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Abstract
Objectives Among primary prevention-type adults not on lipid-lowering therapy, conflicting results exist on the relationship between low-density lipoprotein cholesterol (LDL-C) and long-term mortality. We evaluated this relationship in a real-world evidence population of adults.
Design Retrospective cohort study.
Setting Electronic medical record data for adults, from 4 January 2000 through 31 December 2022, were extracted from the University of Pittsburgh Medical Center healthcare system.
Participants Adults without diabetes aged 50–89 years not on statin therapy at baseline or within 1 year and classified as primary prevention-type patients. To mitigate potential reverse causation, patients who died within 1 year or had baseline total cholesterol (T-C) ≤120 mg/dL or LDL-C <30 mg/dL were excluded.
Main exposure measure Baseline LDL-C categories of 30–79, 80–99, 100–129, 130–159, 160–189 or ≥190 mg/dL.
Main outcome measure All-cause mortality with follow-up starting 365 days after baseline cholesterol measurement.
Results 177 860 patients with a mean (SD) age of 61.1 (8.8) years and mean (SD) LDL-C of 119 (31) mg/dL were evaluated over a mean of 6.1 years of follow-up. A U-shaped relationship was observed between the six LDL-C categories and mortality with crude 10-year mortality rates of 19.8%, 14.7%, 11.7%, 10.7%, 10.1% and 14.0%, respectively. Adjusted mortality HRs as compared with the referent group of LDL-C 80–99 mg/dL were: 30–79 mg/dL (HR 1.23, 95% CI 1.17 to 1.30), 100–129 mg/dL (0.87, 0.83–0.91), 130–159 mg/dL (0.88, 0.84–0.93), 160–189 mg/dL (0.91, 0.84–0.98) and ≥190 mg/dL (1.19, 1.06–1.34), respectively. Unlike LDL-C, both T-C/HDL cholesterol (high-density lipoprotein cholesterol) and triglycerides/HDL cholesterol ratios were independently associated with long-term mortality.
Conclusions Among primary prevention-type patients aged 50–89 years without diabetes and not on statin therapy, the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100–189 mg/dL, which is much higher than current recommendations. For counselling these patients, minimal consideration should be given to LDL-C concentration.
- epidemiology
- primary prevention
- adult cardiology
Data availability statement
Data are available upon reasonable request. Study protocol: No separate study protocol was required a priori, as this retrospective analysis was deemed a quality improvement initiative with ethical review and approval granted by the UPMC Quality Improvement Review Committee and Institutional Review Board. Statistical code: Selected statistical code may be requested from Dr Kevin Kip (e-mail, kipke2@upmc.edu). Data set: The data set contains protected health information and will not be available.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Data availability statement
Data are available upon reasonable request. Study protocol: No separate study protocol was required a priori, as this retrospective analysis was deemed a quality improvement initiative with ethical review and approval granted by the UPMC Quality Improvement Review Committee and Institutional Review Board. Statistical code: Selected statistical code may be requested from Dr Kevin Kip (e-mail, kipke2@upmc.edu). Data set: The data set contains protected health information and will not be available.
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Footnotes
Contributors KEK: Conception, statistical analysis, writing and editing. DD: Conception, critical review and editing. SM: Critical review and editing. OCM: Conception, critical review and editing. K.E.K serves as guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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