AJH
1991;
4:168S-171S
Decreased Fibrinolytic Activity and Increased Platelet Function in Hypertension Possible Influence of Calcium Antagonism Gitte Gleerup and Kaj Winther
Twelve patients w i t h mild hypertension were com p a r e d , after 14 d a y s of p l a c e b o , w i t h a n a g e - a n d g e n d e r - m a t c h e d g r o u p of 12 h e a l t h y v o l u n t e e r s for p l a t e l e t a g g r e g a b i l i t y a n d fibrinolytic activity. Fol l o w i n g t h i s , 10 of t h e 12 h y p e r t e n s i v e s w e r e t r e a t e d w i t h t h e c a l c i u m a n t a g o n i s t i s r a d i p i n e for 12 m o n t h s . Blood w a s d r a w n for d e t e r m i n a t i o n s of p l a t e l e t a g g r e g a t i o n a n d fibrinolytic activity after t w o w e e k s a n d 12 m o n t h s of t r e a t m e n t . Platelet a g g r e g a t i o n t e n d e d to i n c r e a s e i n t h e h y p e r t e n s i v e s c o m p a r e d w i t h controls, i n d i c a t e d b y a l o w e r i n g of t h e a d e n o s i n e d i p h o s p h a t e (ADP) t h r e s h o l d v a l u e for i r r e v e r s i b l e a g g r e g a t i o n . T i s s u e - p l a s m i n o g e n activator (t-PA) activity w a s significantly d e c r e a s e d
i n h y p e r t e n s i v e s c o m p a r e d to controls (P < .05). D u r i n g therapy, platelet aggregation decreased a n d t - P A activity i n c r e a s e d (P < .05). T h e p r e s e n t d a t a suggest t h a t fibrinolytic activity is d e c r e a s e d a n d p l a t e l e t a g g r e g a t i o n i n c r e a s e d i n m i l d h y p e r t e n s i o n . Besides t h e b l o o d p r e s s u r e - l o w e r i n g effect, i s r a d i p i n e m a y protect a g a i n s t t h r o m boembolic diseases b y modifying platelet function a n d fibrinolytic activity. A m J H y p e r t e n s 1991;4:168S-171S
T
rameters of lowering the blood pressure by treatment with the dihydropyridine calcium antagonist isradipine.
h e higher t h a n n o r m a l incidence of t h r o m b o e m bolism in hypertension may, in part, be the re sult of the e n h a n c e d platelet activity reported in the disease. However, the role of fibrinolytic activity, w h i c h serves as a natural protection against thrombosis, h a s still not, to our knowledge, b e e n d e fined in hypertension. The aims of the present study were twofold: to m e a s u r e the influence of untreated mild hypertension on fibrinolytic activity a n d platelet aggregability; a n d to assess the effect on these t w o p a 1
From the Medical Department B, Frederiksberg Hospital; Depart ment of Clinical Chemistry, Frederiksberg and Hvidovre HospitalCopenhagen, Denmark. Address correspondence and reprint requests to Kaj Winther, M D , Department of Clinical Chemistry, Hvidovre Hospital, DK-2650 Hvidovre, Denmark.
© 1991 by the American Journal of Hypertension,
Inc.
KEY WORDS: F i b r i n o l y s i s , p l a t e l e t s , h y p e r t e n s i o n , calcium a n t a g o n i s m .
PATIENTS A N D METHODS Twelve voluntary patients (nine m e n a n d three w o m e n ; m e a n age 55 years, range 42 to 76 years) with mild hypertension, defined as a diastolic blood pressure (DBP) > 90 m m Hg, were c o m p a r e d after 14 days of placebo with a n age - a n d g e n d e r - m a t c h e d g r o u p of 12 healthy volunteers for their platelet aggregability a n d fibrinolytic activity. Ten of the hypertensive patients (seven m e n , three w o m e n ) w e r e t h e n treated w i t h 2.5 m g isradipine twice daily for 12 m o n t h s . Blood s a m ples for evaluation of fibrinolytic activity a n d platelet aggregation w e r e taken after t w o weeks a n d 12 m o n t h s of active treatment. T w o h o u r s after drug administration, w e m e a s u r e d the blood pressure in the supine position after 30 min of rest using a mercury s p h y g m o m a n o m e t e r a n d heart rate 0895-7061/'91/'$3.50
AJH-FEBRUARY
1991-VOL
4, NO. 2, PART 2
FIBRINOLYTIC ACTIVITY A N D PLATELET F U N C T I O N
PAI
t-PA Controls
Hypertensives
Controls
Hypertensives
20
1.0
Ε
Ε
•—,
D
< CL
169S
0.5
10
1991;
4:168S-171S
Decreased Fibrinolytic Activity and Increased Platelet Function in Hypertension Possible Influence of Calcium Antagonism Gitte Gleerup and Kaj Winther
Twelve patients w i t h mild hypertension were com p a r e d , after 14 d a y s of p l a c e b o , w i t h a n a g e - a n d g e n d e r - m a t c h e d g r o u p of 12 h e a l t h y v o l u n t e e r s for p l a t e l e t a g g r e g a b i l i t y a n d fibrinolytic activity. Fol l o w i n g t h i s , 10 of t h e 12 h y p e r t e n s i v e s w e r e t r e a t e d w i t h t h e c a l c i u m a n t a g o n i s t i s r a d i p i n e for 12 m o n t h s . Blood w a s d r a w n for d e t e r m i n a t i o n s of p l a t e l e t a g g r e g a t i o n a n d fibrinolytic activity after t w o w e e k s a n d 12 m o n t h s of t r e a t m e n t . Platelet a g g r e g a t i o n t e n d e d to i n c r e a s e i n t h e h y p e r t e n s i v e s c o m p a r e d w i t h controls, i n d i c a t e d b y a l o w e r i n g of t h e a d e n o s i n e d i p h o s p h a t e (ADP) t h r e s h o l d v a l u e for i r r e v e r s i b l e a g g r e g a t i o n . T i s s u e - p l a s m i n o g e n activator (t-PA) activity w a s significantly d e c r e a s e d
i n h y p e r t e n s i v e s c o m p a r e d to controls (P < .05). D u r i n g therapy, platelet aggregation decreased a n d t - P A activity i n c r e a s e d (P < .05). T h e p r e s e n t d a t a suggest t h a t fibrinolytic activity is d e c r e a s e d a n d p l a t e l e t a g g r e g a t i o n i n c r e a s e d i n m i l d h y p e r t e n s i o n . Besides t h e b l o o d p r e s s u r e - l o w e r i n g effect, i s r a d i p i n e m a y protect a g a i n s t t h r o m boembolic diseases b y modifying platelet function a n d fibrinolytic activity. A m J H y p e r t e n s 1991;4:168S-171S
T
rameters of lowering the blood pressure by treatment with the dihydropyridine calcium antagonist isradipine.
h e higher t h a n n o r m a l incidence of t h r o m b o e m bolism in hypertension may, in part, be the re sult of the e n h a n c e d platelet activity reported in the disease. However, the role of fibrinolytic activity, w h i c h serves as a natural protection against thrombosis, h a s still not, to our knowledge, b e e n d e fined in hypertension. The aims of the present study were twofold: to m e a s u r e the influence of untreated mild hypertension on fibrinolytic activity a n d platelet aggregability; a n d to assess the effect on these t w o p a 1
From the Medical Department B, Frederiksberg Hospital; Depart ment of Clinical Chemistry, Frederiksberg and Hvidovre HospitalCopenhagen, Denmark. Address correspondence and reprint requests to Kaj Winther, M D , Department of Clinical Chemistry, Hvidovre Hospital, DK-2650 Hvidovre, Denmark.
© 1991 by the American Journal of Hypertension,
Inc.
KEY WORDS: F i b r i n o l y s i s , p l a t e l e t s , h y p e r t e n s i o n , calcium a n t a g o n i s m .
PATIENTS A N D METHODS Twelve voluntary patients (nine m e n a n d three w o m e n ; m e a n age 55 years, range 42 to 76 years) with mild hypertension, defined as a diastolic blood pressure (DBP) > 90 m m Hg, were c o m p a r e d after 14 days of placebo with a n age - a n d g e n d e r - m a t c h e d g r o u p of 12 healthy volunteers for their platelet aggregability a n d fibrinolytic activity. Ten of the hypertensive patients (seven m e n , three w o m e n ) w e r e t h e n treated w i t h 2.5 m g isradipine twice daily for 12 m o n t h s . Blood s a m ples for evaluation of fibrinolytic activity a n d platelet aggregation w e r e taken after t w o weeks a n d 12 m o n t h s of active treatment. T w o h o u r s after drug administration, w e m e a s u r e d the blood pressure in the supine position after 30 min of rest using a mercury s p h y g m o m a n o m e t e r a n d heart rate 0895-7061/'91/'$3.50
AJH-FEBRUARY
1991-VOL
4, NO. 2, PART 2
FIBRINOLYTIC ACTIVITY A N D PLATELET F U N C T I O N
PAI
t-PA Controls
Hypertensives
Controls
Hypertensives
20
1.0
Ε
Ε
•—,
D
< CL
169S
0.5
10
