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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
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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.).
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The Central European diet as an alternative to the Mediterranean diet in atherosclerosis prevention in postmenopausal obese women with a high risk of metabolic syndrome - a randomized nutrition-al trial.
Duś-Żuchowska, M, Bajerska, J, Krzyżanowska, P, Chmurzyńska, A, Miśkiewicz-Chotnicka, A, Muzsik, A, Walkowiak, J
Acta scientiarum polonorum. Technologia alimentaria. 2018;(4):399-407
Abstract
BACKGROUND Metabolic syndrome (MS) is a powerful risk factor for atherosclerosis (AT). The crucial meth- od of minimizing the development of atherosclerosis and its clinical manifestations is lifestyle modifications, including following a healthy diet. The aim of the study was to check if the Central European Diet (CED) could be an alternative to the Mediterranean Diet (MED) in the prevention of AT in patients with a risk of MS. METHODS The randomized, single-blind nutritional trial involved 144 obese women with a risk of MS. The subjects were randomly assigned to two groups and followed MED (n = 72) or CED (n = 72) for 16 weeks. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and asymmetrical dimethylarginine (ADMA) were measured before and after nutritional intervention. RESULTS In both studied groups, the concentrations of hs-CRP decreased significantly after the nutritional in- tervention (CED: p = 0.0107; MED: p = 0.0002). The ADMA levels were significantly lower after nutritional intervention in the CED group (p = 0.0187) but not in the MED group (p = 0.8354). However, the observed changes of hs-CRP concentrations (Δhs-CRP) and ADMA levels (ΔADMA) were not different between the groups (p = 0.5307 and p = 0.0905, respectively). CONCLUSIONS In the Central European post-menopausal obese population, a well-designed, energy-restricted diet with the use of food items traditional for the region (CED) could be a good alternative to MED in terms of AT prevention.