Sex-specific differences in trimethylamine N-oxide (TMAO) concentrations before and after cardiac rehabilitation in acute myocardial infarction patients.

Trimethylamine N-oxide (TMAO) is a biomarker of cardiovascular risk and may enhance the progression of atherosclerosis. The aim of the study was to determine whether there are sex-specific differences in TMAO concentrations before and after cardiac rehabilitation in acute myocardial infarction (AMI) patients. A total of 56 participants [45/56 (80.4 %) males, 11/56 (19.6 %) females] were drawn from AMI inpatients hospitalized at the Division of Cardiology, Medical University of Graz, Austria. For the assessment of TMAO, serum samples were collected within the first day after hospital admission due to AMI and at the start and end of cardiac rehabilitation. Shortly after hospital admission due to AMI, females had significantly higher TMAO blood concentrations than males. These initially high TMAO levels remained almost unchanged in the female AMI patients until the start of cardiac rehabilitation and only reached the lower TMAO concentrations observed in the male patients after rehabilitation [female patients: TMAO (acute myocardial infarction) = 5.93 µmol/L (SE = 1.835); TMAO (start of rehabilitation) = 5.68 µmol/L (SE = 1.217); TMAO (end of rehabilitation) = 3.89 µmol/L (SE = 0.554); male patients: TMAO (acute myocardial infarction) = 3.02 µmol/L (SE = 0.255), TMAO (start of rehabilitation) = 3.91 µmol/L (SE = 0.346), TMAO (end of rehabilitation) = 4.04 µmol/L (SE = 0.363)]. After AMI, women might be at higher cardiovascular risk due to persistently higher levels of TMAO. High TMAO levels in women might decrease after cardiac rehabilitation due to cardiac rehabilitation-associated lifestyle modifications. These lifestyle modifications after AMI might also prevent increases in TMAO concentrations in men.

Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction.

Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.

Antecedentes: El trastorno de estrés postraumático (TEPT) es un trastorno relacionado con el estrés que se observa con frecuencia después de un infarto agudo de miocardio (IAM) y se caracteriza por numerosos síntomas, como flashbacks, intrusiones y ansiedad, así como pensamientos y sentimientos incontrolables relacionados con el trauma. Los correlatos biológicos del estrés severo podrían contribuir a identificar a los pacientes vulnerables al TEPT en una etapa temprana.Objetivo: Los objetivos del estudio fueron (1) determinar si los niveles sanguíneos de N-óxido de trimetilamina (TMAO, por sus siglas en ingles) varían inmediatamente después del IAM en pacientes con o sin sintomatología de TEPT inducida por IAM, (2) investigar si el TMAO es un biomarcador potencial que podría ser útil en la predicción de TEPT y los subgrupos de síntomas de TEPT que experimentan, evitación e hiperactivación, y (3) para investigar si el TMAO varía inmediatamente después del IAM en pacientes con o sin depresión 6 meses después del IAM.Método: Un total de 114 pacientes con IAM fueron evaluados con la Escala de Depresión de Hamilton tras su ingreso al hospital y 6 meses después. La Escala de TEPT para el DSM-5 administrada por el médico se utilizó para explorar los síntomas de TEPT en el momento del IAM y 6 meses después del IAM. Para evaluar el estado de TMAO de los pacientes, se recolectaron muestras de suero en la hospitalización y 6 meses después del IAM.Resultados: Los participantes con sintomatología de TEPT tenían niveles de TMAO significativamente más altos inmediatamente después del IAM que los pacientes sin síntomas de TEPT (ANCOVA: TMAO (TEPT x tiempo), F = 4.544, df = 1, p = 0.035). Con la inclusión de predictores clínicos adicionales en un modelo de regresión logística jerárquica, TMAO se convirtió en un predictor significativo de la sintomatología del TEPT. No se detectaron diferencias significativas en los niveles de TMAO inmediatamente después del IAM entre individuos con o sin depresión 6 meses después del IAM.Conclusiones: Un nivel elevado de TMAO inmediatamente después del IAM podría reflejar un estrés severo en pacientes vulnerables al TEPT, lo que también podría conducir a un aumento a corto plazo de la permeabilidad intestinal a la trimetilamina, el precursor de TMAO. Por lo tanto, un nivel elevado de TMAO podría ser un correlato biológico del estrés severo asociado con la vulnerabilidad al TEPT.

Heart Rate Performance Curve Is Dependent on Age, Sex, and Performance.

Introduction: The Heart Rate Performance Curve (HRPC) is neither linear nor uniform and related to ß1-adrenoceptor sensitivity. As aging and exercise influence ß1-adrenoceptors we suggested age, sex and performance effects on the HRPC. Aim of the study was to examine the effects of aging on the deflection of the HRPC in maximal incremental cycle ergometer exercise (CE) in a large cohort of healthy subjects. Methods: Heart rate (HR) data of 2,980 men (51 ± 15 years) and 1,944 women (52 ± 14 years) were classified into age groups (≤20 up to >80 years). We analyzed age and performance (Plow 25%-quartile and Phigh 75%-quartile of age predicted power) effects on HRmax and on the degree (k) and the type (regular downward deflection k > 0.1, linear -0.1 ≤ k ≤ 0.1 and atypical upward deflection k < -0.1) of the HRPC. Results:k-values decreased significantly with age in men and women and were significantly higher in women. Atypical HRPC's increased by a linear trend from ≤20 to 70 years (m) respectively 80 years (w) from 10 to 43% (m) and 9 to 30% (w). HRmax of all age groups was lower in Plow and overall number of atypical HRPC's was 21% (m) and 16% (w) higher compared to Phigh. Conclusion: Aging increased the number of atypical HRPC's with upward deflection in CE tests, which influences exercise intensity prescription especially when using fixed percentages of HRmax. Changes in HRPC's were affected by sex and performance, where women generally and subjects with higher performance presented less atypical HRPC's even at older age.

Efficacy of extended, comprehensive outpatient cardiac rehabilitation on cardiovascular risk factors: A nationwide registry.

AIM: Cardiac rehabilitation (CR) is a key component of the treatment of cardiac diseases. The Austrian outpatient CR model is unique, as it provides patients with an extended professionally supervised, multidisciplinary program of 4-6 weeks of phase II (OUT-II) and 6-12 months of phase III (OUT-III) CR. The aim of this analysis was to assess the efficacy of the Austrian outpatient CR model using a nationwide registry. METHODS: Data of all consecutive patients (N = 7560) who completed OUT-II and/or OUT-III between 1 January 2005 and 31 December 2015 were entered prospectively into a registry. OUT-III patients were analyzed separately according to whether the preceding phase II was performed as outpatient (OUT-II/OUT-III, N = 2403) or in-patient (IN-II/OUT-III, N = 2789). All patients underwent assessment of anthropometry, resting blood pressure, lipid profile, fasting blood glucose, exercise capacity, quality of life, anxiety and depression. RESULTS: During OUT-II, patients significantly improved their metabolic risk factor profile and increased exercise capacity by 14.3%. OUT-II/OUT-III patients achieved an additional increase in exercise capacity by 10%, further improvement in high-density lipoprotein (HDL) and stabilization of the remaining risk factors. IN-II/OUT-III patients increased their maximal exercise capacity by 18.4% and there was improvement in blood pressure, HDL, low-density lipoprotein and glucose levels. CONCLUSION: Extended, professionally supervised, multidisciplinary outpatient CR in a large nationwide registry of consecutive patients consistently improved maximal exercise capacity and relevant modifiable cardiovascular risk factors beyond effects seen after IN- or OUT-II alone.

Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study.

Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn't show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key pointsHigh-intensity interval exercise (HIIE) with short peak workload durations (tpeak) induce a lower acute metabolic and peak cardiorespiratory response compared to intervals with long tpeak despite higher peak workload intensities and identical mean load. No significant difference for any physiological parameter was found between short HIIE and CE.Between short HIIE, long HIIE, and CE, no significant difference was found in the increase (or decrease, respectively,) of health related markers such as cardiovascular biomarkers, catecholamines, or inflammatory parameters during exercise.During all exercise modes, all risk markers remained in a normal range except for NT-proBNP which was, however, already elevated at baseline.Short HIIE, long HIIE, and CE were safely performed by patients with CHD or myocarditis in cardiac rehabilitation by using our methodological approach to exercise prescription. This approach included the prescription of exercise intensities with respect to LTP1, LTP2, and Pmax as well as a conscious setting of Pmean at a moderate level (80 % of PLTP2). Importantly, all exercise modes were matched for Pmean and exercise duration in order to enable a comparison of the three protocols.

Long-term effects of outpatient cardiac rehabilitation in Austria: a nationwide registry.

AIM: Our Working Group on Out-Patient Cardiac Rehabilitation (AGAKAR) has previously published guidelines, which were endorsed by the Austrian Society of Cardiology. It was the aim of this study to assess the short-term (phase II) and long-term (phase III) effects of these guidelines by use of a nationwide registry. METHODS: All Austrian out-patient rehabilitation facilities entered data into a database of all consecutive patients who completed phase II (4-6 weeks) and/or III (6-12 months) rehabilitation between 1.1.2009-30.11.2011. RESULTS: Data of 1432 phase II and 1390 phase III patients were assessed. Despite the wide spectrum of cardiac diseases patients' exercise capacity improved during phase II by 20 (-193 to 240) watts; 91.0% reached a systolic blood pressure <140 mmHg; 68.1% an LDL <100 mg/dl; 69.8% triglycerides <150 mg/dl, and 66.2% of male patients had a waist circumference <102 cm. During phase III improvement in cardiovascular risk factors, quality of life, anxiety, and depression were further improved in an increasing number of patients. CONCLUSIONS: Our data demonstrate beneficial short- and long-term effects of the Austrian model of out-patient cardiac rehabilitation and provide support for comprehensive long-term rehabilitation programs. Furthermore, our model might be helpful for those who are at the verge of initiating or modifying their programs. It is also hoped that these data will motivate colleagues to refer their patients to out-patient cardiac rehabilitation facilities and that our results may stimulate insurance companies to grant further and comprehensive contracts to provide access for all suitable patients.