Noninvasive tests for arterial structure, function, and compliance: do they identify risk or diagnose disease?

BACKGROUND: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk for CAD developing. METHODS: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. RESULTS: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P =.01); smoking history (P =.002); hypercholesterolemia (P =.002); and hypertension (P =.004) (model R = 0.82; P =.0001). The independent predictors of CAD were: IMT (P =.001); BAR (P =.04); sex (P =.005); and hypertension (P =.005) (model R = 0.80; P =.0001). CONCLUSION: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.     

Psychosoziale Arbeitsbelastungen und muskulo-skeletale Beschwerden: Bedeutung für die Prävention

Psychosocial risk factors of musculoskeletal disorders have been increasingly discussed in recent past, in addition to physical determinants. This study investigates associations of an adverse psychosocial work environment with musculo-skeletal pain in a cohort of 316 middle-aged male and female employees (44,6 ± 7,5) of an urban transport company. The effort-reward imbalance model that identifies high cost/low gain’ conditions at work measures an adverse psychosocial work environment. In this cross-sectional investigation, effects of the three reward components of the model are analyzed separately. Musculoskeletal pain is assessed by a validated questionnaire (12 months and 7 days prevalence). Based on logistic regression analyses that adjust for relevant confounders, expected results were, overall, confirmed. The strongest associations are observed with respect to an imbalance between effort and esteem reward. The relative risks for neck, back and hip pain are two to three folds higher for people in the high imbalance group. Implications of the results for preventive efforts are discussed in the frame of work site health promotion.     

Better Living Through Chemistry: Does It Still Apply to Patients After Myocardial Infarction?

Sudden cardiac death is an elusive process that claims a significant number of lives annually in the United States. It is often associated with increased mortality within the first year after myocardial infarction, with the highest frequency occurring among patients with left ventricular dysfunction. Therefore, increasing survival rates in patients with a history of both disorders is an important goal of therapy. Recent trials suggested that an implantable cardioverter-defibrillator (ICD) in these patients may be superior to medical intervention in reducing the high mortality rate. Four major trials measured the benefits of an ICD for patients at risk for life-threatening ventricular arrhythmias. We assessed whether patients in these trials received adequate drug therapy as directed by American College of Cardiology-American Heart Association guidelines. One aim was to determine if medicated patients who served as controls in the trials were fairly represented. Furthermore, the need for improved overall guideline adherence was apparent.     

Patients with early diabetic heart disease demonstrate a normal myocardial response to dobutamine

OBJECTIVES: We sought to use quantitative markers of the regional left ventricular (LV) response to stress to infer whether diabetic cardiomyopathy is associated with ischemia. BACKGROUND: Diabetic cardiomyopathy has been identified in clinical and experimental studies, but its cause remains unclear. METHODS: We studied 41 diabetic patients with normal resting LV function and a normal dobutamine echo and 41 control subjects with a low probability of coronary disease. Peak myocardial systolic velocity (Sm) and early diastolic velocity (Em) in each segment were averaged, and mean Sm and Em were compared between diabetic patients and controls and among different stages of dobutamine stress. RESULTS: Both Sm and Em progressively increased from rest to peak dobutamine stress. In the diabetic group, Sm was significantly lower than in control subjects at baseline (4.2 +/- 0.9 cm/s vs. 4.7 +/- 0.9 cm/s, p = 0.012). However, Sm at a low dose (6.0 +/- 1.3), before peak (8.4 +/- 1.8), and at peak stress (8.9 +/- 1.8) in diabetic patients was not significantly different from that of controls (6.3 +/- 1.4, 8.9 +/- 1.6, and 9.6 +/- 2.1 cm/s, respectively). The Em (cm/s) in the diabetic group (rest: 4.2 +/- 1.2; low dose: 5.0 +/- 1.4; pre-peak: 5.3 +/- 1.1; peak: 5.9 +/- 1.5) was significantly lower than that of controls (rest: 5.8 +/- 1.5; low dose: 6.6 +/- 1.5; pre-peak: 6.9 +/- 1.3; peak: 7.3 +/- 1.7; all p < 0.001). However, the absolute and relative increases in Sm or Em from rest to peak stress were similar in diabetic and control groups. CONCLUSIONS: Subtle LV dysfunction is present in diabetic patients without overt cardiac disease. The normal response to stress suggests that ischemia due to small-vessel disease may not be important in early diabetic heart muscle disease.     

Survivin as a prognostic/predictive marker and molecular target in cancer therapy

Evasion from apoptotic cell death is reported to be a pivotal mechanism by which tumor cells acquire resistance to therapeutic treatment. Targeting the apoptotic pathways may constitute a promising strategy to counteract therapy resistance and to re-sensitize cancer cells. Expression of survivin, the smallest and structurally unique member of the inhibitor of apoptosis protein (IAP) family, has been shown to be associated with poor clinical outcome, more aggressive clinicopathologic features and resistance to both, conventional chemo and radiation therapy. Moreover, survivin detection in cancer tissue, in circulating tumor cells and in patient's serum has prognostic and predictive relevance and may display a prerequisite for marker based molecular therapies. Indeed, due to its universal over expression in malignant tissue, and its prominent role at disparate networks of cellular division, intracellular signaling, apoptosis and adaption to unfavorable surroundings, survivin has been shown to be a suitable target for a targeted therapy. The applicability of survivindriven strategies in clinical practice is currently under investigation as the first survivin antagonists (small molecule inhibitors, antisense oligonucleotides and immunotherapy) successfully entered phase I/II trials. Taken together, these data provide a rationale for the implementation of both, survivin as a molecular diagnostic tool and survivin targeted therapies, within future clinical practice.     

Use of tissue Doppler imaging to facilitate the prediction of events in patients with abnormal left ventricular function by dobutamine echocardiography

The extent of abnormality in patients with positive dobutamine echocardiography (DE) is predictive of risk, but the wall motion score (WMS) has low concordance among observers. We sought whether quantifying the extent of abnormal wall motion using tissue Doppler (TD) could guide risk assessment in patients with abnormal DE in 576 patients with known or suspected coronary artery disease; standard DE was combined with color TD imaging at peak dose. WMS was assessed by an expert observer and studies were identified as abnormal in the presence of >/=1 segments with resting or stress-induced wall motion abnormalities. Patients with abnormal DE had peak systolic velocity measured in each segment. Tissue tracking was used to measure myocardial displacement. Follow-up for death or infarction was performed after 16 +/- 12 months. Of 251 patients with abnormal DE, 22 patients died (20 from cardiac causes) and 7 had nonfatal myocardial infarctions. The average WMS in patients with events was 1.8 +/- 0.5, compared with 1.7 +/- 0.5 in patients without events (p = NS). The average systolic velocity in patients with events was 4.9 +/- 1.7 cm/s and 6.4 +/- 6.5 cm/s in the patients without events (p <0.001). The average tissue tracking in patients with events was 4.5 +/- 1.5 mm and was significant (5.7 +/- 3.1 mm) in those without events (p <0.001). Thus, TD is an alternative to WMS for quantifying the total extent of abnormal left ventricular function at DE, and appears to be superior for predicting adverse outcomes.     

Usefulness of B-type natriuretic peptide in hypertensive patients with exertional dyspnea and normal left ventricular ejection fraction and correlation with new echocardiographic indexes of systolic and diastolic function

B-type natriuretic peptide (BNP) levels increase in systolic heart failure (HF). However, the value of BNP in hypertensive patients with suspected diastolic HF (symptoms suggestive of HF but normal ejection fraction) and its relation to myocardial function in these patients is unclear. We prospectively studied 72 ambulatory hypertensive subjects (40 women, mean age 58 ± 8 years) with exertional dyspnea and ejection fraction ≥50%. Diastolic function was evaluated with transmitral and pulmonary venous Doppler, mitral annular velocities (pulsed-wave tissue Doppler), and flow propagation velocity (color M-mode). Systolic function was assessed with strain and strain rate derived from color tissue Doppler imaging. BNP was related to myocardial function and the presence or absence of global diastolic dysfunction. By conventional Doppler criteria, 34 patients had normal left ventricular diastolic function and 38 had isolated diastolic dysfunction. BNP values were higher in patients with diastolic dysfunction (46 ± 48 vs 20 ± 20 pg/ml, P = 0.004) and were related independently to blood pressure, systolic strain rate, left atrial function (p <0.01 for all), and age (p = 0.015). Patients with diastolic dysfunction and pseudonormal filling had higher BNP levels compared with impaired relaxation (89 ± 47 vs 35 ± 42 pg/ml, P = 0.001). However, 79% of patients with diastolic dysfunction had BNP levels within the normal range. We conclude that in ambulatory hypertensive patients with symptoms suggestive of mild HF and normal ejection fraction, BNP is related to atrial and ventricular systolic parameters, blood pressure, and age. Although elevated in the presence of diastolic dysfunction, the BNP level mostly is in the normal range and, therefore, has limited diagnostic value in stable patients with suspected diastolic HF.     

Use of body weight and insulin resistance to select obese patients for echocardiographic assessment of subclinical left ventricular dysfunction

Obesity is associated with heart failure. Recognition of subclinical left ventricular (LV) dysfunction may permit the initiation of therapy to prevent the development of heart failure. In this study of anthropometric, biochemical, and echocardiographic measurements in 295 healthy overweight subjects, we sought to investigate the effect of insulin resistance and severity of obesity on LV function and to establish a strategy for detection of LV dysfunction using metabolic and echocardiographic measurements. Correlates of subclinical dysfunction (defined from myocardial deformation in a matched group of 98 slim controls) were sought, and receiver operator characteristic curves for clinical and laboratory parameters were performed to identify optimal cutoffs to permit an effective diagnostic strategy. Subclinical impairment of LV function (average strain<18%) was present in 124 subjects (42%), and 52% of severely obese patients (body mass index [BMI]>35 kg/m2). Independent correlates of strain were BMI (beta=-0.25, p<0.0001), fasting insulin (beta=-0.22, p<0.001), and age (beta=-0.18, p<0.003). In patients with a BMI<35 kg/m2, subclinical impairment was uncommon in the absence of hyperinsulinemia. Using a BMI<35 kg/m2 and an insulin level<13 mIU/L to select patients for further testing allowed echocardiography to be avoided in 35% of subjects in whom the prevalence of LV dysfunction was low. In conclusion, obesity and insulin resistance are important contributors to LV dysfunction, a deleterious effect of hyperinsulinemia on LV performance is particularly seen in overweight and moderately obese subjects, and the combination of BMI, fasting insulin, and echocardiography appears optimal for efficient identification of subclinical LV dysfunction in overweight and obese subjects.