Growth hormone therapy and the heart.

The growth hormone (GH)-insulin-like growth factor-1 axis has great relevance for the regulation of cardiac growth, structure, and function. GH deficiency may result in impaired cardiac performance, manifest by a reduction in left ventricular mass and ejection fraction, but data are inconsistent. GH therapy is recommended treatment in adult patients with GH deficiency, but in acromegaly, in which there is excess GH, the main cause of mortality is cardiovascular disease. The purposes of this study were to perform (1) a case-controlled study comparing cardiac morphology and function in 53 GH-deficient patients (34 men, mean age 38.1 +/- 15.2 years, 22 with childhood-onset GH deficiency) and 46 healthy controls (29 men, mean age 37.8 +/- 12.4 years) and (2) a longitudinal study to assess the effect of introducing GH therapy in 37 subjects for a mean period of 26 +/- 22 months. At study entry, all subjects underwent electrocardiography and 24-hour ambulatory electrocardiographic monitoring, systolic and diastolic blood pressure assessment, detailed echocardiography, and exercise tolerance tests. There were no significant differences in left ventricular mass, left ventricular dimensions, systolic or diastolic function indexes, or blood pressure at rest in patients compared with controls. Exercise duration was significantly shorter and peak heart rate during exercise (chronotropic response) lower in the GH-deficiency group than in controls (p <0.05). After GH treatment, there were no significant changes in echocardiographic parameters or blood pressure, but an improvement in exercise duration (p = 0.019) was found, particularly in the subgroup with childhood-onset GH deficiency (n = 16). In conclusion, patients with GH deficiency did not show cardiac structural or functional differences compared with healthy controls, with no significant changes after GH treatment. However, these patients exhibited improved exercise capacity, especially those with childhood-onset GH deficiency.

[Effect of maximum dose of atorvastatin on inflammation, thrombogenesis and fibrinolysis in high-risk patients with ischemic heart disease]. / Efecto de dosis máximas de atorvastatina en la inflamación, la trombogénesis y la función fibrinolítica en pacientes con cardiopatía isquémica de alto riesgo.

INTRODUCTION AND OBJECTIVES: It has been suggested that high doses of statins can be more effective in reducing the incidence of new cardiovascular events than conventional doses. The present study analyzed the effect of increasing the atorvastatin dose to 80 mg/day on indices of inflammation (C-reactive protein or CRP), thrombogenesis (prothrombin fragment [F1+2]) and fibrinolysis (tissue-type plasminogen activator antigen, t-PA, and its inhibitor PAI-1) in high-risk patients with ischemic heart disease. PATIENTS AND METHOD: We studied 27 patients with high-risk coronary heart disease who had lipid levels above those recommended despite treatment with atorvastatin at 40 mg/day. At baseline, patients were compared with 21 normocholesterolemic subjects without arteriosclerotic disease. Twenty-four patients were reevaluated 3 months after the atorvastatin dose was increased to 80 mg/day. RESULTS: The CRP, F1+2, t-PA and PAI-1 levels were significantly higher in patients than control subjects (all P<.05). After the atorvastatin dose was increased, significant reductions in CRP, F1+2, and PAI-1 levels were observed (P<.05). There was a significant positive correlation between the reduction in cholesterol level and that in F1+2 (r=0.43; P=.023). No other significant correlations were found. CONCLUSIONS: In a group of patient with high-risk heart disease and elevated lipid levels, increasing the atorvastatin dose led to significant improvements in inflammatory, thrombogenic, and hypofibrinolytic states.

Fractional shortening-velocity ratio for assessment of aortic stenosis severity in patients with systolic dysfunction.

BACKGROUND: In the study of severity of aortic stenosis many different methods derived from transthoracic echocardiography are used. Their principal limitations are left ventricular dysfunction and calcified aortic valve. The objective of this study was to assess the utility of a described echocardiographic index: the fractional shortening-velocity ratio (FSVR=FS/4Vmax2) in those patients with left ventricular systolic dysfunction. METHODS: We studied 72 patients with aortic stenosis and aortic valvular area (AVA)< or =2 cm2. AVA was assessed by the Gorlin equation. Left ventricular systolic dysfunction was defined by FS< or =29%. Using receiver operating characteristic curves analysis to test the predictive discrimination of patients with and without critical aortic stenosis, we studied the best FSVR value to assess aortic stenosis severity. RESULTS: We found a significant linear correlation between AVA and FSVR (r=0.59; P<0.001). A value of FSVR < or =0.78 allowed the identification of patients with AVA< or =0.8 cm2 with good sensitivity and specificity (sensitivity: 94.5%; specificity: 60%; positive predictive value: 90% and negative predictive value: 75%). In our population, 22 patients (32%) showed a systolic dysfunction. The correlation AVA-FSVR was also significant in this group (r=0.68; P<0.001) and it may be even better than in the total group. However, the FSVR with the best sensitivity-specificity relation was different to the value used in the global group. A FSVR value <0.65 showed the best sensitivity-specificity relation in identifying patients with severe aortic stenosis (sensitivity: 100% and specificity: 56%). CONCLUSION: The FSVR is a very simple and noninvasive index. It allows identification of patients with severe aortic stenosis with excellent sensitivity and good specificity. It may be useful in the evaluation of patients with aortic stenosis and left ventricular dysfunction, although, there is not an accepted FSVR value with the best-combined sensitivity-specificity, to identify a critical aortic stenosis.

Effects of atorvastatin 80 mg daily on indices of matrix remodelling in 'high-risk' patients with ischemic heart disease.

Recent evidence suggests that higher doses of statins could improve clinical outcomes compared to conventional doses, but whether this benefit is due to "additional" pleiotropic effects is uncertain. We tested the hypothesis that atorvastatin 80 mg/day would have beneficial effects on indices of matrix remodelling (matrix metalloproteinase-1, MMP-1, and its tissue inhibitor, TIMP-1) in high-risk cardiovascular disease. We studied 27 "high-risk" patients (inclusion criteria: severe triple vessel but rejected for by-pass for extensive coronary disease, severe effort angina after coronary artery by-pass and premature coronary disease with > or =3 risk factors) with an abnormal lipid profile despite atorvastatin 40 mg/day, at baseline and at 3 months after increasing the statin dose to 80 mg/day. Baseline results in patients were compared to 22 healthy controls. At baseline, patients had lower levels of MMP-1 compared to controls. When atorvastatin was increased to 80 mg/day, significant reduction in LDL-cholesterol was observed, whereas MMP-1 and TIMP-1 levels were increased. These, despite of atorvastatin 40 mg daily, 'high-risk' patients still demonstrated abnormal extracellular remodelling indices. Doubling the dose of atorvastatin resulted in significant improvement in extracellular remodelling indices.

Short- and long-term effects of growth hormone on the heart.

OBJECTIVE: To make a critical analysis of using growth hormone (GH) in patients with chronic heart failure and to asses its effects on the heart in long-term replacement. METHODS: We have studied 27 GHD patients (20 men; mean age: 36+/-15 years; 11 with childhood onset GHD) in a longitudinal, prospective study to assess the effect of GH therapy on the cardiovascular system with a long-term follow-up. RESULTS: After a mean period of 45.3+/-29.6 months, there were no significant differences in echocardiographic parameters of cardiac structure or function. By contrast, the duration of exercise test improved after treatment (8:19+/-3:27 versus 10:23+/-3:25 min; p=0.01) especially in the subgroup of patients with childhood onset of GH deficiency (7:02+/-4:23 versus 11:33+/-3:07 min; p=0.004) but not in the adult onset GHD subgroup. Systolic blood pressure was significantly higher after treatment in the global group (118+/-18.2 mmHg versus 128+/-17.9 mmHg; p=0.004) and in both subgroups. CONCLUSIONS: The beneficial effects of GH replacement on the cardiovascular system is suggested but not fully proved and long-term GH substitution in GHD syndrome is not associated with significant changes in cardiac structure or function although these patients exhibit improved exercise capacity.

Does smoking status influence the effect of physical exercise on fibrinolytic function in healthy volunteers?

UNLABELLED: Exercise has been reported to simultaneously trigger and protect against sudden death, the so-called "The Paradox of Exercise". Differences in fibrinolytic function appear to exist between chronic and acute exercise. The aim of the present study was to assess the fibrinolytic system after strenuous exercise in healthy people and explored the influence of smoking habit. METHODS: 23 healthy male volunteers were studied (14 non-smokers; 9 current smokers). Citrated plasma blood samples were taken before and 30 minutes after a maximal exercise treadmill test, and levels of tissue type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen and lipoprotein-a, Lp(a), [all ELISA] were measured as indices of fibrinolytic function. RESULTS: Smokers had higher body mass index and higher heart rate at baseline than non smokers (p = 0.046 and p = 0.001, respectively). At baseline, smokers showed increased plasma Lp(a) levels than non smokers (p = 0.04), with no differences in t-PA and PAI-1 antigen levels. Following the exercise treadmill test, smokers had a shorter exercise duration and lower exercise capacity than non smokers (p = 0.008 and p = 0.004, respectively). This was associated with a reduction in t-PA antigen levels in the whole study population, (p = 0.048) without differences in PAI-1 levels, with no significant differences between smokers and non smokers. Lp(a) levels were also significantly reduced (p = 0.0001). CONCLUSIONS: Acute exercise alters plasma tPA antigen and Lp(a) levels, but there was no significant effect of smoking status in healthy subjects.

Effects of pretreatment with intravenous flecainide on efficacy of external cardioversion of persistent atrial fibrillation.

Electrical cardioversion is the most effective and safe method to restore sinus rhythm in patients with persistent AF. However, at least 25% of electrical cardioversions are unsuccessful. The aim of the present study was to evaluate, in a prospective, randomized and double-blind study, the efficacy of a pretreatment with intravenous flecainide in patients who underwent electrical cardioversion. Fifty-four consecutive patients with persistent AF, mean arrhythmia duration 8 (mean 3-18) weeks, were randomized in two groups. In the first group (n = 26), patients received flecainide (2 mg/kg as a 30-minute IV infusion) before electrical cardioversion. In the second group (n = 28), 100 mL IV infusion of 5% glucose was administered 30 minutes before electrical cardioversion. The study evaluated the (1). acute efficacy of electrical cardioversion, (2). mean and maximal energy required, (3). mean number of shocks needed, and (4). incidence of complications. The two groups were similar in terms of age, sex, mean AF duration, left ventricular systolic function, atrial dimension, and cardiovascular risk factors. Seventy-seven percent of patients recovered sinus rhythm with electrical cardioversion. No statistical difference was noted between the two groups: flecainide 19/26 (73%) versus placebo 23/28 (82%). No significant differences were found concerning mean or maximal energy and number of shocks required. No major complications were observed. After a 30-day follow-up, 54% of patients maintained sinus rhythm with no difference between the two groups. Pretreatment with intravenous flecainide before electrical cardioversion is not useful in reducing technical failure of cardioversion, however, flecainide does not diminish the effectiveness of electrical cardioversion.

Efecto de dosis máximas de atorvastatina en la inflamación, la trombogénesis y la función fibrinolítica en pacientes con cardiopatía isquémica de alto riesgo / Effect of maximum dose of atorvastatin on inflammation, thrombogenesis and fibrinolysisin high-risk patients with ischemic heart disease

Introducción y objetivos. Se ha indicado que la utilización de dosis altas de estatinas podría reducir la aparición de nuevos eventos cardiovasculares en comparación con las dosis convencionales. Nuestro objetivo fue estudiar el efecto del incremento de la dosis de atorvastatina (80 mg/día) en diferentes marcadores del sistema inflamatorio (proteína C reactiva [PCR]), hemostático (fragmento F 1+2 de la protrombina [F1+2]) y fibrinolítico(activador tisular del plasminógeno antigénico [t-PA] y suinhibidor [PAI-1]). Pacientes y método. Se estudió a 27 pacientes concardiopatía isquémica de alto riesgo que presentaban cifras lipídicas superiores a las recomendadas a pesar del tratamiento con 40 mg/día de atorvastatina. Se compararon con 21 sujetos normocolesterolémicos sin enfermedad arteriosclerótica conocida. Se revaluó a 24 pacientesa los 3 meses del incremento de la dosis. Resultados. Los pacientes presentaron cifras elevadas de PCR, F1+2, t-PA, y PAI-1 en comparación con el grupo control (en todos, las variables tuvieron un valor de p <0,05). Tras incrementar la dosis de atorvastatina se ob-servó una reducción de las cifras de PCR, F1+2 y PAI-1 (p< 0,05). Se observó una correlación positiva entre losporcentajes de reducción de colesterol y del F1+2 (r =0,46; p = 0,023), sin que se hallara otra correlación significativa entre los demás parámetros. Conclusiones. Al incrementar las dosis de atorvastatina a 80 mg/día se consigue una reducción de los estadosinflamatorios, trombógenicos e hipofibrinolíticos en un grupo de pacientes con cardiopatía isquémica de altoriesgo y cifras elevadas de lípidos a pesar del tratamientocon dosis de 40 mg/día de atorvastatina

Introduction and objectives. It has been suggestedthat high doses of statins can be more effective in reducing the incidence of new cardiovascular events than con-ventional doses. The present study analyzed the effect ofincreasing the atorvastatin dose to 80 mg/day on indicesof inflammation (C-reactive protein or CRP), thrombogenesis (prothrombin fragment [F1+2]) and fibrinolysis (tissue-type plasminogen activator antigen, t-PA, and its inhibitor PAI-1) in high-risk patients with ischemic heart disease. Patients and method. We studied 27 patients withhigh-risk coronary heart disease who had lipid levels above those recommended despite treatment with atorvastatin at 40 mg/day. At baseline, patients were compared with 21 normocholesterolemic subjects without arteriosclerotic disease. Twenty-four patients were reevaluated 3months after the atorvastatin dose was increased to 80 mg/day. Results.The CRP, F1+2, t-PA and PAI-1 levels weresignificantly higher in patients than control subjects (all P<.05). After the atorvastatin dose was increased, significant reductions in CRP, F1+2, and PAI-1 levels were ob-served (P<.05). There was a significant positive correla-tion between the reduction in cholesterol level and that in F1+2 (r=0.43; P=.023). No other significant correlationswere found. Conclusions. In a group of patient with high-risk heartdisease and elevated lipid levels, increasing the atorvastatin dose led to significant improvements in inflammatory, thrombogenic, and hypofibrinolytic states