[Immunomodulating, metabolic and cardioprotective effects of AT1-angiotensin receptors blocker losartan in patients with coronary heart disease and type 2 diabetes mellitus].
OBJECTIVE
To evaluate effects of 6-month therapy with losartan in combination with indapamide on a clinical course, immunological, metabolic parameters, left ventricular function, exercise tolerance and quality of life in patients with coronary heart disease (CHD) associated with metabolic syndrome (MS).


METHODS
Forty six CHD patients with postinfarction cardiac dysfunction in MS were randomized into two groups. Group 1 consisted of 22 patients with impaired glucose tolerance, group 2--of 24 type 2 diabetics. Treatment included combination of losartan (50 mg/day) with indapamide (1.5 mg/day), on demand nitrates, nebivolol. Basic therapy in diabetes included sugar-reducing drugs. Clinical condition, findings of echocardiography, parameters of lipid and carbohydrate metabolisms, immunoglobulins, circulating immune complexes, autoantibodies to cardiolipin (AB to CL), spectrum of proinflammatory cytokines were studied before and 3 months after course treatment.


RESULTS
Overactivation of cytokines (primarily IL-2, IL-1, TNF alpha) with high expression of IgA, IgG, CIC, AB to CL was found in CHD patients with type 2 diabetes mellitus and less evident in impaired glucose tolerance. Losartan in both groups had an antihypertensive effect, stabilized LV hypertrophy, improved clinical symptoms leading to cytokines expression decline: TNF alpha by 9.8%, IL-1--by 6.1%, IL-6--by 6.7%. Losartan was well tolerated, caused no negative metabolic effects.


CONCLUSIONS
New original facts of cytokine overactivation and humoral immunity disturbances were discovered which play an essential role in pathogenesis of postinfarction dysfunction and LV remodeling developing in type 2 diabetes mellitus. Losartan 6-month treatment in the fixed combination has a positive effect on clinicohemodynamic and immunometabolic indices. This gives grounds for wider use of losartan in CHD combined with type 2 diabetes mellitus.
Tepliakov
A T
AT
Maianskaia
S D
SD
Bolotskaia
L A
LA
Vdovina
T V
TV
Stepacheva
T A
TA
Kuznetsova
A V
AV
Lukinov
A V
AV
Derbeneva
N V
NV
Frants
M V
MV
Shilov
S N
SN
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007190:Indapamide / Q000008:administration & dosage / Q000627:therapeutic use; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; D011446:Prospective Studies; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D016207:Cytokines; D007136:Immunoglobulins; D007155:Immunologic Factors; D007190:Indapamide; D019808:Losartan