Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects

2021 ◽  
Author(s):  
Graziella E. Ronsein ◽  
Tomas Vaisar ◽  
W. Sean Davidson ◽  
Karin E. Bornfeldt ◽  
Jeffrey L. Probstfield ◽  
...  
Keyword(s):  
Combination Therapy ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Unique Identifier ◽  
Statin Monotherapy ◽  
Phospholipid Transfer ◽  
Low Hdl

Objective: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). Approach and Results: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APO (apolipoprotein) C1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobin-related proteins; P ≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. Conclusions: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00715273; NCT00880178; NCT00120289.

Triglyceride and High-Density Lipoprotein Cholesterol: Predicting Disorders in Parents From Their Children

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 824-831
Author(s):  
Sheldon M. Polonsky ◽  
Loretta A. Simbartl ◽  
Dennis L. Sprecher
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Lipid Disorder ◽  
Lipid Disorders ◽  
Parents And Children ◽  
Low Hdl

Objective. To determine whether lipid disorders can be predicted in parents after such disorders are identified initially in their children. Although this relation has been well determined for children with high cholesterol or low-density lipoprotein cholesterol (LDL-C), it has not been as well described for disorders involving triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C), or their interaction with LDL-C. Methods. Serum lipid values were obtained from 232 families in the comparison population of a large genetics study. Subjects were classified into four groups based on their lipid status: 1) isolated LDL-C disorder, defined by a high LDL-C level and normal TG and HDL-C levels; 2) isolated TG/HDL-C disorder, defined by either high TG, low HDL-C, or both, and normal LDL-C; 3) combined disorder, defined by high LDL-C in addition to either high TG, low HDL-C, or both; and 4) normal, defined by the absence of any of the above disorders. The frequencies of these disorders were noted in both parents and children, and logistic regression analyses were conducted to determine whether the presence of these disorders in at least one child in the family could predict similar disorders in the parents. Results. Children with isolated LDL-C or TG/HDL-C disorder were more likely to have parents with the same disorder as themselves (P = .002 and P = .04, respectively). Children with the combined disorder were more likely to have parents with any lipid disorder (P = .009), but especially isolated LDL-C (P = .002) and isolated TG/HDL-C (P = .05). Conclusion. A classification scheme defining disorders of TG and HDL-C, LDL-C, or a combination can be useful for predicting lipid disorders in parents after such disorders are identified initially in their children.

“Isolated” Low High-Density Lipoprotein Cholesterol

1997 ◽  
Vol 31 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Vickie M Wilt ◽  
John G Gums
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Lifestyle Modification ◽  
Density Lipoprotein ◽  
Additional Treatment ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Estrogen Replacement ◽  
Review Articles ◽  
Low Hdl

OBJECTIVE: To present information on the function, structure, and importance of high-density lipoprotein cholesterol (HDL-C) and to evaluate the current literature regarding the controversy of managing patients with an “isolated” low HDL-C concentration. DATA SOURCE: A MEDLINE search was performed (1966–June 1996) to identify English-language clinical and review articles pertaining to HDL-C. Some articles were identified through the bibliography of selected articles. STUDY SELECTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA EXTRACTION: Important historical lipid studies, recent review articles, and clinical trials involving therapy for HDL-C were evaluated. DATA SYNTHESIS: The structure, function, and measurement of HDL-C and the state of an isolated low HDL-C are discussed for background. Lifestyle modification measures to increase HDL-C, medications to avoid, estrogen replacement, and lipid-altering agents used to raise an isolated low HDL-C are presented. CONCLUSIONS: An isolated low HDL-C concentration poses a risk for coronary heart disease. The management of this state is controversial. The first step in management is in agreement with experts and includes lifestyle modification (e.g., weight reduction, diet, smoking cessation, aerobic exercise). Estrogen replacement therapy and discontinuance of drugs that secondarily lower HDL-C are additional treatment options. The use of lipid-altering agents has been used in some patients. Nicotinic acid appears to be an effective agent for an isolated low HDL-C. A large clinical trial evaluating the effect of treating an isolated low HDL-C for primary and secondary prevention of coronary events is needed.

The influence of ultra-processed food consumption in anthropometric and atherogenic indices of adolescents

2021 ◽  
Vol 34 ◽  
Author(s):  
Larisse Monteles NASCIMENTO ◽  
Nayara Vieira do Nascimento MONTEIRO ◽  
Thiana Magalhães VILAR ◽  
Cyntia Regina Lúcio de Sousa IBIAPINA ◽  
Karoline de Macedo Gonçalves FROTA
Keyword(s):  
High Density Lipoprotein ◽  
Food Consumption ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Processed Foods ◽  
Atherogenic Indices

ABSTRACT Objective To investigate the influence of ultra-processed food consumption on anthropometric and atherogenic indices. Methods A cross-sectional study was conducted with 327 adolescents aged 14 to 19 years. Sociodemographic, anthropometric, biochemical, and food consumption data were evaluated. The ratios of atherogenic indices were calculated using the Castelli I (Total Cholesterol/High Density Lipoprotein Cholesterol), Castelli II (Low Density Lipoprotein Cholesterol/High Density Lipoprotein Cholesterol), and estimated Low Density Lipoprotein Cholesterol particle size (Atherogenic Index of Plasma=Triglycerides/High-Density Lipoprotein Cholesterol) indices. Logistic regression was used for the unadjusted and adjusted analysis between ultra-processed foods consumption, anthropometric, and atherogenic indices. The level of significance was 5%. Results Most participants were female (59.3%). Girls had a higher consumption of ultra-processed foods (26.6% vs. 20.5%). Of the total number of adolescents, 16.5% were overweight and 65.7% were from public schools. Adolescents with altered values for the Castelli I and II Index, and for the Atherogenic Index of Plasma had significantly higher weights, Waist Circumference, Waist Circumference/ Height and Body Mass Index/ Age values. The adjusted analysis identified a significant association (Odds ratio=2.29; 95% Confidence interval: 1.23-4.28) between the high consumption of ultra-processed foods and the Castelli II index. Conclusion The associations between atherogenic indices and anthropometric indices and the consumption of ultra-processed foods highlight the negative influence of these foods on adolescents’ cardiovascular health.

The Effects of Low-Density Lipoprotein and High-Density Lipoprotein on Blood Viscosity Correlate with their Association with Risk of Atherosclerosis in Humans

1997 ◽  
Vol 92 (5) ◽  
pp. 473-479 ◽  
Author(s):  
Gregory D. Sloop ◽  
David W. Garber
Keyword(s):  
High Density Lipoprotein ◽  
Total Cholesterol ◽  
High Density Lipoprotein Cholesterol ◽  
Blood Viscosity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

1. Increased blood or plasma viscosity has been observed in almost all conditions associated with accelerated atherosclerosis. Cognizant of the enlarging body of evidence implicating increased viscosity in atherogenesis, we hypothesize that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis. 2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen, serum viscosity, total cholesterol, high-density lipoprotein-cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol. 3. Low-density lipoprotein-cholesterol was more strongly correlated with blood viscosity than was total cholesterol (r = 0.4149, P = 0.0281, compared with r = 0.2790, P = 0.1505). High-density lipoprotein-cholesterol levels were inversely associated with blood viscosity (r = −0.4018, P = 0.0341). 4. To confirm these effects, viscometry was performed on erythrocytes, suspended in saline, which had been incubated in plasma of various low-density lipoprotein/high-density lipoprotein ratios. Viscosity correlated directly with low-density lipoprotein/high-density lipoprotein ratio (n = 23, r = 0.8561, P < 0.01). 5. Low-density lipoprotein receptor occupancy data suggests that these effects on viscosity are mediated by erythrocyte aggregation. 6. These results demonstrate that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity in healthy subjects correlate with their association with risk of atherosclerosis. These effects on viscosity may play a role in atherogenesis by modulating the dwell or residence time of atherogenic particles in the vicinity of the endothelium.

scholarly journals Fontan‐Associated Dyslipidemia

2021 ◽  
Author(s):  
Adam M. Lubert ◽  
Tarek Alsaied ◽  
Joseph J. Palermo ◽  
Nadeem Anwar ◽  
Elaine M. Urbina ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Fontan Circulation ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Reactive Protein

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, P <0.0001), low‐density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P <0.0001), and high‐density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P <0.0001) than controls. In those with a Fontan, high‐density lipoprotein cholesterol was inversely correlated with body mass index ( r =−0.30, P <0.0001), high‐sensitivity C‐reactive protein ( r =−0.27, P =0.0006), and alanine aminotransferase ( r =−0.18, P =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 [ P =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 [ P =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.

scholarly journals Lipid Profiles in Patients With Ulcerative Colitis Receiving Tofacitinib—Implications for Cardiovascular Risk and Patient Management

2020 ◽  
Author(s):  
Bruce E Sands ◽  
Jean-Frédéric Colombel ◽  
Christina Ha ◽  
Michel Farnier ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Major Adverse Cardiovascular Events ◽  
Lipid Levels

Abstract Background Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms “lipid,” “cholesterol,” “lipoprotein,” “cardiovascular,” “inflammation,” “atherosclerosis,” “tofacitinib,” “rheumatoid arthritis,” “psoriasis,” “inflammatory bowel disease,” “ulcerative colitis,” “hyperlipidemia,” and “guidelines”) and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure). Results In the OLE study, tofacitinib treatment was not associated with major changes from baseline in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol/high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, with lipid levels and ratios generally remaining stable over time. The major adverse cardiovascular events incidence rate was 0.26/100 patient-years (95% confidence interval, 0.11-0.54). Conclusions Lipid levels and ratios remained generally unchanged from baseline in the OLE study after tofacitinib treatment, and major adverse cardiovascular events were infrequent. Long-term studies are ongoing. ClinicalTrials.gov identifiers NCT01465763, NCT01458951, NCT01458574, NCT01470612

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