Discordance of Low-Density Lipoprotein and High-Density Lipoprotein Cholesterol Particle Versus Cholesterol Concentration for the Prediction of Cardiovascular Disease in Patients With Metabolic Syndrome and Diabetes Mellitus (from the Multi-Ethnic Study of Atherosclerosis [MESA])

Metabolic Syndrome and Related Disorders

McKenzie²,

Kränkel

et al. 2020

103

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.

Section: Insulin Resistance/compensatory Hyperinsulinemia/prediabetesmentioning

confidence: 99%

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Metabolic Syndrome and Related Disorders

McKenzie²,

Kränkel

et al. 2020

103

“…The best example of this is the use of nuclear magnetic resonance (NMR) spectroscopy for measuring HDL particle number, which has been shown in several large studies to be superior to HDL-C in predicting future cardiovascular events (4,183,184 ). NMR can also be used to quantify specific HDL subfractions, such as apoB-containing lipoproteins, as well as LDL and HDL particle size and distribution, which may also be predictive of increased mortality in a wide range of disease states (185)(186)(187)(188)(189)(190). Correlations between specific HDL subfractions particle concentration and other cardiovascular measures have also been identified using NMR.…”

Section: Hdl Assays Based On Physical Propertiesmentioning

confidence: 99%

The Changing Face of HDL and the Best Way to Measure It

Karathanasis¹,

Freeman

Gordon

et al. 2017

Clinical Chemistry

BACKGROUND: HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests. CONTENT:This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.

“…Daraus ergibt sich ein erhöhter hepatischer Output triglyzeridreicher VLDL-Partikel, welcher zu einer Reihe von proatherogenen Veränderungen im Lipoproteinprofil führt: ▪ erhöhte Triglyzeride ▪ erniedrigtes HDL-C ▪ ungünstige LDL-Partikelqualität (sdLDL) ▪ erhöhte Anzahl ApoB-haltiger Lipoproteine (≈LDL-P) [40] Die LDL-Cholesterinkonzentration (LDL-C) erfasst weder die qualitativen Veränderungen im Lipoproteinprofil, noch spiegelt sie per se die Anzahl ApoB-haltiger Lipoproteine (≈LDL-P) wider. Denn eine Konkordanz von LDL-C und LDL-P ist bei Insulinresistenzund somit bei weiten Teilen der Bevölkerungnicht gegeben [41]. Die Anzahl ApoB-haltiger Lipoproteine (≈LDL-P) ist somit, verglichen mit dem Cholesteringehalt in den Partikeln (LDL-C), der aussagekräftigere Lipidmarker für das kardiovaskuläre Risiko [42].…”

Section: Atherogene Dyslipidämieunclassified

Ernährungsempfehlungen beim metabolisch-vaskulären Syndrom

Erickson

et al. 2018

Aktuel Ernahrungsmed

Cardiovascular disease is the number one cause of death globally. Poor diet constitutes a key factor in the initiation and progression of cardiovascular disease and has become the leading risk factor for disability and death worldwide. Therefore, addressing suboptimal nutrition is of key prognostic relevance in primary and secondary prevention of metabolic vascular syndrome. Metabolic vascular syndrome is a multidimensional network of acquired cardiometabolic risk factors closely related to insulin resistance (IR) and compensatory hyperinsulinemia. IR, being the underlying cause of metabolic vascular syndrome and certain types of cancer, should attract the attention of every clinician. As changes in lipoprotein metabolism are one of the earliest indicators of metabolic dysfunction, a relevant biomarker for identifying individuals with IR is the TAG/HDL-C ratio. Hyperinsulinemia ? and concomitant metabolic vascular risk ? can be effectively treated by lifestyle intervention. If IR is present, dietary carbohydrate restriction has consistently been shown to be superior to dietary fat restriction in reversing metabolic dysfunction. The beneficial effects of carbohydrate restricted diets on metabolic vascular risk are independent of BMI ? diet quality therefore confers patient benefit beyond weight reduction. Targeting IR with a low glycemic load, real food diet will reduce overall energy density and will improve all risk factors of metabolic vascular syndrome. In particular, replacing refined carbohydrates with healthy fats in the context of a Mediterranean style-, low carbohydrate and calorie-unrestricted dietary pattern has been shown to significantly reduce burden of metabolic vascular disease. The effect of single nutrients on isolated lipid surrogate markers such as LDL-C does not capture their global effect on metabolic vascular risk.