Cholesterol Reduction and Clinical Benefit: Are There Limits to Our Expectations?
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Abstract Encouraging intervention trials drive our expectations toward more aggressive cholesterol-lowering therapies, lower target levels, and less severe hypercholesterolemia. Available studies may predict which patients, degrees of total cholesterol (TC) reduction, and baseline and target levels of TC provide the most clinical benefit. Data were pooled from seven primary and nine secondary controlled trials with major coronary heart disease (CHD) events as primary endpoints. The analysis showed that we can expect large reductions in CHD from TC reduction in primary and secondary prevention. However, the reduction is much larger in subjects with high TC and/or previous CHD events. The percent reduction in CHD increased exponentially with increasing percent TC reductions, which predicted >70% of the change in CHD. Consequently, we cannot expect cost-effective clinical benefits from mean reductions in TC >15 (LDL cholesterol >20)%. The TC level at the study endpoint correlated with CHD incidence irrespective of the study group and explained almost 45% of CHD incidence. The relationship was progressive and leveled off at a TC level below about 150 mg/dL (3.9 mmol/L) (LDL cholesterol ≈110 mg/dL [≈2.8 mmol/L]). Little extra clinical benefit can be expected from further reductions. We can expect an average 2% reduction in CHD events per percent reduction in TC. We can also expect a 2-fold greater clinical benefit among subjects with high initial TC levels than among those with low levels. Finally, we can expect that the cholesterol-attributable risk is reset to that predicted by the TC level achieved within 4 to 6 years.
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Employees of large companies have an extremely low incidence rate of MI compared to the general population.
“employees of large companies have an extremely low incidence rate of MI compared to the general population346).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [346]
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- Authors
- Fager, G., & Wiklund, O.
- Affiliations
- Sahlgrenska University Hospital (SE)
- ORCID
- Wiklund, Olov
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 1997-12
- Volume
- 17
- Issue
- 12
- Pages
- 3527-3533
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W1979794075
- Cited by
- 62
- References
- 34
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hjärt-Lungfonden
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- cholesterol-lowering therapy, total cholesterol, LDL cholesterol, coronary artery disease, hypercholesterolemia, clinical benefit, cost-effectiveness, primary and secondary prevention
- MeSH terms
- Anticholesteremic Agents, Cholesterol, Clinical Trials as Topic, Coronary Disease, Humans
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