Biomedical subjects

Kent R Bailey

Publications and source records attributed to Kent R Bailey.

At least 37 records · Page 2Linked to original sources

PubMed2006

Exertional changes in circulating cardiac natriuretic peptides in patients with suggested coronary artery disease.

BACKGROUND: We measured plasma brain natriuretic peptide (BNP) and N-terminal atrial natriuretic peptide (ANP) levels before and after exercise stress testing and correlated results with echocardiographic evidence of ischemia. METHODS: Sixty patients with left ventricular ejection fraction greater than 50% referred for clinically indicated exercise echocardiogram were studied. Peptides were measured at rest and 5 minutes after symptom-limited exercise. RESULTS: Echocardiography was positive for ischemia in 19 (32%). With exercise, ANP level increased in all 60 patients (median at rest 2501 [799-6440]-3167 [977-8563] pg/mL after exercise [P < .0001]). BNP increased in 54 patients (90%) (19 [<3.9-213]-30 [<3.9-318] pg/mL [P < .0001]). In multivariable analysis, both exercise BNP level and exertional change in BNP were closely associated with rest BNP (P < .0001); both were also significantly associated with change in wall-motion score index and workload (P = .001 and P = .01, respectively). Exercise ANP was strongly related to rest level (P < .0001); change in ANP was related to workload (P < .0001). CONCLUSION: In patients with suggested coronary artery disease, exertional levels of BNP are influenced not only by development of stress-induced ischemia, but also by resting levels.

Aged↗

PubMed2006

The trained observer better predicts daytime ABPM diastolic blood pressure in hypertensive patients than does an automated (Omron) device.

OBJECTIVES: Accurate blood pressure measurement is critical to successful clinical trials. Concerns about observer errors have led to the use of automated oscillometric devices without evidence that their performance is similar to that of trained observers. This study compares blood pressures obtained by trained observers and with an oscillometric device (Omron 705CP) to 24-h ambulatory blood pressure monitoring. METHODS: We performed a post-hoc analysis of 313 untreated hypertensive patients at the end of the washout phase of a Novartis hypertension trial. Patients had three seated trained observer mercury auscultatory blood pressure measurements followed by 24-h ambulatory blood pressure monitoring. The next day, the ambulatory blood pressure monitoring was removed and three seated readings were obtained with an Omron 705CP. Correlations for systolic blood pressure and diastolic blood pressure were obtained between daytime ambulatory blood pressure monitoring (0900 and 2100) and the two office methods. In addition, we investigated the degree of difference of trained observer and Omron measurements from ambulatory blood pressure monitoring. RESULTS: For systolic blood pressure, the correlation with ambulatory blood pressure monitoring of the trained observer was significantly better than with that of the Omron 705CP (0.641 vs. 0.555, P=0.01). For diastolic blood pressure values, even greater disparity between the two office method correlations with ambulatory blood pressure monitoring was observed (trained observer=0.593 vs. Omron=0.319, P<0.0001). Both trained observer and Omron readings were consistently higher than ambulatory blood pressure monitoring for systolic blood pressure (P<0.0001) and diastolic blood pressure (P<0.0001). Omron measurements, however, deviated from ambulatory blood pressure monitoring more than those of the trained observer (P<0.0001 for systolic blood pressure and diastolic blood pressure). CONCLUSIONS: For clinical trials using diastolic blood pressure targets, the Omron 705CP cannot replace the auscultatory blood pressure measurements of a trained observer. For systolic blood pressure, the Omron device and the trained observer had similar correlations with ambulatory blood pressure monitoring; however, both methods gave consistently higher systolic blood pressure values. Further study of oscillometric devices should be conducted before universally replacing auscultatory blood pressure determinations by trained observers in clinical trials.

Adult↗

PubMed2006

The occurrence of the alerting response is independent of the method of blood pressure measurement in hypertensive patients.

OBJECTIVE: Current guidelines stress the need for more than one measurement of blood pressure in the hypertensive patient. The frequency with which the first blood pressure significantly exceeds subsequent blood pressures (alerting response) is unknown. Participants in a hypertension treatment trial before initiation of therapy were included in post-hoc analyses to investigate the alerting response separately for trained nurse blood pressure measurements with mercury sphygmomanometer and measurements taken by an Omron 705 CP automated device. BASIC METHODS: A total of 313 participants were included. Each participant had three nurse blood pressure readings before a 24-h automated blood pressure monitoring device was attached, and three Omron measurements at the time the automated blood pressure monitoring device was removed. Alerting response was defined separately for systolic and diastolic measures as a decrease of > or =8 or > or =6 mmHg, respectively, from first measure to the average of the second and third measures. MAIN RESULTS: An alerting response was observed in 20.4% of nurse-performed blood pressure measurements and 28.4% of Omron measurements. A large range of variation between first blood pressure and average second and third measures was observed, with changes of up to 30 mmHg systolic and 20 mmHg diastolic. The only demographic factor associated with the alerting response was body mass index, with obese patients more likely to exhibit an alerting response (P=0.004) in nurse-measured blood pressure. CONCLUSIONS: We found the alerting response with both methods of blood pressure measurement; however, it was not consistently observed in the same individuals. This confirms that hypertensive patients require multiple blood pressure measurements.

Adult↗

PubMed2006

An echocardiographic left ventricular wall area index for functional detection of myocardial injury in hemodynamically unloaded hearts.

Functional assessment of the left ventricle is affected by loading conditions. Detection of rejection-mediated myocardial injury in a heterotopic heart transplant model is a challenge for the echocardiographer because the heart is in an unloaded state. We examined the relationship of a novel left ventricular (LV) wall area index (LVWAI) and serum cardiac troponin T (cTnT) levels. The LVWAI, based on prior methods of determining LV mass, was defined as the difference between epicardial and endocardial areas divided by the epicardial area. The biphasic morphometric response of LVWAI reflected changes in the cTnT levels and allowed echocardiographic detection of myocardial injury in hemodynamically unloaded hearts.

Animals↗

PubMed2006

Correspondence between the adult treatment panel III criteria for metabolic syndrome and insulin resistance.

OBJECTIVE: The aim of the present study was to assess the diagnostic accuracy of the Adult Treatment Panel III (ATP-III) definition of the metabolic syndrome in identifying insulin-resistant individuals and to explore alternative approaches to improve identification of insulin-resistant individuals among asymptomatic adults from the general population. RESEARCH DESIGN AND METHODS: The sample consisted of 256 non-Hispanic white subjects without treated hypertension or diabetes, from the Rochester (Minnesota) Heart Family Study (123 men and 133 women; aged 20-60 years). Frequently sampled intravenous glucose tolerance tests were performed in all subjects. The reference standard for insulin resistance was determined by Bergman's minimal model; insulin resistance was defined as an insulin sensitivity index <2 x 10 min(-1) . microU(-1) . ml(-1). Component metabolic syndrome measures included blood pressure determined by sphygmomanometer; fasting serum triglycerides, HDL cholesterol, and glucose concentrations determined enzymatically; and waist circumference determined by tape measure. RESULTS: By ATP-III criteria, the prevalence of metabolic syndrome was 15.6% (16.3% in men and 15.1% in women; P = 0.465). The presence of metabolic syndrome had low sensitivity to identify insulin resistance (45% in men and 39% in women; sex difference, P = 0.137) but high specificity (93% in men and 95% in women; sex difference, P = 0.345). Based on the area under the receiver operating characteristic curve (AUC) constructed by counting metabolic syndrome components as recommended by ATP-III, diagnostic accuracy was fair (AUC = 0.797 in men and 0.747 in women). When component metabolic syndrome measures were considered as quantitative traits rather than dichotomized, use of waist circumference alone, rather than counting metabolic syndrome components, improved diagnostic accuracy for insulin resistance (in men, AUC = 0.906, P = 0.001; in women, AUC = 0.822, P = 0.10). CONCLUSIONS: Application of the ATP-III metabolic syndrome criteria provides good specificity but low sensitivity to screen asymptomatic white adults for insulin resistance. Measuring just waist circumference is simpler and may provide greater accuracy for identifying insulin resistance.

Adult↗

PubMed2006

Association of plasma homocysteine with coronary artery calcification in different categories of coronary heart disease risk.

OBJECTIVE: To Investigate the association of plasma homocystelne with coronary artery calcification (CAC) in strata based on 10-year risk of coronary heart disease (CHD) in a cohort enriched in persons with hypertension. PARTICIPANTS AND METHODS: Fasting plasma homocystelne was measured by liquid chromatography electrospray tandem mass spectrometry. Coronary artery calcification was measured noninvasively by electron beam computed tomography and CAC score calculated using the method of Agatston et al. The 10-year CHD risk was calculated based on the Framingham risk score. The association of homocysteine with log-transformed CAC score was assessed in the pooled sample and within each risk stratum by linear regression after adjustment for conventional risk factors. RESULTS: In the 1071 participants studied, homocysteine was associated with CAC quantity (P = .01) after adjustment for CHD risk factors (age, male sex, total and high-density lipoproteln cholesterol, diabetes, history of smoking, body mass Index, and systolic blood pressure), serum creatinine, and statin and hypertension medication use. When the association was assessed in strata based on 10-year CHD risk, homocysteine was significantly (P = .003) associated with CAC quantity in participants at Intermediate 10-year risk of CHD (6%-20%) independent of other risk factors but not in those at lower risk or higher risk. CONCLUSION: Plasma homocysteine is associated with quantity of CAC Independent of CHD risk factors. When studied in categories of 10-year CHD risk, the association was significant in participants at intermediate risk but not in those at low or high risk. Plasma homocysteine levels may have clinical utility as a marker of CHD risk in such individuals.

Aged↗

PubMed2006

Temporal trends in prevalence of diabetes mellitus in a population-based cohort of incident myocardial infarction and impact of diabetes on survival.

OBJECTIVE: To determine the temporal trends in prevalence of confirmed diabetes mellitus (DM), time from the date DM criteria were met to myocardial infarction (MI), and impact of DM on survival. SUBJECTS AND METHODS: A retrospective cohort design was used to identify residents of Olmsted County, Minnesota, with incident MI from 1979 to 1998. The MI cases were characterized according to prevalent DM. Cases with and without DM were followed up for vital status until January 1, 2003. RESULTS: Of 2171 MI cases, 364 (17%) met criteria for prevalent DM. In the age- and sex-adjusted logistic regression models, the odds of prevalent DM Increased 3% with each Increasing year between 1979 and 1998 (95% confidence Interval [CI], 1%-5%; P=.007). Survival for MI cases with DM was unchanged between 1979-1983 and 1994-1998 (P=.74). For all MI cases, age-, sex-, and DM-adjusted risk of death decreased 3% from 1979 to 1998 (95% CI, 1%-5%) per year for 28-day survival (P=.02) and 2% (95% CI, 1%-3%) per year for 5-year survival (P=.02). There was a significant adverse effect of DM on 5-year survival after MI (age-, sex-, and calendar year-adjusted hazard ratio, 1.70; 95% CI, 1.38-2.09; P<.001). The adverse effect of DM persisted after adjusting for other cardiovascular disease risk factors, MI severity, and reperfusion therapy (hazard ratio, 1.66; 95% CI, 1.34-2.05; P<.001) and was unchanged over time (interaction between DM and calendar year, P=-.63). CONCLUSION: These data indicate that the prevalence of DM among patients with MI is increasing and that its adverse impact on survival after MI remains unchanged.

Adolescent↗

PubMed2005

Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study.

BACKGROUND: The risk for venous thromboembolism during pregnancy or postpartum is uncertain. OBJECTIVES: To estimate the relative and absolute risk for deep venous thrombosis and pulmonary embolism during pregnancy and postpartum and to describe trends in incidence. DESIGN: Population-based inception cohort study using the resources of the Rochester Epidemiology Project. SETTING: Olmsted County, Minnesota. PATIENTS: Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester). MEASUREMENTS: The authors obtained yearly counts of live births in Olmsted County between 1966 and 1995 from the Minnesota Department of Health. RESULTS: The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100,000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100,000). Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold. LIMITATIONS: Because the Olmsted County population was 98% white and of non-Hispanic ethnicity, the results may not be generalizable to other ethnicities. CONCLUSIONS: Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women. Although the incidence of pulmonary embolism has decreased over time, the incidence of deep venous thrombosis remains unchanged, indicating the need to better identify pregnant women at increased risk.

Adolescent↗

PubMed2005

Role of endothelial NO synthase phosphorylation in cerebrovascular protective effect of recombinant erythropoietin during subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND AND PURPOSE: In the present study, the effect of subarachnoid hemorrhage (SAH) on the phosphorylation of endothelial NO synthase (eNOS) and the ability of recombinant erythropoietin (Epo) to augment this vasodilator mechanism in the spastic arteries were studied. METHODS: Recombinant adenoviral vectors (10(9) plaque-forming units per animal) encoding genes for human Epo (AdEpo), and beta-galactosidase were injected immediately after injection of autologous arterial blood into the cisterna magna (day 0) of rabbits. Cerebral angiography was performed on day 0 and day 2, and basilar arteries were harvested for Western blots, measurement of cGMP levels, and analysis of vasomotor functions. RESULTS: Injection of autologous arterial blood into cisterna magna resulted in significant vasospasm of the basilar arteries. Despite the narrowing of arterial diameter and reduced expression of eNOS, expressions of phosphorylated protein kinase B (Akt) and phosphorylated eNOS were significantly increased in spastic arteries. Gene transfer of AdEpo reversed the vasospasm. AdEpo-transduced basilar arteries demonstrated significant augmentation of the endothelium-dependent relaxations to acetylcholine, whereas the relaxations to an NO donor, 2-(N,N-diethylamino)diazenolate-2-oxide sodium salt, were not affected. Transduction with AdEpo further increased the expression of phosphorylated Akt and eNOS and elevated basal levels of cGMP in the spastic arteries. CONCLUSIONS: Phosphorylation of eNOS appears to be an adaptive mechanism activated during development of vasospasm. The vascular protective effect of Epo against cerebral vasospasm induced by SAH may be mediated in part by phosphorylation of Akt/eNOS.

Animals↗

PubMed2005

Time trends of ischemic stroke incidence and mortality in patients diagnosed with first atrial fibrillation in 1980 to 2000: report of a community-based study.

BACKGROUND AND PURPOSE: With the changes in management of atrial fibrillation (AF) over time, it is possible that the time trends of post-AF stroke incidence and mortality have changed. We sought to determine whether the incidence and survival of ischemic stroke after AF diagnosis have improved. METHODS: We identified the Olmsted County, Minn, residents who developed first AF from 1980 to 2000 and followed them in medical records to 2004. The outcomes were first ischemic stroke and death. RESULTS: Of the 4117 subjects diagnosed with first AF and without previous stroke, 446 (11%) sustained a first ischemic stroke during a mean follow-up time of 5.5+/-5.0 years. The age- and sex-adjusted incidence of stroke decreased, on average, by 3.4% per year (P=0.0001), concurrent with an increase in warfarin and aspirin use (both P<0.0001) and reduction of systolic blood pressure (P<0.001). The age-adjusted ischemic stroke incidence was higher in women (P=0.039), but not after adjusting for systolic blood pressure (P=0.41). Compared with the general Minnesota white population, the relative mortality hazard ratio was 1.88 for men and 1.84 for women without stroke and 3.03 for men and 3.80 for women (P<0.05) with stroke. The relative mortality hazard did not vary by age or calendar year of AF diagnosis. CONCLUSIONS: Post-AF ischemic stroke incidence decreased significantly from 1980 to 2000, during which time a substantial increase in the use of antithrombotic therapy and reduction of systolic blood pressure was evident. The relative mortality risk of stroke, however, had not improved over time.

Adolescent↗

PubMed2005

Sinus venosus atrial septal defect: long-term postoperative outcome for 115 patients.

BACKGROUND: Sinus venosus atrial septal defect (SVASD) differs from secundum atrial septal defect by its atrial septal location and its association with anomalous pulmonary venous connection (APVC). Data on long-term outcome after surgical repair are limited. METHODS AND RESULTS: We reviewed outcomes of 115 patients (mean age+/-SD 34+/-23 years) with SVASD who had repair from 1972 through 1996. APVC was present in 112 patients (97%). Early mortality was 0.9%. Complete follow-up was obtained for 108 patients (95%) at 144+/-99 months. Symptomatic improvement was noted in 83 patients (77%), and deterioration was noted in 17 patients (16%). At follow-up, 7 (6%) of 108 patients had sinus node dysfunction, a permanent pacemaker, or both, and 15 (14%) of 108 patients had atrial fibrillation. Older age at repair was predictive of postoperative atrial fibrillation (P=0.033). No reoperations were required during follow-up. Survival was not different from expected for an age- and sex-matched population. Clinical improvement was more common with older age at surgery (P=0.014). Older age at repair (P=0.008) and preoperative New York Heart Association class III or IV (P=0.038) were independent predictors of late mortality. CONCLUSIONS: Operation for SVASD is associated with low morbidity and mortality, and postoperative subjective clinical improvement occurs irrespective of age at surgery. Postoperative atrial fibrillation appears to be related to older age at operation. SVASD repair achieves survival similar to that of a matched population and should be considered whenever repair may impact survival or symptoms.

Adolescent↗

PubMed2005

Usefulness of left atrial volume in predicting first congestive heart failure in patients > or = 65 years of age with well-preserved left ventricular systolic function.

Left atrial (LA) volume is a barometer of diastolic dysfunction. Whether it predicts congestive heart failure (CHF) in patients with preserved left ventricular (LV) systolic function is not known. Olmsted County, Minnesota, residents aged > or = 65 years referred for transthoracic echocardiography from 1990 to 1998, who were in sinus rhythm without a history of CHF were followed in the medical records to 2003 (mean follow-up duration 4.3 +/- 2.7 years). Of the 1,495 patients identified, 1,375 (92%) with LV ejection fractions > or = 50% (mean age 75 +/- 7 years; 59% women) constituted the study population, 138 (10%) of whom developed CHF. Baseline LA volume > or = 32 ml/m2 was an independent predictor of first CHF (p <0.001). Of the 138 patients who had first CHF, ejection fractions were assessed within 4 weeks of diagnosis in 98 subjects, 74 (76%) of whom had ejection fractions remaining at > or = 50%, with a mean increase in LA volume of 8 +/- 10 ml/m2 (p <0.001) from baseline. The age-adjusted CHF-free survival rates for LA volume tertiles (< 28, 28 to < or = 37, and > 37 ml/m2) were 95%, 91%, and 83%, respectively (p <0.001). In conclusion, LA volume independently predicted first CHF in an elderly cohort with well-preserved LV systolic function.

Aged↗

PubMed2005

Left atrial volume predicts cardiovascular events in patients originally diagnosed with lone atrial fibrillation: three-decade follow-up.

AIMS: The objectives of this study were to determine the long-term outcome and the predictors of adverse events in patients originally diagnosed with lone atrial fibrillation (AF). METHODS AND RESULTS: This population-based historical cohort study comprised 46 residents of Olmsted County, MN, USA, with well-documented, clinically defined lone AF and a complete two-dimensional echocardiographic examination. The original echocardiographic videotape recordings were analysed in a blinded fashion for left atrial volume (LAV) and left ventricular ejection fraction. With 1296 person-years of follow-up, the median duration of AF was 27 (first quartile=24, third quartile=33) years. Twenty-three (50%) patients developed events. Cerebral infarction occurred in seven patients, myocardial infarction in 11, and congestive heart failure in 16. In a multivariable analysis, patients with indexed LAV >or=32 mL/m(2) had a significantly worse event-free survival (adjusted HR, 4.46; 95% CI, 1.56-12.74; P=0.005). All cerebral infarctions occurred in patients with an indexed LAV >32 mL/m(2). CONCLUSION: Patients originally diagnosed with benign lone AF follow divergent courses based on LAV. Those originally diagnosed with lone AF and normal sized atria had a benign clinical course throughout the long-term follow-up. Patients with increased LAV at diagnosis or later during the follow-up experienced adverse events.

Aged↗

PubMed2005

Cyclosporine decreases vascular progenitor cell numbers after cardiac transplantation and attenuates progenitor cell growth in vitro.

OBJECTIVE: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. METHODS: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC(CFU)) and smooth muscle outgrowth colony numbers (SOC(CFU)) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. RESULTS: In the sham alone series there were no changes to either EOC(CFU) or SOC(CFU). In the sham with immunosuppression and the transplant series, both EOC(CFU) and SOC(CFU) fell in the first 2 weeks (p < 0.05) compared with baseline (EOC(CFU), 3.4 +/- 0.6; SOC(CFU), 11.1 +/- 2.8). EOC(CFU) recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 +/- 3.9; p = 0.01). SOC(CFU) showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. CONCLUSION: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.

Animals↗

PubMed2005

Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up.

BACKGROUND: This study assessed the long-term outcome of a large, asymptomatic population with hemodynamically significant aortic stenosis (AS). METHODS AND RESULTS: We identified 622 patients with isolated, asymptomatic AS and peak systolic velocity > or =4 m/s by Doppler echocardiography who did not undergo surgery at the initial evaluation and obtained follow-up (5.4+/-4.0 years) in all. Mean age (+/-SD) was 72+/-11 years; there were 384 (62%) men. The probability of remaining free of cardiac symptoms while unoperated was 82%, 67%, and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left ventricular hypertrophy predicted symptom development. During follow-up, 352 (57%) patients were referred for aortic valve surgery and 265 (43%) patients died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities of remaining free of surgery or cardiac death were 80%, 63%, and 25%, respectively. Multivariate predictors of all-cause mortality were age (hazard ratio [HR], 1.05; P<0.0001), chronic renal failure (HR, 2.41; P=0.004), inactivity (HR, 2.00; P=0.001), and aortic valve velocity (HR, 1.46; P=0.03). Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated patients. Patients with peak velocity > or =4.5 m/s had a higher likelihood of developing symptoms (relative risk, 1.34) or having surgery or cardiac death (relative risk, 1.48). CONCLUSIONS: Most patients with asymptomatic, hemodynamically significant AS will develop symptoms within 5 years. Sudden death occurs in approximately 1%/y. Age, chronic renal failure, inactivity, and aortic valve velocity are independently predictive of all-cause mortality.

Aged↗

PubMed2005

Semi-parametric and non-parametric methods for clinical trials with incomplete data.

Last observation carried forward (LOCF) and analysis using only data from subjects who complete a trial (Completers) are commonly used techniques for analysing data in clinical trials with incomplete data when the endpoint is change from baseline at last scheduled visit. We propose two alternative methods. The semi-parametric method, which cumulates changes observed between consecutive time points, is conceptually similar to the familiar life-table method and corresponding Kaplan-Meier estimation when the primary endpoint is time to event. A non-parametric analogue of LOCF is obtained by carrying forward, not the observed value, but the rank of the change from baseline at the last observation for each subject. We refer to this method as the LRCF method. Both procedures retain the simplicity of LOCF and Completers analyses and, like these methods, do not require data imputation or modelling assumptions. In the absence of any incomplete data they reduce to the usual two-sample tests. In simulations intended to reflect chronic diseases that one might encounter in practice, LOCF was observed to produce markedly biased estimates and markedly inflated type I error rates when censoring was unequal in the two treatment arms. These problems did not arise with the Completers, Cumulative Change, or LRCF methods. Cumulative Change and LRCF were more powerful than Completers, and the Cumulative Change test provided more efficient estimates than the Completers analysis, in all simulations. We conclude that the Cumulative Change and LRCF methods are preferable to LOCF and Completers analyses. Mixed model repeated measures (MMRM) performed similarly to Cumulative Change and LRCF and makes somewhat less restrictive assumptions about missingness mechanisms, so that it is also a reasonable alternative to LOCF and Completers analyses.

Alzheimer Disease↗

PubMed2005

Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure.

BACKGROUND: Beta-blocker therapy improves symptoms, left ventricular ejection fraction (LVEF), and survival in patients with congestive heart failure, but chronic effects on neurohormones have not been extensively investigated. Therefore, we examined the neurohumoral effects of carvedilol. METHODS: Fifty-five patients with New York Heart Association (NYHA) classes II-III congestive heart failure and LVEF < or =35% entered the study with intention to assess LVEF, NYHA class, plasma brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NANP), big-endothelin, endothelin-1, norepinephrine, and angiotensin II at baseline and at 6 and 12 months after initiation of carvedilol. RESULTS: Forty-six patients completed 12 months of follow-up. Left ventricular ejection fraction improved from 26% +/- 8% at baseline to 39% +/- 14% at 12 months. New York Heart Association class improved from 2.3 +/- 0.4 at baseline to 1.8 +/- 0.7 at 12 months. Brain natriuretic peptide fell from 453 +/- 784 to 208 +/- 393 pg/mL at 6 months and 223 +/- 334 pg/mL at 12 months ( P = .01 vs baseline). N-terminal atrial natriuretic peptide did not change between baseline and 6 months but fell at 12 months (2117 +/- 1678, 2015 +/- 1532, and 1438 +/- 1442 pg/mL, respectively, P = .001 between baseline and 12 months). Angiotensin II was lower at 6 and 12 months than at baseline (12.6 +/- 10, 7.8 +/- 5.5 pg/mL, P < 0.001, and 11.3 +/- 17.1 pg/mL, P = .02, respectively). Left ventricular ejection fraction at 12 months correlated inversely with BNP level at 12 months (r = -0.55, P = .001). CONCLUSIONS: Carvedilol therapy is associated with a sustained decline in BNP and NANP levels. Serial BNP levels can provide some guidance regarding probability of LVEF improvement, but the relationship is not strong enough for BNP levels to supplant measurement of LVEF.

Adrenergic alpha-Antagonists↗

PubMed2005

C-reactive protein is related to arterial wave reflection and stiffness in asymptomatic subjects from the community.

BACKGROUND: Emerging data suggest that C-reactive protein (CRP), a marker of inflammation, is associated with functional properties of arteries. We investigated the relationship of CRP to measures of arterial wave reflection and stiffness (aortic augmentation index [AIX], carotid-femoral pulse wave velocity [PWV], and pulse pressure) in asymptomatic individuals from the community. METHODS: Subjects (n = 214) had a mean age of 59 years and 53% were men. CRP was measured by a high-sensitivity assay and values were log-transformed to reduce skewness. Radial artery waveforms were obtained by applanation tonometry, a validated transfer function was used to derive an ascending aortic pressure waveform, and AIX calculated. PWV was calculated from electrocardiogram-gated waveforms of the right carotid and right femoral artery obtained by applanation tonometry. RESULTS: Log CRP was correlated with AIX (r = 0.24, P = .0005), PWV (r = 0.25, P = .0002), and pulse pressure (r = 0.29, P < or = .0001). In separate backward elimination multiple regression analyses, log CRP was significantly associated with AIX (P = .038) and pulse pressure (P = .036), and marginally significantly associated with PWV (P = .054), after adjustment for heart rate, height, and coronary heart disease (CHD) risk factors (age, sex, body mass index, mean arterial pressure, total cholesterol, HDL cholesterol, diabetes, hypertension, and history of smoking). CONCLUSIONS: These results suggest that CRP, a marker of systemic inflammation, is related to measures of arterial wave reflection and stiffness in asymptomatic subjects from the community. Further studies are needed to understand the mechanisms underlying this association and the implications for assessment and management of CHD risk.

Aged↗