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Journal of Clinical Lipidology 2022In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of... (Review)
Review
In contrast to strong evidence-based clinical recommendations for lipid-lowering treatment, there is no analogous definitive diagnostic definition of hypercholesterolemia and its various subtypes. For many clinicians, guideline indications for hypolipidemic treatment can become broadly conflated with hypercholesterolemia in a non-specific sense. In this statement, we propose a unified definition and mechanism-based classification of hypercholesterolemia, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction.
Topics: Humans; Hypercholesterolemia
PubMed: 36229375
DOI: 10.1016/j.jacl.2022.09.006 -
The American Journal of Managed Care Jun 2017Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels.1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age; therefore, early detection and treatment are imperative to reduce cardiovascular events and premature death. Statins are the mainstay treatment for hyperlipidemia; however, the limitations of statins include treatment resistance, intolerance due to adverse events, and a lack of adherence which contribute to poor outcomes. As such, many patients require adjunct therapies to properly control hyperlipidemia including niacin, bile acid sequestrants, fibric acids, and ezetimibe. FH can be even more challenging to treat, often requiring the use of lomitapide, mipomersen, proprotein convertase subtilisin/kexin type 9 inhibitors, or low-density lipoprotein cholesterol apheresis, in addition to high dose conjunction with statins or other agents.2 The approach to determining the appropriate treatment options has also undergone important changes. Guidelines for the management of patients with hyperlipidemia vary in their recommendations, with the American College of Cardiology/American Heart Association recommending that treatment decisions be based on the intensity of response associated with various statins, while multiple other guidelines (eg, National Lipid Association (NLA) and the American Association of Clinical Endocrinologists and American College of Endocrinology) still support attaining prespecified lipid values to reduce cardiovascular risk.3-5 This article will review the epidemiology of hyperlipidemia and FH, risk factors associated with the development of disease, as well as the efficacy and safety of statins and adjunct treatment options.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Practice Guidelines as Topic; Risk Factors
PubMed: 28978219
DOI: No ID Found -
American Journal of Respiratory and... Feb 2022The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex... (Review)
Review
The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.
Topics: Cholesterol; Humans; Hypercholesterolemia; Prognosis; Sepsis
PubMed: 34715007
DOI: 10.1164/rccm.202105-1197TR -
Archives of Biochemistry and Biophysics Jul 2017Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by... (Review)
Review
Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane. PCSK9 also appears to modulate glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension. The magnitude of PCSK9's involvement in the onset of these metabolic abnormalities appears to be associated with age, sex, and ethnic background. Another regulator, the inducible degrader of the LDL receptor (IDOL), works by enhancing the ubiquitination of the LDL receptor. Herein, we will review the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Plaque, Atherosclerotic; Proprotein Convertase 9; Receptors, LDL; Ubiquitin-Protein Ligases
PubMed: 28587771
DOI: 10.1016/j.abb.2017.06.001 -
European Heart Journal Apr 2023
Topics: Humans; Triglycerides; Cholesterol; Hypercholesterolemia; Cardiovascular System; Heart
PubMed: 36650915
DOI: 10.1093/eurheartj/ehac783 -
Clinica E Investigacion En... May 2021The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development....
The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development. Multiple experimental, epidemiological, and clinical evidence underpins this association. Atherosclerotic cardiovascular disease remains as the major cause of mortality in the world. Recent genetic studies of Mendelian randomisation and randomised clinical trials aimed at LDL cholesterol reduction, are summarised in this article. They, unequivocally ratify the aetiological role of LDL cholesterol in the development of atherosclerosis. Thus, LDL cholesterol lowering is the cornerstone of lipid lowering therapy for the reduction of cardiovascular complications of atherosclerosis.
Topics: Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypercholesterolemia; Randomized Controlled Trials as Topic
PubMed: 33966809
DOI: 10.1016/j.arteri.2020.12.004 -
Clinica E Investigacion En... Dec 2019The reduction of low density lipoprotein-cholesterol (LDL-chol) has been associated with a decrease in cardiovascular morbidity and mortality. It has been demonstrated... (Review)
Review
The reduction of low density lipoprotein-cholesterol (LDL-chol) has been associated with a decrease in cardiovascular morbidity and mortality. It has been demonstrated that there is no value of LDL-chol below which there ceases to be a preventive benefit with its reduction, and neither has it been observed that there is a higher incidence of secondary effects associated with lower concentrations of LDL-chol. Although there is a wide range of lipid-lowering drugs available, a high percentage of patients do not achieve the desired LDL-chol levels. The high-potency statins reduce the LDL-chol by 15-30%, and can double the percentage of patients that reach their desired level. This combination has shown to be safe and effective in the primary and secondary prevention of cardiovascular disease. Another option is the combination of statins with exchange resins, although this requires a more complex management. The inhibition of PCSK9 protein with monoclonal antibodies reduces the LDL-chol by more than 60%, and is effective in the prevention of cardiovascular disease. However, due to its cost, its use is restricted to patients with ischaemia or familial hypercholesterolaemia that do not achieve the desired levels with conventional drugs. The evidence base as regards the benefit and safety of achieving the desired levels of LDL-chol is very wide and is still increasing. In the next few years, it may be necessary to adjust the intensity of the hypercholesterolaemia treatment to the level of vascular risk of the patients, and to the level of reduction necessary to achieve the therapeutic targets. This will result in a more effective cardiovascular prevention and in a better quality of life, particularly in the large group of patients at higher vascular risk.
Topics: Anion Exchange Resins; Antibodies, Monoclonal; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors; Risk
PubMed: 31813618
DOI: 10.1016/j.arteri.2019.10.003 -
Journal of the American College of... Jun 2019
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Topics: American Heart Association; Anticholesteremic Agents; Biomarkers; Cardiology; Cardiovascular Diseases; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Medication Therapy Management; PCSK9 Inhibitors; Risk Assessment; Risk Reduction Behavior; United States
PubMed: 30423391
DOI: 10.1016/j.jacc.2018.11.002 -
Cell Metabolism Oct 2021High levels of cholesterol are generally considered to be associated with atherosclerosis. In the past two decades, however, a number of studies have shown that excess... (Review)
Review
High levels of cholesterol are generally considered to be associated with atherosclerosis. In the past two decades, however, a number of studies have shown that excess cholesterol accumulation in various tissues and organs plays a critical role in the pathogenesis of multiple diseases. Here, we summarize the effects of excess cholesterol on disease pathogenesis, including liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, osteoporosis, osteoarthritis, pituitary-thyroid axis dysfunction, immune disorders, and COVID-19, while proposing that excess cholesterol-induced toxicity is ubiquitous. We believe this concept will help broaden the appreciation of the toxic effect of excess cholesterol, and thus potentially expand the therapeutic use of cholesterol-lowering medications.
Topics: Animals; Anticholesteremic Agents; Atherosclerosis; Biomarkers; COVID-19; Cholesterol; Humans; Hypercholesterolemia; Prognosis; Risk Factors; COVID-19 Drug Treatment
PubMed: 34562355
DOI: 10.1016/j.cmet.2021.09.001 -
Clinica E Investigacion En... 2021During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance,...
During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance, oestrogens, progesterone, and placental lactogen, although their reference values are not exactly known, TG levels can increase up to 300mg/dL, and TC can go as high as 350mg/dL. When the cholesterol concentration exceeds the 95 percentile (familial hypercholesterolaemia (FH) and transient maternal hypercholesterolaemia), there is a predisposition to oxidative stress in foetal vessels, exposing the newborn to a greater fatty streaks formation and a higher risk of atherosclerosis. However, the current treatment of pregnant women with hyperlipidaemia consists of a diet and suspension of lipid-lowering drugs. The most prevalent maternal hypertriglyceridaemia (HTG) is due to secondary causes, like diabetes, obesity, drugs, etc. The case of severe HTG due to genetic causes is less prevalent, and can be a higher risk of maternal-foetal complications, such as, acute pancreatitis (AP), pre-eclampsia, preterm labour, and gestational diabetes. Severe HTG-AP is a rare but potentially lethal pregnancy complication, for the mother and the foetus, usually occurs during the third trimester or in the immediate postpartum period, and there are no specific protocols for its diagnosis and treatment. In conclusion, it is crucial that dyslipidaemia during pregnancy must be carefully evaluated, not just because of the acute complications, but also because of the future cardiovascular morbidity and mortality of the newborn child. That is why the establishment of consensus protocols or guidelines is essential for its management.
Topics: Cholesterol; Dyslipidemias; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Triglycerides
PubMed: 33309071
DOI: 10.1016/j.arteri.2020.10.002