Sarcopenia and Cardiovascular Diseases.

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be particularly important among those with chronic disease states. Early recognition of sarcopenia is important because it can provide an opportunity for interventions to reverse or delay the progression of muscle disorder, which may ultimately impact cardiovascular outcomes. Relying on body mass index is not useful for screening because many patients will have sarcopenic obesity, a particularly important phenotype among older cardiac patients. In this review, we aimed to: (1) provide a definition of sarcopenia within the context of muscle wasting disorders; (2) summarize the associations between sarcopenia and different cardiovascular diseases; (3) highlight an approach for a diagnostic evaluation; (4) discuss management strategies for sarcopenia; and (5) outline key gaps in knowledge with implications for the future of the field.

Statins and the Liver.

Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease.

Assessment of the Effects of Age, Gender, and Exercise Training on the Cardiac Sympathetic Nervous System Using Positron Emission Tomography Imaging.

BACKGROUND: Using positron emission tomography (PET) imaging, we sought to determine whether normal age or exercise training cause changes in the cardiac sympathetic nervous system function in male or female healthy volunteers. METHODS: Healthy sedentary participants underwent PET studies before and after 6 months of supervised exercise training. Presynaptic uptake by the norepinephrine transporter-1 function was measured using PET imaging of [(11)C]-meta-hydroxyephedrine, a norepinephrine analog, and expressed as a permeability-surface area product (PSnt in mL/min/mL). Postsynaptic function was measured as ß-adrenergic receptor density (ß'max in pmol/mL tissue) by imaging the ß-receptor antagonist [(11)C]-CGP12177. Myocardial blood flow (MBF in mL/min/mL tissue) was measured by imaging [(15)O]-water. RESULTS: At baseline, there was no age difference in ß'max or MBF but PSnt declined with age (1.12±0.11 young vs 0.87±0.06 old, p = .036). Before training, women had significantly greater MBF (0.87±0.03 vs 0.69±0.03, p < .0001) and PSnt (1.14±0.08 vs 0.75±0.07, p < .001) than men. Training increased VO2 max by 13% (p < .0001), but there were no training effects on ß'max, PSnt, or MBF. Greater MBF in females and a trend to increased PSnt post-training persisted. CONCLUSION: With age, presynaptic uptake as measured by PSnt declines, but there were no differences in ß'max. Endurance training significantly increased VO2 max but did not cause any changes in the measures of cardiac sympathetic nervous system function. These findings suggest that significant changes do not occur or that current PET imaging methods may be inadequate to measure small serial differences in a highly reproducible manner.

Exercise training bradycardia is largely explained by reduced intrinsic heart rate.

INTRODUCTION: Resting heart rate (RHR) declines with exercise training. Possible mechanisms include: 1) increased parasympathetic tone, 2) decreased responsiveness to beta-adrenergic stimulation, 3) decreased intrinsic heart rate or 4) combination of these factors. OBJECTIVE: To determine whether an increase in resting parasympathetic tone or decrease in response to beta-adrenergic stimulation contributes to the decrease in RHR with training. METHODS: 51 screened healthy subjects aged 18-32 (n=20, mean age 26, 11 female) or 65-80 (n=31, mean age 69, 16 female) were tested before and after 6months of supervised exercise training. Heart rate response to parasympathetic withdrawal was assessed using atropine and beta-adrenergic responsiveness during parasympathetic withdrawal using isoproterenol. RESULTS: Training increased VO2 max by 17% (28.7±7.7 to 33.6±9.20ml/kg/min, P<0.001). RHR decreased from 62.8±6.6 to 57.6±7.2 beats per minute (P<0.0001). The increase in heart rate in response to parasympathetic withdrawal was unchanged after training (+37.3±12.8 pre vs. +36.4±12.2 beats per min post, P=0.41). There was no change in the heart rate response to isoproterenol after parasympathetic blockade with training (+31.9±10.9 pre vs. +31.0±12.0 post beats per min, P=0.56). The findings were similar in all four subgroups. CONCLUSIONS: We did not find evidence that an increase in parasympathetic tone or a decrease in responsiveness to beta-adrenergic activity accounts for the reduction in resting heart rate with exercise training. We suggest that a decline in heart rate with training is most likely due to decrease in the intrinsic heart rate.

Statins and the liver.

Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease.

Increased mortality in patients with conflicting diastolic parameters.

The aim of this study was to describe the clinical characteristics and mortality of patients with conflicting diastolic function during follow-up. Up to 30% of patients have conflicting diastolic function by echo Doppler and therefore cannot be classified into a distinct diastolic dysfunction category of stage 1, 2 or 3. Using our established echocardiography data base, we studied a cohort of 250 subjects with conflicting diastolic function. Each individual was compared to two controls with normal diastolic and systolic function. The pre-specified goal of the analysis was a 6-year follow-up. Patients with conflicting diastolic function were more likely to have diabetes, hypertension, and established coronary artery disease. The Cox proportional hazards model determined that the risk of death was significantly higher for conflicting patients compared to patients with normal diastolic parameters (HR: 1.83; 95% CI: 1.32-2.53), P < 0.001. After adjustment for covariates, the risk of death remained elevated for the conflicting group (HR: 1.56; 95% CI: 1.11-2.18), P = 0.009. Conflicting diastolic dysfunction is associated with an increased risk of death compared to individuals with normal function. In conclusion, this emphasizes the need to attain a more precise characterization and categorization for patients with diastolic dysfunction.

Right ventricular strain rate predicts clinical outcomes in patients with acute pulmonary embolism.

BACKGROUND: Echocardiographic quantification of global and regional right ventricular (RV) function is critical in patients with acute pulmonary embolism (PE), but remains a challenge particularly in acute RV dilatation. METHODS: Apical two-dimensional images of patients with acute PE were analyzed using both conventional and speckle tracking imaging compared with controls; patients with PE were divided into those who received thrombolysis and those who did not. The basal, mid and apical segments of the RV free wall and septum were analyzed. Correlations between speckle tracking measurements and in-hospital mortality were made. RESULTS: 53 patients with PE were compared with 15 controls. Of the PE patients, 98.1% were treated with systemic anticoagulation, 15.1% with thrombolysis; 38% required ICU admission and 5.6% died. Strain rate of the mid interventricular septum and strain of the basal and mid interventricular septal segments were significantly lower in patients with PE than control. However, strain rate of the basal RV free wall was higher than controls. In thrombolysed patients, basal RV free wall strain rate was lower than in non-thrombolysed patients. RV strain rate significantly correlated with in-hospital mortality. CONCLUSIONS: Speckle tracking may be a sensitive tool for assessing RV dysfunction and predicting mortality in patients with PE in this pilot study.

Initial experience using contrast enhanced real-time three-dimensional exercise stress echocardiography in a low-risk population.

Although emerging data support the utility of real-time three-dimensional echocardiography (RT3DE) during dobutamine stress testing, the feasibility of performing contrast enhanced RT3DE during exercise treadmill stress has not been explored. Two-dimensional (2D) and three-dimensional (3D) acquisition were performed in 39 patients at rest and peak exercise. Contrast was used in 29 patients (74%). Reconstruction was performed manually by generating short axis cut planes at the base, mid-ventricle and apex, and automatically by generating 9 short axis slices. Three-dimensional acquisition was feasible during rest and stress regardless of the use of contrast. Time to acquire stress images was reduced using 3D (35.2±17.9 s) as compared to 2D acquisition (51.6±14.7 s; P<0.05). Using a 17-segment model, of all 663 segments, 588 resting (88.6%) and 563 stress segments (84.9%) were adequately visualized using manually reconstructed 3D data, compared with 618 resting (93.2%) and 606 stress segments (91.4%) using 2D data (P rest=0.06; P stress=0.07). We concluded that contrast enhanced RT3DE is feasible during treadmill stress echocardiography.