Explore the vast range of titles available.

In patients who have, or are at risk for, coronary artery disease, niacin added to statin therapy resulted in regression of the carotid intima–media thickness. In contrast, ezetimibe added to statin therapy paradoxically resulted in progression of the carotid intima–media thickness. Treatment with 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors reduces low-density lipoprotein (LDL) cholesterol levels and results in clinically significant reductions in the relative risk of major cardiovascular events. 1 However, because of the residual cardiovascular risk seen with statin monotherapy, treatment may be intensified with the use of combination therapy, aimed at either further reducing the LDL cholesterol level or at altering levels of other lipids, such as high-density lipoprotein (HDL) cholesterol. Progressive lowering of the LDL cholesterol level through intensification of statin therapy leads to a 16% reduction in the odds of cardiovascular events and death from cardiovascular causes. 2 This approach has . . .

ObjectiveThe aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese.Design, setting, patients, interventions and resultsA prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima–media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima–media thickness from baseline to month 30 was 0.010±0.095 mm in the rimonabant group and 0.012±0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005±0.042 mm for the rimonabant-treated group and 0.007±0.043 mm for the placebo-treated group (p=0.45).ConclusionsThere was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima–media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome.Clinical trial registration informationclinicaltrials.gov Identifier: NCT00228176.

OBJECTIVE: To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium. RESEARCH DESIGN AND METHODS: A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 μg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated. RESULTS: After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects. CONCLUSIONS: Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

Background The atherosclerotic process progresses more dynamically in hemodialysis (HD) patients than in the general population. In HD patients, lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery. We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness (IMT) in HD patients. Materials and methods A total of 47 patients on HD were included in the study. Patients were randomly divided into two groups: group A (Mg group), in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B (control group), in which patients received only calcium acetate therapy as a phosphate binder. At baseline and 2 months later, all patients underwent a carotid artery ultrasound scan to measure carotid IMT. Results At the end of 2 months, mean serum calcium, phosphorus, and calcium × phosphorus product were not changed in both groups. As expected, mean serum Mg level significantly increased in the Mg group at the end of 2 months. In addition, serum parathyroid hormone (PTH) level significantly decreased in the Mg group at the end of 2 months ( P  = 0.003). Baseline carotid IMT was similar between the groups. Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values ( P  = 0.001 for left, P  = 0.002 for right). Conclusion Based on the present data, magnesium may play an important protective role in the progression of atherosclerosis in patients on dialysis. Further studies are needed to assess more accurately the role of magnesium in atherosclerotic regression in dialysis patients.

Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (CIMT) to determine their relative potential to reduce cardiovascular risk independent of their antihyperglycemic actions. Ninety-two subjects with suboptimally controlled diabetes mellitus (hemoglobin A 1c [HbA 1c] >7.0%) were assigned to therapy with either rosiglitazone 4 mg once daily or metformin 850 mg twice daily for 24 weeks. The primary end point was the change in hsCRP after 24 weeks. The change in CIMT was prespecified as a secondary end point. Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA 1c −1.08% in the rosiglitazone group and −1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 ± 0.88 to 1.91 ± 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 ± 0.83 to 5.46 ± 0.92 mg/L; P = nonsignificant). Maximal CIMT progressed in the metformin group (+0.084 ± 0.038 mm), whereas regression of maximal CIMT was observed in the rosiglitazone group (−0.037 ± 0.031 mm; P = .02 for the between group comparison). Similar changes were observed for mean CIMT. The change in hsCRP and maximal CIMT were related in a multivariable model controlling for changes in HbA 1c and lipid parameters ( r = .31; P = .01). Rosiglitazone, compared to metformin, induced a prompt and profound reduction in hsCRP levels independent of its effect on glycemia. This change was associated with regression of CIMT after 24 weeks.

Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors exert antiatherosclerotic effects in preclinical models and antioxidant effects in patients. However, whether ACE inhibitors have any clinically significant antiatherogenic effects remains still debated. In mildly hypertensive patients, we evaluated the effect of the sulfhydryl ACE inhibitor zofenopril in comparison with the carboxylic ACE inhibitor enalapril on carotid atherosclerosis (intima-media thickness [IMT] and vascular lumen diameter) and systemic oxidative stress (nitrite/nitrate, asymmetrical dimethyl- l-arginine, and isoprostanes). In 2001, we started a small prospective randomized clinical trial on 48 newly diagnosed mildly hypertensive patients with no additional risk factors for atherosclerosis (eg, hyperlipidemia, smoke habit, familiar history of atherosclerosis-related diseases or diabetes). Patients were randomly assigned either to the enalapril (20 mg/d, n = 24) or the zofenopril group (30 mg/d, n = 24); the planned duration of the trial was 5 years. Carotid IMT and vascular lumen diameter were determined by ultrasonography for all patients at baseline and at 1, 3, and 5 years. Furthermore, nitrite/nitrate, asymmetrical dimethyl- l-arginine, and isoprostane levels were measured. In our conditions, IMT of the right and left common carotid arteries was similar at baseline in both groups ( P = NS). Intima-media thickness measurements until 5 years revealed a significant reduction in the zofenopril group but not in the enalapril group ( P < .05 vs enalapril-treated group). This effect was coupled with a favorable nitric oxide/oxidative stress profile in the zofenopril group. Long-term treatment with the sulfhydryl ACE inhibitor zofenopril besides its blood pressure–lowering effects may slow the progression of IMT of the carotid artery in newly diagnosed mildly hypertensive patients.

Metformin is a well-known oral hypoglycaemic agent and has been commonly used, in combination with sulphonylurea, to treat type 2 diabetes. However, the advantageous effect of metformin plus sulphonylurea on diabetic macroangiopathy has yet to be clarified. To evaluate whether sulphonylurea or sulphonylurea plus metformin prevent diabetic macroangiopathy, we examined the progression of carotid artery intima-media thickness (IMT) as a surrogate end point. Subjects with type 2 diabetes were divided into three groups, receiving the following treatments: (i) glibenclamide (n=59); (ii) gliclazide (n=30); and (iii) glibenclamide + metformin (n=29). Maximum IMT and average IMT (the greatest value among 6 average values of each 3 points including greatest thickness) were measured at the beginning and end of the observation period. For the follow-up period of 3 years, the annual change in average IMT of the glibenclamide plus metformin group (0.003+/-0.048 mm) was smaller than that of the glibenclamide group (0.064+/-0.045 mm) and gliclazide group (0.032+/-0.036 mm) (p<0.0001 and p=0.043 respectively). In the gliclazide group, average IMT increased during the follow-up period, but annual change in average IMT was significantly smaller than that of the glibenclamide group (p=0.005). Glibenclamide + metformin or gliclazide also attenuated the progression of maximum IMT, compared with that of glibenclamide (0.041+/-0.105, 0.044+/-0.106, 0.114+/-0.131 mm/year respectively, p=0.029 and p=0.035 respectively). Multivariable regression analysis implied that administration of metformin or gliclazide significantly and independently (p<0.05) reduces the progression of average IMT, compared with glibenclamide monotherapy. These data indicate that metformin or gliclazide, rather than glibenclamide, have a potent anti-atherogenic effect in type 2 diabetes.

Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease Edith D. Beishuizen , MD 1 , Marcel A. van de Ree , MD, PHD 2 , J. Wouter Jukema , MD, PHD 3 , Jouke T. Tamsma , MD, PHD 1 , J. Carel M. van der Vijver , MD, PHD 4 , A. Edo Meinders , MD, PHD 1 , Hein Putter , PHD 5 and Menno V. Huisman , MD, PHD 1 1 Department of General Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands 2 Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands 3 Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands 4 Department of Internal Medicine, Leyenburg Hospital, the Hague, the Netherlands 5 Department of Biostatistics, Leiden University Medical Center, Leiden, the Netherlands Address correspondence and reprint requests to E.D. Beishuizen, Department of General Internal Medicine, C1-R41, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. E-mail: e.d.beishuizen{at}lumc.nl or m.v.huisman{at}lumc.nl Abstract OBJECTIVE —Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS —A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years. RESULTS —Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group ( P < 0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group ( P = 0.006). CONCLUSIONS —There was no effect of 2 years’ statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group. ALT, alanine aminotransferase CAD, coronary artery disease CVD, cardiovascular disease IMT, intima-media thickness Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted September 11, 2004. Received June 25, 2004. DIABETES CARE

Cilostazol, a phosphodiesterase III inhibitor, is known to have anti-proliferative activity. We investigated the effects of cilostazol 200 mg, in addition to aspirin 100 mg and clopidogrel 75 mg, on carotid intima-media thickness (IMT) progression during a 2-year follow-up period in patients with acute coronary syndrome (ACS) requiring stent implantation. Patients with ACS ( n  = 130) were randomly assigned to the cilostazol group ( n  = 64) or the control group ( n  = 66). Longitudinal images of left and right carotid IMT were measured at baseline, at 6, 12, and 24 months using a 10-MHz linear vascular probe. The primary endpoint was to compare the changes in maximum carotid IMT at 2 years. Other parameters such as inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and adiponectin] and bleeding risk were also compared. The carotid IMT showed no significant progression from baseline in the cilostazol group compared to significant progression in the control group at 12 months (0.78 ± 0.38 and 0.85 ± 0.41 mm, p  = 0.034, respectively) and 24 months (0.82 ± 0.41 and 0.96 ± 0.39 mm, p  = 0.022, respectively). Major bleeding ( p  = 1.00), minor bleeding ( p  = 0.68), and total bleeding rates ( p  = 0.74) were similar between the two groups during the 2-year follow-up. Decreases from baseline in IL-6 (−2.79 ± 2.83 and −2.14 ± 3.36 pg/ml, p  = 0.010, respectively) and TNF-α (−2.81 ± 1.97 and −2.21 ± 2.68 pg/ml, p  = 0.029, respectively) were significantly greater in the cilostazol group than the control group during the follow-up. Cilostazol treatment, with greater anti-inflammatory effect, inhibited the progression of carotid IMT without increasing the risk of bleeding in patients with ACS during the 2-year follow-up.

Tamoxifen is a selective estrogen-receptor modulator shown to improve several cardiovascular risk factors in postmenopausal women with breast cancer. In animal studies tamoxifen inhibits the progression of atherosclerosis. Although the presence of a history with tamoxifen treatment is related to a lower intima-media thickness (IMT) of the common carotid artery, data from controlled follow-up studies are lacking to support this observation. We examined 14 postmenopausal women with early stage breast cancer with indication for tamoxifen treatment (20 mg/d) and 13 healthy postmenopausal women. Flow-mediated dilatation (FMD) of the brachial artery, combined carotid IMT, and aortic pulse wave were measured before and 6 months after treatment in the tamoxifen group and at the same times in the control group. FMD and IMT were significantly increased and decreased, respectively, in the treatment group compared to the control group (FMD: +2.2% ± 0.9% vs +0.085% ± 1%, P = .012; IMT: −0.088 ± 0.03 mm vs +0.04 ± 0.03 mm, P = .018, mean ± standard error of the mean, treatment vs control group). These differences remained significant even when adjusted for age, duration of menopause, and cardiovascular risk factors. Low-density lipoprotein cholesterol was also significantly reduced after tamoxifen treatment. Tamoxifen treatment slows the progression of atherosclerosis in postmenopausal women with breast cancer as assessed by changes in carotid IMT. An improvement in endothelial function and blood lipid profile may be the reason for this beneficial effect.