Prognostic Value of Aldosterone in the Valsartan Heart Failure Trial (Val-HeFT)

Linda Brookes, MSc

Disclosures

December 30, 2003

Editorial Collaboration

Medscape &

Presenter: Inder S Anand, MD, DPhil, Veterans Administration Medical Center (Minneapolis, Minnesota)[1]

Elevated aldosterone levels may contribute to left ventricular (LV) structural remodeling post myocardial infarction (MI) and in patients with advanced heart failure, and aldosterone receptor blockade has been shown to reduce mortality in these patients.[2] Now, however, an analysis of data from the Valsartan Heart Failure Trial (Val-HeFT)[3] has shown that plasma aldosterone may not be an important independent predictor of mortality but may predict morbidity in patients with heart failure.

During Val-HeFT, aldosterone was measured by radioimmunoassay at baseline and during follow-up in over 4000 patients, and the changes were shown over time to relate to outcomes in heart failure. Baseline aldosterone was classified as above or below a median of 104.1 pg/mL and divided into quartiles:

Quartile 1< 64 pg/mL
Quartile 264.0-104.1 pg/mL
Quartile 3104.1-180.0 pg/mL
Quartile 4> 180 pg/mL

Cox proportional hazard analyses and log rank analyses were conducted for all-cause mortality and first morbid event, defined as 1 of the following:

  • All-cause death

  • Sudden death with resuscitation

  • Heart failure hospitalization

  • Use of inotropic or vasodilator intravenous therapy for ≥ 4 h without hospitalization

Heart failure hospitalization was the first morbid event in most cases. A similar analysis was performed to determine change in aldosterone from baseline to 4 months in quartiles related to subsequent mortality and first morbid event.

Heart failure patients with baseline plasma aldosterone ≥ 104.1 pg/mL were generally sicker, with significantly higher NYHA heart failure class, lower blood pressure, higher heart rate, lower ejection fraction, higher Minnesota Living With Heart Failure score, and generally a much worse neurohormonal profile. Baseline aldosterone correlated weakly with a range of variables known to be prognostic markers for heart failure, except for plasma renin activity (correlation coefficient 0.24, P < .0001).

Aldosterone as a continuous variable in univariate analysis was a significant determinant of both all-cause mortality and first morbid event, but in multivariate analysis, aldosterone was significantly associated only with the first morbid event and not with mortality (Table).

Table. Aldosterone as a Continuous Variable in Multivariate Analysis
Variable Mortality First Morbid Event
Risk ratio P value Risk ratio P value
Aldosterone 1.000 .28252 1.000 .02441

When aldosterone was analyzed as a dichotomized variable, patients with baseline aldosterone ≥ 104.1 pg/mL showed significantly higher rates of all-cause mortality and first morbid events by univariate analysis. By multivariate analysis, however, aldosterone was significantly associated only with first morbid event and not with mortality.

Mortality was similar for baseline aldosterone Quartiles 1, 2, and 3, but was significantly higher for patients in Quartile 4, suggesting that only high levels of aldosterone are associated with increased morbidity and mortality. No direct relationship to subsequent mortality or morbidity was observed when the absolute change in aldosterone from baseline to 4 months in quartiles was examined.

Dr Anand suggested that decreased circulating aldosterone may not attenuate the progression of heart failure. It is possible that tissue levels of aldosterone may be more important for the pathogenesis of heart failure, as demonstrated in trials of aldosterone receptor blockers in heart failure. He noted that the patients with the greatest suppression of aldosterone in Val-HeFT did not appear to benefit from any added effect of this suppression; rather, administration of a specific aldosterone receptor-blocking agent such as eplerenone or spironolactone is necessary to get an added effect.

References
  1. Anand IS, Latini R, Glazer R, et al. Prognostic value of aldosterone in heart failure – Results from Val-HeFT. Abstracts from Scientific Sessions 2003; November 9-12, 2003; Orlando, Florida. Circulation. 2003;106(17 suppl):IV-484. Abstract 2217.

  2. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709-717.

  3. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667-1675.

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