healthy compartments, higher than that in patients with only hypertension or hyperhomocysteinemia. Moreover, additive interaction of hypertension and hyperhomocysteinemia was significant (relative excess risk due to interaction: 2.107, 95% CI: 1.071-3.143; the attributable proportion due to interaction: 0.415, 95% CI: 0.270-0.561; synergy index: 2.072, 95% CI: 1.449-2.962). Finally, subgroup analyses elucidated the interaction was robust in those with only reduced estimated glomerular filtration rate or albuminuria, and stratification analyses based on gender showed consistency with the main results. Hypertension and hyperhomocysteinemia may act synergistically toward a greater renal injury than the sum of their independent effects. Our findings suggest the coexistence itself also correlates with a deteriorative impact on renal function in addition to the effects of hypertension and diabetes themselves. The results may support the rationality and value of simultaneous tight control of hypertension and hyperhomocysteinemia to prevent CKD.