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OBJECTIVE Although chronotropic incompetence (CI) represents an independent predictor of mortality and incidence of coronary artery disease, its pathophysiological mechanisms remain unknown. The purpose of this investigation was to evaluate wall motion abnormalities of the left ventricle and location of coronary arterial lesions in patients with and without CI. METHODS After exclusion of confounding factors, 610 patients (mean age of 58.4 +/- 11 years; 275 men) with ischaemia who underwent exercise echocardiography were studied. Based on heart rate (HR) reached in treadmill testing, patients were divided into two groups: Chl (97 patients who did not reach 85% of maximum HR recommended for age) and ChC (513 patients who achieved 85% of the maximum age-predicted HR). RESULTS There was a higher frequency of dyspnoea (5.2% vs. 0.6%, P = 0.003), systemic hypertension (69.1% vs. 57.3%, P = 0.031) and obesity (38.1% vs. 22.6%, P = 0.001), and a lower tolerance to effort (dyspnoea as limitation of physical effort: 36.1% vs. 8.0%, P < 0.0001; duration of treadmill test: 4.4 +/- 2.2 vs. 7.2 +/- 2.8, P < 0.0001; METs: 6.0 +/- 2.6 vs. 8.4 +/- 2.9, P = 0.002) in Chl compared to ChC. The wall motion score index (WMSI) was higher in Chl than in ChC, both at rest (1.15 +/- 0.29 vs. 1.07 +/- 0.19, P = 0.011) and after exercise (1.24 +/- 0.29 vs. 1.15 +/- 0.19, P = 0.002). Systolic function, which was evaluated in peak exercise through WMSI, was significantly more altered in the Chl group. The presence of severe injuries in right coronary was independently associated with CI (adjusted OR = 3.57, CI 95%: 1.86-6.87). CONCLUSION Chronotropic incompetence is associated with ventricular dysfunction in peak exercise and critical right coronary artery lesions.

FUNDAMENTO: O teste ergometrico (TE), inicialmente indicado para diagnostico e estratificacao de risco da doenca arterial coronariana (DAC), apresenta baixa sensibilidade, o que pode implicar em falha na deteccao de pacientes com risco aumentado de eventos adversos. OBJETIVO: Avaliar a ecocardiografia sob estresse fisico (EEF) na predicao de eventos cardiacos maiores (ECM) e obitos por todas as causas em pacientes com probabilidade pre-teste intermediaria de DAC e TE normal. METODO: Trata-se de estudo retrospectivo em que foram estudados 397 pacientes, com probabilidade pre-teste intermediaria de DAC pelo metodo de Morise e TE normal, submetidos a EEF. Dividiu-se em dois grupos: EEF negativo (G1) ou positivo (G2) para isquemia miocardica. Os desfechos avaliados foram mortalidade por qualquer causa e ECM, definidos como obito cardiaco e infarto agudo do miocardio (IAM) nao fatal. RESULTADOS: O grupo G1 constituiu-se de 329 (82,8%) pacientes. A idade media foi de 57,37 ± 11 anos e 44,1% eram do genero masculino. Durante o seguimento medio de 75,94 ± 17,24 meses, ocorreram 13 obitos, dentre eles tres por causas cardiacas (IAM), alem de 13 IAM nao fatais. Isquemia miocardica permaneceu como preditor independente de ECM (RR 2,49; [IC] 95% 1,74-3,58). As variaveis preditoras de mortalidade por qualquer causa foram genero masculino (RR 9,83; [IC] 95% 2,15-44,97) e idade > 60 anos (RR 4,57; [IC] 95% 1,39-15,23). CONCLUSAO: A EEF positiva e preditora de ECM na amostra estudada, o que auxilia na identificacao de um subgrupo de pacientes sob maior risco de eventos adversos, apesar de apresentarem TE normal.

Background: GH deficiency (GHD) is often associated with cardiovascular risk factors, including abdominal fat accumulation, hypercholesterolemia, and increased C-reactive protein. Despite the presence of these risk factors, adults with congenital lifetime isolated GHD (IGHD) due to an inactivating mutation in the GHRH receptor gene do not have premature atherosclerosis.Objective: The aim was to study the serum levels of adiponectin and leptin (antiatherogenic and atherogenic adipokine, respectively), and the urinary albumin excretion (UAE) in these IGHD individuals.Design and Patients: We conducted a cross-sectional study of 20 IGHD individuals (seven males; age, 50.8 ± 14.6 yr) and 22 control subjects (eight males; age, 49.9 ± 11.5 yr).Main Outcome Measures: Anthropometric factors, body composition, blood pressure, serum adiponectin, leptin, and UAE were measured.Results: Adiponectin was higher [12.8 (7.1) vs. 9.7 (5) ng/ml; P = 0.041] in IGHD subjects, whereas no difference was observed in leptin [7.3 (6.3) vs. 9.3 (18.7 ng/ml] and UAE [8.6 (13.8) vs. 8.5 (11.1) μg/min].Conclusions: Subjects with lifetime untreated IGHD have an adipokine profile with high adiponectin and normal leptin levels that may delay vascular damage and lesions of the renal endothelium.

Context: Reduced longevity observed in hypopituitarism has been attributed to GH deficiency (GHD). It is, however, unclear whether GHD or other confounding factors cause this early mortality. Objective: The aim was to study longevity in subjects from a large kindred with untreated, lifetime isolated GHD (IGHD) due to a homozygous mutation in the GHRH receptor gene and in heterozygous carriers of the mutation. Design, Setting, and Participants: We carried out a retrospective cohort study on three groups. We first compared mortality risk of 65 IGHD individuals and their 128 unaffected siblings from 34 families. We then compared mean age of death of the IGHD to the general population. A transversal study was carried out to compare the rate of heterozygosity for the mutation in two groups of young (20–40 yr old) and old (60–80 yr old) normal-appearing subjects from the same county. Main Outcome Measure: We measured longevity. Results: The risk of death of IGHD subjects was not different from their siblings. Life span in IGHD individuals was shorter than the general population. When stratified by sex, this difference persisted only in females, due to a high frequency of IGHD deaths in females aged 4–20. There was no significant difference in life span between IGHD subjects and siblings or the general population when analyzing subjects who reached age 20. The prevalence of heterozygosity did not differ in young and old groups, suggesting no survival advantage or disadvantage. Conclusions: In a selected genetic background, lifelong untreated IGHD does not affect longevity.