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Revista Da Associacao Medica Brasileira... Dec 2019
Topics: Brazil; Cardiovascular Diseases; Humans; Hypercholesterolemia; Hypertension; Hypertriglyceridemia; Risk Factors
PubMed: 31994618
DOI: 10.1590/1806-9282.65.12.1421 -
Ageing Research Reviews Jan 2024Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly... (Review)
Review
Familial hypercholesterolemia (FH) is a metabolic condition caused mainly by a mutation in the low-density lipoprotein (LDL) receptor gene (LDLR), which is highly prevalent in the population. Besides being an important causative factor of cardiovascular diseases, FH has been considered an early risk factor for Alzheimer's disease. Cognitive and emotional behavioral impairments in LDL receptor knockout (LDLr) mice are associated with neuroinflammation, blood-brain barrier dysfunction, impaired neurogenesis, brain oxidative stress, and mitochondrial dysfunction. Notably, today, LDLr mice, a widely used animal model for studying cardiovascular diseases and atherosclerosis, are also considered an interesting tool for studying dementia. Here, we reviewed the main findings in LDLr mice regarding the relationship between FH and brain dysfunctions and dementia development.
Topics: Humans; Animals; Mice; Hypercholesterolemia; Cardiovascular Diseases; Risk Factors; Hyperlipoproteinemia Type II; Brain; Cognition; Alzheimer Disease; Heart Disease Risk Factors
PubMed: 38056504
DOI: 10.1016/j.arr.2023.102149 -
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 -
International Journal of Molecular... Apr 2018Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been... (Review)
Review
Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. β‑glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of β‑glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of β‑glucans on cholesterol levels.
Topics: Animals; Anticholesteremic Agents; Cholesterol; Dietary Fiber; Humans; Hypercholesterolemia; Immunologic Factors; beta-Glucans
PubMed: 29393350
DOI: 10.3892/ijmm.2018.3411 -
Expert Review of Clinical Pharmacology Jun 2017Prescription of statins for low-density lipoprotein cholesterol (LDL-C) reduction is the standard of care in primary and secondary prevention of cardiovascular disease;... (Review)
Review
Prescription of statins for low-density lipoprotein cholesterol (LDL-C) reduction is the standard of care in primary and secondary prevention of cardiovascular disease; nevertheless, a large number of patients treated with statins are unable to reach the recommended LDL-C targets. Therefore, there is need for safe and effective novel therapies for the pharmacological management of hypercholesterolaemia, in addition or as alternative to lipid-lowering therapies (LLT) currently in use. Areas covered: In 2015, the Food and Drug Administration and the European Medicines Agency approved alirocumab (Praluent®; Sanofi), a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), for the treatment of hypercholesterolaemic patients unable to meet LDL-C targets, as an adjunct to diet in addition/alternative to LLT. The authors review the pharmacological features, clinical efficacy, and safety of alirocumab in lowering LDL-C, and discuss its therapeutic perspectives based on the most recent clinical trials. Expert commentary: Alirocumab causes a marked reduction in LDL-C, presents good safety and tolerability, and represents a promising approach for LDL-C lowering, particularly in patients with intolerance to statin or elevated LDL-C despite maximal statin therapy; nevertheless, further long-term data on safety and efficacy are necessary, such as data on the improvement of cardiovascular outcomes.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors
PubMed: 28395555
DOI: 10.1080/17512433.2017.1318063 -
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 Pediatric Reviews 2017Atherosclerotic disease is a leading cause of morbidity and mortality in adults and is generally thought of as only affecting adults. However, the pathologic changes in... (Review)
Review
BACKGROUND
Atherosclerotic disease is a leading cause of morbidity and mortality in adults and is generally thought of as only affecting adults. However, the pathologic changes in vessels leading to atherosclerosis, and an increased risk of cardiovascular disease, have been shown to begin in early adolescence.
OBJECTIVES
There is a growing body of literature suggesting that earlier treatment, through lifestyle changes and pharmacotherapy, can help reduce this risk. A growing number of children are presenting with elevated cholesterol because of the increased prevalence of obesity and diabetes mellitus.
METHODS
In addition, an increasing number of children are living with previously fatal diseases that increase the risk of atherosclerosis, either because of the disease process or as adverse effect of the treatment, such as human immunodeficiency virus, Kawasaki disease, and cardiac transplantation.
RESULT AND CONCLUSION
In addition, specific disorders of cholesterol metabolism, such as Familial Hypercholesterolemia (FH) may be encountered in a pediatric practice.
Topics: Adolescent; Anticholesteremic Agents; Atherosclerosis; Child; Healthy Lifestyle; Humans; Hypercholesterolemia; Risk Factors
PubMed: 29332588
DOI: 10.2174/1573396314666180111143900 -
Vnitrni Lekarstvi 2018Hypercholesterolemia is one of the most important risk factors of cardiovascular (CV) disease. Epidemiology follows the prevalence, the incidence and the possibilities...
Hypercholesterolemia is one of the most important risk factors of cardiovascular (CV) disease. Epidemiology follows the prevalence, the incidence and the possibilities of risk factors or diseases intervention. A review of observation epidemiologic studies, pharmacotherapy and treatment perspectives is presented. The first epidemiologic studies, e.g. the Framingham Heart Study or MRFIT showed hyperlipidemia is associated with the incidence of CV disease. The North Karelia Project showed the intervention of CV risk factors is useful on population-based principles. Interventional studies with statins showed the usefulness of LDL cholesterol lowering to decrease CV morbidity and mortality and also total mortality. Anyway, the control of CV risk factors is unsatisfactory.Key words: epidemiology - hypercholesterolemia - intervention.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Risk Factors
PubMed: 29498873
DOI: No ID Found -
Clinical Science (London, England :... Jul 2017Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of... (Review)
Review
Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors-diabetes, hypercholesterolaemia, hypertension and smoking-are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here.
Topics: Alzheimer Disease; Cerebral Hemorrhage; Dementia, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Risk Factors
PubMed: 28667059
DOI: 10.1042/CS20160382