L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study
BackgroundChloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. H...
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| Format: | Article |
| Language: | English |
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JMIR Publications
2023-11-01
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| Series: | JMIR Public Health and Surveillance |
| Online Access: | https://publichealth.jmir.org/2023/1/e49291 |
| _version_ | 1797629281752317952 |
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| author | Xinran Hou Wei Xu Chengliang Zhang Zongbin Song Maoen Zhu Qulian Guo Jian Wang |
| author_facet | Xinran Hou Wei Xu Chengliang Zhang Zongbin Song Maoen Zhu Qulian Guo Jian Wang |
| author_sort | Xinran Hou |
| collection | DOAJ |
| description |
BackgroundChloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated.
ObjectiveThis study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population.
MethodsData were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality.
ResultsA total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05).
ConclusionsIn American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality. |
| first_indexed | 2024-03-11T10:52:06Z |
| format | Article |
| id | doaj.art-6ff5d36a6268461ebd07c17416c7a105 |
| institution | Directory Open Access Journal |
| issn | 2369-2960 |
| language | English |
| last_indexed | 2024-03-11T10:52:06Z |
| publishDate | 2023-11-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Public Health and Surveillance |
| spelling | doaj.art-6ff5d36a6268461ebd07c17416c7a1052023-11-13T15:45:42ZengJMIR PublicationsJMIR Public Health and Surveillance2369-29602023-11-019e4929110.2196/49291L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort StudyXinran Houhttps://orcid.org/0000-0003-4446-7537Wei Xuhttps://orcid.org/0009-0009-8162-3915Chengliang Zhanghttps://orcid.org/0000-0003-0072-8037Zongbin Songhttps://orcid.org/0000-0002-0447-8648Maoen Zhuhttps://orcid.org/0000-0002-7385-1557Qulian Guohttps://orcid.org/0000-0002-5958-2258Jian Wanghttps://orcid.org/0009-0003-3693-0613 BackgroundChloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. ObjectiveThis study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. MethodsData were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. ResultsA total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). ConclusionsIn American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.https://publichealth.jmir.org/2023/1/e49291 |
| spellingShingle | Xinran Hou Wei Xu Chengliang Zhang Zongbin Song Maoen Zhu Qulian Guo Jian Wang L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study JMIR Public Health and Surveillance |
| title | L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study |
| title_full | L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study |
| title_fullStr | L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study |
| title_full_unstemmed | L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study |
| title_short | L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study |
| title_sort | l shaped association of serum chloride level with all cause and cause specific mortality in american adults population based prospective cohort study |
| url | https://publichealth.jmir.org/2023/1/e49291 |
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