Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).
OBJECTIVE
Hypertensive left ventricular hypertrophy (LVH) is associated with cardiomyocyte hypertrophy and an excess in myocardial collagen. Myocardial fibrosis may cause diastolic dysfunction and heart failure. Circulating levels of the carboxy-terminal propeptide of procollagen type I (PICP), an index of collagen type I synthesis, correlate with the extent of myocardial fibrosis. This study examines myocardial fibrosis in relation to blood pressure, left ventricular mass (LVM), and diastolic function.


METHODS
We examined PICP levels in 115 patients with hypertensive LVH, 38 with hypertension but no hypertrophy, and 38 normotensive subjects. Patients with LVH were subsequently randomly assigned to the angiotensin II type 1 receptor blocker irbesartan or the beta1 receptor blocker atenolol for 48 weeks. Diastolic function was evaluated by tissue velocity echocardiography (n=134). We measured basal septal wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm).


RESULTS
Compared with the normotensive group, PICP was elevated and left ventricular diastolic function was impaired in the hypertensive groups, with little difference between patients with and without LVH. PICP related to blood pressure, IVRTm, Em, and E/Em, but not to LVM. Irbesartan and atenolol reduced PICP similarly. Only in the irbesartan group did changes in PICP relate to changes in IVRTm, and LVM.


CONCLUSIONS
Myocardial fibrosis and diastolic dysfunction are present in hypertension before LVH develops. The findings with irbesartan suggest a role for angiotensin II in the control of myocardial fibrosis and diastolic function in patients with hypertension with LVH.
Müller-Brunotte
Richard
R
Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden, and Department of Cardiology and Cardiovascular Surgery, School of Medicine, University of Navarra, Pamplona, Spain. richard.muller-brunotte@ds.se
Kahan
Thomas
T
López
Begoña
B
Edner
Magnus
M
González
Arantxa
A
Díez
Javier
J
Malmqvist
Karin
K
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D024042:Collagen Type I / Q000378:metabolism; D003971:Diastole; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D024042:Collagen Type I; D013777:Tetrazoles; D001262:Atenolol; D000077405:Irbesartan