Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up

Vallejo-Vaz, Antonio J.; Robertson, Michele; Catapano, Alberico L.; Watts, Gerald F.; Kastelein, John J.; Packard, Chris J.; Ford, Ian; Ray, Kausik K.

doi:10.1161/circulationaha.117.027966

Cited by 185Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCancer, Lipids, and Metabolism

Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up

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Vallejo-Vaz, Antonio J., Robertson, Michele, Catapano, Alberico L., Watts, Gerald F., Kastelein, John J., Packard, Chris J., Ford, Ian, Ray, Kausik K.·2017·Circulation

DOI 10.1161/circulationaha.117.027966

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Abstract

Background: Patients with primary elevations of low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomized trial evidence supporting these recommendations in primary prevention. In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL. Methods: We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL). The effect of pravastatin versus placebo on coronary heart disease and major adverse cardiovascular events were assessed over the 4.9-year randomized controlled trial phase and on mortality outcomes over a total of 20 years of follow-up. Results: Among 5529 individuals without vascular disease, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.002) and major adverse cardiovascular events by 25% ( P =0.004) consistently among those with and without LDL-C ≥190 mg/dL ( P -interaction >0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.033) and major adverse cardiovascular events by 25% ( P =0.037) during the initial trial phase and the risk of coronary heart disease death, cardiovascular death, and all-cause mortality by 28% ( P =0.020), 25% ( P =0.009), and 18% ( P =0.004), respectively, over a total of 20 years of follow-up. Conclusions: The present analyses provide robust novel evidence for the short- and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL.

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The graded intervention approach in Table 5 is based on evidence from multiple meta-analyses and randomized controlled trials showing consistent and graded reduction in atherosclerotic cardiovascular disease risk with reductions in total cholesterol and LDL-C.
“This graded approach is based on evidence from multiple meta-analyses and individual randomized controlled trials (RCTs), which show a consistent and graded reduction in ASCVD risk in response to reductions in TC and LDL-C levels (see Recommendations for cardiovascular disease risk estimation below) [31-41].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [40]

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Appropriateness of statin prescription in the elderly
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Epidemiology of familial hypercholesterolaemia: Community and clinical
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The Knowns and Unknowns of Contemporary Statin Therapy for Familial Hypercholesterolemia
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Variation in Lipid-Lowering Therapy Use in Patients With Low-Density Lipoprotein Cholesterol ≥190 mg/dL: Insights From the National Cardiovascular Data Registry–Practice Innovation and Clinical Excellence Registry
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Cholesterol-Lowering Agents
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Going to the negative: genomics for optimized medical prescription
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Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality
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Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice
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Differential use of E2 ubiquitin conjugating enzymes for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis
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Familial Hypercholesterolaemia in 2020: A Leading Tier 1 Genomic Application
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Comparing a novel machine learning method to the Friedewald formula and Martin-Hopkins equation for low-density lipoprotein estimation
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Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis
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Earlier treatment in adults with high lifetime risk of cardiovascular diseases: What prevention trials are feasible and could change clinical practice? Report of a National Heart, Lung, and Blood Institute (NHLBI) Workshop
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Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants
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Success in Achieving the Targets of the 20-Year Infancy-Onset Dietary Intervention: Association With Insulin Sensitivity and Serum Lipids
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Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats
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2022 Taiwan lipid guidelines for primary prevention
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Patient adherence, compliance, and perspectives on evolocumab for the management of resistant hypercholesterolemia
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Origination, change, and modulation of geriatric disease-related gut microbiota during life
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Cardiac Troponin - diagnostic problems and impact on cardiovascular disease
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Comparison of the effects of twice-daily exenatide and insulin on carotid intima-media thickness in type 2 diabetes mellitus patients: a 52-week randomized, open-label, controlled trial
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Effects of medication, treatment, and behavioral beliefs on intentions to take medication in patients with familial hypercholesterolemia
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The Role of Statins in Current Guidelines
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Age and sex specific effects of APOE genotypes on ischemic heart disease and its risk factors in the UK Biobank
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Association of low-density lipoprotein cholesterol levels with the risk of mortality and cardiovascular events: A meta-analysis of cohort studies with 1,232,694 participants
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The lipidomic correlates of epigenetic aging across the adult lifespan: A population‐based study
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The relationship between NLR, LDL-C/HDL-C, NHR and coronary artery disease
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Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review
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Cost-Effectiveness of Evolocumab Therapy for Myocardial Infarction: The Chinese Healthcare Perspective
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Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins
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Survival after breast cancer in women with type 2 diabetes using antidiabetic medication and statins: a retrospective cohort study
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The evaluation and management of patients with LDL-C ≥ 190 mg/dL in a large health care system
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LDL-cholesterol lowering and clinical outcomes in hypercholesterolemic subjects with and without a familial hypercholesterolemia phenotype: Analysis from the secondary prevention 4S trial
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Low-density lipoprotein cholesterol lowering and risk of major adverse cardiovascular events in primary prevention trials: A meta-analysis
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The impact of the cumulative burden of LDL-c and hs-CRP on cardiovascular risk: a prospective, population-based study
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Prolonged hyperlipidemia exposure increases the risk of arterial stiffness in young adults: a cross-sectional study in a cohort of Chinese
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Low-Density Lipoprotein Cholesterol
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VLDL receptor gene therapy for reducing atherogenic lipoproteins
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Economic evaluation of lipid lowering with PCSK9 inhibitors in patients with familial hypercholesterolemia: Methodological aspects
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Recent advances in research and care of familial hypercholesterolaemia
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The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events
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Efficacy and safety of bempedoic acid in patients with heterozygous familial hypercholesterolemia: analysis of pooled patient-level data from phase 3 clinical trials
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Long-term effects of different hypoglycemic drugs on carotid intima-media thickness progression: a systematic review and network meta-analysis
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The Era of Polypills in the Management of Cardiovascular Diseases: Are We There Yet?
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Long-Term Mortality in Patients With Severe Hypercholesterolemia Phenotype From a Racial and Ethnically Diverse US Cohort
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Gut Microbiome and Its Cofactors Are Linked to Lipoprotein Distribution Profiles
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Prevalence, treatment, and control of severe hyperlipidemia
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The potential of chronopharmacology for treatment of atherosclerosis
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Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention: A Review Part 2
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Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults
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Pharmacotherapy in familial hypercholesterolemia - Current state and emerging paradigms
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Association of low-density lipoprotein-cholesterol with all-cause and cause-specific mortality
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Current Perspectives on the Attainment of Lipid Modification Goals Relating to the Use of Statins and Ezetimibe for the Prevention of Cardiovascular Disease in the United Kingdom
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Implementation of a self-determination based clinical program to reduce cardiovascular disease risk
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Reduction of cardiovascular events with the use of lipid-lowering medication in patients with familial hypercholesterolemia or severe primary hypercholesterolemia: A systematic review
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The Habit Formation trial of behavioral economic interventions to improve statin use and reduce the risk of cardiovascular disease: Rationale, design and methodologies
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Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach—Where Do We Stand?
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Impact of Cholesterol on Ischemic Stroke in Different Human-Like Hamster Models: A New Animal Model for Ischemic Stroke Study
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Real-world prescribing in accordance to ACC/AHA guidelines for lipid-lowering therapy in high-risk primary and secondary prevention of ASCVD
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AUF-1 knockdown in mice undermines gut microbial butyrate-driven hypocholesterolemia through AUF-1–Dicer-1–mir-122 hierarchy
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Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy
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Patient and Physician Reported Perception on Hypercholesterolemia Management in Primary Prevention in Germany: Results from a Nationwide Online Survey
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Primary Prevention of Cardiovascular Disease at Community Clinics in the State of Sao Paulo, Brazil: Results from the Epidemiological Information Study of Communities
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Preventive Pharmacotherapy for Cardiovascular Disease: A Modelling Study Considering Health Gain, Costs, and Cost-Effectiveness when Stratifying by Absolute Risk
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Hypercholesterolaemia and coronary artery disease: A silent killer with several faces
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The protective effect and experimental research progress of pleotropic statins in intervertebral disc degeneration
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Safety Net Program to Improve Statin Initiation Among Adults With High Low-Density Lipoprotein Cholesterol
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First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults
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Response by Vallejo-Vaz et al to Letters Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
Vallejo‐Vaz, A. J., Packard, C. J., & Ray, K. K. (2018) · Circulation · doi:10.1161/circulationaha.118.033781 · Cited by 2 · see citing works
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Letter by Koh Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
Koh, K. K. (2018) · Circulation · doi:10.1161/circulationaha.117.033136 · Cited by 1 · see citing works
Letter by Löwe et al Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
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Association between Lowering Low-Density Lipoprotein Cholesterol with Pravastatin and Primary Prevention of Cardiovascular Disease in Mild to Moderate Hypercholesterolemic Japanese
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Low-density lipoprotein cholesterol lowering and risk of major adverse cardiovascular events in primary prevention trials: A meta-analysis
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Self-citation

Authors: Vallejo-Vaz, A. J., Robertson, M., Catapano, A. L., Watts, G. F., Kastelein, J. J., Packard, C. J., Ford, I., & Ray, K. K.
Affiliations: Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, United Kingdom (A.J.V.-V., K.K.R.).
University of Glasgow (GB)
University of Milan (IT)
The University of Western Australia (AU)
Amsterdam UMC Location University of Amsterdam (NL)
Imperial College London (GB)
ORCID: Robertson, Michele
Catapano, Alberico L.
Watts, Gerald F.
Kastelein, John J.
Packard, Chris J.
Ford, Ian
Ray, Kausik K.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2017-11-14
Volume: 136
Issue: 20
Pages: 1878-1891
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.117.027966
OpenAlex: W2751778625
Cited by: 185
References: 33
Citations by year: 2026: 9 · 2025: 11 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 20 · 2020: 23 · 2019: 25 · 2018: 38 · 2017: 6
FWCI: 25.75
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
UWA Profiles and Research Repository (UWA) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion, other-oa)
Spiral (Imperial College London) (submittedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: LDL cholesterol lowering, primary prevention, hypercholesterolemia, pravastatin, statin therapy, coronary artery disease, major adverse cardiovascular events, cardiovascular mortality, atherosclerotic cardiovascular disease, WOSCOPS, men
MeSH terms: Anticholesteremic Agents, Cardiovascular Diseases, Coronary Disease, Follow-Up Studies, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Primary Prevention, Scotland, Pravastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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