Objective: To determine whether the benefits of dapagliflozin in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes in DAPA-HF varied by background glucose-lowering therapy (GLT). Research design and methods: We examined the effect of study treatment by the use or not of GLT, and by GLT classes and combinations. The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Results: In the 2139 type 2 diabetes patients, the effect of dapagliflozin on the primary outcome was consistent by GLT use/no use (hazard ratio 0.72 [95%CI 0.58-0.88] versus 0.86 [0.60-1.23]; P-interaction=0.39) and across GLT classes. Conclusions: In DAPA-HF, dapagliflozin improved outcomes irrespective of use/no use of GLT or by GLT type used in patients with type 2 diabetes and HFrEF.
Purified C-reactive protein induces the production of autoantibodies to lipoprotein Bcontaining lipoproteins in animals. This is due to a C-reactive protein idiotype that permits the interference of C-reactive protein in the idiotype-anti-idiotypical ilmnunological reactions and stimulation of autoimmune response to lipoproteins. Key Words: C-reactive protein; low-and very low-density lipoproteins; autoantibodies; Miotype-anti-idiotypic regulationInflammatory processes often involve shifts in the plasma lipoprotein (LP)spectrum [5,11]. C-reactive protein (CRP), a factor of acute phase of inflammation, is involved in LP metabolism. Binding to low-(LDLP) and very low-density LP (VLDLP) [10], CRP activates their take-up by macrophages [6] and promotes their accumulation in arterial walls [8,9]. Due to affinity for phosphorylcholine, CRP idiotype is similar to antibodies to it [ 12] and simulates their capacity of selective regulation of immune response to phosphorylcholine-containing antigens [7]. CRP may be involved in autoimmune reaction to LP. The role of CRP in specific regulation of immune response to LP is not clear.We investigated the effect of CRP on humoral immune response to LP. MATERIALS AND METHODSNative human pentamer CRP (pCRP) or its monomers (mCRP), CRP immune complex with asinine IgG antibodies, human LP, or control preparations (phosphate-buffered saline, pH 7.2, IgG and human serum albumin, or human IgG) with complete Freund's adjuvant during the first 2-3 weeks and Departments of Immunology and Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg then without it were twice injected to two-monthold male CBA/CaJ mice and Chinchilla rabbits from Rappolovo Breeding Center. To rabbits the first dose (300 ~g protein) was injected in the hind paw pads and the second (100 ~tg) in the popliteal lymph nodes; to mouse both doses (100 ktg protein) were injected intraperitoneally. We used electrophoretically homogeneous pCRP [2] free from apolipoprotein B-containing LP (according to agarose and cellulose acetate electrophoresis, gradient electrophoresis with SDS, rocket imlnunoelectrophoresis, immunoblotting, and passive helnagglutination inhibition test with rabbit antibodies to human apolipoprotein B). Lipoproteins were isolated from human and animal plasma by sequential ultracentrifugation [4] and analyzed for the presence of CRP in passive hemagglutination test with commercial asinine antiserum to human pCRP and rabbit antisera to human pCRP and mCRP [2] exhausted with human VLDLP. Guinea pig antibodies to rabbit apolipoprotein B and rabbit antibodies to human LDLP and VLDLP and the corresponding antiidiotypic sera were used [1]. LDLP-specific antibody-producing cells were detected in mouse spleens by Jerne's method [3]. Circulating antibodies to LP, CRP, and control proteins were detected by passive hemagglutination test and anti-idiotypic antibodies by passive hemagglutination inhibition test.
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