Related Experiment Video
Updated: Aug 22, 2025
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with
Masashi Sakuma1, Satoshi Iimuro2, Tomohiro Shinozaki3
1Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.
Insights
The optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular events appears to be around 70 mg/dl. Lowering LDL-C below this threshold did not further reduce event risk in Japanese patients with coronary artery disease.
Area of Science:
- Cardiology
- Preventive Medicine
- Clinical Research
Background:
- High-dose statin therapy is established for secondary prevention of coronary artery disease (CAD).
- The concept of "lower is better" for low-density lipoprotein cholesterol (LDL-C) levels remains debated.
- A potential optimal LDL-C threshold, below which cardiovascular event incidence is no longer reduced, was hypothesized.
Purpose of the Study:
- To investigate the existence of an optimal LDL-C threshold for cardiovascular event reduction.
- To determine if a monotonic relationship exists between LDL-C levels and cardiovascular outcomes.
- To analyze a sub-study of the REAL-CAD trial for optimal LDL-C targeting.
Main Methods:
- Subanalysis of 11,105 CAD patients from the REAL-CAD study.
- Assessment of LDL-C levels at 6 months post-randomization and 5-year cardiovascular outcomes.
- Utilized a Cox model with an artificial covariate to identify a threshold LDL-C value, testing thresholds from 40 to 100 mg/dl.
Main Results:
- The best model fit, assessed by log-likelihood, was achieved with an LDL-C threshold of 70 mg/dl for primary composite outcomes.
- In the model with LDL-C ≥ 70 mg/dl, a 10 mg/dl increase in LDL-C correlated with a hazard ratio of 1.07 (95% CI: 1.01-1.13).
- Cardiovascular event risk decreased monotonically until LDL-C reached 70 mg/dl; further reduction showed no additional benefit.
Conclusions:
- An optimal LDL-C threshold may exist for secondary prevention in Japanese CAD patients.
- The identified threshold for primary composite outcomes is approximately 70 mg/dl.
- Lowering LDL-C below 70 mg/dl did not appear to further reduce cardiovascular event risk.
Background:
Aggressive lipid lowering by high-dose statin treatment has been established for the secondary prevention of coronary artery disease (CAD). Regarding the low-density lipoprotein cholesterol (LDL-C) level, however, the "The lower is the better" concept has been controversial to date. We hypothesized that there is an optimal LDL-C level, i.e., a "threshold" value, below which the incidence of cardiovascular events is no longer reduced. We undertook a subanalysis of the REAL-CAD study to explore whether such an optimal target LDL-C level exists by a novel analysis procedure to verify the existence of a monotonic relationship.
Methods:
For a total of 11,105 patients with CAD enrolled in the REAL-CAD study, the LDL-C level at 6 months after randomization and 5-year cardiovascular outcomes were assessed. We set the "threshold" value of the LDL-C level under which the hazards were assumed to be constant, by including an artificial covariate max (0, LDL-C - threshold) in the Cox model. The analysis was repeated with different LDL-C thresholds (every 10 mg/dl from 40 to 100 mg/dl) and the model fit was assessed by log-likelihood.
Results:
For primary outcomes such as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization, the model fit assessed by log-likelihood was best when a threshold LDL-C value of 70 mg/dl was assumed. And in the model with a threshold LDL-C ≥ 70 mg/dl, the hazard ratio was 1.07 (95% confidence interval 1.01-1.13) as the LDL-C increased by 10 mg/dl. Therefore, the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C.
Conclusions:
Our analysis model suggests that a "threshold" value of LDL-C might exist for the secondary prevention of cardiovascular events in Japanese patients with CAD, and this threshold might be 70 mg/dl for primary composite outcomes.
Trial Registration:
http://www.
Clinicaltrials:
gov . Unique identifier: NCT01042730.
More Related Videos
08:45LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Related Concept Videos
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:26Coronary Artery Disease IV: Preventive Measures
01:26Atherosclerosis III: Management
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:18Lipids: Dietary Sources and Requirements