scholarly journals Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors

Author(s):  
Tomas Vaisar ◽  
Jennifer L. Gordon ◽  
Jake Wimberger ◽  
Jay W. Heinecke ◽  
Alan L. Hinderliter ◽  
...  
Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2847-2856 ◽  
Author(s):  
Hiurma Sánchez-Pérez ◽  
Juan Carlos Quevedo-Abeledo ◽  
Laura de Armas-Rillo ◽  
Íñigo  Rua--Figueroa ◽  
Beatriz Tejera-Segura ◽  
...  

Abstract Objectives Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients. Methods The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis. Results CEC was downregulated in SLE patients [8.1  (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile–related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014]. Conclusion CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
David Rhainds ◽  
Marie Boule ◽  
Sonia Alem ◽  
Mathieu R Brodeur ◽  
Daniel Charpentier ◽  
...  

Inhibition of cholesteryl ester transfer protein (CETP) is an approach aiming at raising HDL-cholesterol levels and reducing cardiovascular risk. The dal-PLAQUE-2 phase III study recruited 988 subjects with stable coronary artery disease. Its primary objective was to evaluate the effect of dalcetrapib on the progression of carotid atherosclerotic disease measured by intima-media thickness after one year of therapy. As dalcetrapib showed a neutral effect on cardiovascular risk in the dal-OUTCOMES study, our objective was to evaluate its effect on cIMT and markers of HDL mass, lipoprotein subclass distribution and HDL function. All subjects from dal-PLAQUE-2 who had provided serum samples at baseline and one year were included in our substudy of 193 subjects on placebo and 186 subjects on dalcetrapib. Comparisons between groups at one year were made by ANCOVA after adjustment for baseline levels. No significant differences between groups for all variables considered were observed at baseline. Dalcetrapib reduced CETP activity as measured by a fluorescent method by 30% after 1 year (p<0.001), which resulted in increases in HDL-cholesterol and apoA-I levels by 32% and 11%, respectively (both p<0.001). Dalcetrapib markedly increased the concentration of large HDL particles measured by NMR profiling (+59%, p<0.001), at the expense of small HDL particles (-9.5%, p<0.001). Cholesterol efflux capacity of serum was measured from J774 macrophages under basal conditions and after cAMP stimulation. Dalcetrapib increased basal and stimulated efflux by 7.1% and 5.5% (both p<0.001), but was without effect on the ABCA1-dependent component (p=0.26). Despite these effects, dalcetrapib had no impact on mean and maximal cIMT (p=0.98 and p=0.85). While the change in cIMT was inversely correlated with basal cholesterol efflux in the placebo group (Spearman r=-0.163, p<0.05), such a relationship was not found in the dalcetrapib group. Moreover, the change in total HDL particles concentration was inversely correlated with change in cIMT (r=0.181, p<0.05) in the placebo arm only. In conclusion, dalcetrapib raised HDL-C and larger HDL, but this had minimal effects on cholesterol efflux capacity of patients’ serum and had a neutral effect on carotid artery plaque burden.


2020 ◽  
Author(s):  
Iván Ferraz-Amaro ◽  
Esmeralda Delgado-Frías ◽  
Vanesa Hernández-Hernández ◽  
Hiurma Sánchez-Pérez ◽  
Laura de Armas-Rillo ◽  
...  

Abstract Objective. It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients respect to controls and whether these changes were associated with disease-related data. Methods. Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences. Results. The multivariate analysis adjusted for demographic characteristics, cardiovascular risk factors and lipid-related molecules showed that total cholesterol (beta coefficient: -22 [95%CI -37- -7], p=0.004), triglycerides (beta coefficient: 24 [95%CI 2-47], p=0.033), lipoprotein A (beta coefficient: 22 [95%CI 2-43], p=0.033) and CEC (beta coefficient: -6 [95%CI -10- -2]%,p=0.002) were significantly differences between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: -0.21 [95%CI -0.37- -0.05]%, p=0.011) after multivariable adjustment. Conclusion. SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sanam Ebtehaj ◽  
Chantal Kopecky ◽  
Bernd Genser ◽  
Christiane Drechsler ◽  
Vera Krane ◽  
...  

The cardioprotective effect of HDL (High-Density Lipoprotein) is largely determined by its cholesterol efflux capacity, which was shown to correlate inversely with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with end-stage renal disease suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, we investigated in a post-hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis participating in the 4D Study (The German Diabetes Dialysis Study), if the HDL cholesterol efflux capacity is predictive of cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apolipoprotein B-depleted serum. During a median follow-up of 4.1 years n=423 patients reached the combined primary endpoint (composite of cardiac death, nonfatal myocardial infarction and stroke), n=410 experienced cardiac events and n=561 died (all-cause mortality). Strikingly, in Cox regression analysis we found no association of efflux capacity with the combined primary endpoint (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88 – 1.06, p =0.417), cardiac events (HR, 0.92; CI, 0.83-1.02; p =0.108) or all-cause mortality (HR 0.96; 95% CI, 0.88-1.05; p =0.390). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in diabetic patients on hemodialysis.


2018 ◽  
Vol 108 (6) ◽  
pp. 1166-1182 ◽  
Author(s):  
Alexandra T Wade ◽  
Courtney R Davis ◽  
Kathryn A Dyer ◽  
Jonathan M Hodgson ◽  
Richard J Woodman ◽  
...  

ABSTRACT Background The Mediterranean diet (MedDiet) offers benefits to cardiovascular health but may not meet Western recommendations for calcium and dairy intake, which could impede long-term adoption. Objective The current study aimed to determine the effect of a MedDiet supplemented with dairy foods on cardiovascular risk factors. Design A randomized, controlled, crossover design compared a MedDiet with 3–4 daily servings of dairy (MedDairy) and a low-fat (LF) control diet. Forty-one participants aged ≥45 y and at risk of cardiovascular disease (CVD) were randomly allocated to their first intervention, either the MedDairy or LF diet. Participants followed each intervention for 8 wk, and an 8-wk washout period separated interventions. The primary outcome was home-measured systolic blood pressure (SBP) assessed in the morning, afternoon, and evening. Secondary outcomes included clinic-measured blood pressure (morning), body composition, blood lipids, C-reactive protein (CRP), plasma glucose, serum insulin, and the Framingham Risk Score. Results Compared with the LF intervention, the MedDairy intervention resulted in a significantly lower morning SBP (mean difference: −1.6 mm Hg; 95% CI: −2.8, −0.4 mm Hg; P = 0.01), lower morning diastolic blood pressure (mean difference: −1.0; 95% CI: −1.7, −0.2 mm Hg; P = 0.01) and clinic SBP (mean difference: −3.5 mm Hg; 95% CI: −6.4, −0.7 mm Hg; P = 0.02), significantly higher HDL cholesterol (mean difference: 0.04 mmol/L; 95% CI: 0.01, 0.06 mmol/L; P < 0.01), lower triglycerides (mean difference: = −0.05 mmol/L; 95% CI: −0.08, −0.01 mmol/L; P < 0.01), and lower ratio of total to HDL cholesterol (mean difference: −0.4; 95% CI: −0.6, −0.2; P < 0.001). No effects were observed for other outcome measures. Conclusions Following a MedDiet with additional dairy foods led to significant changes in markers of cardiovascular risk over 8 wk. The MedDiet supplemented with dairy may be appropriate for an improvement in cardiovascular risk factors in a population at risk of CVD. This trial was registered at anzctr.org.au as ACTRN12616000309482.


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