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Comparison of the effectiveness of Martin's equation, Friedewald's equation, and a Novel equation in low-density lipoprotein cholesterol estimation.
Song, Y, Lee, HS, Baik, SJ, Jeon, S, Han, D, Choi, SY, Chun, EJ, Han, HW, Park, SH, Sung, J, et al
Scientific reports. 2021;(1):13545
Abstract
Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R2, RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R2 = 0.88/0.91; vs FLDL RMSE = 13.66/10.42 mg/dL; R2 = 0.82/0.89; vs SLDL RMSE = 12.36/9.39 mg/dL; R2 = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500-600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin's equation may be optimal for LDL-C and ASCVD risk estimation.
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Extra Virgin Olive Oil Prevents the Age-Related Shifts of the Distribution of HDL Subclasses and Improves Their Functionality.
Otrante, A, Trigui, A, Walha, R, Berrougui, H, Fulop, T, Khalil, A
Nutrients. 2021;(7)
Abstract
High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = -0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (β = 0.28, p < 0.002, and β = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.
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Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.
Tarkin, JM, Joshi, FR, Evans, NR, Chowdhury, MM, Figg, NL, Shah, AV, Starks, LT, Martin-Garrido, A, Manavaki, R, Yu, E, et al
Journal of the American College of Cardiology. 2017;(14):1774-1791
Abstract
BACKGROUND Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES This study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. METHODS We confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis. RESULTS Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. CONCLUSIONS We validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).
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64Cu-DOTATATE for Noninvasive Assessment of Atherosclerosis in Large Arteries and Its Correlation with Risk Factors: Head-to-Head Comparison with 68Ga-DOTATOC in 60 Patients.
Malmberg, C, Ripa, RS, Johnbeck, CB, Knigge, U, Langer, SW, Mortensen, J, Oturai, P, Loft, A, Hag, AM, Kjær, A
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2015;(12):1895-900
Abstract
UNLABELLED The somatostatin receptor subtype 2 is expressed on macrophages, an abundant cell type in the atherosclerotic plaque. Visualization of somatostatin receptor subtype 2, for oncologic purposes, is frequently made using the DOTA-derived somatostatin analogs DOTATOC or DOTATATE for PET. We aimed to compare the uptake of the PET tracers (68)Ga-DOTATOC and (64)Cu-DOTATATE in large arteries, in the assessment of atherosclerosis by noninvasive imaging technique, combining PET and CT. Further, the correlation of uptake and cardiovascular risk factors was investigated. METHODS Sixty consecutive patients with neuroendocrine tumors underwent both (68)Ga-DOTATOC and (64)Cu-DOTATATE PET/CT scans, in random order. For each scan, the maximum and mean standardized uptake values (SUVs) were calculated in 5 arterial segments. In addition, the blood-pool-corrected target-to-background ratio was calculated. Uptake of the tracers was correlated with cardiovascular risk factors collected from medical records. RESULTS We found detectable uptake of both tracers in all arterial segments studied. Uptake of (64)Cu-DOTATATE was significantly higher than (68)Ga-DOTATOC in the vascular regions both when calculated as maximum and mean uptake. There was a significant association between Framingham risk score and the overall maximum uptake of (64)Cu-DOTATATE using SUV (r = 0.4; P = 0.004) as well as target-to-background ratio (r = 0.3; P = 0.04), whereas no association was found with (68)Ga-DOTATOC. The association of risk factors and maximum SUV of (64)Cu-DOTATATE was found driven by body mass index, smoking, diabetes, and coronary calcium score (P < 0.001, P = 0.01, P = 0.005, and P = 0.03, respectively). CONCLUSION In a series of oncologic patients, vascular uptake of (68)Ga-DOTATOC and (64)Cu-DOTATATE was found, with highest uptake of the latter. Uptake of (64)Cu-DOTATATE, but not of (68)Ga-DOTATOC, was correlated with cardiovascular risk factors, suggesting a potential role for (64)Cu-DOTATATE in the assessment of atherosclerosis.
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Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity.
Frazier-Wood, AC, Manichaikul, A, Aslibekyan, S, Borecki, IB, Goff, DC, Hopkins, PN, Lai, CQ, Ordovas, JM, Post, WS, Rich, SS, et al
Human genetics. 2013;(4):405-13
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Abstract
Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial/ethnic groups on lipoprotein profile. Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P < 1.97 × 10(-05) (the level at which we achieved at least 80% power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N = 2,430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N = 1,594), Chinese (N = 758), and Hispanic (N = 1,422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only. Our findings suggest that the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race/ethnicity.
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Risk factor differences for aortic versus coronary calcified atherosclerosis: the multiethnic study of atherosclerosis.
Criqui, MH, Kamineni, A, Allison, MA, Ix, JH, Carr, JJ, Cushman, M, Detrano, R, Post, W, Wong, ND
Arteriosclerosis, thrombosis, and vascular biology. 2010;(11):2289-96
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OBJECTIVE The goal of this study was to compare and contrast coronary artery calcium (CAC) with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel cardiovascular disease (CVD) risk factors. METHODS AND RESULTS We measured both AAC and CAC using computed tomography scans in 1974 men and women aged 45 to 84 years from a multiethnic cohort. Traditional and novel CVD risk factors were examined separately in relation to AAC and CAC, using logistic regression for qualitative categorical comparisons and multiple linear regression for quantitative continuous comparisons. AAC was significantly associated with cigarette smoking and dyslipidemia and showed no gender difference. In contrast, CAC showed much weaker associations with smoking and dyslipidemia and a strong male predominance. Age and hypertension were associated similarly and significantly with AAC and CAC. Novel risk factors generally showed no independent association with either calcium measure, although in subset analyses, phosphorus, but not calcium, was related to CAC. The receiver operating characteristic curves for the qualitative results and the r(2) values for the quantitative analyses were both much higher for AAC than for CAC. CONCLUSIONS AAC showed stronger correlations with most CVD risk factors than did CAC. The predictive value of AAC compared with CAC for incident CVD events remains to be evaluated.
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Embolic protection device use in renal artery stent placement.
Thatipelli, MR, Misra, S, Sanikommu, SR, Schainfeld, RM, Sharma, SK, Soukas, PA
Journal of vascular and interventional radiology : JVIR. 2009;(5):580-6
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PURPOSE The purpose of the present study was to report safety, efficacy, and renal function outcomes with use of the GuardWire embolic protection device (EPD) in renal artery stent placement for patients with renal artery stenosis (RAS) and chronic renal insufficiency (CRI). MATERIALS AND METHODS This was a retrospective study of all patients with RAS and CRI treated concomitantly with a GuardWire EPD and renal artery stents from December 2002 through June 2006. Renal function was determined by calculating the estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease formula, and subjects were divided into Kidney Disease Outcomes and Quality Initiative (K-DOQI) classes based on baseline eGFR. After revascularization, an improvement from baseline of at least one K-DOQI class was defined as improvement, unchanged K-DOQI class as stabilization, and worsening of at least one K-DOQI class as deterioration. RESULTS There were 63 patients (54% men) with a mean age of 75.2 years +/- 7.7. The mean baseline serum creatinine level and eGFR were 1.87 mg/dL +/- 0.6 (range, 1-3.8 mg/dL) and 36.63 mL/min per 1.73 m(2) +/- 11.42 (range, 13.85-59.99 mL/min per 1.73 m(2)), respectively, and at the last clinical follow-up, the respective measurements were 1.96 mg/dL +/- 0.72 and 38.75 mL/min per 1.73 m(2) +/- 13.25 (P = not significant). Over a mean follow-up period of 16 months +/- 12, 14 patients (25%) showed improvement, 33 (58%) had stable renal function, and 10 (18%) showed deterioration. There was one GuardWire-related dissection, which was successfully treated with a stent. CONCLUSIONS The GuardWire EPD, used during renal artery stent placement, is safe and was associated with stabilization or improvement in kidney function in 83% of patients with RAS and CRI.
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Persistence of an atherogenic lipid profile after treatment of acute infection with Brucella.
Apostolou, F, Gazi, IF, Kostoula, A, Tellis, CC, Tselepis, AD, Elisaf, M, Liberopoulos, EN
Journal of lipid research. 2009;(12):2532-9
Abstract
Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and levels of cytokines [interleukins (IL)-1beta, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA(2) activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA(2) activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.
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Intermittent doses of statin in hemodialysis patients with spontaneous low LDL cholesterol levels.
Suassuna, PG, Bastos, MG
Arquivos brasileiros de cardiologia. 2008;(2):104-11
Abstract
BACKGROUND Mortality in dialysis patients remains high and is due mainly to cardiovascular causes. Inflammation has a role in the genesis of accelerated atherosclerosis, vascular calcification, malnutrition and anemia, and a huge impact on the survival of these patients. The pleiotropic effects of statins can be a therapeutic option for reducing chronic inflammatory processes of patients undergoing hemodialysis. OBJECTIVE To evaluate the effects of low doses of simvastatin on inflammatory markers, hematimetric and nutritional parameters of patients undergoing hemodialysis. METHODS Clinically-stable patients undergoing hemodialysis were classified according to their baseline LDL-cholesterol levels in two groups: those with levels below 100mg/dl (Group 1) and those with levels equal to or greater than 100mg/dl (Group-2), and were treated with simvastatin during eight weeks. Group 1 received 20mg only after each session of hemodialysis (intermittent dose), whereas Group 2 received 20mg/daily. Laboratory data, erythropoietin resistance index and nutritional parameters were obtained before and after treatment. RESULTS A significant and equivalent reduction in C-reactive protein levels in both groups was observed (35.97+/-49.23% vs 38.32+/-32.69%, p=0.86). In group 1, there was also a tendency towards reduced resistance to erythropoietin (228.6+/-16.2 vs 208.9+/-16.2, p=0.058) and improvement of hematimetric parameters (hematocrit: 33.1+/-5.9% vs 36.1+/-4.5%, p=0.021). CONCLUSION Intermittent doses proved to be as effective as the usual dose in reducing C-reactive protein levels and resistance to erythropoietin, besides improving the hematimetric parameters, indicating an important reduction of the cardiovascular risk evaluated by these parameters.
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Pioglitazone reduces atherogenic outcomes in type 2 diabetic patients.
Igarashi, M, Hirata, A, Yamaguchi, H, Jimbu, Y, Tominaga, M
Journal of atherosclerosis and thrombosis. 2008;(1):34-40
Abstract
AIM: The aim of this study was to evaluate the anti-atherogenic outcomes of pioglitazone, a thiazolidinedione derivative, in type 2 diabetic patients. METHODS Eight patients with poor diabetic control were treated with 15 mg of pioglitazone for 4 months. Blood samples were collected monthly, and the levels of fasting plasma glucose (FPG), HbA1c, and lipids, such as triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were measured. Other parameters, including immunorecative insulin (IRI), remnant-like particle-cholesterol (RLP-C), adiponectin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor (TNF)- alpha , leptin, brain natriuretic peptide (BNP), and high-sensitivity (hs)-C-reactive protein (CRP), were examined at the beginning and end of the study. In addition, clinically adverse side-effects were evaluated. RESULTS Treatment with pioglitazone significantly decreased the levels of HbA1c, FPG, the homeostasis model assessment of insulin resistance (HOMA-IR) index, RLP-C, PAI-1, TNF- alpha , and hs-CRP, but not the level, IRI, lipids, or leptin. In contrast, adverse side-effects, including body weight gain, liver dysfunction and edema, were not observed during this study. CONCLUSION These results strongly suggested that treatment with pioglitazone has a greater clinical benefit for the prevention of atherosclerosis, including coronary heart diseases, without any adverse side-effects.