Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)
Open accessAbstract
Background—: Lipoprotein(a) [Lp(a)] is a low-density lipoprotein–like particle largely independent of known risk factors and predictive of cardiovascular disease. Statins may offset the risk associated with elevated Lp(a), but it is unknown whether Lp(a) is a determinant of residual risk in the setting of low low-density lipoprotein cholesterol after potent statin therapy. Methods and Results—: Baseline and on-treatment Lp(a) concentrations were assessed in 9612 multiethnic participants in the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) before and after random allocation to rosuvastatin 20 mg/d or placebo, with outcomes reported for whites (n=7746). Lp(a) concentrations (median [25th–75th percentile], in nmol/L) were highest in blacks (60 [34–100]), then Asians (38 [18–60]), Hispanics (24 [11–46]), and whites (23 [10–50]; P <0.001). Although the median change in Lp(a) with rosuvastatin and placebo was zero, rosuvastatin nonetheless resulted in a small but statistically significant positive shift in the overall Lp(a) distribution ( P <0.0001). Baseline Lp(a) concentrations were associated with incident cardiovascular disease (adjusted hazard ratio per 1-SD increment in Ln[Lp(a)], 1.18; 95% confidence interval, 1.03–1.34; P =0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of cardiovascular disease (adjusted hazard ratio, 1.27; 95% confidence interval, 1.01–1.59; P =0.04), which was independent of low-density lipoprotein cholesterol and other factors. Rosuvastatin significantly reduced incident cardiovascular disease among participants with baseline Lp(a) greater than or equal to the median (hazard ratio, 0.62; 95% confidence interval, 0.43–0.90) and Lp(a) less than the median (hazard ratio, 0.46; 95% confidence interval, 0.30–0.72), with no evidence of interaction. Similar results were obtained when analyses included nonwhites. Conclusion—: Among white JUPITER participants treated with potent statin therapy, Lp(a) was a significant determinant of residual risk. The magnitude of relative risk reduction with rosuvastatin was similar among participants with high or low Lp(a). Clinical Trials Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.
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Studies reported no or only a minor increase in Lp(a) levels among patients treated with statins.
“Studies reported no or only a minor increase in lipoprotein (a) (Lp(a)) levels among patients treated with statins [33, 34].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [34]
Soy's cholesterol-lowering effect is generally attributed to isoflavones and phytoestrogens, whose content falls with increasing soybean processing.
“The cholesterol-lowering effect of soy is generally attributed to its isoflavone and phytoestrogen content, which decreases progressively with the increasing degree of soybean processing.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [187]
Because high-quality randomized trials are lacking, berberine's efficacy for dyslipidaemia requires further validation, and the bioavailability of different berberine preparations is debated.
“However, due to the lack of highquality randomized clinical trials, the efficacy of berberine for treating dyslipidaemia needs to be further validated.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [187]
The dose of fibre needed for a clinically relevant LDL-C reduction of 3-5% ranges from 3 to 10 g per day depending on fibre type.
“However, the dosage needed to achieve a clinically relevant reduction in levels of LDL-C of 3-5% varies from 3 to 10 g per day according to the specific type of fibre [187].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [187]
Soy protein has been suggested to modestly lower LDL-C when replacing animal protein, but this was not confirmed after accounting for changes in other dietary components.
“Soy protein has also been indicated as being able to induce a modest LDL-C-lowering effect when replacing animal protein foods. However, this was not confirmed when changes in other dietary components were taken into account [187,188].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [187]
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“Studies reported no or only a minor increase in lipoprotein (a) (Lp(a)) levels among patients treated with statins [33, 34].”
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- Authors
- Khera, A. V., Everett, B. M., Caulfield, M. P., Hantash, F. M., Wohlgemuth, J., Ridker, P. M., & Mora, S.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Circulation
- Published
- 2014-02-11
- Volume
- 129
- Issue
- 6
- Pages
- 635-642
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3946056
- OpenAlex
- W2169920876
- Semantic Scholar
- 8a23d8bdaae1df77acc905664e33c0dfac940435
- Cited by
- 461
- References
- 32
- Citations by year
- 2026: 31 · 2025: 43 · 2024: 44 · 2023: 50 · 2022: 37 · 2021: 38 · 2020: 40 · 2019: 37 · 2018: 28 · 2017: 35 · 2016: 41 · 2015: 23 · 2014: 14
- FWCI
- 25.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Quest Diagnostics
- National Heart, Lung, and Blood Institute (R01HL117861)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- lipoprotein(a), rosuvastatin, residual cardiovascular risk, statin therapy, cardiovascular disease prevention, low LDL cholesterol, JUPITER trial, non-white populations, cardiovascular risk stratification, LDL-C lowering therapy, cardiovascular risk reduction
- MeSH terms
- Rosuvastatin Calcium, Aged, Cardiovascular Diseases, Double-Blind Method, Female, Fluorobenzenes, Follow-Up Studies, Hispanic or Latino, Humans, Male, Middle Aged, Placebos, Pyrimidines, Risk Factors, Sulfonamides, Incidence, Treatment Outcome, Lipoprotein(a), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Black People, White People
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