Myocardial oxygen uptake (M
·
V
O
2
) is a helpful indica-
tor of the response of the coronary circulation to
myocardial metabolic demand. Although a direct mea-
sure of M
·
V
O
2
is difficult in routine clinical practice, it
can be easily and accurately indirectly estimated during
exercise stress testing by the product of systolic blood
pressure and heart rate, generally defined pressure-rate
product (PRP) or double product.
1-3
To take into account the value of systolic blood pres-
sure recorded at rest, some authors proposed to calcu-
late the PRP change from rest to maximal exercise
(dPRP) and showed that low values of the measure
have a negative prognostic significance.
4
Besides their use in the evaluation of functional capac-
ity, both PRP and dPRP were shown to be reliable prog-
nostic indicators in previous studies conducted before
the widespread diffusion of systemic thrombolysis.
5-8
Thrombolytic treatment, decreasing infarct size, and
improving left ventricular (LV) function was suggested
to have changed the postinfarction exercise test
Secondary Prevention and Rehabilitation
Prognostic significance of double product and
inadequate double product response to maximal
symptom-limited exercise stress testing after
myocardial infarction in 6296 patients treated with
thrombolytic agents
Massimo Villella, MD, Alessandro Villella, MD, Simona Barlera, MS, Maria Grazia Franzosi, PhD, and
Aldo P. Maggioni, MD, on behalf of the GISSI-2 Investigators* Milan, Italy
Background
The aim of this study was to evaluate the prognostic significance of the pressure-rate product (PRP)
obtained during exercise stress testing and of its change from rest to maximal exercise (dPRP) in a population of survivors of
acute myocardial infarction treated with thrombolytic agents.
Methods and Results
Survivors of acute myocardial infarction (n = 6251) from the GISSI-2 database, who underwent
a maximal symptom-limited exercise test with either bicycle ergometer or treadmill, were followed up for 6 months. PRP and dPRP
values were dichotomized (≤21,700 and >21,700, ≤11,600 and >11,600, respectively) and analyzed in a multivariate Cox model
individually and simultaneously with other ergometric variables. Six-month mortality rate was 0.8% in the high PRP group and 2.0%
in the low PRP group. Low PRP was an independent predictor of 6-month mortality rate (relative risk [RR] 1.97, 95% confidence inter-
val [CI] 1.24 to 3.13). Patients with low dPRP had mortality rates higher than patients with high dPRP (2.1% vs 0.8%). At the multi-
variate analysis, low dPRP showed negative predictive value (RR 1.97, 95% CI 1.23 to 3.16). A further multivariate analysis was per-
formed with PRP and dPRP, also adjusting for low work capacity, abnormal systolic blood pressure response to exercise, and
symptomatic-induced ischemia. The results showed that low work capacity, low PRP, and symptomatic exercise-induced ischemia
were still significantly associated with higher 6-month mortality rate (P = .04, .02, and .05; RR = 1.68, 1.71, and 1.78 respectively).
Conclusions
PRP is a predictive index to assess prognosis in survivors of acute myocardial infarction treated with
thrombolytic agents able to perform an exercise test after acute myocardial infarction, but its usefulness appears to be lim-
ited, considering that these patients were at low risk. (Am Heart J 1999;137:443-52.)
From Ospedale “Casa Sollievo della Sofferenza” IRCCS, S Giovanni Rotondo; and
Istituto di Ricerche Farmacologiche Mario Negri.
*A complete list of the investigators and centers participating in GISSI-2 has been
published (Lancet 1990;336:65-71). The Steering Committee consisted of G.A. Fer-
uglio, A. Lotto, F. Rovelli, P. Solinas, L. Tavazzi, and G. Tognoni. The study was
endorsed by the Associazione Nazionale Medici Cardiologi Ospedalieri and the
Istituto di Ricerche Farmacologiche Mario Negri.
Submitted July 30, 1997; accepted April 17, 1998.
Reprint requests to: Massimo Villella, MD, GISSI-2 Coordinating Centre, Via Eritrea,
62-20157 Milano, Italy.
Copyright © 1999 by Mosby, Inc.
0002-8703/99/$8.00 + 0 4/1/91121