Background <p>Cardiovascular-kidney-metabolic (CKM) syndrome, characterized by the interplay of metabolic risk factors, chronic kidney disease, and cardiovascular dysfunction, is a key driver of cardiovascular disease (CVD) incidence. The cholesterol, high-density lipoprotein, and glucose (CHG) index, which integrates total cholesterol, high-density lipoprotein, and fasting blood glucose, and its modified indices (combined with obesity indicators) have potential for CVD risk prediction. However, their role across CKM stages 0–3 remains unclear.</p> Methods <p>A nationwide prospective cohort study included 5,404 participants with CKM stages 0–3, screened from 17,708 individuals screened between 2011 and 2020. CHG index and modified indices (CHG-BMI, CHG-Wc, CHG-WHtR) were calculated. Logistic regression, restricted cubic spline (RCS) analysis, subgroup analysis, and sensitivity analysis were used to evaluate associations with CVD incidence and identify exploratory threshold association.</p> Results <p>During follow-up, 25.5% of participants developed CVD. CHG and modified indices were independently associated with increased CVD risk (all <i>P</i> &lt; 0.001). In fully adjusted models, CHG as continuous data showed a 28% higher risk (OR = 1.28, 95% CI: 1.06–1.58) of outcome, and CHG-WHtR was 54% higher (OR = 1.28, 95% CI: 1.16–2.04). Meanwhile, the highest quartile (Q4) of CHG-WHtR was associated with a 43% higher risk (OR = 1.43, 95% CI: 1.03–1.98) compared to Q1, while CHG-BMI (OR = 1.68, 95% CI: 1.22–2.31) showed stronger associations. RCS analysis identified exploratory inflection points like CHG ≥ 5.15 and CHG-WHtR ≥ 2.41, above which CVD risk significantly increased (<i>P</i> &lt; 0.005) and validated by bootstrap sampling. Subgroup analysis confirmed consistent associations across age, gender, and CKM stages subpopulations. Multiple sensitivity analysis supported the robustness of these associations across CKM stages.</p> Conclusion <p>CHG index and its modified indices, particularly CHG-WHtR and CHG-Wc, are valuable indicators associated with reported incident CVD across CKM stages 0–3. Their stage-specific associations and exploratory threshold association support their utility in risk stratification for CKM syndrome.</p>

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Association of cholesterol, high-density lipoprotein, and glucose index and modified indices in predicting cardiovascular diseases incidence among population with cardiovascular-kidney-metabolic syndrome stages 0–3: a nationwide prospective cohort study

  • Zhen Zhao,
  • Pengchong Du,
  • Manning Jian,
  • Yuanyuan Liu,
  • Hongyi Pan,
  • Qing Liu

摘要

Background

Cardiovascular-kidney-metabolic (CKM) syndrome, characterized by the interplay of metabolic risk factors, chronic kidney disease, and cardiovascular dysfunction, is a key driver of cardiovascular disease (CVD) incidence. The cholesterol, high-density lipoprotein, and glucose (CHG) index, which integrates total cholesterol, high-density lipoprotein, and fasting blood glucose, and its modified indices (combined with obesity indicators) have potential for CVD risk prediction. However, their role across CKM stages 0–3 remains unclear.

Methods

A nationwide prospective cohort study included 5,404 participants with CKM stages 0–3, screened from 17,708 individuals screened between 2011 and 2020. CHG index and modified indices (CHG-BMI, CHG-Wc, CHG-WHtR) were calculated. Logistic regression, restricted cubic spline (RCS) analysis, subgroup analysis, and sensitivity analysis were used to evaluate associations with CVD incidence and identify exploratory threshold association.

Results

During follow-up, 25.5% of participants developed CVD. CHG and modified indices were independently associated with increased CVD risk (all P < 0.001). In fully adjusted models, CHG as continuous data showed a 28% higher risk (OR = 1.28, 95% CI: 1.06–1.58) of outcome, and CHG-WHtR was 54% higher (OR = 1.28, 95% CI: 1.16–2.04). Meanwhile, the highest quartile (Q4) of CHG-WHtR was associated with a 43% higher risk (OR = 1.43, 95% CI: 1.03–1.98) compared to Q1, while CHG-BMI (OR = 1.68, 95% CI: 1.22–2.31) showed stronger associations. RCS analysis identified exploratory inflection points like CHG ≥ 5.15 and CHG-WHtR ≥ 2.41, above which CVD risk significantly increased (P < 0.005) and validated by bootstrap sampling. Subgroup analysis confirmed consistent associations across age, gender, and CKM stages subpopulations. Multiple sensitivity analysis supported the robustness of these associations across CKM stages.

Conclusion

CHG index and its modified indices, particularly CHG-WHtR and CHG-Wc, are valuable indicators associated with reported incident CVD across CKM stages 0–3. Their stage-specific associations and exploratory threshold association support their utility in risk stratification for CKM syndrome.