Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension.
BACKGROUND
Type 2 diabetes mellitus (T2DM) with microalbuminuria (MA) is associated with increased risk of cardiovascular events (CVE) that may be attenuated by angiotensin-converting enzyme inhibitors (ACEIs), unless microalbuminuria persists (PMA). African-Americans (AA) have a higher prevalence of nephropathy with suboptimal response to ACEIs. We studied the effects of beta-blockers addition and comparative effects of carvedilol with metoprolol on 24-h urinary-albumin excretion (UAE) and endothelial function (EF) in AA with PMA.


METHODS
Thirty-four AA 30-70 years of age with T2DM and PMA despite ACEI therapy were randomized to receive carvedilol or metoprolol in addition to ACEI and any other concurrent therapy. Carvedilol/metoprolol dose was titrated to achieve blood pressure (BP) <130/80 mm Hg. UAE and brachial-artery reactivity were studied at baseline and 12 weeks. We analyzed the effects of addition of beta-blockers and whether there was any difference in response between the two beta-blockers.


RESULTS
Thirty-three subjects completed the study; BP decreased to <135/80 mm Hg. After 12 weeks, beta-blocker treatment resulted in significant increase in flow-mediated dilatation (FMD) from 3.5+/-1% to 8.5+/-1% (P=.004) and significant reduction in mean log-transformed UAE from 2.655 g/g Cr+/-0.087 to 2.533 g/g Cr+/-0.093 (P=.028). FMD increased by 240% (P=.033) with carvedilol and by 110% (P=.096; NS) with metoprolol. UAE decreased with carvedilol by 0.35 g/g Cr (P=.023) and with metoprolol by 0.23 g/g Cr (P=.298; NS).


CONCLUSIONS
Our results clearly indicate that addition of beta-blockers to ACEI improves EF and reduces UAE in high-risk AA T2DM patients with PMA. Carvedilol but not metoprolol improves EF and reduces UAE in AA with identical BP control. Larger trials are needed to further elucidate the differential effects of carvedilol/metoprolol on EF and UAE and its impact on CVE in such patients.
Jawa
Ali
A
King Edward Medical University, Lahore, Pakistan.
Nachimuthu
Senthil
S
Pendergrass
Merri
M
Asnani
Sunil
S
Fonseca
Vivian
V
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D001741:Black or African American; D000368:Aged; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077261:Carvedilol; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000418:Albumins; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol