Abstract. Reunanen A, Karjalainen J, Ristola P, Helio Èvaara M, Knekt P, Aromaa A (National Public Health Institute, Helsinki, Central Military Hospital, Helsinki, and Kvaerner Masa-Yards Helsinki New Shipyard, Helsinki, Finland). Heart rate and mortality. J Intern Med 2000; 247: 231±239.Objectives. Increased heart rate has shown to be associated with risk of mortality from cardiovascular diseases in some studies, but not in others. Increased heart rate has also been linked to causes of death other than cardiovascular. To clarify the role of heart rate as a predictor of death we studied its predictive value in a large population study. Design. A prospective population study with a follow-up time of 23 years. Subjects and methods. The study population comprised 5598 men and 5119 women 30±59 years of age on entry. Heart rate was measured from resting ECGs. Main outcome measure. Mortality from specified causes. Results. A total of 1848 men and 840 women died during the follow-up period. Increased heart rate was significantly associated with death from all causes, cardiovascular causes, and natural noncardiovascular, nonmalignant causes of death. Increased heart rate was associated with death from cancer in men with heart disease but not in men without heart disease on entry into the study. The increase in cardiovascular mortality with high heart rate was explained by the close association between heart rate and blood pressure. Adjustment for risk factors did not alter the significance of the association between increased heart rate and mortality from noncardiovascular causes. Conclusions. High heart rate is simple to observe clinically and a significant if nonspecific predictor of mortality. Increased risk of mortality from cardiovascular diseases can be explained by association with high blood pressure. The increased mortality risk associated with high heart rate related mainly to a group of diseases of noncardiovascular or nonmalignant origin.

Objective-To evaluate the value of QT interval as a cardiac risk factor in middle aged people. Methods-The association between QT interval and cardiac risk factors and mortality in a middle aged Finnish population of 5598 men and 5119 women was evaluated over a 23 year follow up. To adjust the QT interval confidently for heart rate, a nomogram was constructed from the baseline electrocardiograms separately for men and women. Results-Nomogram-corrected QT interval (QTNc) prolongation was associated with elevated blood pressure and signs of cardiovascular disease; QTNC shortening was associated with smoking. Over 10% prolongation of QTNC predicted death in men with heart disease: adjusted relative risk (RR) was 2*17 (95% confidence interval 0.67-7-45) for sudden death; [2][3][4][5][6][7][8][9][10][11][12] (1-25-3.59) for total cardiovascular mortality; and 1-92 (1.23-3.00) for all cause mortality. In healthy men the increase in RR was not significant: sudden death, 1-48 (0-67-3.25); total cardiovascular mortality, 125 (0-92-1*70); al cause mortality, 1-21 (0-96-1-53). However, healthy men with long QTNC in the lowest heart rate quartile exhibited an KR of 2-75 (1-00-7*40) for sudden death. Over 10% shortened QTNC predicted cardiovascular death in men with heart disease who smoked; (1.45-9.54). Non-smoking men with short QTNC had low mortality risks irrespective of possible signs of cardiovascular disease. The trends in mortality risks were similar but weaker for women. Conclusions-In a middle aged population, prolonged QT interval predicts cardiac mortality in men with signs of cardiovascular disease. In women and healthy men this risk is weak and may reflect subclinical heart disease. A shortened QT interval predicts death in men with heart disease who smoke. (Heart 1997;77:543-548) Keywords: QT interval; cardiovascular mortality; cardiac risk factors; smoking The QT interval in the electrocardiogram reflects the time registered for depolarisation and repolarisation of the ventricular myocardium-that is, the summation of action potential durations in the ventricles.1 Theoretically, long and disparate duration of ventricular action potentials predispose to reentrant ventricular arrhythmias, which are harbingers of sudden death especially in cardiac patients.2 Short action potentials, on the other hand, reflect rapid electrical recovery enabling short cycle length in ventricular arrhythmias' and may predispose to ventricular fibrillation. Factors influencing action potentials change the QT interval; heart rate and autonomic tone are particularly important.4 For clinical and research purposes, QT intervals are corrected for heart rate. The most widely used method is based on Bazett's formula, despite the fact that this equation over corrects the QT interval at high heart rates and under corrects it at low heart rates.5Clinical studies in subjects with congenital or acquired long QT syndrome and in patients with acute myocardial infarction have shown that long QT intervals predispose to malignant ventric...

Determinants of the response to coumarin anticoagulant, warfarin, have been analysed in a series of 19 patients with acute myocardial infarction. Cardiac failure developing in the acute phase of the disease seemed to be without any great influence on the plasma half‐life of warfarin, with the exception of patients in whom serious circulatory catastrophes occurred. In patients who had received other drugs regularly before the hospital admission the plasma half‐life of warfarin showed a significant prolongation within 3 weeks—a phenomenon apparently caused by a decreasing induction of microsomal drug‐metabolizing enzymes in the liver. The plasma half‐life of warfarin was found to explain 44% of the variance in the daily requirement of warfarin during maintenance treatment. The steady state “therapeutic” plasma warfarin level showed a wide range of individual variation—from 0.8 to 4.1 mg/l, with a median value of 1.5 mg/l. The results indicate that in addition to the rate of coumarin anticoagulant metabolism other factors have a marked influence on the response to coumarin drugs in patients with myocardial infarction.