Effect on the atherogenic marker plasminogen activator inhibitor type-1 of addition of the ACE inhibitor imidapril to angiotensin II type 1 receptor antagonist therapy in hypertensive patients with abnormal glucose metabolism: a prospective cohort study in primary care.
OBJECTIVE
Renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), are recommended by the American Diabetes Association for blood pressure control and prevention or management of cardiovascular disease in patients with diabetes mellitus. However, some investigators have suggested that ARBs may increase the risk of myocardial infarction in hypertensive patients. Activation of the RAS is associated with an increased risk of ischaemic events. Angiotensin II stimulates the production of plasminogen activator inhibitor type-1 (PAI-1), a powerful predictor of cardiovascular disease. ACE inhibitors are reported to reduce PAI-1 levels and activity, while ARBs do not reduce or may even elevate levels of this atherogenic marker. The objective of this study was to determine whether the ACE inhibitor imidapril reduces PAI-1 levels in hypertensive patients already being treated with an ARB.


METHODS
This was a prospective cohort study carried out in primary care with a follow-up period of 6 months. Estimating the alpha error (p-value) at 0.05, the power of the test as 80%, and the difference in PAI-1 levels as 10 + or - 15 ng/mL, the required sample size was calculated to be 40. Participants were hypertensive patients taking ARBs for more than 8 weeks, and having dyslipidaemia, obesity or abnormal glucose metabolism. Imidapril 5-10 mg/day was prescribed for 6 months to reduce blood pressure to <130/80 mmHg. The main outcome measure, PAI-1 level, was measured before and 6 months after the addition of imidapril to ARBs in 21 subjects (13 men, eight women), all with abnormal glucose metabolism, nine with dyslipidaemia, and six who were obese. Bodyweight, body mass index, blood pressure, homeostasis model assessment of insulin resistance, glycosylated haemoglobin, creatinine, potassium, high sensitivity C-reactive protein (hs-CRP), and high molecular weight adiponectin levels were measured as secondary outcomes.


RESULTS
PAI-1 level was not significantly changed overall. Hs-CRP level was also not significantly changed; however, the high molecular weight adiponectin level was significantly increased (p = 0.044), especially in men (p = 0.026). There were no significant changes in the other outcomes measured.


CONCLUSIONS
The current study showed that imidapril added to ARBs did not decrease PAI-1 levels in hypertensive patients with abnormal glucose metabolism; however, this combination therapy significantly increased high molecular weight adiponectin levels in men.
Yajima
Ken
K
Department of Internal Medicine, Federation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, 4-2-22 Nishikicho, Tachikawa,Tokyo 190-8531, Japan. k-yajima@rondo.plala.or.jp
Shimada
Akira
A
Hirose
Hiroshi
H
Oikawa
Yoichi
Y
Yamada
Satoru
S
Meguro
Shu
S
Irie
Junichiro
J
Irie
Seiko
S
D052242:Adiponectin / Q000378:metabolism; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D048289:Imidazolidines / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011320:Primary Health Care; D011446:Prospective Studies; D016896:Treatment Outcome
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D002097:C-Reactive Protein; C065166:imidapril; D005947:Glucose