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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 -
Journal of Clinical Lipidology 2022The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited... (Review)
Review
The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals.
Topics: Humans; Abetalipoproteinemia; Hypobetalipoproteinemias; Lipid Metabolism Disorders; Homozygote; Vitamins
PubMed: 36243606
DOI: 10.1016/j.jacl.2022.08.009 -
Journal of Stroke Jan 2017Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. ICH is more common in... (Review)
Review
Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. ICH is more common in Asians, advanced age, male sex, and low- and middle-income countries. The case fatality rate of ICH is high (40% at 1 month and 54% at 1 year), and only 12% to 39% of survivors can achieve long-term functional independence. Risk factors of ICH are hypertension, current smoking, excessive alcohol consumption, hypocholesterolemia, and drugs. Old age, male sex, Asian ethnicity, chronic kidney disease, cerebral amyloid angiopathy (CAA), and cerebral microbleeds (CMBs) increase the risk of ICH. Clinical presentation varies according to the size and location of hematoma, and intraventricular extension of hemorrhage. Patients with CAA-related ICH frequently have concomitant cognitive impairment. Anticoagulation related ICH is increasing recently as the elderly population who have atrial fibrillation is increasing. As non-vitamin K antagonist oral anticoagulants (NOACs) are currently replacing warfarin, management of NOAC-associated ICH has become an emerging issue.
PubMed: 28178408
DOI: 10.5853/jos.2016.00864 -
Journal of Internal Medicine Jun 2017Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and... (Review)
Review
Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important.
Topics: Bone and Bones; Brain; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immune System Phenomena; Lipoproteins, LDL; Mutation; Neoplasms; Proprotein Convertase 9; Risk Factors
PubMed: 28295777
DOI: 10.1111/joim.12614 -
Journal of the American Heart... Apr 2021Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver...
Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8-34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, <0.0001), low-density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, <0.0001), and high-density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, <0.0001) than controls. In those with a Fontan, high-density lipoprotein cholesterol was inversely correlated with body mass index (=-0.30, <0.0001), high-sensitivity C-reactive protein (=-0.27, =0.0006), and alanine aminotransferase (=-0.18, =0.02) but not with other liver disease markers. Lower high-density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04-1.81 [=0.03]). This relationship was attenuated when log high-sensitivity C-reactive protein was added to the model (HR, 1.26; 95% CI, 0.95-1.67 [=0.10]). Total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high-density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan-associated liver disease and lipid metabolism.
Topics: Adult; Biomarkers; Cholesterol; Dyslipidemias; Female; Follow-Up Studies; Fontan Procedure; Heart Defects, Congenital; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Prognosis; Prospective Studies; United States; Young Adult
PubMed: 33787283
DOI: 10.1161/JAHA.120.019578 -
International Journal of Rheumatology 2012Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The...
Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4(+) plasma cells (IgG4(+)/IgG(+) plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman's disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.
PubMed: 22719769
DOI: 10.1155/2012/572539 -
Critical Care Explorations Feb 2023To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis. (Review)
Review
UNLABELLED
To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis.
DATA SOURCES
Systematic review and meta-analysis of published studies on PubMed and Embase.
STUDY SELECTION
All observational studies reporting ICU admission cholesterol and triglyceride levels in critically ill patients with sepsis were included. Authors were contacted for further data.
DATA EXTRACTION
Eighteen observational studies were identified, including 1,283 patients with a crude overall mortality of 33.3%. Data were assessed using Revman (Version 5.1, Cochrane Collaboration, Oxford, United Kingdom) and presented as mean difference (MD) with 95% CIs, values, and values.
DATA SYNTHESIS
Admission levels of total cholesterol (17 studies, 1,204 patients; MD = 0.52 mmol/L [0.27-0.77 mmol/L]; < 0.001; = 91%), high-density lipoprotein (HDL)-cholesterol (14 studies, 991 patients; MD = 0.08 mmol/L [0.01-0.15 mmol/L]; = 0.02; = 61%), and low-density lipoprotein (LDL)-cholesterol (15 studies, 1,017 patients; MD = 0.18 mmol/L [0.04-0.32 mmol/L]; = 0.01; = 71%) were significantly lower in eventual nonsurvivors compared with survivors. No association was seen between admission triglyceride levels and mortality (15 studies, 1,070 patients; MD = 0.00 mmol/L [-0.16 to 0.15 mmol/L]; = -0.95; = 79%).
CONCLUSIONS
Mortality was associated with lower levels of total cholesterol, HDL-cholesterol, and LDL-cholesterol, but not triglyceride levels, in patients admitted to ICU with sepsis. The impact of cholesterol replacement on patient outcomes in sepsis, particularly in at-risk groups, merits investigation.
PubMed: 36751516
DOI: 10.1097/CCE.0000000000000860 -
Jornal Brasileiro de Pneumologia :... Oct 2008This article aims to review the physiopathology, diagnosis and treatment of cystic fibrosis-related dyslipidemia (CFD). Bibliographic searches of the Medline and Latin... (Review)
Review
This article aims to review the physiopathology, diagnosis and treatment of cystic fibrosis-related dyslipidemia (CFD). Bibliographic searches of the Medline and Latin American and Caribbean Health Sciences Literature databases were made (year range, 1987-2007), and the most representative papers on the theme were selected. The characteristic symptoms of CFD are hypertriglyceridemia-with or without hypocholesterolemia-and essential fatty acid deficiency. The principal CFD risk factors are pancreatic insufficiency, high-carbohydrate diet, liver diseases, inflammatory state and corticosteroid therapy. There are no specific recommendations regarding screening, which is typically performed based on the diagnosis, and at regular intervals, and more frequently in individuals belonging to high-risk groups. Treatment includes a balanced diet, micronutrient supplementation, and regular physical exercise according to individual tolerance. In the great majority of the cases, CFD-related hypertriglyceridemia does not reach values for which the use of hypolipidemic drugs is indicated. We conclude that there are few articles in the literature regarding the frequency, etiology and management of CFD. Preventive and therapeutic recommendations for hypertriglyceridemia are extrapolated from studies in individuals without cystic fibrosis. Further research is necessary to investigate the association of essential fatty acid deficiency and the physiopathology of cystic fibrosis . Since hypertriglyceridemia is an important risk factor for coronary artery disease, prospective studies will contribute for a better understanding of the natural history of this condition and define how to prevent and treat it.
Topics: Adolescent; Adult; Child; Cholesterol; Cystic Fibrosis; Dietary Fats; Dyslipidemias; Fatty Acids, Essential; Humans; Hypertriglyceridemia; Lipid Metabolism; Reference Values; Triglycerides; Young Adult
PubMed: 19009217
DOI: 10.1590/s1806-37132008001000012