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CNAA / Theses / 2007 / May /

Some pharmacological aspects of hypertensive diastolic dysfunction: nonselective beta-adrenoblockade versus third generation dihydropiridine

Author: Popescu Liuba
Degree:doctor of medicine
Speciality: 14.00.06 - Cardiology and Reumatology
Scientific adviser: Alexandru Carauş
doctor habilitat, professor
Scientific council:


The thesis was presented on the 22 May, 2007
Approved by NCAA on the 14 June, 2007


Adobe PDF document0.35 Mb / in romanian


CZU 616.12-008.331.1-091-085.225.2

Adobe PDF document 1.06 Mb / in romanian
140 pages


arterial hypertension, non-selective beta-blocker, third generation dihydropyridine, diastolic dysfunction


In this study are presented the results of a long-term 12 months follow-up of 101 patients with essential arterial hypertension of II-III degree with associated diastolic dysfunction. They were studied by means of echocardiography and ambulatory blood pressure recording.

Despite the preserved systolic function (EF 60,50,7%), the functional classe NYHA 1,60,08 was determined on patients with severe hypertension.

The diastolic function in patients with severe hypertension was affected predominantly by the "relaxation abnormality" type in 90,2%, sometimes – "restrictive physiology" – 7,8% and insignificant – "pseudonormalization" type in 2%. The high incidence of circadian sistolic blood pressure rhytm "night-picker" and "non-dipper" has been established in 72,4% and circadian diastolic blood pressure rhytm in 71,7% of the patients with arterial hypertension and diastolic dysfunction.

The combination of triple antihypertensive agents (Indapamide + Lisinopril + Timolol or Amlodipine) during 12 months demonstrated a significant reduction of the variability blood pressure. Some indices as: STD SBP mean daytime and STD SBP mean nighttime; STD DBP mean daytime and STD DBP mean nighttime were significantly diminished in Timolol vs Amlodipin (46,2% vs 43,6%, 58,4% vs 51%, 53,4% vs 42,2%, 59,6 vs 49,5%).

After 12 months we observed the best results in the I group (Timolol), with improved diastolic function. Increased ratio E/A - 98,5% Timolol versus 91,3% Amlodipine and improved peak of early LV filling; reduced izovolumetric relaxation time - 29,3% vs 26,4% and deceleration time - 19,1% vs 14,4%. Thus, during a 12 months treatment, there was established the rate pattern of ventricular filling by "relaxation abnormality" type in – 34,2% Amlodipine vs 10% Timolol.

Using the nonselective beta-blocker, it was establshed a more significant reduction of the hypertrophy of the left ventricular myocardium at all stages of investigation.

Both therapeutical regimens exert a favorable effect on the exercise capacity, which directly dependents of the treatment’s duration, but this effect is better in combined therapy with non-selective beta-blocker Timolol. The "6 minutes walk" test is significantly interdepending of some parameters of the exercise test: the test’s duration and power of last steps (the corelation coefficient - 0,38, p<0,001) and the total volume of the work (the corelation coefficient - 0,36, p<0,001).

It has been established the degree of corelation between the variability of blood pressure with the diastolic dysfunction: STD SBP mean nighttime and ratio E/A – 0,38 (p0,001); STD DBP mean nighttime and ratio E/A – 0,37 (p<0,001); izovolumetric relaxation time – 0,33 (p<0,001).

The results of the study demonstrate the benefic effect of both agents on diurn profile of blood pressure and diastolic function, with predominant effects following to the treatment with beta-blocker – Timolol.