title: Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress.
abstract: The side effects of thiazide-type diuretics include metabolic abnormality and increased oxidative stress, which might cause endothelial dysfunction despite blood pressure reduction. In hypertensive patients with heart failure, treatment with an aldosterone antagonist resulted in improvements in endothelial function and significant blood pressure reduction. The purpose of the present study was to evaluate the differences between spironolactone and chlorthalidone in hypertensive elderly patients treated with calcium antagonists and angiotensin II receptor blockers. Fourteen uncontrolled hypertensive patients treated with amlodipine and candesartan were included in this study. The study was an open-label randomized crossover comparison of 16 weeks treatment with spironolactone against chlorthalidone added to amlodipine and candesartan. Blood pressure significantly decreased in patients treated with both spironolactone and chlorthalidone. Chlorthalidone reduced flow mediated dilation significantly compared to the baseline condition and spironolactone. Serum high sensitively C-reactive protein and uric acid increased significantly in chlorthalidone-treated patients compared to spironolactone treated patients. We conclude that spironolactone may be a more useful add-on therapy than chlorthalidone in hypertensive patients inadequately controlled on candesartan and amlodipine, because spironolactone preserves endothelial function and reduces inflammation compared to chlorthalidone.
authors.affiliation: Yamanari Clinic, Yoshii-cho, Ibara, Japan. hiyama@ibara.ne.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamanari
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Daiji
authors.initials: D
authors.lastname: Miura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamanari
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002752:Chlorthalidone / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011188:Potassium / Q000097:blood; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013148:Spironolactone / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D013148:Spironolactone; D002097:C-Reactive Protein; D002752:Chlorthalidone; D011188:Potassium