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A dose-dependent association of total cholesterol with all-cause and specific mortality: results from the National Health and Nutrition Examination Survey
Ying-qing Feng
Guangdong Cardiovascular Institute
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0443-5506
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality.
Methods: All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999-2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression model and Cox models with penalized splines were applied to explore non-linear and irregular shape relationships. Kaplan-Meier survival curve and subgroup analyses were conducted.
Results: The sample studied comprised 17853 men and 18922 women, categorized as 27927 adults aged 18–65 years and 8848 adults more than 65 years old. A total of 4441 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations with nadir at 213 mg/dL, 200 mg/dL, and 218mg/dL after adjusting for confounding variables in the restricted cubic spline analysis. HRs of all-cause, CVD, and cancer mortality was particularly negatively related to TC levels in the lower range <200 mg/dL, especially in the range <120 mg/dL (HR 1.95; 95% CI 1.59, 2.38, HR 1.78; 95% CI 1.16, 2.72, HR 2.18; 95% CI 1.46, 3.25, respectively). The lowest cumulative survival rate was recorded in the lowest TC level group.
Conclusions: A U-curve association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.
Keywords
Total cholesterol, All-cause mortality, Cancer, Cardiovascular disease
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CURRENT STATUS: Under Review
Version (no preprint)
Posted 05 Jan, 2021
Editorial decision: Minor revision
On 05 Jan, 2021
Review #1 received
Received 01 Jan, 2021
Review #2 received
Received 01 Jan, 2021
Reviewer #2 agreed
On 27 Dec, 2020
Reviewers invited
Invitations sent on 27 Dec, 2020
Reviewer #1 agreed
On 27 Dec, 2020
Editor assigned
On 13 Dec, 2020
Submission checks complete
On 13 Dec, 2020
Editor invited
On 13 Dec, 2020
This version was not preprinted
Version 1
Posted 17 Sep, 2020
No community comments so far
Editorial decision: Major revision
On 24 Nov, 2020
Review #2 received
Received 18 Nov, 2020
Reviewer #2 agreed
On 08 Nov, 2020
Review #1 received
Received 07 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Reviewers invited
Invitations sent on 30 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 15 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nutrition & Dietetics
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This preprint is under consideration at Nutrition & Metabolism. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
A dose-dependent association of total cholesterol with all-cause and specific mortality: results from the National Health and Nutrition Examination Survey
Ying-qing Feng
Guangdong Cardiovascular Institute
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0443-5506
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 05 Jan, 2021
Editorial decision: Minor revision
On 05 Jan, 2021
Review #1 received
Received 01 Jan, 2021
Review #2 received
Received 01 Jan, 2021
Reviewer #2 agreed
On 27 Dec, 2020
Reviewers invited
Invitations sent on 27 Dec, 2020
Reviewer #1 agreed
On 27 Dec, 2020
Editor assigned
On 13 Dec, 2020
Submission checks complete
On 13 Dec, 2020
Editor invited
On 13 Dec, 2020
This version was not preprinted
Version 1
Posted 17 Sep, 2020
No community comments so far
Editorial decision: Major revision
On 24 Nov, 2020
Review #2 received
Received 18 Nov, 2020
Reviewer #2 agreed
On 08 Nov, 2020
Review #1 received
Received 07 Nov, 2020
Reviewer #1 agreed
On 05 Nov, 2020
Reviewers invited
Invitations sent on 30 Sep, 2020
Editor assigned
On 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 15 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nutrition & Dietetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality.
Methods: All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999-2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression model and Cox models with penalized splines were applied to explore non-linear and irregular shape relationships. Kaplan-Meier survival curve and subgroup analyses were conducted.
Results: The sample studied comprised 17853 men and 18922 women, categorized as 27927 adults aged 18–65 years and 8848 adults more than 65 years old. A total of 4441 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations with nadir at 213 mg/dL, 200 mg/dL, and 218mg/dL after adjusting for confounding variables in the restricted cubic spline analysis. HRs of all-cause, CVD, and cancer mortality was particularly negatively related to TC levels in the lower range <200 mg/dL, especially in the range <120 mg/dL (HR 1.95; 95% CI 1.59, 2.38, HR 1.78; 95% CI 1.16, 2.72, HR 2.18; 95% CI 1.46, 3.25, respectively). The lowest cumulative survival rate was recorded in the lowest TC level group.
Conclusions: A U-curve association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.
Figure 1
Figure 2
Figure 3