Phenotype vs. genotype in severe familial hypercholesterolemia: what matters most for the clinician?

Abstract:

PURPOSE OF REVIEW:Familial hypercholesterolemia is associated with a high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). However, this risk is variable. This review evaluates recent evidence related to ASCVD risk stratification in familial hypercholesterolemia considering aspects of phenotype and genotype. RECENT FINDINGS:The heterogeneity in clinical, laboratory characteristics, and in ASCVD risk in both homozygous and heterozygous familial hypercholesterolemia individuals in part can be attributed to the type of molecular defect. In most individuals with LDL cholesterol more than 190 mg/dl, a familial hypercholesterolemia-causing variant is not encountered, however, when present, a variant implicates an even higher ASCVD risk for such individuals. Previous ASCVD events, elevated blood lipoprotein(a), cutaneous markers of cholesterol deposit are among other factors that indicate a higher ASCVD risk in familial hypercholesterolemia individuals underlying a more severe form of the phenotype. SUMMARY:Both clinical and genetic parameters help identify higher ASCVD risk among severe familial hypercholesterolemia individuals.

journal_name

Curr Opin Lipidol

authors

Santos RD

doi

10.1097/MOL.0000000000000391

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

130-135

issue

2

eissn

0957-9672

issn

1473-6535

journal_volume

28

pub_type

杂志文章,评审
  • Lifetime risk: does it help to decide who gets statins and when?

    abstract:PURPOSE OF REVIEW:The new risk-based guidelines on blood cholesterol treatment from the American College of Cardiology and the American Heart Association reflect the now widespread international agreement that lipid-lowering treatment decisions should be based primarily on individuals' predicted cardiovascular disease ...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000089

    authors: Jackson R

    更新日期:2014-08-01 00:00:00

  • Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.

    abstract:PURPOSE OF REVIEW:Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章

    doi:10.1097/MOL.0000000000000663

    authors: Welty FK

    更新日期:2020-04-01 00:00:00

  • n-3 polyunsaturated fatty acids and human cytokine synthesis.

    abstract::The cytokines interleukin-1 and tumor necrosis factor contribute to the pathogenesis of inflammatory diseases and, potentially, to atherogenesis. The synthesis of these cytokines in humans can be suppressed by oral intake of n-3 polyunsaturated fatty acids. This mechanism may contribute to the beneficial effect of lon...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-199602000-00011

    authors: Endres S,von Schacky C

    更新日期:1996-02-01 00:00:00

  • The ever-expanding saga of the proprotein convertases and their roles in body homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9 functions and regulation.

    abstract:PURPOSE OF REVIEW:The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concent...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000484

    authors: Seidah NG,Chrétien M,Mbikay M

    更新日期:2018-04-01 00:00:00

  • How do microRNAs affect vascular smooth muscle cell biology?

    abstract:PURPOSE OF REVIEW:Control of vascular smooth muscle cell (VSMC) phenotype is essential in the development and maintenance of a healthy vasculature. Acquisition of a synthetic, proproliferative phenotype by VSMCs following vascular insult is central to neointimal formation and the development of vascular pathology. Micr...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e32835719a1

    authors: Robinson HC,Baker AH

    更新日期:2012-10-01 00:00:00

  • Role of sortilin in lipid metabolism.

    abstract:PURPOSE OF REVIEW:Sortilin, encoded SORT1 gene at chromosome 1p13.3, is a multiligand receptor that traffics protein from the Golgi to the endosomes, secretory vesicles, and the cell surface. Genome-wide association studies (GWAS) revealed an association between sortilin and reduced plasma LDL-cholesterol (LDL-C) as we...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000598

    authors: Conlon DM

    更新日期:2019-06-01 00:00:00

  • What have we learnt from the clinical outcomes trials with the cetrapibs?

    abstract:PURPOSE OF REVIEW:The current review considers what we have learnt from the clinical outcome trials with the cetrapibs; the inhibitors of cholesteryl ester transfer protein that increase HDL cholesterol levels; torcetrapib, dalcetrapib, evacetrapib and anacetrapib. RECENT FINDINGS:Although an off-target increase in bl...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000518

    authors: Doggrell SA

    更新日期:2018-08-01 00:00:00

  • Is oxidized low-density lipoprotein present in vivo?

    abstract::Basic research has provided strong evidence that oxidation of LDL plays an important role in the pathogenesis of atherosclerosis. Several mechanisms have been identified which can lead to LDL oxidation in vivo. Clinical and epidemiological studies have provided circumstantial evidence that oxidized LDL, as measured by...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-199808000-00009

    authors: Ylä-Herttuala S

    更新日期:1998-08-01 00:00:00

  • Fatty acids, hyperinsulinemia, and insulin resistance: which comes first?

    abstract::The inhibiting effect of insulin on the mobilization of free fatty acids (FFA) from adipose tissue is halted in prevalent conditions with systemic insulin resistance. The nature and cause of this perturbation are unknown, but steroid hormones may be involved. The consequence is the creation or amplification of insulin...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-199405030-00003

    authors: Björntorp P

    更新日期:1994-06-01 00:00:00

  • Novel benefits of peroxisome proliferator-activated receptors on cardiovascular risk.

    abstract:PURPOSE OF REVIEW:This review provides an overview of newly described mechanisms by which peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ) regulate several factors associated with cardiovascular risk. RECENT FINDINGS:PPAR agonists have known effects on plasma lipoprotein levels, inflammation, and insu...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e3283613a7d

    authors: Millar JS

    更新日期:2013-06-01 00:00:00

  • Adipose tissue failure and mitochondria as a possible target for improvement by bioactive food components.

    abstract:PURPOSE OF REVIEW:Adipose tissue is an essential, highly dynamic and metabolically active tissue that vigorously communicates to support its primary function: the storage of lipids. It performs this function to secure energy supply and prevent lipotoxicity. Adipose tissue is essential for maintaining a healthy glucose ...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e3282f39f95

    authors: Keijer J,van Schothorst EM

    更新日期:2008-02-01 00:00:00

  • Dysbetalipoproteinemia: an extreme disorder of remnant metabolism.

    abstract:PURPOSE OF REVIEW:Lipoprotein metabolism and the role of apolipoprotein E in the pathogenesis of dysbetalipoproteinemia. RECENT FINDINGS:Remnant lipoproteins, modulated by lifestyle and genetic factors, are atherogenic. Dysbetalipoproteinemia could be viewed as a monogenic disorder of remnant metabolism. SUMMARY:Elev...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000192

    authors: Marais D

    更新日期:2015-08-01 00:00:00

  • HDL infusion for the management of atherosclerosis: current developments and new directions.

    abstract:PURPOSE OF REVIEW:Because human genetic studies and large clinical trials have demonstrated that HDL-cholesterol levels are not causally related to cardiovascular disease risk, attention has shifted toward the functional properties of HDL. Infusion of HDL mimetics containing apolipoprotein A-I remains a potential strat...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000349

    authors: Zheng KH,Stroes ES

    更新日期:2016-12-01 00:00:00

  • Metabolic and health effects of isomeric fatty acids.

    abstract:PURPOSE OF REVIEW:Isomeric fatty acids have the same number of carbon and hydrogen atoms, but may have distinct metabolic and health effects. Two well-known examples of isomeric fatty acids are cis and trans monounsaturated fatty acids, and conjugated isomers of linoleic acid (CLA). The purpose of this review is to sum...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-200502000-00006

    authors: Mensink RP

    更新日期:2005-02-01 00:00:00

  • Cholesterol efflux capacity, macrophage reverse cholesterol transport and cardioprotective HDL.

    abstract:PURPOSE OF REVIEW:Randomized clinical trials provide strong evidence that pharmacological elevation of HDL-cholesterol (HDL-C) fails to reduce cardiovascular disease (CVD) risk in statin-treated humans. It is thus critical to identify new metrics that capture HDL's cardioprotective effects. RECENT FINDINGS:We review r...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000209

    authors: Hutchins PM,Heinecke JW

    更新日期:2015-10-01 00:00:00

  • Transcriptional regulatory mechanisms of the human apolipoprotein genes in vitro and in vivo.

    abstract::The present review summarizes recent advances in the transcriptional regulation of the human apolipoprotein genes, focusing mostly, but not exclusively, on in-vivo studies and signaling mechanisms that affect apolipoprotein gene transcription. An attempt is made to explain how interactions of transcription factors tha...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-200104000-00012

    authors: Zannis VI,Kan HY,Kritis A,Zanni EE,Kardassis D

    更新日期:2001-04-01 00:00:00

  • Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans.

    abstract:PURPOSE OF REVIEW:Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antio...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e32835a4f40

    authors: Saito M,Yoneshiro T

    更新日期:2013-02-01 00:00:00

  • Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders.

    abstract:PURPOSE OF REVIEW:To examine the role of gut microbiota in the regulation of host energy homeostasis and its role in the pathogenesis of obesity, diabetes and nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS:Experimental models highlight several mechanisms connecting gut microbiota to host energy metabolism: ...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e3283347ebb

    authors: Musso G,Gambino R,Cassader M

    更新日期:2010-02-01 00:00:00

  • Cardiovascular risk factors in inflammatory arthritis.

    abstract:PURPOSE OF REVIEW:To assess factors that promote atherogenesis and cardiovascular disease (CVD) in rheumatoid arthritis (RA). Also, to determine how control of inflammation with conventional and biological antirheumatic drugs affects cardiovascular risk. RECENT FINDINGS:An excess risk of CVD occurs early in the RA dis...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e3283488c50

    authors: Mirjafari H,Al-Husain A,Bruce IN

    更新日期:2011-08-01 00:00:00

  • Dietary monounsaturated versus polyunsaturated fatty acids: which is really better for protection from coronary heart disease?

    abstract:PURPOSE OF REVIEW:The purpose is to evaluate recent findings concerning dietary fats and the risk of coronary heart disease. Monounsaturated fatty acids are often regarded as healthy, and many have recommended their consumption instead of saturated fatty acids and polyunsaturated fatty acids. Support for the benefits o...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-200302000-00008

    authors: Lada AT,Rudel LL

    更新日期:2003-02-01 00:00:00

  • Estrogens, lipoproteins, and cardiovascular risk factors: an update following the randomized placebo-controlled trials of hormone-replacement therapy.

    abstract:PURPOSE OF REVIEW:The effects of hormone-replacement therapy on cardiovascular risk factors are examined. In an attempt to explain the results of recent randomized controlled trials in which no benefit of hormone-replacement therapy for postmenopausal women has been observed, RECENT FINDINGS:Changes in lipoproteins in...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/01.mol.0000137231.84772.80

    authors: Seed M,Knopp RH

    更新日期:2004-08-01 00:00:00

  • Hyperlipidaemia associated with genetic variation in the apolipoprotein B gene.

    abstract::Common variants at the apolipoprotein B gene locus are associated with hyperlipidaemia, but conflicting data have been presented in the literature concerning the size of the effects and which polymorphisms give the best signal in the different groups of individuals studied. In this review, we will present a critique o...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-199508000-00005

    authors: Humphries SE,Talmud PJ

    更新日期:1995-08-01 00:00:00

  • The future of imaging in cardiovascular disease intervention trials: 2017 and beyond.

    abstract:PURPOSE OF REVIEW:As our understanding of cardiovascular disease has advanced over the past decades, multiple novel treatment strategies have been developed with the hope of reducing the global morbidity and mortality associated with this condition. Large-scale trials to test such novel therapies using clinical end poi...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000350

    authors: Doris MK,Dweck MR,Fayad ZA

    更新日期:2016-12-01 00:00:00

  • Impact drugs targeting cardiometabolic risk on the gut microbiota.

    abstract:PURPOSE OF REVIEW:Alterations in the gut microbiome composition or function are associated with risk factors for cardiometabolic diseases, including hypertension, hyperlipidemia and hyperglycemia. Based on recent evidence that also oral medications used to treat these conditions could alter the gut microbiome compositi...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章

    doi:10.1097/MOL.0000000000000727

    authors: Balvers M,van den Born BH,Levin E,Nieuwdorp M

    更新日期:2021-02-01 00:00:00

  • Understanding coronary heart disease as a consequence of defective regulation of apolipoprotein B metabolism.

    abstract::Further understanding of the causative link between plasma lipids and coronary heart disease will come from a deeper appreciation of the impact of lipoprotein heterogeneity on the processes of atherosclerosis and thrombosis. It is now widely appreciated that remnants of triglyceride-rich lipoproteins, IDL and specific...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-199906000-00006

    authors: Packard CJ

    更新日期:1999-06-01 00:00:00

  • Recent insights into factors affecting remnant lipoprotein uptake.

    abstract:PURPOSE OF REVIEW:Remnant lipoproteins that persist in the bloodstream after each meal have become increasingly important contributors to atherosclerotic vascular disease, owing to the spread of overnutrition, underexertion, obesity, insulin resistance, and type 2 diabetes. Here, we review recent work that clarified lo...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0b013e328338cabc

    authors: Williams KJ,Chen K

    更新日期:2010-06-01 00:00:00

  • Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism.

    abstract:PURPOSE OF REVIEW:The aim of this review is to summarize and discuss recent advances in the understanding of the physiological role of lipoprotein lipase in lipid and energy metabolism. RECENT FINDINGS:Studies on the transcriptional and the posttranscriptional level of lipoprotein lipase expression have provided new i...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/00041433-200210000-00002

    authors: Preiss-Landl K,Zimmermann R,Hämmerle G,Zechner R

    更新日期:2002-10-01 00:00:00

  • The role of registries and genetic databases in familial hypercholesterolemia.

    abstract:PURPOSE OF REVIEW:To review how leveraging familial hypercholesterolemia registries can impact molecular genetic research and precision medicine. RECENT FINDINGS:Familial hypercholesterolemia is both much more common and more phenotypically heterogeneous than previously thought with some evidence for significant genot...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000398

    authors: Kindt I,Mata P,Knowles JW

    更新日期:2017-04-01 00:00:00

  • n-3 Fatty acid supplementation and proresolving mediators of inflammation.

    abstract:PURPOSE OF REVIEW:The review presents recent developments in the identification of specialized proresolving mediators (SPMs) of inflammation following supplementation with n-3 fatty acids in humans. RECENT FINDINGS:A number of reports have measured SPMs in human plasma after n-3 fatty acid supplementation. Although st...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审

    doi:10.1097/MOL.0000000000000262

    authors: Barden AE,Mas E,Mori TA

    更新日期:2016-02-01 00:00:00

  • Unstable coronary plaques and cardiac events in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits: questions and quandaries.

    abstract:PURPOSE OF REVIEW:Use of suitable animal models is essential for investigation of the mechanisms underlying cardiac events and development of the therapeutic strategies; however, ideal animal models that can recapitulate human coronary atherosclerosis and subsequent acute myocardial infarction are still lacking. In thi...

    journal_title:Current opinion in lipidology

    pub_type: 社论,评审

    doi:10.1097/MOL.0b013e3283189c18

    authors: Shiomi M,Fan J

    更新日期:2008-12-01 00:00:00