Analysis of the Association of Urine Sodium Excretion and Serum Aldosterone with Clinical Outcomes.
relationship between dietary sodium intake and clinically important outcomes remains
controversial. Recent large observational studies have suggested a U-shaped relationship
between sodium intake and kidney disease progression, cardiovascular disease, and
all-cause mortality, with an increased risk of adverse events occurring in persons
consuming high and low levels of sodium. W... read moree hypothesized that serum aldosterone, which
has known vasculopathic properties, may be higher in individuals who consume lower
amounts of sodium and may explain the association of low sodium intake with an increased
risk of adverse outcomes. Using a case-cohort design in the Health Aging and Body
Composition (Health ABC) Study, we assayed urine sodium, as a proxy for dietary sodium
intake, and serum aldosterone. A subcohort (n=501) was randomly selected from the parent
cohort of healthy individuals, and all additional cases who demonstrated progression of
kidney disease, heart failure events, and cardiovascular events were added using the
case-cohort method. We used linear regression to evaluate the association of urine
sodium excretion and serum aldosterone at baseline. We used Cox proportional hazards to
examine the associations of serum aldosterone levels and urine sodium levels with
progression of kidney disease, incident heart failure, incident atherosclerotic
cardiovascular disease (CVD), and all-cause mortality. We evaluated whether adjustment
for serum aldosterone attenuated the relationship of urine sodium with these outcomes.
The mean (SD) age of the Health ABC subcohort was 73.6 (2.8) years; 49% were women, and
61% were white. Sixty-four percent of the subcohort had hypertension, and 54% of these
individuals were on antihypertensive medications. The mean (SD) estimated urine sodium
excretion in the subcohort was 4,174 (1,546) mg/24 hours while median (25th, 75th) serum
aldosterone was 5.12 (3.15, 8.85) ng/dL. There was an inverse relationship between urine
sodium excretion and serum aldosterone; each 1 gram higher urine sodium excretion was
associated with a 0.93 ng/dL lower serum aldosterone in multivariable adjusted analyses.
In the entire case-cohort, there were 420 individuals who demonstrated progression of
kidney disease, 220 incident heart failure events, 230 incident atherosclerotic CVD
events, and 236 deaths. There was no association between serum aldosterone and
progression of kidney disease, incident heart failure, or all-cause mortality in
continuous or quartile models. Higher levels of serum aldosterone were associated with a
lower risk of incident atherosclerotic CVD [HR per aldosterone doubling 0.85 (0.72,
0.99)] although the relationship was not linear. There was no association between
increased urine sodium excretion and progression of kidney disease or all-cause
mortality [HR per 1 standard deviation higher urine sodium 1.04 (0.89, 1.22) and 1.05
(0.92, 1.20) respectively], while lower levels of urine sodium showed a trend towards a
higher risk of heart failure and atherosclerotic CVD [HR per 1 standard deviation higher
urine sodium 0.92 (0.76, 1.10) and 0.87 (0.70, 1.08) respectively]. Serum aldosterone
did not attenuate the relationship of low urine sodium with our principal study outcomes
when examined as a continuous variable or according to quartiles. Lower levels of urine
sodium were associated with higher levels of serum aldosterone. There was no consistent
relationship between serum aldosterone with any of the clinical outcomes examined. Lower
levels of urine sodium showed a trend towards higher risk of heart failure and
atherosclerotic CVD. Serum aldosterone did not explain the relationship of low urine
sodium with the outcomes under study. Further studies are needed to evaluate the
mechanisms by which low urine sodium excretion may be associated with an increased risk
of adverse outcomes.
Thesis (M.S.)--Tufts University, 2016.
Submitted to the Dept. of Clinical & Translational Science.
Advisor: Mark Sarnak.
Committee: Hocine Tighiouart, and Lesley Inker.
Keyword: Medicine.read less