A new French study has found that men whose heart rate increased the most in the
period just before an exercise test had twice the risk of sudden cardiac death
(SCD) in later life than those whose heart rate did not increase to the same
extent [1]. These results are "novel and largely unexpected," say Dr Xavier
Jouven (Hôpital Européen Georges Pompidou, Paris, France) and colleagues in
their paper published online April 28, 2009 in the European Heart Journal.

They explain that this "mild mental stress" just before exercise is usually
associated with an increase in heart rate by just a few beats per minute (bpm).
They have previously shown an association between SCD and heart-rate increase
during physical stress and that an insufficient increase in heart rate during
strenuous exercise is predictive of SCD, but this is first time an association
of this kind has been seen, they note.

Taking a pulse during this time period could provide a simple tool for
identifying people who may be at increased risk of SCD, they conclude.

"This study shows that the heart-rate increase during mild mental stress in
preparation for exercise is a strong predictor of sudden death. The findings
have significant clinical implications," says Jouven in a European Society
Cardiology statement [2]. "Sudden death . . . is a major public-health problem.
Less than 5% of people suffering a heart attack are successfully resuscitated,
and so being able to identify early on those who are at greatest risk in a
general and apparently healthy population would be a big step forward in
preventing some of these deaths."

Long, Prospective Study

The researchers analyzed data from 7746 French policemen participating in the
Paris Prospective Study, who were aged 42 to 53. The men were examined between
1967 and 1972 and given ECGs and physical examinations, and their resting heart
rate was measured. Heart rate was measured again in the few minutes before they
took an exercise stress test, during the test, and afterward during the recovery
period.

Complete data on the exercise stress test were available for 6456 men; 388 of
these were excluded from the analysis because of an ischemic response to
exercise or an impaired chronotropic response.

During an average 23 years of follow-up, there were 1516 deaths--including 81
sudden cardiac deaths and 129 non–sudden cardiac deaths--and 355 men were lost
to follow-up.

The risk of SCD rose progressively with heart-rate increase during the
mild-mental-stress period before the exercise test (p for trend=0.02). After
multifactorial adjustment, men who had the highest increase in heart rate during
this period (an increase of more than 12 bpm) had twice the risk of SCD of those
who had the lowest increase in heart rate (increase of less than 4 bpm), a
relative risk of 2.09. No such relationship was observed for non–sudden cardiac
death. There were no SCDs among the 440 men who increased their heart rate the
least during this period and the most during the exercise test. The highest
proportion of SCDs was among the 471 men who increased their heart rate the most
during mild mental stress and the least during exercise.

Different Neural Responses Have Differential Impact on Arrhythmic Risk

The findings indicate that different neural responses to different types of
stress give a differential impact on arrhythmic risk, say Jouven et al.

"Our underlying assumption, which this study appears to have proved correct, is
that the faster the vagal withdrawal in response to mental stress, the greater
will be--during an ischemic episode--the damaging effect of sympathetic
activation unopposed by vagal activity," Jouven explained.

In addition, he and his colleagues found that the risk of SCD was influenced
strongly by genetic predisposition: it increased nearly threefold in men whose
mothers had died suddenly and nearly 10-fold when both parents had died
suddenly, compared with those whose parents had not died in this way.

This raises "the intriguing possibility of a genetic predisposition to the
autonomic responses associated with higher or lower risk for SCD," the
researchers say.

Pulse Can Be Used as Prognostic Marker, But Only in Men

"Few measurements in medicine are as inexpensive and as easy to obtain in large
general populations as to measure the heart-rate difference between resting and
being ready to perform an exercise test," Jouven notes.

"Taking a person's pulse has been part of clinical examinations for thousands of
years," he continues, "and now our study shows it can be used as a prognostic
marker. The results will contribute toward a better understanding of the
mechanisms of cardiac death.

"People who showed a higher heart-rate increase with mild mental stress could be
considered for additional investigations and for tailored preventive strategies,
aimed in the first place at reducing the probability of heart disease," he
concludes.

He and his colleagues point out, however, that the study was carried out in men
only, so it is possible that findings in women may be different.