0
selected
-
1.
Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.
Ridker, PM, Everett, BM, Pradhan, A, MacFadyen, JG, Solomon, DH, Zaharris, E, Mam, V, Hasan, A, Rosenberg, Y, Iturriaga, E, et al
The New England journal of medicine. 2019;(8):752-762
-
-
Free full text
-
Abstract
BACKGROUND Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1β, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).
-
2.
The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) study.
Purnell, JQ, Zinman, B, Brunzell, JD, ,
Circulation. 2013;(2):180-7
-
-
Free full text
-
Abstract
BACKGROUND Intensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease. METHODS AND RESULTS Subjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+5%, P < 0.001 EDIC year 1, P = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49; P = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (P = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4; P = 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment. CONCLUSIONS Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC. CLINICAL TRIAL REGISTRATION URL for DCCT http://clinicaltrials.gov; Unique identifier: NCT00360815. URL for EDIC http://clinicaltrials.gov; Unique identifier: NCT00360893.
-
3.
Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome.
Fitch, K, Abbara, S, Lee, H, Stavrou, E, Sacks, R, Michel, T, Hemphill, L, Torriani, M, Grinspoon, S
AIDS (London, England). 2012;(5):587-97
-
-
Free full text
-
Abstract
OBJECTIVE Metabolic abnormalities including diabetes, dyslipidemia, hypertension, and abdominal obesity occur commonly in HIV patients, are associated with increased coronary artery calcification (CAC), and contribute to increased cardiovascular disease (CVD) in this population. We hypothesized that lifestyle modification (LSM) and metformin would improve CVD indices in HIV patients with metabolic syndrome. DESIGN A randomized, placebo-controlled trial to investigate LSM and metformin, alone and in combination, over 1 year, among 50 HIV-infected patients with metabolic syndrome. METHODS We assessed CAC, cardiovascular and metabolic indices. RESULTS Among the participants, duration of HIV-infection was 14 ± 1 year and duration of antiretroviral therapy was 6 ± 1 year. Metformin-treated patients demonstrated significantly less progression of CAC (-1 ± 2 vs. 33 ± 17, P = 0.004, metformin vs. placebo), whereas the effect of LSM on CAC progression was not significant (8 ± 6 vs. 21 ± 14, P = 0.82, LSM vs. no-LSM). Metformin had a significantly greater effect on CAC than LSM (P = 0.01). Metformin-treated patients also demonstrated less progression in calcified plaque volume (-0.4 ± 1.9 vs. 27.6 ± 13.8 μl, P = 0.008) and improved homeostatic model of assessment-insulin resistance (HOMA-IR) (P = 0.05) compared with placebo. Participants randomized to LSM vs. no-LSM showed significant improvement in HDL (P = 0.03), high-sensitivity C-reactive protein (hsCRP) (P = 0.05), and cardiorespiratory fitness. Changes in CAC among the four groups--no-LSM-placebo (43 ± 30); LSM-placebo (19 ± 7); no-LSM-metformin (1 ± 1) and LSM-metformin (-4 ± 6)--were different (P = 0.03 for ANOVA and linear trend across groups), and the majority of this effect was mediated by metformin. Results are mean ± SEM. CONCLUSION Metformin prevents plaque progression in HIV-infected patients with the metabolic syndrome.
-
4.
The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome.
Thoenes, M, Oguchi, A, Nagamia, S, Vaccari, CS, Hammoud, R, Umpierrez, GE, Khan, BV
International journal of clinical practice. 2007;(11):1942-8
-
-
Free full text
-
Abstract
BACKGROUND Niacin is an agent that significantly increases high-density lipoprotein cholesterol (HDL-C), but its effects on surrogate markers of atherosclerosis and inflammatory markers are less clear. We studied the effects of niacin on carotid intimal media thickness (IMT), brachial artery reactivity as well as markers of inflammation and the metabolic profile of patients with metabolic syndrome. METHODS AND RESULTS Fifty patients with the metabolic syndrome (Adult Treatment Panel (ATP) III criteria) were randomised to either extended-release niacin (1000 mg/day) or placebo. After 52 weeks of treatment, there was a change of carotid IMT of +0.009 +/- 0.003 mm in the placebo group and -0.005 +/- 0.002 mm in the niacin group (p = 0.021 between groups). Endothelial function improved by 22% in the group treated with niacin (p < 0.001), whereas no significant changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p = 0.013). Niacin increased HDL-C (p < 0.001) and decreased low-density lipoprotein cholesterol and triglycerides (p < 0.001) significantly, and there were no adverse effects on fasting glucose levels after 52 weeks of treatment. CONCLUSION Extended-release niacin therapy effects a regression in carotid intimal medial thickness and improvement in metabolic parameters (increased HDL and reduced triglycerides). Furthermore, extended-release niacin may demonstrate an anti-atherogenic effect in the metabolic syndrome by improving endothelial function and decreasing vascular inflammation.