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Background <p>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.</p> Methods <p>In this retrospective analysis of prospective observational cohort, we analyzed data from 3,377 residents aged ≥ 40&#xa0;years living in Takahata, Japan. Baseline data were collected between 2004 and 2006. Eligibility for inclusion required an estimated GFR of ≥ 30&#xa0;mL/min/1.73 m<sup>2</sup> 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.</p> Results <p>Median follow-up period was 18.6&#xa0;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 <i>p</i> &lt; 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.</p> Conclusion <p>In the Japanese general population aged ≥ 40&#xa0;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.</p>

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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

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Tomohiro Takehara,
  • Yoichiro Otaki,
  • Kai Matsuo,
  • Tetsuro Goto,
  • Yuzuka Kuramasu,
  • Takaya Suzuki,
  • Masahiro Miyata,
  • Takaaki Nawano,
  • Eri Matsuki,
  • Sayumi Watanabe,
  • Keita Kamei,
  • Natsuko Suzuki,
  • Kazunobu Ichikawa,
  • Tetsu Watanabe,
  • Tsuneo Konta,
  • Masafumi Watanabe

摘要

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 m2 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.