Adverse cardiac effects of salt with fludrocortisone in hypertension.
The effect of salt on blood pressure (BP) is controversial. A more important question is whether salt can produce cardiac target-organ damage, irrespective of its effect on BP. We assessed the effect of salt with fludrocortisone on QT dispersion and echocardiographic left ventricular diastolic function in a prospective interventional study involving 29 hypertensive subjects with a raised aldosterone/renin ratio who were hospitalized for investigation of possible primary aldosteronism. Each subject over 4 days was given a total of 28.8 g (480 mmol) of sodium chloride and 1.5 mg of fludrocortisone with potassium supplementation. Baseline and posttreatment 12-lead ECGs and echocardiograms were obtained. There were no significant changes in body weight, pulse rate, or BP after treatment with salt and fludrocortisone. Plasma sodium was significantly increased from 141.4 (SD 2.1) to 142.6 (SD 2.4) mmol/L (P:=0.001). QT and QTc dispersion both significantly increased: +19.6 (SD 16.5) ms (95% CI, 13.4 to 25.9) (P:<0.001) and +19.8 (SD 20.9) ms (95% CI, 11.8 to 27.7) (P:<0.001), respectively. There were no significant changes in (n=15) left ventricular dimensions or systolic function, but all diastolic filling indexes, including the preload-independent index, flow propagation velocity (55.49 [SD 10.91] to 48.96 [SD 11.40] cm/s, P:=0.018) worsened, suggesting significant deterioration of left ventricular diastolic function with salt and fludrocortisone. In conclusion, a combination of salt with fludrocortisone increased QT dispersion and impaired left ventricular diastolic relaxation in hypertensive patients with high aldosterone/renin ratios. This raises the possibility that salt may have BP-independent adverse cardiac effects in susceptible hypertensive subjects.
Hypertension Research Center, Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
P O
PO
Lim
C A
CA
Farquharson
P
P
Shiels
R T
RT
Jung
A D
AD
Struthers
T M
TM
MacDonald
D000450:Aldosterone / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D004452:Echocardiography; D004562:Electrocardiography; D004573:Electrolytes / Q000097:blood; D005260:Female; D005438:Fludrocortisone / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000009:adverse effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D004573:Electrolytes; D012965:Sodium Chloride; D000450:Aldosterone; D012083:Renin; D005438:Fludrocortisone