Circulating periostin levels do not differ between postmenopausal women with normal and low bone mass and are not affected by zoledronic acid treatment.

Periostin is a secreted extracellular matrix protein preferentially expressed in bone by osteocytes and periosteal osteoblasts. Reduced periostin expression may affect osteoblast differentiation and collagen type I synthesis and predispose to osteoporosis and increased fracture risk. We aimed to evaluate circulating periostin levels in postmenopausal women with low bone mass, their possible correlations with clinical and laboratory parameters, as well as the 3-month effect of zoledronic acid. Serum samples for periostin, 25-hydroxyvitamin D, parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTx), and total alkaline phosphatase (tALP) were obtained from 46 postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion and from 30 age-matched, postmenopausal controls with normal bone mass at baseline. There was no difference in periostin levels between women with normal and low bone mass (250±15 vs. 272±14 ng/ml, respectively; p=0.279). Periostin remained essentially unchanged after zoledronic acid infusion (262±18 ng/ml; p=0.130). Serum periostin levels at baseline were not affected by previous bisphosphonate treatment, and were correlated only to tALP (rs=0.351; p=0.018). In multiple linear regression analysis, tALP (B=3.17; 95% CI=0.59-5.79; p=0.018) was associated with serum periostin levels at baseline, independently from previous anti-osteoporotic treatment, age, body mass index, and 25-hydroxyvitamin D. In conclusion, serum periostin levels do not differ between postmenopausal women with normal and low bone mass and are not affected by zoledronic acid treatment. Women with higher tALP have independently higher periostin levels.

Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment.

UNLABELLED: Activin-A is expressed in bone and seems to regulate osteoclastogenesis. In this study, serum activin-A was increased in postmenopausal women with low bone mass and was positively correlated to age and negatively to lumbar spinal bone mineral density (BMD). Serum activin-A levels did not change 3 months after zoledronic acid infusion. INTRODUCTION: The aims of the study were to evaluate prospectively the circulating activin-A levels in postmenopausal women with low bone mass and explore possible correlations with clinical and laboratory data, as well as the 3-month effect of zoledronic acid infusion. METHODS: Postmenopausal women with low bone mass assigned to receive zoledronic acid infusion (Patients, n = 47) and age-matched, postmenopausal women with normal bone mass (Controls, n = 27) were recruited on an outpatient basis. Main outcome measurement was serum activin-A levels. RESULTS: Serum activin-A was higher in patients at baseline compared to controls (p < 0.001) and activin-A in the serum of patients and controls was positively correlated with age (Spearman's coefficient of correlation [rs] = 0.325; p = 0.005) and negatively with lumbar spinal (LS) BMD (rs = -0.425; p < 0.001). In multiple linear regression analysis, only age (B = 8.93; 95 % CI = 4.39-13.46; p < 0.001) was associated with serum activin-A levels at baseline, independent from group (patients or controls), previous anti-osteoporotic treatment, LS BMD and follicle-stimulating hormone. Circulating activin-A levels were not affected 3 months after zoledronic acid infusion. CONCLUSIONS: Serum activin-A is increased in postmenopausal women with low bone mass compared with postmenopausal women with normal bone mass and is positively correlated to age and negatively to LS BMD.

Can myocardial ischemia be recognized by the exercise electrocardiogram in coronary disease patients with abnormal resting Q waves?

This study was performed in order to determine whether exercise-induced myocardial ischemia demonstrated by thallium-201 imaging could be detected by ST segment shifts in patients with abnormal Q waves at rest. Fifty-four patients with coronary artery disease and exercise-induced thallium-201 defects were compared to 22 patients with similar Q wave patterns but without thallium-201 exercise defects and to 14 normal subjects. Exercise data were analyzed visually in the 12-lead ECG and for spatial ST vector shifts. Both ST segment depression observed on the 12-lead ECG and spatial criteria were reasonably sensitive and specific for ischemia when the resting ECG showed no Q waves or inferior Q waves (range 69% to 93%). However, when anterior Q waves were present, ST segment shifts could not distinguish patients with ischemia from those with normal perfusion as determined by thallium imaging.

Failure of transdermal nitroglycerin to improve exercise capacity in patients with angina pectoris.

Sixteen patients with stable angina pectoris were studied in a double blind crossover manner utilizing treadmill exercise testing with the direct measurement of total body oxygen uptake, 1 and 24 hours after application of a 20 cm2 transdermal nitroglycerin system and identical placebo. Testing was performed after a 3 day lead-in period of treatment with either an active patch or placebo. Points of analysis were peak angina and the submaximal work load occurring at 4 minutes of exercise. No statistically significant differences were observed between nitroglycerin and placebo treatment in any of the rest hemodynamic or peak angina variables at 1 or 24 hours. A significant increase in the rate-pressure product at the submaximal work load was observed 1 hour after transdermal nitroglycerin relative to placebo application. However, no significant differences were observed in any of the other measured variables at the submaximal work load, 1 or 24 hours after nitroglycerin application. The once daily application of a 20 cm2 transdermal nitroglycerin system was ineffective in altering the exercise capacity of patients with angina pectoris. The lack of efficacy at 1 hour appears to be due to inadequate nitroglycerin blood levels; at 24 hours it may be due to tolerance.

Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy.

In order to determine whether areas of ischemia identified by thallium-201 scintigraphy could be localized by exercise ECG, we studied 54 patients with stable coronary heart disease. All 54 patients had exercise-induced thallium-201 scintigraphic defects. Their exercise ECG test results were compared to their thallium-201 images and also to 14 low-risk normal subjects. Exercise data were analyzed for spatial ST vector shifts, using a computer program in order to most accurately classify ST segment depression and elevation. Thallium-201 ischemic defects detected in our patients included areas in the septum and the inferior, lateral, and anterior walls. Twenty-six of these 54 patients also had coronary angiography for classification and comparison as having either localized or generalized disease. None of the scintigraphic ischemic sites or angiographic diseased areas could be specifically identified by exercise-induced ST vector shifts. Therefore, the surface exercise ECG has limitations in localizing ischemia to specific areas of the myocardium.

The reproducibility of hemodynamic, electrocardiographic, and gas exchange data during treadmill exercise in patients with stable angina pectoris.

Fourteen male patients with exercise test-induced angina and ST-segment depression underwent treadmill testing on three consecutive days to evaluate the reproducibility of certain treadmill variables. Computerized ST-segment analysis and expired gas analysis, including anaerobic threshold, were evaluated for reproducibility using an intra-class correlation coefficient analysis. Measured oxygen uptake at peak exercise displayed better reproducibility than total treadmill time, the onset of angina, and the gas exchange anaerobic threshold (ATGE). The double product, heart rate, and ST-segment displacement in lead X were found to be reproducible at peak exercise, the onset of angina, and the ATGE. The incorporation of gas exchange analysis can provide accurate physiologic determinants of exercise capacity in patients with angina pectoris. In addition, noninvasive estimates of myocardial oxygen demand and ischemia can be reproducibly determined. These findings have important implications for the design of studies evaluating the effects of an intervention on angina pectoris.

Computer analysis of exercise-induced changes in electrocardiographic variables. Comparison of methods and criteria.

In order to evaluate computerized methods of electrocardiographic signal processing, determination of QRS end, and measurement of criteria for ischemia, we analyzed the data from 42 male patients with coronary heart disease who underwent maximal treadmill testing. Electrocardiographic data were digitized on-line and leads X, V5, Y and Eigen V were later analyzed for noise content, isoelectric baseline, and ST parameters using the UCSD spatial electrocardiographic computer program. Various ST segment criteria for ischemia were calculated and compared. Noise was greater in lead Y and in all leads when the median was used for signal averaging. Two isoelectric baseline algorithms and three ST segment slope algorithms gave similar results. Spatially derived QRS end was highly correlated with the amplitude measured using a fixed time interval after peak R wave. Both ST area and ST midpoint estimates differed widely using two different algorithms for each. Regression equations were derived that make it possible to estimate QRS end or ST60 amplitudes in V5 from values in X or vice versa.

Limitations of electrocardiographic scoring systems for estimation of left ventricular function.

Four electrocardiographic scoring systems for the assessment of left ventricular function or presence of myocardial infarction were evaluated in 231 patients with coronary artery disease. Electrocardiographic scores were compared with radionuclide ejection fraction and thallium perfusion studies. The correlation between Wagner's modified QRS score and ejection fraction was only fair (r = -0.60). Askenazi's sum of R wave voltage score correlated poorly with ejection fraction (r = 0.44), as did Gottwik's sum of voltage score from the Frank lead electrocardiogram (r = 0.44). Rautaharju's Cardiac Infarction Injury Score did not reliably predict presence of infarction in the patient group, nor did it correlate well with ejection fraction (r = -0.49). None of the correlations were significantly improved when only patients with a history of a myocardial infarction, a thallium defect compatible with a scar or a diagnostic Q wave were considered. Although Wagner's QRS score correlated best with ejection fraction, all scoring systems had limited clinical usefulness for estimating ejection fraction.