Use of natriuretic peptides in pre-participation screening of college athletes

Current screening methods have poor specificity and sensitivity for detecting cardiac abnormalities that predispose young athletes to sudden death. Natriuretic peptides (NPs) show promise in screening asymptomatic populations for structural heart disease, but little is known about their use in student athletes. This study sought to describe the distribution and characteristics of NP levels in a population of college athletes and determine the relationship between NPs and the pre-participation exam (PPE) and hand-held echocardiography (HHE). We evaluated 457 college varsity athletes with B-type NP (BNP) and N-terminal proBNP (NT-proBNP) levels and a standard PPE; 200 also underwent HHE. NT-proBNP and BNP levels were highly correlated (r=0.87, p<0.001), with a median of 21 pg/ml and 8 pg/ml respectively. 95% of athletes had NT-proBNP<84 pg/ml and 95% had BNP<33 pg/ml. Levels were higher in athletes with a history of exertional dizziness/syncope but did not correlate with other elements of the PPE or with HHE, although no major cardiac structural abnormalities were identified in this population. In men, there were weak correlations between NP levels and number of days per week performing distance running, strenuous exercise, or sprinting. In conclusion, NPs are only weakly correlated with intensity of physical training, and most college athletes have low NP levels; further studies are needed to elucidate the significance of elevated NP levels in this population, as they may provide incremental information beyond that provided by the PPE and echocardiography.     

Inspiratory stridor in elite athletes

STUDY OBJECTIVES: Diagnosis and medical intervention for exercise-induced bronchospasm (EIB) are often based on self-reported symptoms, without spirometric confirmation. Inspiratory stridor (IS), a symptom of vocal cord dysfunction (VCD), is frequently mistaken for EIB wheeze. Athletes with exercise IS that spontaneously resolves on activity cessation are suspect for VCD and may not have EIB. This study estimated IS prevalence in elite athletes and determined its relationship to EIB. Subjects/methods: Three hundred seventy athletes (174 female and 196 male subjects) provided a medical history, and underwent spirometry before and after exercise challenge. Exercise challenges were conducted in cold, dry ambient conditions. EIB positive (EIB +) was defined as a > or = 10% postexercise fall in FEV(1). Athletes were monitored for IS during exercise; 78.4% of the athletes in this study (n = 290) were tested on multiple occasions. RESULTS: EIB was identified in 30% of 370 athletes tested (58 female and 53 male subjects). IS was observed in 5.1% (18 female and 1 male subjects) during exercise and spontaneously resolved in these subjects within 5 min after exercise cessation. Ten IS-positive (IS +) athletes (52.6%) were EIB +, and 8 of these athletes had a previous EIB diagnosis; however, beta(2)-agonist treatment resolved IS in only 2 subjects. Eight of nine IS +/EIB-negative (EIB -) athletes had a previous EIB diagnosis; seven subjects received beta(2)-agonist treatment with no IS resolution. Resting spirometric measurements did not distinguish IS, but postexercise mid-flow (FEF(50)/FIF(50)) ratio > 1.5 was more frequent (33%, p < 0.05) among IS + athletes. The FEF(50)/FIF(50) ratio was higher for IS +/EIB + athletes than for IS -/EIB + athletes (1.97 +/- 1.69 vs 0.81 +/- 0.39, p < 0.05). The postexercise fall in FVC was greater (p < 0.05) for IS +/EIB - athletes (9.2 +/- 5.0%) than for IS-negative (IS -) /EIB - athletes (5.3 +/- 4.3%). No difference in postexercise FEV(1) was identified between IS + and IS - athletes (within EIB + or EIB - groups). CONCLUSIONS: Five percent of athletes were IS +, with EIB comorbidity observed in 53% of these subjects. Misdiagnosis of IS as EIB is common. The lack of a beta(2)-agonist response in combination with postexercise serial spirometry can be useful in excluding solitary IS and confirming EIB diagnosis.     

Airway hyperresponsiveness in elite athletes

It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC(20) < 16 mg/ml), with a mean PC(20) of 16.9 mg/ml, compared with 28% (PC(20): 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC(20) (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC(20) (r = -0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.     

Young elite athletes of different sport disciplines present with an increase in pulsatile secretion of growth hormone compared with non-elite athletes and sedentary subjects

Acute exercise is a well-known stimulus for GH secretion but the effect of chronic training on GH secretion still remains equivocal. The aim of our study was to analyse spontaneous pulsatile GH secretion (during a period of 2 hours in the morning) in a group of young elite athletes (EA) compared with non-elite athletes (NEA), and sedentary subjects (SS). Mean and peak GH levels proved significantly higher in EA than in NEA and SS (p=0.0004 and p<0.0001, respectively). The same differences in mean and peak GH levels were also demonstrated in males and females when considered separately (males: p=0.0062 and p=0.0025; females: p=0.0056 and p=0.0032). In addition, GH levels (mean and peak) were higher in females than in males in SS while no differences were demonstrated between the 2 sexes in the EA and NEA groups. IGF-I levels were within the normal range for age in all the subjects with no difference between the 3 groups. Body mass index (BMI) exhibited no difference between groups, while EA showed higher lean mass (p=0.0063) and lower fat mass (p=0.0139) than NEA and SS measured by dual-energy x-ray absorptiometry. A strong positive correlation between GH levels (mean and peak) and hours of training a week was demonstrated (p=0.0101; r2=0.1184; p=0.0022; r2=0.1640, respectively). In conclusion, GH levels were higher in EA than NEA and SS without any modification of IGF-I levels; a strong positive correlation was present between GH levels and intensity of training. An increase in the knowledge of the effect of chronic training on GH secretion could improve the training programme to elicit the greatest exercise- induced GH response.     

Clinical applications of B-type natriuretic peptides.

Diagnostic, prognostic and therapeutic applications of B-type natriuretic peptides (NPs) will probably become part of routine management of heart failure within five years. Cardiac release of NPs rises with increasing cardiac dysfunction. Their secretion and plasma levels respond to intracardiac distending pressures, with other modulating influences including age, sex, renal function and other aspects of neurohormonal status. Single and serial plasma NP measurements, particularly of B-type and N-terminal pro-B-type NP, show promise in diagnosis of heart failure, risk stratification in those with known heart disease, and in adjustment of anti-failure therapy. Recombinant B-type NP is an effective parenteral treatment in decompensated heart failure. These applications of B-type NPs require confirmation before they become established in routine management of heart failure.     

Prevalence and significance of an isolated long QT interval in elite athletes.

AIMS: Identification of a prolonged, corrected QT (QTc) interval in athletes may be a recommendation for disqualification from competitive sports. However, the prevalence and diagnostic significance of an isolated prolonged QTc in asymptomatic athletes without familial disease is unknown. METHODS AND RESULTS: Between 1996 and 2006, 2000 elite athletes (mean age, 20.2 years) underwent 12-lead ECG and 2-D echocardiography. The QT interval was corrected for heart rate (QTc). Athletes with QTc > 460 ms underwent 48 h Holter monitor and an exercise stress test. All athletes with a prolonged QTc interval were offered genetic testing and first-degree relatives were invited for ECG. The QTc was prolonged in seven (0.4%) athletes ranging from 460 to 570 ms. Three athletes had a QTc value of >500 ms and all exhibited one of: paradoxical prolongation of QTc during exercise, a confirmatory genetic mutation, or prolonged QTc in a first-degree relative. In contrast, none of the athletes with a QTc value of <500 ms had any other features to indicate long QT syndrome (LQTS). CONCLUSION: The prevalence of prolonged QTc in elite athletes is 0.4%. A QTc of >500 ms is highly suggestive of LQTS. A QTc of <500 ms in the absence of symptoms or familial disease is unlikely to represent LQTS in elite athletes.     

Potential future therapies: natriuretic peptides.

Congestive heart failure has become a major public health problem. A hallmark of this syndrome is neurohumoral activation, with elevation of natriuretic peptides, in particular atrial natriuretic peptide and brain natriuretic peptide of myocardial origin, which occurs with the onset of ventricular dysfunction. The natriuretic peptide system is important in cardiorenal regulation, specifically in the integrated control of intravascular volume and arterial pressure to maintain optimal circulatory integrity. Several therapeutic approaches have been established to mimic or potentiate the unique cardiovascular and renal beneficial actions of these peptides during heart failure. Recent investigations have also established a diagnostic utility for the natriuretic peptides to diagnose early asymptomatic left ventricular dysfunction. Thus, diagnostic and therapeutic use of the natriuretic peptides is emerging as a new strategy to delay the natural history of progressive heart failure from its earliest phase to chronic congestive heart failure.     

Prohormone atrial natriuretic peptides 1-30 and 31-67 increase in hyperthyroidism and decrease in hypothyroidism

Hyperthyroidism characteristically has natriuresis and vasodilation associated with it, whereas hypothyroidism is associated with impaired water excretion and vasoconstriction. This investigation was designed to determine if the plasma concentration(s) of three newly described hormones synthesized in the heart are increased in patients with hyperthyroidism and/or decreased in patients with hypothyroidism compared to normal subjects. The three hormones consist of amino acids 1-30, 31-67, and 99-126 (ANF) of the 126 amino acid prohormone of atrial natriuretic factor. Prohormone atrial natriuretic peptides (pro ANFs) 1-30, 31-67, and ANF were increased threefold, fourfold, and twofold respectively in hyperthyroid patients compared to the mean circulating concentration of 54 healthy persons without thyroid disease. Plasma concentrations of the three peptides in hypothyroid patients were only one-half that of the 54 persons without thyroid disease. With appropriate treatment of hyperthyroidism and hypothyroidism, the levels of the three peptides returned to normal. The peptide hormones increased proportionately with the increasing dosages of L-thyroxine of 50 micrograms/day and 100 micrograms/day in the hypothyroid patients. In persons with hypothyroidism complicated by congestive heart failure, the levels of pro ANFs 1-30, 31-67, and 99-126 were increased, demonstrating that abnormalities of salt and water metabolism are a strong stimulus to the release of these peptides.