scholarly journals Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6862
Author(s):  
William Hancock-Cerutti ◽  
John S. Millar ◽  
Silvia Valentini ◽  
Jason Liu ◽  
Jeffrey T. Billheimer ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cholesterol Efflux ◽  
Ex Vivo ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Fractional Clearance ◽  
Artery Disease ◽  
Pool Sizes

High-density lipoprotein cholesterol (HDL-C) is thought to be atheroprotective yet some patients with elevated HDL-C levels develop cardiovascular disease, possibly due to the presence of dysfunctional HDL. We aimed to assess the metabolic fate of circulating HDL particles in patients with high HDL-C with and without coronary artery disease (CAD) using in vivo dual labeling of its cholesterol and protein moieties. We measured HDL apolipoprotein (apo) A-I, apoA-II, free cholesterol (FC), and cholesteryl ester (CE) kinetics using stable isotope-labeled tracers (D3-leucine and 13C2-acetate) as well as ex vivo cholesterol efflux to HDL in subjects with (n = 6) and without (n = 6) CAD that had HDL-C levels >90th percentile. Healthy controls with HDL-C within the normal range (n = 6) who underwent the same procedures were used as the reference. Subjects with high HDL-C with and without CAD had similar plasma lipid levels and similar apoA-I, apoA-II, HDL FC, and CE pool sizes with no significant differences in fractional clearance rates (FCRs) or production rates (PRs) of these components between groups. Subjects with high HDL-C with and without CAD also had similar basal and cAMP-stimulated ex vivo cholesterol efflux to HDL. When all subjects were considered (n = 18), unstimulated non-ABCA1-mediated efflux (but not ABCA1-specific efflux) was correlated positively with apoA-I production (r = 0.552, p = 0.017) and HDL FC and CE pool sizes, and negatively with the fractional clearance rate of FC (r = −0.759, p = 4.1 × 10−4) and CE (r = −0.652, p = 4.57 × 10−3). Our data are consistent with the concept that ex vivo non-ABCA1 efflux capacity may correlate with slower in vivo turnover of HDL cholesterol moieties. The use of a dual labeling protocol provided for the first time the opportunity to assess the association of ex vivo cholesterol efflux capacity with in vivo HDL cholesterol metabolic parameters.

scholarly journals LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of the Anti-EL (Endothelial Lipase) Antibody MEDI5884 in Patients With Stable Coronary Artery Disease

2021 ◽  
Author(s):  
Christian T. Ruff ◽  
Michael J. Koren ◽  
Joseph Grimsby ◽  
Anton I. Rosenbaum ◽  
Xiao Tu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Statin Therapy ◽  
High Intensity ◽  
Cholesterol Efflux ◽  
Stable Coronary Artery Disease ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Endothelial Lipase ◽  
Artery Disease

Objective: Functional HDL (high-density lipoprotein) particles that facilitate cholesterol efflux may be cardioprotective. EL (endothelial lipase) hydrolyzes phospholipids promoting catabolism of HDL and subsequent renal excretion. MEDI5884 is a selective, humanized, monoclonal, EL-neutralizing antibody. We sought to determine the safety, pharmacokinetics, and pharmacodynamic effects of multiple doses of MEDI5884 in patients with stable coronary artery disease. Approach and Results: LEGACY was a phase 2a, double-blind, placebo-controlled, parallel-design trial that randomized 132 patients with stable coronary artery disease receiving high-intensity statin therapy to 3 monthly doses of 1 of 5 dose levels of MEDI5884 (50, 100, 200, 350, or 500 mg SC) or matching placebo. The primary end point was the safety and tolerability of MEDI5884 through the end of the study (day 151). Additional end points included change in HDL cholesterol and cholesterol efflux from baseline to day 91, hepatic uptake of cholesterol at day 91, changes in various other lipid parameters. The incidence of adverse events was similar between the placebo and MEDI5884 groups. In a dose-dependent manner, MEDI5884 increased HDL cholesterol up to 51.4% ( P <0.0001) and global cholesterol efflux up to 26.2% ([95% CI, 14.3–38.0] P <0.0001). MEDI5884 increased HDL particle number up to 14.4%. At the highest dose tested, an increase in LDL (low-density lipoprotein) cholesterol up to 28.7% ( P <0.0001) and apoB (apolipoprotein B) up to 13.1% ( P =0.04) was observed with MEDI5884. However, at the potential target doses for future studies, there was no meaningful increase in LDL cholesterol or apoB. Conclusions: Inhibition of EL by MEDI5884 increases the quantity and quality of functional HDL in patients with stable coronary artery disease on high-intensity statin therapy without an adverse safety signal at the likely dose to be used. These data support further clinical investigation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03351738.

scholarly journals AGE RELATED DIFFERENCE IN THE LIPID PROFILE IN NORMAL HEALTHY WOMEN

2014 ◽  
Vol 04 (02) ◽  
pp. 094-097
Author(s):  
Deepti G. I. ◽  
Sukanya Shetty ◽  
Ashalatha V. Rao ◽  
Sarfraz Ahmad
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
Hdl Cholesterol ◽  
Cvd Risk ◽  
Lipid Disorder ◽  
Age Related ◽  
Artery Disease

Abstract: Background and objectives: Lipid disorder is a major risk factor for the progression of coronary artery disease. Age alone is a significant predictor of CVD risk in men and women. Before menopause, women have a much lower risk for cardiovascular events compared with men of their age. Reasons for protection from CVD in premenopausal women are complex, but a significant contribution can be assigned to the greater high-density lipoprotein (HDL) levels in younger women, which is an effect of estrogen. Methods: Fasting blood samples were collected from 40 healthy individuals (40 females divided into 2 groups according to age). Serum total cholesterol, triglycerides, and HDL- Cholesterol were estimated by enzymatic methods and LDL was calculated by Friedewald's equation. Results: The result showed increase in jyounger age group. Conclusion: It can be concluded that serum lipid profile changes can possibly be mediated by changing hormonal profile, especially estrogen which has role in lipid metabolism and indirectly on coronary artery disease.

scholarly journals Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

2013 ◽  
Vol 35 ◽  
pp. 97-103 ◽  
Author(s):  
Chiyan Zhou ◽  
Jia Cao ◽  
Liang Shang ◽  
Chuanfeng Tong ◽  
Hanling Hu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Control Group ◽  
Potential Biomarker ◽  
Artery Disease

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/−mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS  ≤ 40) (P<0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r=-0.393,P<0.001). PON1 activity may be a potential biomarker for the severity of CAD.

scholarly journals Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes

2000 ◽  
Vol 106 (10) ◽  
pp. 1263-1270 ◽  
Author(s):  
Susanne M. Clee ◽  
John J.P. Kastelein ◽  
Marjel van Dam ◽  
Michel Marcil ◽  
Kirsten Roomp ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Cholesterol Levels ◽  
Artery Disease

Intravascular Ultrasound Data and Results of Serum Biochemical Indices at the Time of Stenting and after Six Months in Patients with Coronary Artery Disease

Pteridines ◽  
2006 ◽  
Vol 17 (3) ◽  
pp. 95-99
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Andrejs Erglis
Keyword(s):  
Coronary Artery Disease ◽  
Lipid Metabolism ◽  
Coronary Artery ◽  
Intravascular Ultrasound ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipoprotein Cholesterol ◽  
Artery Disease ◽  
Biochemical Indices

Abstract Thirty healthy individuals and 23 patients with coronary artery disease (CAD) verfied by coronary angiography were examined at the time of stenting and 6 months after percutaneous transluminal coronary angioplasty (PTCA) followed by intravascular ultrasound ( IVUS)-guided stenting and treatment with statins. Analysis of IVUS volumetric measurement for all stented segments after 6 months showed a small but significant decrease of mean minimal square area (18.39%), mean minimal lumen diameter ( 12.77%), and mean minimal lumen volume (12.66%), if compared with values obtained at the time of stenting. Before stenting we observed an increase of serum triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-cholesterol) concentrations, cholesterol to phospholipid ratio and the percentage of saturated fatty acids in phospholipids, while serum high density lipoprotein cholesterol (HDL-cholesterol) and phospholipids concentrations as well as the percentage of unsaturated fatty acid in phospholipids were lowered. Six months after stenting and treatment with statins a significant increase of HDL-cholesterol was found, while other indices of lipids mentioned above remained unchanged. Before stenting we have also observed increased scrum concentration of C'-reactive protein (CRP), neopterin, total homocysteine, and kynurenine concentrations, while pyridoxal-5-phosphate (P-5-P) concentration was lowered. Six months after stenting and treatment with statins, CRP, neopterin, homocysteine, and P-5-P serum concentrations remained unchanged, while kynurenine concentration increased (P <0.02).The results of this study as well as data of our previous investigations suggest that improvement of blood circulation of the heart muscle due to stenting does not normalise intercellular metabolism in patient with CAD. Some improvement observed in lipid metabolism can be the result of treatment with statins, although these changes in lipid metabolism were not followed by improvement of other biochemical indices examined in CAD patients of this study. At present the role of kynurenine in the course of CAD is obscure. Therefore further investigations are necessary.

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease

2001 ◽  
Vol 100 (2) ◽  
pp. 183-190 ◽  
Author(s):  
Ll. MASANA ◽  
G. FEBRER ◽  
J. CAVANNA ◽  
M. G. BARONI ◽  
W. MARZ ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lipoprotein Lipase ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Transport ◽  
Premature Coronary Artery Disease ◽  
Artery Disease

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P < 0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P < 0.05 and P < 0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P < 0.05), HDL-cholesterol (P < 0.02), plasma triacylglycerols (P < 0.05) and the triacylglycerol/HDL ratio (P < 0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P = 0.02). The possible functional effects of these common mutations are discussed.

Effects of Resistance versus Aerobic Training on Coronary Artery Disease Risk Factors

2003 ◽  
Vol 228 (4) ◽  
pp. 434-440 ◽  
Author(s):  
William J. Banz ◽  
Margaret A. Maher ◽  
Warren G. Thompson ◽  
David R. Bassett ◽  
Wayne Moore ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Resistance Training ◽  
Aerobic Training ◽  
Disease Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Waist To Hip Ratio ◽  
Artery Disease

Individuals exhibiting “the metabolic syndrome” have multiple coronary artery disease risk factors, including insulin resistance, hyperlipidemia, hypertension, and android obesity. We performed a randomized trial to compare the effects of aerobic and resistance training regimens on coronary risk factors. Twenty-six volunteers who exhibited android obesity and at least one other risk factor for coronary artery disease were randomized to aerobic or resistance training groups. Body mass index, waist-to-hip ratio, glucose, insulin, body composition, 24-hr urinary albumin, fibrinogen, blood pressure, and lipid profile were measured at baseline and after 10 weeks of exercise training. Both groups showed a significant reduction in waist-to-hip ratio and the resistance training group also showed a reduction in total body fat. There was no significant change in mean arterial blood pressure in either group. Fasting plasma glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were unchanged in both groups. High-density lipoprotein (HDL) cholesterol increased (13%) with aerobic training only. Plasma fibrinogen was increased (28% and 34%, P < 0.02) in both groups and both groups showed a significant decrease (34% and 28%, P < 0.03) in microalbuminuria after their respective training regimen. In conclusion, resistance training was effective in improving body composition of middle-aged obese sedentary males. Only aerobic training was effective in raising HDL cholesterol. More studies are warranted to assess the effects of exercise on plasma fibrinogen and microalbuminuria.

Metabolic determinants of the course of coronary artery disease in men

1994 ◽  
Vol 40 (12) ◽  
pp. 2240-2246 ◽  
Author(s):  
G F Watts ◽  
S Mandalia ◽  
B M Slavin ◽  
J N Brunt ◽  
D J Coltart ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Quantitative Coronary Angiography ◽  
Change In The Mean ◽  
Artery Disease

Abstract We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).

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