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Modern medical treatment with or without carotid endarterectomy for severe asymptomatic carotid atherosclerosis.
Kolos, I, Troitskiy, A, Balakhonova, T, Shariya, M, Skrypnik, D, Tvorogova, T, Deev, A, Boytsov, S, ,
Journal of vascular surgery. 2015;(4):914-22
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Abstract
OBJECTIVE This study assessed the value of modern medical treatment (MMT) with and without carotid endarterectomy (CEA) in patients with asymptomatic severe carotid artery stenosis. METHODS We conducted a randomized trial involving 55 patients with 70% to 79% carotid stenosis at three Russian centers. Between 2009 and 2013, 31 patients were randomized to undergo CEA with MMT (CEA group) and 24 to receive MMT alone. The primary end point was nonfatal ipsilateral stroke or death from any cause during a follow-up period of 5.0 years. The secondary end point was any nonfatal stroke, carotid revascularization, or death from any cause during follow-up. RESULTS The trial was stopped after a median follow-up of 3.3 years (maximum, 5.0 years). There were two primary events in the CEA group and nine events in the MMT group. The 3.3-year cumulative primary event rates were 6.5% in the CEA group and 37.5% in the MMT group (hazard ratio for the MMT group, 5.06; 95% confidence interval, 1.53-16.79; P = .008). The 3.3-year cumulative secondary end point was 12.9% in the CEA group and 50.0% in the MMT group (hazard ratio for the MMT group, 4.23; 95% confidence interval, 1.55-11.53; P = .0048). CONCLUSIONS CEA as an initial management strategy could reduce the risk of death and major cerebrovascular events when added to MMT.
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The effect of wet cupping on serum lipid concentrations of clinically healthy young men: a randomized controlled trial.
Niasari, M, Kosari, F, Ahmadi, A
Journal of alternative and complementary medicine (New York, N.Y.). 2007;(1):79-82
Abstract
OBJECTIVE The aim of this study was to determine if a reduction in serum lipoproteins, especially LDL cholesterol, is a preventive approach against atherosclerosis. Phlebotomy has been a recommended method to reduce serum lipoprotein levels. The present study was conducted to investigate the effects of wet cupping on serum lipoprotein concentrations. SUBJECTS AND METHODS In this randomized controlled trial, 47 men (18 to 25 years old), without chronic disease or a history of hyperlipidemia and antihyperlipidemic drug consumption were randomly assigned into control (N = 24) and treated (N = 23) groups. Men in the treated group were subjected to wet cupping, whereas men in the control group remained untreated. The serum concentrations of lipids, collected from brachial veins, were determined at the time of wet cupping and then once a week for 3 weeks. Data were analyzed using a repeated measure ANOVA. RESULTS A substantial decrease in LDL cholesterol (p < 0.0001) and in the LDL/HDL ratio (p < 0.0001) was found in the treated group compared to the control. There were no significant changes in serum triglyceride between groups (p > 0.05). Although there were no statistically significant variations in total cholesterol and HDL cholesterol (p > 0.05), a 7% decrease in total cholesterol and 3% increase in HDL cholesterol may be clinically important. CONCLUSIONS Wet cupping may be an effective method of reducing LDL cholesterol in men and consequently may have a preventive effect against atherosclerosis.
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Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome.
Deedwania, PC, Hunninghake, DB, Bays, HE, Jones, PH, Cain, VA, Blasetto, JW, ,
The American journal of cardiology. 2005;(3):360-6
Abstract
The metabolic syndrome (MS) is a constellation of coronary risk factors. Atherogenic dyslipidemia is an important factor in cardiovascular risk in these patients, and treatment of atherogenic dyslipidemia has been identified as an important goal of therapy in patients with MS. This post hoc analysis of data from a 6-week, randomized, open-label, parallel-group, comparative trial (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin [STELLAR]) assessed the effects of rosuvastatin 10, 20, and 40 mg, atorvastatin 10, 20, 40, and 80 mg, simvastatin 10, 20, 40, and 80 mg, and pravastatin 10, 20, and 40 mg on plasma lipids in hypercholesterolemic patients (low-density lipoprotein cholesterol ≥160 and <250 mg/dl; triglycerides <400 mg/dl) who had ≥3 of the 5 National Cholesterol Education Program Adult Treatment Panel III criteria for MS (body mass index >30 kg/m(2) substituted for waist circumference). Of 2,268 patients, 811 met criteria for MS. Percent reductions in low-density lipoprotein cholesterol ranged from 20% in the pravastatin 10-mg group to 55% in the rosuvastatin 40-mg group. In patients with MS, triglyceride reductions were 22% to 34% with rosuvastatin, 23% to 33% with atorvastatin, 15% to 23% with simvastatin, and 12% to 15% with pravastatin. High-density lipoprotein cholesterol increased by 8% to 11% with rosuvastatin, 5% to 9% with atorvastatin, 8% to 10% with simvastatin, and 3% to 7% with pravastatin. Rosuvastatin, atorvastatin, simvastatin, and pravastatin treatment had favorable effects in hypercholesterolemic patients on the atherogenic dyslipidemia associated with MS. Rosuvastatin had the most favorable effect on the atherogenic lipid profile of MS overall.
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Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers.
Estruch, R, Sacanella, E, Badia, E, Antúnez, E, Nicolás, JM, Fernández-Solá, J, Rotilio, D, de Gaetano, G, Rubin, E, Urbano-Márquez, A
Atherosclerosis. 2004;(1):117-23
Abstract
BACKGROUND No intervention studies have explored the anti-inflammatory effects of different alcoholic beverages on markers of atherosclerosis. We embarked on a randomized, crossover, single-blinded trial to evaluate the effects of wine and gin on inflammatory biomarkers of atherosclerosis. METHODS AND RESULTS Forty healthy men (mean age, 37.6 years) consumed 30 g ethanol per day as either wine or gin for 28 days. Before and after each intervention, we measured the expression of lymphocyte function-associated antigen 1 (LFA-1), Mac-1, very late activation antigen 4 (VLA-4), and monocyte chemoattractant protein (MCP-1) in monocytes, as well as the soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-1alpha (IL-1alpha), C-reactive protein (hs-CRP) and fibrinogen. After either gin or wine consumption, plasma fibrinogen decreased by 5 and 9%, respectively, and cytokine IL-1alpha by 23 and 21%. The expression of LFA-1 (-27%), Mac-1 (-27%), VLA-4 (-32%) and MCP-1 (-46%) decreased significantly after wine, but not after gin. Wine reduced the serum concentrations of hs-CRP (-21%), VCAM-1 (-17%) and ICAM-1 (-9%). CONCLUSIONS Both wine and gin showed anti-inflammatory effects by reducing plasma fibrinogen and IL-1alpha levels. However, wine had the additional effect of decreasing hs-CRP, as well as monocyte and endothelial adhesion molecules.
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Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids.
Eschen, O, Christensen, JH, De Caterina, R, Schmidt, EB
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2004;(4):180-5
Abstract
BACKGROUND AND AIM Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease, and serum levels of soluble cellular adhesion molecules (sCAMs) possibly reflect the inflammatory process underlying atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND RESULTS Sixty healthy volunteers were randomly assigned to receive a daily supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a double blind design. A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry. After supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in sP-selectin, which a gender subanalysis showed to be more marked in men. Among the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects, thus suggesting a decrease in platelet reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose.
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Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism: the key role of early, low-dose flutamide.
Ibáñez, L, Valls, C, Cabré, S, De Zegher, F
The Journal of clinical endocrinology and metabolism. 2004;(9):4716-20
Abstract
A low-dose combination of flutamide-metformin and ethinylestradiol-drospirenone was recently found to reduce the excess of total and abdominal fat, to diminish the deficit in lean mass, and to attenuate the dysadipocytokinemia of young women with ovarian hyperandrogenism, a variant of polycystic ovary syndrome. We questioned the need to give flutamide, an androgen receptor blocker, together with an oral contraceptive that contains drospirenone, a progestin claimed to have antiandrogen properties. The additive effects of low-dose flutamide (62.5 mg/d) were assessed over 3 months in young patients with hyperinsulinemic ovarian hyperandrogenism (n = 40; age, approximately 17 yr; body mass index, approximately 22 kg/m(2)); all participants started on metformin (850 mg/d) and a fourth-generation contraceptive (ethinylestradiol 30 microg plus drospirenone 3 mg, 21 d/month), and they were randomized to receive flutamide in addition (n = 20) or not (n = 20). Fasting blood glucose, serum insulin, lipid profile, testosterone, adiponectin, and IL-6 were determined at baseline and after 3 months, together with body composition (by dual x-ray absorptiometry) and with Doppler assessment of ovarian arterial resistance. At start, the pulsatility and resistance indices of ovarian arteries were elevated. By comparison of 3-month changes between randomized subgroups, the addition of low-dose flutamide was found to have consistently (more) normalizing effects on low-density lipoprotein cholesterol, IL-6, and adiponectin, lean body mass, total and abdominal fat mass, and arterial flow in the ovaries. In conclusion, low-dose flutamide is herewith identified as a pivotal component within a first contraceptive combination therapy that has been shown to attenuate the hypoadiponectinemia, ovarian vascular hyperresistance, lean mass deficit, and central adiposity of young women with polycystic ovary syndrome. Finally, these data challenge any claim that drospirenone, as currently used in a contraceptive, is a clinically significant antiandrogen.
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Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial.
Vermeulen, EG, Stehouwer, CD, Valk, J, van der Knaap, M, van den Berg, M, Twisk, JW, Prevoo, W, Rauwerda, JA
European journal of clinical investigation. 2004;(4):256-61
Abstract
BACKGROUND A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.
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Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study.
Winkler, K, Konrad, T, Füllert, S, Friedrich, I, Destani, R, Baumstark, MW, Krebs, K, Wieland, H, März, W
Diabetes care. 2003;(9):2588-94
Abstract
OBJECTIVE The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment. RESULTS At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.
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Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients.
Marcucci, R, Zanazzi, M, Bertoni, E, Rosati, A, Fedi, S, Lenti, M, Prisco, D, Castellani, S, Abbate, R, Salvadori, M
Transplantation. 2003;(9):1551-5
Abstract
BACKGROUND We previously demonstrated among renal-transplant recipients (RTRs) a high prevalence of hyperhomocysteinemia, which might account for their elevated cardiovascular risk. The purpose of our study was to document, in hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid intima-media thickness (cIMT), which is an early sign of atherosclerosis. METHODS A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All subjects underwent cardiovascular risk-factor assessment, including fasting homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries, at time of enrollment and after 6 months. RESULTS Fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%. Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy levels, had the major percentage of decrease of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation (group B) we documented a significant increase in cIMT after 6 months (0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT increase was + 23.3+/-21.1%. CONCLUSIONS Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs.
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Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia.
van Wissen, S, Smilde, TJ, Trip, MD, de Boo, T, Kastelein, JJ, Stalenhoef, AF
Heart (British Cardiac Society). 2003;(8):893-6
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Abstract
BACKGROUND Raised plasma lipoprotein(a) (Lp(a)) is associated with increased risk of cardiovascular disease. It is unknown whether increased Lp(a) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia (FH) or whether statin treatment can reduce Lp(a) concentrations in the long term. OBJECTIVE To investigate Lp(a) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients. DESIGN A two year, randomised, double blind trial (the ASAP trial). PATIENTS 325 heterozygous FH patients. INTERVENTION Treatment with 80 mg atorvastatin or 40 mg simvastatin. MAIN OUTCOME MEASURE Change in Lp(a) concentrations and intima-media thickness of carotid artery segments at one year and two years. RESULTS At baseline, median Lp(a) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms, respectively (p = 0.03). In the atorvastatin arm, Lp(a) concentrations decreased to 243 mg/l after one year (p < 0.001) and to 263 mg/l after two years (p < 0.001). In the simvastatin arm, Lp(a) concentrations decreased to 437 mg/l after one year (p < 0.001) and to 417 mg/l after two years (p < 0.001). The difference in Lp(a) reduction between the two treatment arms was significant after one year (p = 0.004), but not after two years (p = 0.086). Lp(a) concentrations at baseline were not related to cardiovascular events at baseline. There was no correlation between baseline Lp(a) concentrations and low density lipoprotein cholesterol concentrations or intima-media thickness at baseline. Change in Lp(a) concentrations was not correlated with change in intima-media thickness after one or two years. CONCLUSIONS Long term statin treatment significantly lowers Lp(a) in FH patients. However, this reduction was unrelated to changes in intima-media thickness and casts doubt on the importance of Lp(a) in the progression of atherosclerotic disease in these patients.