Association of Frailty Status with Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome in Middle-Aged and Older Populations: Insights from the 1999–2018 National Health and Nutrition Examination Survey
Abstract
1. Introduction
2. Methods
2.1. Data Sources
2.2. Study Design and Participant Selection
2.3. Extracted Covariates
2.4. Definitions of CKM
2.5. Assessment of Frailty Index
2.6. Mortality Outcomes
2.7. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Relationship Between Frailty Status and CKM-Staging Progression
3.3. Relationship Between Frailty Status and Mortality Outcomes in CKM Patients
3.4. Subgroup Analysis
3.5. Sensitivity Analysis
4. Discussion
Limitation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | All (N = 19,089) | Robust (N = 3056) | Pre-Frail (N = 12,123) | Frail (N = 3910) | p |
---|---|---|---|---|---|
Age, years | 63.00 (54.00, 72.00) | 60.00 (51.00, 67.00) | 63.00 (54.00, 72.00) | 65.00 (56.00, 75.00) | <0.001 |
Male, n (%) | 9741.00 (51.03%) | 1858.00 (60.80%) | 6161.00 (50.82%) | 1722.00 (44.04%) | <0.001 |
Race and ethnicity, n (%) | <0.001 | ||||
Non-Hispanic White | 9552.00 (50.04%) | 1564.00 (51.18%) | 6094.00 (50.27%) | 1894.00 (48.44%) | |
Non-Hispanic Black | 3841.00 (20.12%) | 398.00 (13.02%) | 2537.00 (20.93%) | 906.00 (23.17%) | |
Mexican American | 2908.00 (15.23%) | 545.00 (17.83%) | 1792.00 (14.78%) | 571.00 (14.60%) | |
Hispanic and Others | 2788.00 (14.61%) | 549.00 (17.96%) | 1700.00 (14.02%) | 539.00 (13.79%) | |
Body mass index, kg/m2 | 28.67 (25.36, 32.80) | 27.25 (24.30, 30.84) | 28.59 (25.40, 32.52) | 30.10 (26.14, 35.40) | <0.001 |
Waist circumference, cm | 101.40 (92.50, 111.10) | 97.40 (89.20, 106.30) | 101.20 (92.60, 110.50) | 105.70 (96.30, 116.80) | <0.001 |
Poverty income ratio | 2.29 (1.23, 4.31) | 3.04 (1.63, 5.00) | 2.52 (1.32, 4.52) | 1.47 (0.92, 2.61) | <0.001 |
Education, n (%) | <0.001 | ||||
Less than high school | 2769.00 (14.51%) | 392.00 (12.83%) | 1612.00 (13.30%) | 765.00 (19.57%) | |
High school or equivalent | 7337.00 (38.44%) | 1025.00 (33.54%) | 4590.00 (37.86%) | 1722.00 (44.04%) | |
College or above | 8983.00 (47.06%) | 1639.00 (53.63%) | 5921.00 (48.84%) | 1423.00 (36.39%) | |
Marital status, n (%) | <0.001 | ||||
Unmarried | 1200.00 (6.29%) | 157.00 (5.14%) | 759.00 (6.26%) | 284.00 (7.26%) | |
Married | 11,872.00 (62.19%) | 2200.00 (71.99%) | 7702.00 (63.53%) | 1970.00 (50.38%) | |
Divorcee | 6017.00 (31.52%) | 699.00 (22.87%) | 3662.00 (30.21%) | 1656.00 (42.35%) | |
Smoking status, n (%) | <0.001 | ||||
Never smoker | 9261.00 (48.51%) | 1648.00 (53.93%) | 5991.00 (49.42%) | 1622.00 (41.48%) | |
Former smoker | 6579.00 (34.46%) | 891.00 (29.16%) | 4256.00 (35.11%) | 1432.00 (36.62%) | |
Current smoker | 3249.00 (17.02%) | 517.00 (16.92%) | 1876.00 (15.47%) | 856.00 (21.89%) | |
Alcohol consumption, n (%) | <0.001 | ||||
Non-drinker | 13,538.00 (70.92%) | 1987.00 (65.02%) | 8513.00 (70.22%) | 3038.00 (77.70%) | |
Mild to moderate | 3777.00 (19.79%) | 751.00 (24.57%) | 2469.00 (20.37%) | 557.00 (14.25%) | |
Heavy | 1774.00 (9.29%) | 318.00 (10.41%) | 1141.00 (9.41%) | 315.00 (8.06%) | |
Physical activity, n (%) | <0.001 | ||||
Less than moderate | 11,674.00 (61.16%) | 1702.00 (55.69%) | 7223.00 (59.58%) | 2749.00 (70.31%) | |
Moderate | 4917.00 (25.76%) | 798.00 (26.11%) | 3278.00 (27.04%) | 841.00 (21.51%) | |
Vigorous | 2498.00 (13.09%) | 556.00 (18.19%) | 1622.00 (13.38%) | 320.00 (8.18%) | |
Laboratory indicators | |||||
Hemoglobin A1c, % | 5.70 (5.40, 6.10) | 5.50 (5.30, 5.70) | 5.70 (5.40, 6.10) | 6.00 (5.50, 6.80) | <0.001 |
Total Cholesterol, mg/dL | 198.00 (171.00, 227.00) | 209.00 (187.00, 236.00) | 198.00 (171.00, 226.00) | 186.50 (158.00, 219.00) | <0.001 |
HDL-C, mg/dL | 50.00 (42.00, 62.00) | 52.00 (43.00, 64.00) | 51.00 (42.00, 63.00) | 48.00 (40.00, 59.00) | <0.001 |
eGFR, ml/min/1.73 m2 | 82.69 (67.42, 95.94) | 86.84 (74.35, 97.42) | 83.17 (68.30, 96.05) | 76.06 (57.20, 93.40) | <0.001 |
UACR, mg/g | 8.67 (5.24, 19.74) | 6.72 (4.42, 12.00) | 8.54 (5.22, 18.45) | 12.69 (6.48, 41.08) | <0.001 |
10-year CVD risk score | 10.85 (5.13, 19.97) | 6.49 (3.41, 11.80) | 10.96 (5.25, 19.73) | 15.89 (7.94, 26.45) | <0.001 |
CKM Stage | <0.001 | ||||
CKM Stage 1 | 1215.00 (6.36%) | 451.00 (14.76%) | 711.00 (5.86%) | 53.00 (1.36%) | |
CKM Stage 2 | 11,294.00 (59.16%) | 2320.00 (75.92%) | 7488.00 (61.77%) | 1486.00 (38.01%) | |
CKM Stage 3 | 3151.00 (16.51%) | 245.00 (8.02%) | 2261.00 (18.65%) | 645.00 (16.50%) | |
CKM Stage 4 | 3429.00 (17.96%) | 40.00 (1.31%) | 1663.00 (13.72%) | 1726.00 (44.14%) |
All-Cause Death | Cardiovascular Death | Non Cardiovascular Death | ||||
---|---|---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | |
Model I | ||||||
Robust | Reference | Reference | Reference | |||
Pre-frail | 1.92 (1.74, 2.13) | <0.001 | 2.37 (1.91, 2.94) | <0.001 | 1.80 (1.61, 2.02) | <0.001 |
Frail | 4.10 (3.69, 4.56) | <0.001 | 5.92 (4.74, 7.40) | <0.001 | 3.61 (3.20, 4.08) | <0.001 |
Model II | ||||||
Robust | Reference | Reference | Reference | |||
Pre-frail | 1.47 (1.32, 1.62) | <0.001 | 1.71 (1.37, 2.12) | <0.001 | 1.40 (1.25, 1.57) | <0.001 |
Frail | 2.83 (2.53, 3.17) | <0.001 | 3.78 (3.00, 4.76) | <0.001 | 2.57 (2.26, 2.91) | <0.001 |
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Yang, Z.; Wu, S.; Li, Y.; Liu, H.; Zhao, M.; Xu, Y.; Chen, Y.; Chen, Y.; Lip, G.Y.H. Association of Frailty Status with Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome in Middle-Aged and Older Populations: Insights from the 1999–2018 National Health and Nutrition Examination Survey. J. Clin. Med. 2025, 14, 6008. https://doi.org/10.3390/jcm14176008
Yang Z, Wu S, Li Y, Liu H, Zhao M, Xu Y, Chen Y, Chen Y, Lip GYH. Association of Frailty Status with Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome in Middle-Aged and Older Populations: Insights from the 1999–2018 National Health and Nutrition Examination Survey. Journal of Clinical Medicine. 2025; 14(17):6008. https://doi.org/10.3390/jcm14176008
Chicago/Turabian StyleYang, Zhenkun, Shuang Wu, Yuanjie Li, Hongyu Liu, Manlin Zhao, Yang Xu, Yunyu Chen, Yang Chen, and Gregory Y. H. Lip. 2025. "Association of Frailty Status with Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome in Middle-Aged and Older Populations: Insights from the 1999–2018 National Health and Nutrition Examination Survey" Journal of Clinical Medicine 14, no. 17: 6008. https://doi.org/10.3390/jcm14176008
APA StyleYang, Z., Wu, S., Li, Y., Liu, H., Zhao, M., Xu, Y., Chen, Y., Chen, Y., & Lip, G. Y. H. (2025). Association of Frailty Status with Staging and Mortality Risk of Cardiovascular-Kidney-Metabolic Syndrome in Middle-Aged and Older Populations: Insights from the 1999–2018 National Health and Nutrition Examination Survey. Journal of Clinical Medicine, 14(17), 6008. https://doi.org/10.3390/jcm14176008