Article

Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

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.
Journal of Hypertension (Impact Factor: 4.22). 10/2007; 25(9):1958-66. DOI: 10.1097/HJH.0b013e3282170ada
Source: PubMed

ABSTRACT 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.
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).
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.
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.

1 Bookmark
 · 
91 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibrosis is an accumulation of proteins including collagen in the extracellular space, which has previously been considered as irreversible damage in various cardiovascular diseases including heart failure and hypertension. The pathophysiology of fibrosis is currently better understood and can be evaluated by non-invasive methods. Here, the authors present briefly the impact and molecular mechanisms of fibrosis in the myocardium and the promising therapeutic candidates including anti-hypertensive therapies, heart-rate lowering drugs, anti-inflammatory agents, as well as other innovative approaches such as inhibitors of growth factors, miRNA or cell therapy. Surrogate end points allow for larger clinical trials than previously possible with endomyocardial biopsies, and magnetic resonance and molecular imaging should open new fields of research on cardiac fibrosis. Several pre-clinical findings are very promising, and some clinical data support the proofs of concept, mainly those with inhibitors of the renin-angiotensin system. These approaches open the field for regression of fibrosis and include the following: first, some of these drugs are widely used like renin-angiotensin system inhibitors; second, inflammation modulators; third, in near future entirely new approaches targeting the TGF-β pathways, or others like cell therapies or genetic interventions.
    Expert Review of Cardiovascular Therapy 11/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypertensive myocardial remodeling has an important role in the pathophysiology of hypertensive disease. This study suggests that telmisartan (TEL) can inhibit myocardial fibrosis of hypertensive left ventricular hypertrophy (LVH) through the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. Through echocardiography and hemodynamics, it was shown that TEL could improve cardiac function and reduce the degree of hypertensive LVH in hypertensive rats. Through immunoassay, it was shown that TEL could antagonize renin-angiotensin-aldosterone system expression in plasma and myocardial tissue. By Masson staining, Elisa and alkaline hydrolysis assays, it was demonstrated that TEL could significantly inhibit myocardial fibrosis in hypertensive rats and attenuate extracellular matrix-related proteins associated with pressure overload. Western blotting was used to detect the TGF-β1/Smad signaling pathway protein expression of myocardial tissue, and it was further found that TEL could inhibit activation of the TGF-β1/Smad signaling pathway. In conclusion, TEL could inhibit myocardial local angiotensin II (Ang II) level by directly affecting the Ang II receptor. TEL may also restore the balance of matrix metalloproteinases/tissue inhibitor of metalloproteinases, reduce myocardial collagen fibrosis and delay hypertensive LVH by affecting the TGF-β1/Smad signaling pathway.Hypertension Research advance online publication, 3 October 2013; doi:10.1038/hr.2013.119.
    Hypertension Research 10/2013; · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A) has been reported to contribute to the development of left ventricular (LV) hypertrophy. Little is known, however, about its possible impact on cardiac dysfunction. Enhanced myocardial fibrosis accompanying increased LV mass might represent a link with coexisting functional abnormalities. We investigated the association between the PPARGC1A Gly482Ser polymorphism and LV morphology and performance in essential hypertension, with special consideration of fibrosis intensity. A total of 205 hypertensive patients (60±8 years) underwent echocardiography with assessment of cardiac morphology, LV systolic (strain and strain rate) and diastolic function (peak early diastolic mitral flow velocity/peak late diastolic mitral flow velocity (E/A) ratio, peak early diastolic myocardial velocity (Em), and E/e' ratio (where e' is the peak early diastolic mitral annular velocity)), evaluation of serum procollagen type III amino-terminal propeptide (PIIINP) and procollagen type I carboxy-terminal propeptide (PICP)-markers of fibrosis and the PPARGC1A Gly482Ser genotyping. Subjects with the Ser-Ser genotype demonstrated more profound LV hypertrophy and diastolic function impairment, and higher PICP/PIIINP than the Ser-Gly and Gly-Gly groups. In multivariable analysis, the presence of the Ser-Ser allele was an independent correlate of E/e' (β=0.17, P<0.02), Em (β=-0.18, P<0.01) and LV mass index (β=0.28, P<0.001). In conclusion, in hypertensive patients, the PPARGC1A Gly482Ser polymorphism is associated with LV hypertrophy and diastolic dysfunction, with the presence of the Ser-Ser allele promoting these abnormalities. One of the possible mechanisms mediating the adverse effect on diastolic performance might be a relative increase in the anabolism of rigid collagen type I over that of the more elastic collagen type III, as indicated by an increased ratio of PICP to PIIINP.Journal of Human Hypertension advance online publication, 10 April 2014; doi:10.1038/jhh.2014.26.
    Journal of human hypertension 04/2014; · 2.80 Impact Factor

Full-text (2 Sources)

View
65 Downloads
Available from
May 23, 2014