Fenofibrates and the Prevention of Cardiovascular Risk

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Michael H Davidson
Keyword(s):  
Cardiovascular Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Dyslipidemia ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Chronic Heart Disease ◽  
Ldl Particles ◽  
Chd Risk ◽  
Remnant Lipoproteins

While the primary lipid target for chronic heart disease (CHD) risk management remains low-density lipoprotein (LDL) or ‘bad’ cholesterol, the treatment of elevated triglyceride (TG) is now also recommended. Elevated TG is believed to increase cardiovascular risk because certain TG-rich lipoproteins, called remnant lipoproteins—partially degraded chylomicrons and very low density lipoproteins (VLDL)—are atherogenic. Hypertriglyceridemia, together with low levels of highdensity lipoprotein (HDL) or ‘good’ cholesterol and an increased prevalence of small, dense LDL particles, comprise a triad of lipid risk factors known as atherogenic dyslipidemia.

Triglyceride Management in Cardiovascular Risk Reduction

2005 ◽  
Vol 00 (01) ◽  
pp. 31
Author(s):  
Michael Miller
Keyword(s):  
Metabolic Syndrome ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
The Metabolic Syndrome ◽  
Ldl Particles

Elevated triglycerides are now considered an independent risk factor for coronary heart disease (CHD), even apart from elevated low-density lipoprotein (LDL) cholesterol. While the primary lipid target for CHD risk management remains LDL cholesterol, the treatment of elevated triglycerides is now also recommended. Elevated triglycerides are believed to increase cardiovascular risk because certain triglyceride-rich lipoproteins, called remnant lipoproteins (partially degraded chylomicrons and very-low density lipoproteins (VLDL)), are atherogenic. Hypertri-glyceridemia, together with low levels of high-density lipoprotein (HDL) cholesterol and an increased prevalence of small, dense LDL particles, comprise a triad of lipid risk factors known as atherogenic dyslipidemia.The significance of hypertriglyceridemia as a cardiovascular risk factor is further highlighted by its inclusion as a component of the metabolic syndrome, a cluster of metabolic abnormalities, related to insulin resistance. The other criteria for metabolic syndrome include low HDL cholesterol, central obesity, elevated blood pressure, and abnormal fasting glucose. The metabolic syndrome is recognized as a major risk factor not only for premature CHD but also for type 2 diabetes mellitus.

Familial combined hyperlipidemia: current knowledge about pathophysiology, diagnostics and correction

2021 ◽  
Author(s):  
V. A. Chernyshov
Keyword(s):  
Current Knowledge ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Dyslipidemia ◽  
Low Density ◽  
Omega 3 ◽  
Comorbid Conditions ◽  
Familial Combined Hyperlipidemia ◽  
Very Low Density Lipoproteins ◽  
Nonalcoholic Fatty Liver

The review is devoted to the current knowledge about pathophysiology, diagnostics and correction of familial combined hyperlipidemia (FCHL) that is considered to be the most frequent among primary dyslipidemias in general population (1 — 3 %) as well as among the patients survived after myocardial infarction (20 — 38 %). The current knowledge about genetic characterization of FCHL and its pathophysiology are adduced. FCHL is emphasized to be a heterogenic state and many of genetic determinants are involved in its development. Excessive concentration of apolipoprotein B (ApoB) — containing lipoproteins is shown to be the main biochemical sign of FCHL and hence, the genes of proteins participated in their metabolism could be claimed for genes‑candidates of FCHL. A special attention is paid to the diagnostics of FCHL, the most valuable diagnostic signs of FCHL are emphasized because FCHL is not monogenic disorder and due to its phenotype characterized by high levels of low‑density lipoprotein cholesterol and/or triglyceride (TG), this lipid disorder is not frequently diagnosed. A combination of concentrations of ApoB > 120 mg/dl and TG > 1.5 mmol/l (> 133 mg/dl) with a family history of early cardiovascular debut could be used today for revelation of patients with a probable diagnosis of FCHL. The influence of FCHL on cardiovascular risk (CVR) that is partly realized through its association with metabolic comorbid conditions such as type 2 diabetes mellitus, metabolic syndrome, nonalcoholic fatty liver disease is considered. These comorbid conditions could play a role of etiological causes of cardiovascular disease and could increase a CVR through some common pathophysiological mechanisms such as insulin resistance of muscular and fat tissues and hepatic overproduction of very low‑density lipoproteins. The current approaches to FCHL correction in accordance with acting recommendations are elucidated. They consider its correction to be necessary as a primary atherogenic dyslipidemia and propose to start intervention from the influence on modified factors of CVR (smoking, alcohol consumption, excessive body mass, obesity). Some differential approaches to correction of lipid exchange disorders in FCHL from the beginning of the first line hypolipidemic agent (statin of fibrate) or their combined usage depended on dyslipidemia phenotype revealed during diagnostics of FCHL are discussed. Update combinations of hypolipidemic agents with an addition to statin and fibrate omega‑3 fatty acids, ezetimibe and inhibitors of PCSK9 (alirocumab, evolocumab) from the point of their influence on a reduction of CVR as well as on the components of dyslipidemia phenotype occurred in FCHL are considered.

scholarly journals The Association between Cardiovascular Risk and Elevated Triglycerides

2017 ◽  
Vol 9 (1) ◽  
pp. 17
Author(s):  
Djanggan Sargowo ◽  
Olivia Handayani
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Target Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Atherogenic Dyslipidemia ◽  
Low Density ◽  
Lipid Management

BACKGROUND: The association between elevated triglycerides and cardiovascular risk has been extensively studied. The elevated level of triglycerides occurs through abnormalities in hepatic very low-density lipoprotein (VLDL) production and intestinal chylomicron synthesis, dysfunctional lipoprotein lipase (LPL)-mediated lipolysis or impaired remnant clearance.CONTENT: Hypertriglyceridemia (HTG) commonly leads to a reduction in high-density lipoprotein (HDL) and increase in atherogenic small dense low-density lipoprotein (LDL) cholesterol, called the atherogenic dyslipidemia (AD). Triglycerides may also stimulate atherogenesis by mechanisms, such excessive release of free fatty acids, and production of pro-inflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia (HTG) and high concentration of triglyceride-rich lipoprotein (TRL) as causal risk factors for cardiovascular disease. Therefore, lipid management is crucial in reducing cardiovascular risk. Combination of lipid lowering drug therapy may be needed to achieve both LDL and non-HDL cholesterols treatment goal for cardiovascular disease prevention in patients with elevated triglyceride levels, particularly those with triglyceride ≥500 mg/dL.SUMMARY: LDL and non-HDL cholesterol can be a promising target therapy in HTG. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients.KEYWORDS: hypertriglyceridemia, non-HDL cholesterol, dyslipidemia, CV risk

Discordantly Elevated Apolipoprotein B versus Low-Density Lipoprotein Cholesterol is Associated with Remnant Lipoproteins and Increased Cardiovascular Events

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Paola Ramos ◽  
Leslie Donato ◽  
Linnea Baudhuin ◽  
Vlad Vasile ◽  
Allan Jaffe ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Superior Performance ◽  
Lipid Lowering ◽  
Low Density ◽  
Discovery Cohort ◽  
Ldl Particles ◽  
Remnant Lipoproteins

Abstract Atherosclerotic cardiovascular disease is a result of low-density lipoprotein (LDL) particles becoming trapped in arterial walls and forming plaques which ultimately restrict blood-flow. LDL cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of plaque-causing LDL particles. Both have been shown to predict major adverse cardiac events (MACE). ApoB is also carried on remnant lipoproteins (RLP). RLP-cholesterol (RLP-C) is increasingly appreciated as a MACE risk-factor. This study aimed to define discordances between apoB and LDL-C in a large data set from a clinical reference laboratory. We then applied this definition to evaluate which measure predicted the risk of MACE in a patient cohort referred for coronary angiography with >10 years follow-up. LDL-C was measured by beta-quantification and RLP-C was defined as total cholesterol – LDL-C – HDL-C. Apo B discordance relative to LDL-C was determined by linear regression in a discovery cohort (n=17,203) using beta quantification. Discordance was defined by quartiles of the residual-apoB (expected–actual); discordant-low (<25th percentile), concordant (25th to 75th percentile) and discordant-high (>75th percentile). Associations with prevalence and incident of MACE were evaluated by odds-ratio and logistic regression. Risk of MACE was calculated based on the apoB-discordance and reported MACE events by several years follow up in a separate cohort (n=501). In the discovery cohort, age ranged from 18-95 years, 51% were female and mean (±SD) lipid values were: ApoB: 100.4 ± 30.0mg/dl, LDL-C: 121.7 ± 47.9mg/dl, and RLP-C: 17.2 ± 26.9mg/dl. Expected-apoB was described by the formula: (LDL-c X 0.6278 + 24.07, R=0.88). Residual-apoB (discordance) ranged from -1037 to 581.2 with a mean 0.01±18.6, and notably increased with triglyceride concentration (rho=0.65) and with RLP-C (rho=0.64), but was minimally influenced by apoB (rho=0.35) and LDL-C (rho=0.009) (p<0.001 all cases). In the clinical follow-up cohort, age ranged from 26-77 years, 42% were female, 64% were current/former smokers, and 28% were on lipid-lowering therapy. Mean (±SD) lipids were: apoB: 97.8 ± 20.9mg/dl, LDL-C: 124.6 ± 36.6mg/dl, and RLP-C: 34.9 ± 25.6mg/dl. Serum triglycerides among subjects discordant-low apoB, concordant and discordant-high apoB were 148mg/dL, 157mg/dL and 238mg/dL, respectively; similarly for RLP-C. A total of 192 events occurred during a mean of 9 years follow-up. Subjects with discordantly elevated apoB had a significantly higher incidence of MACE compared to those with concordant values (47% vs. 36%, p=0.03). There was no difference in MACE for subjects with discordantly low apoB (35% vs. 36%). These data support previous reports of an association between apoB and LDL-C and the superior performance of apoB when discordantly elevated. Our data expand on previous studies by applying an externally defined threshold for discordant-apoB. Our data indicate that triglycerides, RLP-C are associated with discordances and MACE.

scholarly journals The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 782
Author(s):  
Anni Kumari ◽  
Kristian K. Kristensen ◽  
Michael Ploug ◽  
Anne-Marie Lund Winther
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Lipoprotein Lipase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Remnant Lipoproteins ◽  
Atherosclerosis Development

Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating the intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to the accumulation of chylomicrons and very low-density lipoproteins (VLDL) in plasma, resulting in hypertriglyceridemia. While low-density lipoprotein cholesterol (LDL-C) is recognized as a primary risk factor for atherosclerosis, hypertriglyceridemia has been shown to be an independent risk factor for cardiovascular disease (CVD) and a residual risk factor in Atherosclerosis development. In this review, we focus on the lipolysis machinery and discuss the potential role of triglycerides, remnant particles, and lipolysis mediators in the onset and progression of Atherosclerotic cardiovascular disease (ASCVD). This review details a number of important factors involved in the maturation and transportation of LPL to the capillaries, where the triglycerides are hydrolyzed, generating remnant lipoproteins. Moreover, LPL and other factors involved in intravascular lipolysis are also reported to impact the clearance of remnant lipoproteins from plasma and promote lipoprotein retention in capillaries. Apolipoproteins (Apo) and angiopoietin-like proteins (ANGPTLs) play a crucial role in regulating LPL activity and recent insights into LPL regulation may elucidate new pharmacological means to address the challenge of hypertriglyceridemia in Atherosclerosis development.

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

scholarly journals The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis

Spinal Cord ◽  
2021 ◽  
Author(s):  
Peter Francis Raguindin ◽  
Gion Fränkl ◽  
Oche Adam Itodo ◽  
Alessandro Bertolo ◽  
Ramona Maria Zeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Blood Pressure ◽  
Spinal Cord ◽  
Cardiovascular Risk ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Cord Injury

Abstract Study design Systematic review and meta-analysis. Objective To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). Methods We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). Results We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, −14.5 mmHg, 95% CI −19.2, −9.9; −7.0 mmHg 95% CI −9.2, −4.8, respectively), lower triglycerides (−10.9 mg/dL, 95% CI −19.7, −2.1), total cholesterol (−9.9 mg/dL, 95% CI −14.5, −5.4), high-density lipoprotein (−1.7 mg/dL, 95% CI −3.3, −0.2) and low-density lipoprotein (−5.8 mg/dL, 95% CI −9.0, −2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (−10.3 mmHg, 95% CI −13.4, −7.1; −5.3 mmHg 95% CI −7.5, −3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. Conclusion In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

scholarly journals Aggregation Susceptibility of Low-Density Lipoproteins—A Novel Modifiable Biomarker of Cardiovascular Risk

2021 ◽  
Vol 10 (8) ◽  
pp. 1769
Author(s):  
Katariina Öörni ◽  
Petri T. Kovanen
Keyword(s):  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Cholesterol Crystals ◽  
Ldl Particles ◽  
Arterial Intima ◽  
Matrix Bound ◽  
Atherosclerotic Cardiovascular Diseases

Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.

scholarly journals Long-term fasting improves lipoprotein-associated atherogenic risk in humans

2021 ◽  
Author(s):  
Franziska Grundler ◽  
Dietmar Plonné ◽  
Robin Mesnage ◽  
Diethard Müller ◽  
Cesare R. Sirtori ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Health Concern ◽  
Low Density ◽  
Lipoprotein Subclasses ◽  
Ldl Particles ◽  
Increased Risk

Abstract Purpose Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. Methods This observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. Results The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. Conclusion Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. Trial Registration Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 “retrospectively registered”.

scholarly journals Detection of the low-density-lipoprotein receptor with biotin-low-density lipoprotein. A rapid new method for ligand blotting

1985 ◽  
Vol 229 (3) ◽  
pp. 785-790 ◽  
Author(s):  
D P Wade ◽  
B L Knight ◽  
A K Soutar
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Receptor Protein ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Cell Extracts ◽  
Density Lipoprotein Receptor ◽  
A New Technique

A new technique has been developed to identify low-density-lipoprotein (LDL) receptors on nitrocellulose membranes, after transfer from SDS/polyacrylamide gels, by ligand blotting with biotin-modified LDL. Modification with biotin hydrazide of periodate-oxidized lipoprotein sugar residues does not affect the ability of the lipoprotein to bind to the LDL receptor. Bound lipoprotein is detected with high sensitivity by a streptavidin-biotin-peroxidase complex, and thus this method eliminates the need for specific antibodies directed against the ligand. The density of the bands obtained is proportional to the amount of pure LDL receptor protein applied to the SDS/polyacrylamide gel, so that it is possible to quantify LDL receptor protein in cell extracts. Biotin can be attached to other lipoproteins, for example very-low-density lipoproteins with beta-mobility, and thus the method will be useful in the identification and isolation of other lipoprotein receptors.

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