Effects of perindopril on elastic and structural properties of large arteries in essential hypertension.
BACKGROUND
Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, is a well-recognized antihypertensive drug. Its ability to protect against cardiovascular events in hypertension has also been demonstrated. It decreases the stiffness of the larger arteries; questions remain as to the mechanisms involved and whether it is blood pressure (BP) control-dependent.


OBJECTIVE
To correlate the BP response to ACE inhibition therapy with changes in arterial stiffness as evaluated by pulse wave velocity (PWV), and to correlate these changes in arterial stiffness with alterations in indicators of vascular collagen metabolism serum levels of metalloproteinase (MMP)-1 and tissue inhibitor of MMP-1 (TIMP-1).


METHODS
A total of 162 patients aged 18 to 70 years with stage 1 and 2 essential hypertension (diastolic BP 95 mmHg to 114 mmHg) were enrolled to receive six months (M6) of therapy with the ACE inhibitor, perindopril. Patients were either treatment-naïve or had not received any antihypertensive treatment for at least six months before the study.


RESULTS
Mean BP was significantly reduced after two months (M2) of therapy (P=0.00001) and remained stable thereafter. In addition to the significant mean changes in PWV observed at M2 (P=0.00001), further reductions in PWV were noted at M6 (P=0.007). The change in PWV between baseline (M0) and M2 was significantly correlated to all BP parameters at M0 (correlation coefficient at M2 was 0.189 or greater). However, no correlation was seen regarding BP parameters at M2 and further M2 to M6 changes in PWV, suggesting a decrease of arterial stiffness independent of BP reduction. The expression of TIMP-1 and MMP-1 was highly variable and demonstrated no correlation with BP or PWV.


CONCLUSIONS
Reductions in BP and PWV appear to be correlated during the first two months of perindopril therapy. After six months, PWV continues to decrease independently of any further reduction in BP, suggesting the occurrence of a pressure-independent pharmacological remodelling of the arterial wall. A long-term, double-blind, randomized trial could be required to confirm that the observed increase in vascular distensibility induced by perindopril is related to a mechanism of action other than a reduction in BP.
Lacourcière
Yves
Y
Centre Hospitalier de l'Université Laval, Sainte-Foy, Québec. yves.lacourciere@crchul.ulaval.ca
Béliveau
Richard
R
Conter
Howard S
HS
Burgess
Ellen D
ED
Lepage
Serge
S
Pesant
Yves
Y
Spence
J David
JD
Asmar
Roland
R
Carrière
Serge
S
Plante
Gérard E
GE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001158:Arteries / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use*; D011673:Pulsatile Flow / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D020913:Perindopril