Ambulatory electrocardiographic findings in top athletes, athletic students and control subjects.

Aim of the present study was to evaluate 24 h electrocardiographic recording in 30 top athletes, 30 athletic students and 30 sedentary control subjects. Each group consisted of 15 males and 15 females and were matched for age (about 24 years). Training was not allowed during the recording. Top athletes had the lowest diurnal and nocturnal heart rate, but the difference between top athletes and athletic students was far less pronounced than between athletic students and controls. This may indicate that bradycardia reaches a lower limit with moderate degrees of training. Atrioventricular (AV) block II was found in 3 top athletes and 4 athletic students and in none of the subjects, the longest pause being 2.4 s in both athletic groups. Most episodes occurred during night and nearly all were Mobitz type I. In all cases of AV block II the QRS complexes were narrow and AV block III did not occur. SA block was found in 3 top athletes, 1 athletic student and 1 control subject, the longest pause being 3.1, 2.9 and 1.9 s, respectively. Ventricular premature beats were rare in all groups and complex ventricular arrhythmias were not found. Half of the subjects were in Lown class 0, the other half in Lown class 1. Supraventricular premature beats were also scarce and most frequent in top athletes, followed by athletic students and sedentary controls (2.0, 1.0, 0.7 beats/h, respectively).

Electrocardiographic findings of repolarization in athletic students and control subjects.

We have investigated resting electrocardiograms in 1,299 athletic students and 151 sedentary control subjects. ST elevations were more frequent and pronounced in athletes compared to controls, whereas there was no difference in ST depressions. Athletes with ST elevation above 2 mm were characterized by lower heart rate, increased PQ duration, increased indices of left, right and septal hypertrophy and T wave amplitude. Negative T waves in 3 of 6 precordial leads, V3-6, were found in 1.5% of athletes and 0.7% of controls, and in V5-6 in 0.4% of athletes and none of controls, the differences not being significant. Athletes had significantly more often a T wave axis between +30 and -180 degrees and less often a frontal T wave axis between +30 and +180 degrees. The mean QRS-T angle was significantly greater in athletes, and U waves were more prominent. Analyzing athletes with QTc below and above 0.430 s, we found an increased heart rate, QRS duration, ST depression and a more pronounced left QRS axis in the group with QTc above 0.430 s. There was a positive correlation between QTc and heart rate which indicates that the use of Bazett's formula leads to an underestimation of QTc at lower heart rates and to an overestimation at higher heart rates. Bazett's formula does not provide an adequate correction for heart rate and should be used with caution. Our finding of a prolonged QTc in athletes compared to control subjects in spite of lower heart rate in the athletic group demonstrates that a real QTc prolongation exists in athletes.

Electrocardiographic findings of left, right and septal hypertrophy in athletic students and sedentary controls.

We have previously demonstrated increased voltage of septal, right and left ventricular depolarization in 1,299 athletic students compared to 151 sedentary controls. In the present investigation we have studied the prevalence of hypertrophy and the correlation between hypertrophy and other ECG findings. An increase of Q waves of more than 0.2 mV was associated with increased indices of right and left ventricular hypertrophy. Right ventricular hypertrophy was associated with an increased prevalence of incomplete right bundle branch block and increased parameters of septal and left ventricular hypertrophy. Left ventricular hypertrophy was associated with increased indices of septal and right ventricular hypertrophy and with bradycardia. Furthermore, left ventricular hypertrophy was characterized by ST elevation and increased T wave amplitudes, but not by repolarization abnormalities. Thus, our data point to a harmonious hypertrophy. Based on our findings we suggest the following normal limits in young people (20-30 years) according to the 97.5 percentile regarding the Sokolow index: for athletic students 5.3 (males) and 3.6 mV (females), for sedentary controls 4.0 (males) and 3.6 mV (females). It remains to be clarified whether these values are also valid in top athletes.

Electrocardiographic and echocardiographic findings in top athletes, athletic students and sedentary controls.

Thirty top level athletes, 30 athletic students and 30 sedentary controls underwent electrocardiographic and echocardiographic investigation. Resting ECG in athletes showed increased indices of hypertrophy compared to controls. The echocardiographic examination demonstrated an increase in left ventricular mass (LVM) of 47% in top athletes and 23% in athletic students compared to controls. The relationship between wall thickness and diameter was similar in all groups, as were parameters of systolic and diastolic left ventricular function at rest. There was no correlation between LVM assessed by echocardiography and ventricular ectopic activity assessed by Holter monitoring in this normotensive population. Highly significant correlations between ECG and echocardiographic parameters of hypertrophy were demonstrated.

Electrocardiographic findings of heart rate and conduction times in athletic students and sedentary control subjects.

We have investigated resting electrocardiograms in 1,299 athletic students and 151 sedentary control subjects. Bradycardia was significantly more common in athletes. The athletic group was divided according to a heart rate < 50, 50-100, and above 100 beats/min. Atrioventricular conduction time, prevalence of ectopic beats and other rhythms, parameters of right and left ventricular hypertrophy, ST elevation, and T wave amplitude were increased in the sinus bradycardia group. A significant negative correlation was found between heart rate and PQ duration in athletes. In the sinus tachycardia group, the PQ duration was shorter and the ST depression more prominent than in the other groups. The subjects were also divided according to PQ > or = 0.22, 0.21-0.12, and < 0.12 s. Parameters of left ventricular hypertrophy were markedly increased in athletes with PQ > or = 0.22 s, while the heart rate was only slightly decreased, suggesting an association between prolonged atrioventricular conduction time and left ventricular hypertrophy. Incomplete right bundle branch block was associated with a lower heart rate, increased duration of QRS and QTC, voltage of precordial Q waves, indices of right ventricular hypertrophy, and negative T waves. These findings are typical of right ventricular hypertrophy, indicating a close relation of incomplete right bundle branch block to right ventricular hypertrophy.

Electrocardiographic findings according to level of fitness and sport activity.

We have investigated 52 ECG parameters in 1,299 athletes and 151 control subjects. Data on fitness were available in 840 athletes. They were split in three groups according to level of fitness and compared with each other and the control group with regard to the ECG findings. The most marked findings with increasing fitness were lower heart rate, increased prevalence of bradycardia, increased precordial ST segment elevation, and increased T wave amplitudes. Only slightly increased parameters of right and left ventricular hypertrophy were found. A highly significant correlation was found between fitness and heart rate, while no such correlation was found between fitness and the Sokolow index. The athletes were subdivided according to sports activity, and ECG parameters were compared in endurance athletes, ball players, strength athletes, gymnasts, and controls. Apart from a lower heart rate in endurance athletes and ball players as compared with strength athletes and gymnasts, few differences were found between the athletic groups. The heart rate is the most important parameter reflecting level of fitness and sports activity. The differences in ECG findings are relatively minor and do not distinguish type of sport activity.

Electrocardiographic findings in athletic students and sedentary controls.

We have investigated resting electrocardiograms from 1,299 athletic students taken in the same laboratory during the years 1973-1982 and compared them with electrocardiograms recorded in 151 age- and sex-matched sedentary controls. Fifty-two parameters were recorded for each electrocardiogram and computerized. We found that athletic students had a significant lower heart rate, longer PQ time and a prolonged QTc compared to control subjects. Athletes had higher maximal Q amplitudes in precordial leads, higher R in V1, and higher indices of right ventricular hypertrophy (RV1 + SV5) and left ventricular hypertrophy (Sokolow-Lyon and Grant indices). Furthermore, the athletes had higher maximal ST elevation and higher maximal T wave amplitudes in precordial leads. Sinus bradycardia was more frequent in athletes. All control subjects were in sinus rhythm whereas 0.9% of the athletes had other rhythms (nodal, coronary sinus or wandering pacemaker). Athletes and control subjects did not differ significantly with regard to premature beats, atrioventricular block, bundle branch block or the Wolff-Parkinson-White pattern. We conclude that training induces significant changes in heart rate, conduction times, ST elevation. QRS and T voltage, slow rhythm disturbances and atrioventricular and sinoatrial block were infrequent in the resting electrocardiogram taken in the supine position and disappeared immediately on sitting and during exercise. Training-induced electrocardiographic changes may partly be due to alterations in autonomic tone and partly to structural changes in the myocardium. Different normal criteria for left ventricular hypertrophy may be warranted in athletes.

Electrocardiographic findings according to sex in athletes and controls.

We have previously compared the electrocardiogram of 1,299 male and female students of physical education and sports with 151 age- and sex-matched sedentary controls and found that the former had lower heart rate, longer conduction times and increased voltages. The same material of 1,450 young adult subjects was split according to sex into 617 females and 833 males in order to analyze the influence of gender on the resting 12-lead electrocardiogram. We found that females had a significant higher heart rate, shortened conduction times (PQ, Q, ventricular activation time and QRS) and a prolonged repolarization time (QTc), decreased P, Q and T amplitudes as well as indices of right, septal and left hypertrophy, and ST elevation in precordial leads were lower in females than in males. These differences were highly significant with p values less than 0.0001 for almost all parameters. Sinus bradycardia was more common in men and sinus tachycardia in women. The prevalence of other rhythms and supraventricular and ventricular premature beats was low in both sexes. AV block grade I was found in 1% of females and 3% of males (p less than 0.02). Notching of R/S in V1-V2 and incomplete right bundle branch block were less common in females (p less than 0.0001). The differences in ECG parameters between the two sexes in the total material persisted also when the athletic and control groups were investigated separately. Gender seems to be highly important for most ECG parameters in the resting ECG. This points to the necessity of discussing different upper normal limits for ECG parameters according to gender.

No metabolic side effects of long-term treatment with verapamil in hypertension.

In a prospective, open study 45 patients (mean age fifty-three years) with essential hypertension were treated with verapamil for four to eight years (mean 5.3 years). Blood pressure was satisfactorily controlled (from 160/104 to 145/91) and the side effects were infrequent, mild, and often transient. Verapamil did not exert any unfavorable metabolic or hematologic effects over the years. HDL-cholesterol was moderately increased (mean 24%) and the other plasma lipids were unaffected. These data suggest that the calcium channel blocker verapamil is a metabolically safe drug to use as monotherapy in essential hypertension.

Serum ionized calcium--a predictor of therapeutic response to slow calcium channel blockade in essential hypertension.

In 20 patients with mild to moderate essential hypertension, serum ionized calcium was determined before and after four weeks of treatment with 240 mg verapamil sustained release bid. Pretreatment systolic blood pressure was inversely correlated to serum ionized calcium (r = -0.44, p = 0.05). Mean blood pressure was significantly (p less than 0.001) reduced (from 161/100 to 145/88 mm Hg), but mean serum ionized calcium did not change during treatment (from 1.23 to 1.24 mmol/L). A significant inverse correlation (r = -0.56, p = 0.01) was found between pretreatment serum ionized calcium and reduction in systolic blood pressure during verapamil treatment. Thus serum ionized calcium in untreated essential hypertensive patients may predict the blood pressure response to the slow calcium channel blocker verapamil.

Can blood pressure reduction induced by slow calcium channel blockade (verapamil) be reversed by calcium infusion?

The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31-63 years, with mild and moderate essential hypertension, being on long-term treatment with the slow calcium channel blocker verapamil. The calcium load induced a significant (P less than 0.001) increase in mean serum ionized calcium (from 1.24 +/- 0.01 to 1.40 +/- 0.2 mmol/l). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verapamil.

Depressor effects of ionized calcium infusion in essential hypertension.

The circulatory effects of an acute increase in serum ionized calcium were assessed in 27 patients with mild to moderate hypertension. Following a control period of fifteen minutes with confirmed circulatory variables, 1,375 mg calcium gluconate was infused over three minutes. Systemic mean arterial blood pressure and heart rate were recorded before, at one-minute intervals during, and for five minutes following the infusion. There was a brief increase of serum ionized calcium concentration (from 1.28 +/- 0.06 mmol/liter to 1.42 +/- 0.07 mmol/liter; p less than 0.001) maximum by one minute after infusion with return toward control by a further four minutes. This was accompanied by a significantly decreased mean arterial blood pressure (from 117 +/- 8 mmHg to 110 +/- 9 mmHg at three minutes; p less than 0.05) and heart rate (from 70 +/- 11 min-1 to 63 +/- 10 min-1 at three minutes; p less than 0.01). There was a significant correlation between the change in ionized calcium and that of the systemic arterial blood pressure (r = 0.68; p less than 0.01). No major side effects were recorded. The blood pressure reduction may theoretically be related to increased membrane stabilization of vascular smooth muscle cells, the acute increase in extracellular ionized calcium impairing calcium ions influx.

A new sustained-release formulation of verapamil in the treatment of hypertension.

The study was carried out in 24 patients with mild to moderate essential hypertension to assess the antihypertensive efficiency and tolerability of a new sustained-release formulation of verapamil (tablets containing 240 mg). The trial was conducted as a single-blind crossover study for periods of 4 weeks, preceded by a 2-week placebo period, comparing sustained-release verapamil twice daily with instant-release verapamil (conventional tablets of 80 mg) mg) 160 mg twice daily. Both regimens induced a significant reduction in blood pressure and heart rate, and this effect was (particularly for sustained-release verapamil) significant from the very first day of treatment. Both formulations were well tolerated. The pharmacokinetic data obtained and the even blood pressure reduction achieved demonstrate that this new verapamil formulation has sustained-release characteristics and is sufficient as a twice-daily medication in mild/moderate essential hypertension.

Instant and sustained-release verapamil in the treatment of essential hypertension.

In a series of controlled studies for periods of 4 to 6 weeks comprising 103 patients altogether, and in 1 long-term trial for 1 year, various dosages of instant and sustained-release verapamil were administered in the treatment of mild and moderate essential hypertension. One of these trials was a double-blind comparison with nifedipine, in which the 2 calcium antagonists had an equally good effect on blood pressure. A significant blood pressure reduction was achieved with verapamil both at rest and during isometric work in most patients. About 10% of the patients were nonresponders. Pharmacokinetic studies demonstrated great interindividual variations in plasma concentrations of verapamil and its active metabolite norverapamil. Except for 1 study, no significant correlation was found between drug concentration and blood pressure reduction. All formulations of verapamil were well tolerated by the patients, and adverse effects were generally mild and often transient. No negative metabolic effects were observed during long-term treatment; serum lipids, in particular, were unaffected. PQ intervals on the electrocardiogram were significantly but moderately prolonged. QRS and QT intervals were unchanged. No increase in body weight occurred. It is concluded that verapamil is an efficacious, safe drug and a first-line treatment alternative in mild and moderate essential hypertension. The recently developed sustained formulation of the drug renders a simple dosage regimen possible.

Studies on verapamil in the treatment of essential hypertension: a review.

Various doses of verapamil, using the conventional and sustained release formulations, have been administered for the treatment of mild or moderate hypertension in different controlled studies for periods of 4-6 weeks, involving a total of 103 patients, and in one long-term trial for 1 year in 12 patients. A double-blind comparison of verapamil and nifedipine showed that the two calcium antagonists had equal antihypertensive action. A significant blood pressure (BP) reduction was achieved with verapamil both at rest and during isometric exercise in the great majority of patients. No significant correlation was found between age and BP reduction, but pretreatment BP and pressure reduction correlated positively. Heart rate (HR) was moderately but significantly reduced by verapamil. The established wide interindividual differences in verapamil pharmacokinetics were confirmed. There was no significant correlation between plasma drug concentrations and BP reduction, but the dosage regimens with the highest mean plasma drug concentrations were associated with the greatest mean reduction in BP. A moderate, but significant, prolongation of AV-conduction was demonstrated. QRS- and QT-intervals were unaffected. Side-effects, with all formulations of verapamil, were generally mild and often transient. No significant haematological or metabolic effects were observed during long-term treatment. It is concluded that the calcium antagonist verapamil is an effective and safe drug. It can be considered as an alternative drug in mild and moderate essential hypertension.

Verapamil compared with nifedipine in the treatment of essential hypertension.

In a double-blind, cross-over study for 6 weeks that included 28 patients with essential hypertension, WHO stage I-II, the hypotensive action of verapamil (160 mg thrice daily) was compared with nifedipine (20 mg slow release twice daily). Twenty-six patients completed the trial. Both regimens reduced the blood pressure significantly in patients in the supine, sitting, and standing positions, with sustained and slightly increasing effect throughout the periods. Verapamil reduced mean diastolic blood pressure significantly more than nifedipine in all positions and lowered mean systolic pressure slightly more than nifedipine. Resting heart rate was significantly decreased by verapamil and insignificantly altered by nifedipine. Serum lipoproteins, liver function tests, serum creatinine, serum electrolytes (Na+, K+, and Cl-), and body weight were not affected by either drug. Atrioventricular (AV) conduction was significantly prolonged by verapamil and unaffected by nifedipine. Subjective side effects were more numerous with nifedipine than with verapamil, but were mainly mild and transient except for one patient in each group who was withdrawn because of severe adverse reactions. It is concluded that the calcium antagonists verapamil and nifedipine have a significant hypotensive effect, more pronounced with verapamil than with nifedipine in the actual doses. Both drugs are treatment alternatives in mild to moderate essential hypertension.