Combined effect of hyperhomocysteinemia and mild-to-moderate chronic kidney disease on mortality and cardiovascular events in the Japanese general population: the Yamagata (Takahata) study.

BACKGROUND

Hyperhomocysteinemia (HHcy) and chronic kidney disease (CKD) are risk factors for cardiovascular events and all-cause mortality. Although their coexistence may further amplify these risks, few studies have evaluated this association, particularly in patients with mild-to-moderate CKD.

METHODS

In this retrospective analysis of prospective observational cohort, we analyzed data from 3,377 residents aged ≥ 40 years living in Takahata, Japan. Baseline data were collected between 2004 and 2006. Eligibility for inclusion required an estimated GFR of ≥ 30 mL/min/1.73 m at baseline. Primary and secondary endpoints were all-cause mortality and cardiovascular events, respectively. We assessed whether a combination of HHcy and mild-to-moderate CKD could predict these outcomes.

RESULTS

Median follow-up period was 18.6 years (interquartile range: 17.2-19.3). The Kaplan-Meier analyses revealed that individuals with both HHcy and CKD had the highest incidence of all-cause mortality and cardiovascular events (log-rank p < 0.001 for both). After adjusting for cardiovascular risk factors, this group remained at the highest risk, with hazard ratios of 2.49 and 2.11 and 95% confidence intervals of 2.00-3.10 and 1.32-3.38 for all-cause mortality and cardiovascular events, respectively.

CONCLUSION

In the Japanese general population aged ≥ 40 years, the coexistence of HHcy and mild-to-moderate CKD was associated with a significantly higher risk of all-cause mortality and cardiovascular events than either condition alone.