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Journal of Cardiovascular Pharmacology... Jul 2020The duration of randomized controlled clinical trials usually is approximately 3 to 5 years although hypercholesterolemia and other risk factors for atherosclerotic... (Review)
Review
BACKGROUND
The duration of randomized controlled clinical trials usually is approximately 3 to 5 years although hypercholesterolemia and other risk factors for atherosclerotic cardiovascular disease (ASCVD) are lifelong conditions.
OBJECTIVES
The legacy effect, defined as the persistence of benefit of pharmacologic interventions in clinical trials after the end of the randomized phase when all participants receive active therapy, is used to examine the long-term benefit. We summarize the evidence for the existence of the legacy effect as it pertains to hypercholesterolemia, describe underlying mechanisms, and discuss its relevance to clinical practice.
METHODS
We examined all published (n = 13) randomized clinical trials of lipid-lowering agents compared to placebo or usual care with follow-up after the randomized phase for the presence or absence of a legacy effect.
RESULTS
A legacy effect was demonstrated in all studies. The current US and European guidelines recommend treatment with high-intensity statins for patients with manifest ASCVD and that individualized approach be used for primary prevention.
CONCLUSION
The legacy effect results in significant long-term clinical benefits by preventing fatal and nonfatal events. This implies that early therapy would result in lower event rates. Long-term follow-up should be a part of clinical trial design in order to evaluate the presence or absence of a legacy effect.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Male; Middle Aged; Primary Prevention; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome
PubMed: 32107938
DOI: 10.1177/1074248420907256 -
Lancet (London, England) Jan 2024Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were...
BACKGROUND
Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.
METHODS
For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia.
FINDINGS
Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified.
INTERPRETATION
Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life.
FUNDING
Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.
Topics: Adult; Child; Humans; Male; Female; Adolescent; Child, Preschool; Cholesterol, LDL; Cross-Sectional Studies; Hypercholesterolemia; Hyperlipoproteinemia Type II; Genetic Testing
PubMed: 38101429
DOI: 10.1016/S0140-6736(23)01842-1 -
JAMA Cardiology Feb 2022
Topics: Humans; Hypercholesterolemia; Hyperlipidemias
PubMed: 34780601
DOI: 10.1001/jamacardio.2021.4987 -
Current Atherosclerosis Reports Jun 2020Statins represent the cornerstone for the treatment of hypercholesterolemia, although muscle-related side effects and dysregulation of glucose metabolism have strongly... (Review)
Review
PURPOSE OF REVIEW
Statins represent the cornerstone for the treatment of hypercholesterolemia, although muscle-related side effects and dysregulation of glucose metabolism have strongly limited their adherence and compliance especially in primary prevention therapy. The purpose of the present review is to provide the most recent evidence of the efficacy and safety of statins in monotherapy or combination with new lipid-lowering drugs.
RECENT FINDINGS
Recent "life-long" analysis conducted on young familial hypercholesterolemia patients, elderly hypocholesterolemic subjects, and from a 20-year follow-up of randomized controlled trial (RCT) have been published confirming that the cardiovascular benefits of statin therapy, in patients for whom it is recommended by current guidelines, greatly outweigh the risks of side effects. In addition, recent therapies to be used in combination with statins have shown to increase the percentage of patients at goal for low-density lipoprotein - cholesterol (LDL-C) with a good safety profile. The cardiovascular (CV) benefits of monoclonal antibodies anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) and ezetimibe, in patients under statin therapy, have been proven by specific RCT, while we are still waiting for the results of bempedoic acid and the small-interfering RNA (si-RNA) anti-PCSK9 inclisiran. Taken together, the approval of new pharmacological agents to be used in combination with statins represents the future for a tailored therapy of cardiovascular disease patients.
Topics: Adolescent; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Atherosclerosis; Child; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors; Primary Prevention; RNA, Small Interfering; Treatment Outcome
PubMed: 32494971
DOI: 10.1007/s11883-020-00844-w -
International Journal of Molecular... Jul 2022The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In... (Review)
Review
The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa.
Topics: Anorexia Nervosa; Feeding and Eating Disorders; Humans; Hypercholesterolemia; Neoplasms
PubMed: 35806470
DOI: 10.3390/ijms23137466 -
Pharmacological Research Jul 2023Despite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability... (Review)
Review
Despite a general improvement in global health conditions in the last decades, cardiovascular diseases (CVDs) are still the first global cause of death and disability worldwide, with ischemic heart disease (IHD) being responsible for half of CVD deaths. Hypercholesterolemia is a major causal risk factor for IHD. Although the availability of effective cholesterol-lowering drugs largely increased in the last few years, we are still facing disparities in the awareness of dyslipidaemia as a CVD-associated risk factor and therefore in health expenditure among different world areas. Although no significant changes have been reported globally in the levels of plasma cholesterol in the last three decades, relevant differences among world areas according to their economic status can be observed. Only high-income countries have experienced an improvement in plasma lipid profile which translated into a substantial decrease in the deaths and disabilities due to IHD, whereas countries in other income groups showed no reduction or even an increase. As expected, most of the deaths for IHD attributable to high LDL-C occur in people aged 60 years and above, although significant differences can be observed according to income. Altogether these observations suggest the need for measures to reduce the gap in treating hypercholesterolemia among income groups, with special attention to women and older people.
Topics: Humans; Female; Aged; Hypercholesterolemia; Myocardial Ischemia; Aging; Cardiovascular Diseases; Risk Factors; Cholesterol
PubMed: 37271426
DOI: 10.1016/j.phrs.2023.106814 -
Nutrients Feb 2021Hypercholesterolemia is a well-known independent risk factor for cardiovascular disease and a recognized target of pharmacological therapeutic agents in both primary and...
Hypercholesterolemia is a well-known independent risk factor for cardiovascular disease and a recognized target of pharmacological therapeutic agents in both primary and secondary prevention [...].
Topics: Cardiovascular Diseases; Diet, Healthy; Dietary Supplements; Food Ingredients; Heart Disease Risk Factors; Humans; Hypercholesterolemia
PubMed: 33652643
DOI: 10.3390/nu13030741 -
Praxis Aug 2022Arterial hypertension and hypercholesterolemia increase the risk of cardiovascular morbidity and mortality. Effectively reducing both blood pressure and circulating...
Arterial hypertension and hypercholesterolemia increase the risk of cardiovascular morbidity and mortality. Effectively reducing both blood pressure and circulating low-density lipoprotein cholesterol may considerably reduce cardiovascular risk. As this is particularly true if the intervention starts early, it is very important to identify and treat hypertension and hypercholesterolemia as early as possible. By improving adherence, a single-pill formulation that offers a combination of different drugs could be an effective way to manage patients with multiple cardiovascular risks.
Topics: Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Hypertension; Risk Factors
PubMed: 35920009
DOI: 10.1024/1661-8157/a003894 -
Current Atherosclerosis Reports Jun 2022Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic... (Review)
Review
PURPOSE OF REVIEW
Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants.
RECENT FINDINGS
Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.
Topics: Cardiovascular Diseases; Heart Disease Risk Factors; Humans; Hypercholesterolemia; Multifactorial Inheritance; Risk Factors
PubMed: 35386091
DOI: 10.1007/s11883-022-01018-6 -
Biomedicine & Pharmacotherapy =... Nov 2022NPC1L1 is a crucial protein involved in sterol lipid absorption and has been shown to play an important role in intestinal cholesterol absorption. Hypercholesterolemia... (Review)
Review
NPC1L1 is a crucial protein involved in sterol lipid absorption and has been shown to play an important role in intestinal cholesterol absorption. Hypercholesterolemia is a significant risk factor for cardiovascular diseases such as coronary heart disease. Screening of NPC1L1 inhibitors is critical for gaining a full understanding of lipid metabolism, developing new cholesterol-lowering medicines, and treating cardiovascular diseases. This work summarized existing methodologies for screening NPC1L1 inhibitors and evaluated their challenges, and will assist the development of novel cholesterol-lowering medications and therapeutic strategies for hypercholesterolemia and other cholesterol-related metabolic disorders.
Topics: Humans; Hypercholesterolemia; Membrane Transport Proteins; Cardiovascular Diseases; Membrane Proteins; Cholesterol; Anticholesteremic Agents; Intestinal Absorption
PubMed: 36166964
DOI: 10.1016/j.biopha.2022.113732