scholarly journals The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 286
Author(s):  
Gualtiero Colombo ◽  
Vanessa Bianconi ◽  
Alice Bonomi ◽  
Sara Simonelli ◽  
Mauro Amato ◽  
...  

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.

Angiology ◽  
2015 ◽  
Vol 67 (5) ◽  
pp. 471-477 ◽  
Author(s):  
Małgorzata Waluś-Miarka ◽  
D. Czarnecka ◽  
W. Wojciechowska ◽  
M. Kloch-Badełek ◽  
M. Kapusta ◽  
...  

Patients with familial hypercholesterolemia (FH) are at increased risk of premature cardiovascular disease. We compared factors associated with the presence of carotid plaques and carotid intima–media thickness (cIMT), markers of subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41 ± 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age, apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1 unit change 1.03, P = .005), high-density lipoprotein cholesterol (HDL-C; OR per 1 standard deviation [SD] change 0.59, P = .015), and non-HDL-C (OR per 1SD change 1.53, P = .04) were significantly associated with the presence of plaques. The cIMT correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C-reactive protein, creatinine, γ-glutamyl transpeptidase, and alanine transaminase ( P < .001). Regression analysis revealed that cIMT was significantly associated with apoB, SBP, and WHR. These results confirm the role of apoB-containing lipoproteins and low HDL-C with the presence of carotid plaques and apoB, BP, and WHR with cIMT.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Kenan Demircioglu ◽  
Feyza Aksu ◽  
Mustafa Caliskan ◽  
Yusuf Yilmaz

Introduction: Gamma-glutamyltransferase(GGT) plays a catalytic role in degradation of glutathione. Serum GGT is accepted as a marker of oxidative stress.The aim of this study is to investigate the relationship between serum GGT levels and epicardial adipose tissue (EFT) thickness, carotid intima media thickness (CIMT) measurements in patients with psoriasis. Methods: The study population included 89 patients with psoriasis and 79 healthy volunteers. After overnight fasting, blood samples were taken for to determine blood glucose levels and establishing cholesterol profiles including TG, TC, LDL cholesterol and high-density lipoprotein (HDL) cholesterol; GGT; and high- sensitivity C-reaktive protein (hs-CRP) levels. A high-resolution B-mode ultrasound machine (Toshiba, aplio XU) with a 7.5 MHz linear transducer used for examing CIMT.The right common carotid artery (CCA), approximately 1 cm proximal to the bifurcation, was longitudinally selected and CIMT was defined as the distance between the intima and the media. Results: 89 patients with psoriasis (age:41.7±10.9 years;41 women, 48 men), and 71 healthy control subjects (age:40.4±8.2 years;39 women, 32 men) were included. There were no significant variation for age and sex between two groups(p>0.05).The hs-CRP and GGT values were significantly higher in psoriasis, compared with the controls (hs-CRP:1.35(0.9-3.6)mg/l for psoriasis group, 0.45(0.29-0.79)mg/l for control group, p<0.001; GGT:20.6±9.6 U/l for psoriasis group, 16.7±8.0 U/l for control group, p=0.02. In psoriatic patients, CIMT and EFT were significantly inreased (0.60(0.50-0.68)mm vs. 0.50 (0.40-0.60)mm;p=0.007, 0.67±0.20cm; 0.27±0.12cm; p<0.001, respectively) compared with the control group. CIMT significantly positively correlated with EFT, age, BMI, diastolic BP and GGT.EFT significantly positively correlated with GGT, CIMT, age, hs-CRP, systolic BP and TG and negatively correlated with HDL cholesterol. Discussion: The pathophysiology of atherosclerosis in psoriasis is not fully explained.GGT may be used as an indicator of subclinical atherosclerosis like CRP.


Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 56 ◽  
Author(s):  
Peter Piko ◽  
Szilvia Fiatal ◽  
Nardos Abebe Werissa ◽  
Bayu Begashaw Bekele ◽  
Gabor Racz ◽  
...  

Background: The triglycerides (TG) to high-density lipoprotein (HDL)-cholesterol (HDL-C) ratio (TG/HDL-C) is a well-known predictor for cardiovascular diseases (CVDs) with great heritability background. The cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) gene affect TG/HDL-C ratio. This study aims to explore the association between haplotypes (H) in CETP (based on 5 single nucleotide polymorphisms (SNPs)) and LIPC (based on 6 SNPs) genes and the TG/HDL-C ratio and its components, among Roma and Hungarian general populations. Methods: The prevalence of haplotypes and their effect on HDL-C, TG and TG/HDL-C ratio were calculated in both populations and compared. Results: Ten haplotypes in CETP and 6 in LIPC gene were identified. Three haplotypes in CETP and 3 in LIPC have significant effect on HDL-C level, whereas two in CETP and 3 in LIPC on TG level. The H6 in CETP (β = 0.52, p = 0.015; odds ratio (OR) = 1.87, p = 0.009) and H5 in LIPC (β = 0.56, p < 0.001; OR = 1.51, p = 0.002) have a significant increasing effect on TG/HDL-C ratio and have shown higher prevalence among the Roma, as compared to Hungarian general population. The H2 in the CETP gene has a decreasing effect on the TG/HDL-C ratio (OR = 0.58, p = 0.019) and is significantly less frequent among the Roma. Conclusions: Accumulation of harmful haplotypes in CETP and LIPC genes might have a role in the elevated TG/HDL-C ratio in the Roma population, which contributes to a higher risk in the development of cardiovascular diseases.


2019 ◽  
Vol 35 (6) ◽  
pp. 453-458 ◽  
Author(s):  
Felicitas U. Idigo ◽  
Eberechukwu N. Ayogu ◽  
Sobechukwu W. I. Onwuzu ◽  
Angel-Mary C. Anakwue ◽  
Uloma B. Nwogu ◽  
...  

Objective. The purpose of this prospective study was to ascertain if lipid profile parameters could serve as predictors of carotid intima-media thickness (CIMT), which, when combined, may improve the sensitivity of sonographic CIMT measurement in the diagnosis of subclinical atherosclerotic changes. Methods. The lipid profiles and CIMT of 181 subjects without cardiovascular risk factors were measured at the internal, external, common, and bulbar segments. Results. The mean CIMT values obtained were 0.620 ± 0.055 cm for men and 0.575 ± 0.051 cm for women, and the η2 values (η2 < 0.04) were used as a measure of association. Across all segments of both carotid arteries, lipid profiles were significantly and moderately associated with but not predictive of CIMT (fasting blood sugar, total cholesterol, and low-density lipoprotein: η2 = 0.99–0.24). Conclusions. Although lipid profiles were moderately associated with CIMT, they are not significant predictors; hence, combining them with CIMT does not improve the diagnostic sensitivity of sonography in atherosclerosis screening.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Gregory W Evans ◽  
Mike K Palmer ◽  
Daniel H O’Leary ◽  
John R Crouse ◽  
Michiel L Bots ◽  
...  

Carotid artery intima-media thickness (CIMT) assessed by B-mode ultrasound is an accepted marker for subclinical atherosclerosis commonly used in clinical trials. Their sample size and power calculations apply 2-sample independent t-tests and within group variance in progression rates from the literature. However, this approach obscures the impact of differences in study designs including length of follow-up and differences in the number of and interval between ultrasound scans. These effects can be assessed using common sample size formula for longitudinal models, but this approach requires decomposition of the total variance into between and within subject components that have not generally been reported in the literature. Here, we derive these variance components for the Measuring Effects on intima-media Thickness: an Evaluation of Rosuvastatin (METEOR) study, a randomized, double-blind trial that demonstrated treatment with 40 mg rosuvastatin significantly slowed CIMT progression in middle-aged patients with a low Framingham risk of coronary heart disease and subclinical atherosclerosis (baseline maximum CIMT ≥1.2-<3.5mm). We examined the impact of differing follow-up periods, use of intermediate scans, and use of duplicate scans using both sample size calculations and actual analyses based on subsets of the METEOR data. Reductions in study length or number of scans result in increased variances and larger sample sizes to detect a given treatment effect. Table shows the impact of duplicate scans at baseline and end of the 2-year study, with and without intermediate scans performed every 6 months, on the sample size required to detect a treatment effect of 0.012 mm/year. These results underscore the importance of considering the number and spacing of ultrasound exams explicitly during study design, and suggest that reductions in scanning frequency may seriously erode study power and/or increase costs by requiring recruitment of additional subjects.


2021 ◽  
Vol 22 (2) ◽  
pp. 257-274 ◽  
Author(s):  
Baris Gencer ◽  
Marco Bonomi ◽  
Maria Pia Adorni ◽  
Cesare R. Sirtori ◽  
François Mach ◽  
...  

AbstractThe cardiovascular (CV) benefit and safety of treating low testosterone conditions is a matter of debate. Although testosterone deficiency has been linked to a rise in major adverse CV events, most of the studies on testosterone replacement therapy were not designed to assess CV risk and thus excluded men with advanced heart failure or recent history of myocardial infarction or stroke. Besides considering observational, interventional and prospective studies, this review article evaluates the impact of testosterone on atherosclerosis process, including lipoprotein functionality, progression of carotid intima media thickness, inflammation, coagulation and thromboembolism, quantification of plaque volume and vascular calcification. Until adequately powered studies evaluating testosterone effects in hypogonadal men at increased CV risk are available (TRAVERSE trial), clinicians should ponder the use of testosterone in men with atherosclerotic cardiovascular disease and discuss benefit and harms with the patients.


2019 ◽  
Vol 33 ◽  
pp. 205873841882243 ◽  
Author(s):  
Elena Passeri ◽  
Daniela Mazzaccaro ◽  
Veronica Sansoni ◽  
Silvia Perego ◽  
Giovanni Nano ◽  
...  

Atherosclerosis and osteoporosis are interrelated entities and share similar pathogenic mechanisms. Recent studies showed that key proteins of bone metabolism, such as osteoprotegerin (OPG) and osteopontin (OPN), are also involved in vascular atherosclerosis and calcifications. The carotid intima-media thickness (CA-IMT) is an early quantitative marker of generalized atherosclerosis. Aim of study was to investigate whether 12-months treatment with zoledronate (ZLN) or teriparatide (TPT) affects CA-IMT and circulating OPG and OPN levels. In this study, 11 postmenopausal osteoporotic women (aged 73, 70.5–74.5 years; median, range interquartile) treated with 5 mg/year iv ZLN; 9 postmenopausal osteoporotic women (aged 70, 62.5–73.5 years) treated with 20 µg/day sc TPT; and 10 aged-, body mass index (BMI)-, glycemic, and lipid profiles-matched, free from anti-osteoporotic and hypocholesterolemic drugs, controls were prospectively investigated at baseline and after 12 months. At baseline, median CA-IMT was similar in the three groups and increased after 12 months. CA-IMT increased significantly in TPT-treated patients (1.0, 0.8–1.2 vs 1.1, 0.9–15 mm, P = 0.04), though the change was minimal. After 12 months of treatment, CA-IMT positively correlated with alkaline phosphatase (ALP) levels (r = 0.767, P = 0.008) and negatively with high-density lipoprotein (HDL) cholesterol levels (r = −0.65, P = 0.03), suggesting interplay between active bone remodeling and lipid profile. At baseline and after 12 months, median serum OPG and OPN levels did not differ among the groups and did not correlate with changes in CA-IMT. In conclusion, ZLN and TPT treatments are safe on carotid walls in osteoporotic women with subclinical atherosclerosis; circulating OPG and OPN are not affected by long-term anti-osteoporotic treatments and do not correlate with CA-IMT.


2020 ◽  
Vol 9 (7) ◽  
pp. 2139
Author(s):  
Maria Belén Vilanova ◽  
Josep Franch-Nadal ◽  
Mireia Falguera ◽  
Josep Ramon Marsal ◽  
Sílvia Canivell ◽  
...  

This was a prospective, observational study to compare the burden of subclinical atherosclerosis as measured by carotid ultrasonography in a cohort of subjects with prediabetes vs. subjects with normal glucose tolerance (NGT) from a non-urban Mediterranean population. Atherosclerosis was assessed through carotid intima-media thickness (c-IMT), the presence/absence of carotid plaques, and plaque number. Among 550 subjects included, 224 (40.7%) had prediabetes. The mean c-IMT and the prevalence of carotid plaque were significantly higher in the prediabetes group compared to the NGT group (0.72 vs. 0.67 mm, p < 0.001; and 37.9% vs. 19.6%; p < 0.001, respectively). Older age, male gender, and increased systolic blood pressure were positively correlated with c-IMT and were independent predictors of the presence of plaques. In contrast, prediabetes and low-density lipoprotein (LDL)-c were predictors of the presence of plaque (odds ratio [OR] = 1.64; 95% confidence interval [CI] = 1.05–2.57; p = 0.03 and OR = 1.01; 95% CI = 1.00–1.02; p = 0.006, respectively) together with tobacco exposure and the leukocyte count (OR = 1.77; 95% CI = 1.08–2.89; p = 0.023 and OR = 1.20; 95% CI = 1.05–1.38; p = 0.008, respectively). In a non-urban Mediterranean population, prediabetes was associated with established subclinical carotid atherosclerosis. These findings could have implications for the prevention and treatment of CV risk in these subjects before the first symptoms of cardiovascular disease appear.


2019 ◽  
Vol 59 (1) ◽  
Author(s):  
Duygu Tecer ◽  
Ismihan Sunar ◽  
Ali Erhan Ozdemirel ◽  
Rabia Tural ◽  
Orhan Kucuksahin ◽  
...  

Abstract Background To investigate the link between carbamylated low-density lipoprotein (ca-LDL), atherogenic index of plasma (AIP), atherogenic coefficient (AC), Castelli’s risk indices I and II (CRI I and II) and subclinic atherosclerosis in psoriatic arthritis (PsA). Methods Thirty-ninepatients and 19 age, sex, body mass index matched healthy controls were included. Insulin resistance (IR) was assessed with homeostasis of model assessment-IR (HOMA-IR). Carotid intima-media thickness (CIMT) was measured at both common carotid arteries and mean CIMT was calculated. Results The mean age was 49.50 ± 11.86 years and 64.1% were females in PsA group. In the PsA group, CIMT and HOMA-IR were significantly higher (p = 0.003, p = 0.043, respectively). AIP, AC, TG/HDL, CRI-1, CRI-2 and ca-LDL levels were similar between groups. In PsA group, CIMT was positively correlated with HOMA-IR, TG/HDL and AIP. Although ca-LDL was positively correlated with serum amyloid A (r = 0.744, p < 0.001), no correlation was detected between ca-LDL and CIMT (r = 0.215, p = 0.195). PsA patients with IR tended to have higher ca-LDL levels than patients without IR, but this difference lacked statistical significance (33.65 ± 26.94, 28.63 ± 28.06, respectively, p = 0.237). Conclusions A significant increase in CIMT was seen in PsA patients without clinically evident cardiovascular disease or any traditional atherosclerosis risk factors. CIMT was correlated with HOMA-IR, TG/HDL and AIP.


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