Adverse Cardiac Effects of Salt With Fludrocortisone in Hypertension

Abstract

Abstract-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 (Pϭ0.001).QT and QTc dispersion both significantly increased: ϩ19.6 (SD 16.5) ms (95% CI, 13.4 to 25.9) (PϽ0.001) and ϩ19.8 (SD 20.9) ms (95% CI, 11.8 to 27.7) (PϽ0.001), respectively. There were no significant changes in (nϭ15) Key Words: sodium Ⅲ fludrocortisone Ⅲ hypertension Ⅲ QT dispersion Ⅲ diastole T he etiologic importance of sodium chloride (salt) in the genesis or maintenance of hypertension remains controversial. Salt is, however, an independent predictor of left ventricular hypertrophy (LVH), 1 which raises the intriguing possibility that salt can damage target organs independently of its effects on blood pressure (BP). In general, confusion about the role of salt may well have arisen for 2 reasons. First, only certain subpopulations of hypertensive patients may be harmed by excess salt. Second, to this point most studies have examined whether salt alters BP per se rather than whether salt adversely affects the target organs independently of any effect on BP. In the present study we examined the effect of salt on QT dispersion and on left ventricular (LV) diastolic function in patients with relative aldosterone excess. QT dispersion is thought to be an index that represents the degree of inhomogeneity of cardiac electric repolarization. QT dispersion Ͼ80 ms has been reported to be a potent prognostic marker of sudden cardiac death in hypertension. 2 The diagnostic test of salt loading with the addition of low-dose fludrocortisone is used in hypertensive subjects who have a raised aldosterone/renin ratio (ARR) to look for evidence of autonomous aldosterone production, as occurs in primary aldosteronism. Patients undergoing this routine procedure provided us with a susceptible group in whom to test our hypothesis that salt could worsen QT dispersion and LV diastolic relaxation. Patients with raised ARR have inappropriate aldosterone activity, 3 and animal studies 4 suggest an important interaction between excess salt and excess aldosterone in producing target-organ damage in the heart. Methods Subject SelectionAll hypertensive patients referred to our center had blood samples taken for plasma renin...

Adverse Cardiovascular Effects of Acute Salt Loading in Young Normotensive Individuals

“…11 Although the magnitude of rise in QT dispersion in the present study was smaller, an effect was still seen in normal healthy young adults. The mechanism for this effect of salt is unclear.…”

“…10 We have previously reported that in hypertensive subjects with increased aldosterone activity, salt loading not only impairs left ventricular diastolic function, but also increases QT dispersion, a measure of cardiac electric depolarization. 11 One study has previously examined the effect of sodium loading on vascular endothelium in 7 normal subjects and found no significant effect on endothelial-dependent vasodilation. 12 However, our prior experience prompted us to repeat this with a larger study group.…”

“…12 However, our prior experience prompted us to repeat this with a larger study group. 11 We therefore explored whether salt loading has adverse effects on cardiovascular system in healthy volunteers. We studied the effects of salt on vascular endothelial function and on NO bioactivity, as it is accepted that endothelial dysfunction precedes frank atherosclerotic disease.…”

Incidence and Predictors of Hypertension Among Rural Chinese Adults: Results From Liaoning Province

“…[14][15][16] Li et al, 16 in a large-scale, blinded randomized trial in rural China, confi rmed that a potassium chloride-containing salt substitute is an effective and acceptable means of blood pressure control. Although our calculated method of salt intake was not precise, results from our analysis also indicated that higher salt intake contributed to the progression of hypertension.…”

Salt Loading on QT Dispersion and the Protective Role of Potassium Supplement in Normotensive Adults

“…Sodium salt is one of the most important environmental factors for hypertension. In this study, QTd was reduced in normotensives after low-salt diet while increased after high-salt diet intervention, suggesting the correlation between salt intake and QTd Lim et al [14]. Reported that QTd had been increased in hypertensive patients after salt loading, while Tzemos et al [9] further observed that QTd had also been increased in normotensive youngs after salt loading.…”