Effects of short-term glucocorticoids on cardiovascular biomarkers.
BACKGROUND
Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized.


OBJECTIVE
Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers.


METHODS
We conducted a randomized, double-blind, placebo-controlled study.


METHODS
The study took place in a tertiary care hospital.


METHODS
Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study.


METHODS
Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test.


METHODS
Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state.


RESULTS
Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers.


CONCLUSIONS
Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.
Brotman
Daniel J
DJ
Department of General Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. dbrotma1@jhmi.edu
Girod
John P
JP
Garcia
Mario J
MJ
Patel
Jeetesh V
JV
Gupta
Manjula
M
Posch
Amy
A
Saunders
Sue
S
Lip
Gregory Y H
GY
Worley
Sarah
S
Reddy
Sethu
S
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D010919:Placebos
D015415:Biomarkers; D005938:Glucocorticoids; D008055:Lipids; D008074:Lipoproteins; D010919:Placebos; D003907:Dexamethasone