Anthony Schork

Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial

BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test the hypothesis that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk. METHODS 15?245 patients, aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a randomised, double-blind, parallel-group comparison of therapy based on valsartan or amlodipine. Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint, defined as a composite of cardiac mortality and morbidity. Patients from 31 countries were followed up for a mean of 4.2 years. FINDINGS Blood pressure was reduced by both treatments, but the effects of the amlodipine-based regimen were more pronounced, especially in the early period (blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month; 1.5/1.3 mm Hg after 1 year; p<0.001 between groups). The primary composite endpoint occurred in 810 patients in the valsartan group (10.6%, 25.5 per 1000 patient-years) and 789 in the amlodipine group (10.4%, 24.7 per 1000 patient-years; hazard ratio 1.04, 95% CI 0.94-1.15, p=0.49). INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups. Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes. The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk.

Predictors of aspiration pneumonia: how important is dysphagia?

Abstract. Aspiration pneumonia is a major cause of morbidity and mortality among the elderly who are hospitalized or in nursing homes. Multiple risk factors for pneumonia have been identified, but no study has effectively compared the relative risk of factors in several different categories, including dysphagia. In this prospective outcomes study, 189 elderly subjects were recruited from the outpatient clinics, inpatient acute care wards, and the nursing home care center at the VA Medical Center in Ann Arbor, Michigan. They were given a variety of assessments to determine oropharyngeal and esophageal swallowing and feeding status, functional status, medical status, and oral/dental status. The subjects were followed for up to 4 years for an outcome of verified aspiration pneumonia. Bivariate analyses identified several factors as significantly associated with pneumonia. Logistic regression analyses then identified the significant predictors of aspiration pneumonia. The best predictors, in one or more groups of subjects, were dependent for feeding, dependent for oral care, number of decayed teeth, tube feeding, more than one medical diagnosis, number of medications, and smoking. The role that each of the significant predictors might play was described in relation to the pathogenesis of aspiration pneumonia. Dysphagia was concluded to be an important risk for aspiration pneumonia, but generally not sufficient to cause pneumonia unless other risk factors are present as well. A dependency upon others for feeding emerged as the dominant risk factor, with an odds ratio of 19.98 in a logistic regression model that excluded tube-fed patients.

Depressed Mood and Other Psychiatric Manifestations of Cushing's Syndrome: Relationship to Hormone Levels

&NA; Thirty‐five consecutive patients with Cushings syndrome were studied prospectively prior to treatment. A consistent constellation of psychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased concentration and memory), and vegetative functions (decreased libido and insomnia). A statistically significant relationship was found between the overall psychiatric disability rating and cortisol and ACTH level. The relationship of depressed mood and hormone levels was examined. Low ACTH levels were significantly associated with milder rather than pronounced depressed mood. The implications of the similarities in psychiatric manifestations between Cushings syndrome and the primary affective disorders are discussed.

Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease.

The diagnostic performance of rubidium-82 (Rb-82) positron emission tomography (PET) and thallium-201 (Tl-201) single-photon emission-computed tomography (SPECT) for detecting coronary artery disease was investigated in 81 patients (52 men, 29 women). PET studies using 60 mCi of Rb-82 were performed at baseline and after intravenous infusion of 0.56 mg/kg dipyridamole in conjunction with handgrip stress. Tl-201 SPECT was performed after dipyridamole-handgrip stress and, in a subset of patients, after treadmill exercise. Sensitivity, specificity and overall diagnostic accuracy were assessed using both visually and quantitatively interpreted coronary angiograms. The overall sensitivity, specificity and accuracy of PET for detection of coronary artery disease (greater than 50% diameter stenosis) were 84, 88 and 85%, respectively. In comparison, the performance of SPECT revealed a sensitivity of 84%, specificity of 53% (p less than 0.05 vs PET) and accuracy of 79%. Similar results were obtained using either visual or quantitative angiographic criteria for severity of coronary artery disease. In 43 patients without prior myocardial infarction, the sensitivity for detection of disease was 71 and 73%, respectively, similar for both PET and SPECT. There was no significant difference in diagnostic performance between imaging modalities when 2 different modes of stress (exercise treadmill vs intravenous dipyridamole plus handgrip) were used with SPECT imaging. Thus, Rb-82 PET provides improved specificity compared with Tl-201 SPECT for identifying coronary artery disease, most likely due to the higher photon energy of Rb-82 and attenuation correction provided by PET. However, post-test referral cannot be entirely excluded as a potential explanation for the lower specificity of Tl-201 SPECT.

The value of the clinical history in the differentiation of syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope

BACKGROUND The present study was undertaken to identify and quantitate the symptoms associated with neurocardiogenic syncope, syncope due to ventricular tachycardia, and syncope resulting from atrioventricular block. PATIENTS AND METHODS Eighty patients referred for evaluation of syncope in whom a diagnosis of neurocardiogenic syncope, atrioventricular block, or ventricular tachycardia was established were studied. Each patient was interviewed using a standard questionnaire. The clinical histories were then compared to identify which variables best differentiated the cause of syncope. RESULTS The clinical histories of patients with syncope due to ventricular tachycardia and atrioventricular block were similar. Only age, the duration of prodromal symptoms, diaphoresis prior to syncope, and fatigue following syncope differed. In contrast, the clinical history in patients with neurocardiogenic syncope differed greatly from that obtained in patients with syncope due to atrioventricular block or ventricular tachycardia. Features of the clinical history that were predictive of syncope due to atrioventricular block or ventricular tachycardia were male sex, age > 54 years, < or = 2 episodes of syncope, and a duration of warning of < or = 5 seconds. Features of the clinical history predictive of syncope not due to ventricular tachycardia or atrioventricular block were palpitations, blurred vision, nausea, warmth, diaphoresis, or lightheadedness prior to syncope, and nausea, warmth, diaphoresis, or fatigue following syncope. CONCLUSIONS The results of this study identify and compare the features of the clinical history obtained in patients with syncope due to ventricular tachycardia, atrioventricular block, and neurocardiogenic syncope and demonstrate that the clinical history is of value in distinguishing patients with these three causes of syncope.

Insulin and blood pressure during weight loss in obese adolescents.

The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

α2-Adrenergic receptor gene polymorphism and hypertension in blacks

alpha 2-Adrenergic receptors are found on presynaptic neurons of the central and peripheral nervous systems, on blood vessels, on platelets, on adipocytes, and in the kidney and pancreas. Activation of these ubiquitous adrenoreceptors results in decreased neuronal norepinephrine release, vasodilation, a fall in blood pressure, platelet aggregation, increased sodium excretion, and decreased insulin release. We hypothesized that defects in alpha 2-adrenergic receptors, or postreceptor defects, could explain the increased prevalence of hypertension in blacks. To test our hypothesis, we first determined whether or not a polymorphism of the alpha 2-adrenergic receptor gene was associated with pathologic elevations in blood pressure in American blacks. Dra-I identified a restriction fragment-length polymorphism (RFLP) of 6.3 and 6.7 kb of the alpha 2-adrenergic receptor gene on chromosome 10 in humans. Of 227 patients studied, 13/107 hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 3/120 normotensive volunteers were homozygotes (P = .008). When analyzed by race, 13/82 black hypertensive subjects were homozygous for the 6.3-kb allele, whereas only 2/59 normotensive blacks were homozygous for the 6.3-kb alleles (P = .02). However, only 1/61 white normotensive and 0/25 white hypertensive subjects were homozygous for the 6.3-kb allele (P = 1.00). Ethnic variation among blacks may explain our findings. Alternatively, a genetic polymorphism in, or near, the alpha 2-adrenergic receptor on chromosome 10 can contribute to the development of hypertension in blacks.

VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk

Abstract Background The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study compares cardiovascular outcomes in 15,314 eligible patients from 31 countries randomized to valsartan or amlodipine-based treatment. Methods The blood pressure (BP) trends are analyzed in 13,449 of VALUE study patients who had baseline BP and 24 months BP and treatment data. Results In a cohort of 12,570 patients, baseline 24 and 30 months BP, but not 30 months treatment data, were available. Of 13,449 patients, 92% ( N = 12,398) received antihypertensive therapy at baseline. The baseline BP was 153.5/86.9 mm Hg in treated compared to 168.1.8/95.3 mm Hg in 1051 untreated patients. After 6 months both groups had indistinguishable BP values. At 12 months the BP decreased to 141.2/82.9 mm Hg ( P P v 12 months), and to 138/79 mm Hg at 30 months ( P v 24 months). The systolic BP control ( Conclusions The achieved BP control exceeds values reported in most published large-scale trials. The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline. When an explicit BP goal is set, and a treatment algorithm is provided, the physicians can achieve better control rates than in their regular practice.

Glutathione and morbidity in a community-based sample of elderly

This study examined the association of blood glutathione level, a potential marker of physiological/functional aging, with a number of biomedical/psychological traits in a subgroup (N = 33) of a representative sample of community-based elderly. Higher glutathione levels were associated with fewer number of illnesses (p < 0.05), higher levels of self-rated health (p < 0.01), lower cholesterol (p < 0.05), lower body mass index, and lower blood pressures. Subjects with diagnoses of arthritis, diabetes, or heart disease (as assessed by physicians) had at least marginally significant lower glutathione levels than those who were disease free. Glutathione, together with age and a measure of suppressed anger, accounted for 39% of the variance of an index of morbidity. Glutathione, by itself, accounted for 24% of the variance. To our knowledge, this is the first evidence of an association of higher glutathione levels with higher levels of physical health in a sample of community-based elderly. Further studies in large samples are needed to investigate glutathione as a potential overall health risk factor for morbidity among the elderly.

Sympathetic hyperactivity in early stages of hypertension: the Ann Arbor data set.

Summary: Patients with borderline hypertension frequently hake a hyperkinetic circulation that is neurogenic and can he normalized with autonomic blockade of the heart. The abnormality is of central nervous system origin and due to increased sympathetic stimulation and decreased vagal inhibition of the heart. A subset of patients characterized by high plasma renin and norepinephrine values clearly has a neurogenic hypertension since their blood pressure becomes normal after cardiac blockade and vascular α-adrenergic blockade. Since many patients with borderline hypertension have a high cardiac output, and the majority of patients with more advanced hypertension hake increased vascular resistance. two questions arise. Is the ‘’hyperkinetic state a special condition unrelated to established hypertension or is there, in the course of hypertension. a transition from “high output” to “high resistance” state? The literature strongly suggests that patients with hyperkinetic borderline hyper-tension later proceed to develop the established high resistance form of hypertension. The most likely mechanism for this transition is a change in cardiac and vascular responsiveness due to prolonged execs pathetic stimulation combined with structural pressure-induced changes in these organs. This analysis of the events in the course of hypertension is of necessity based on an arbitrary definition of the hyperkinetic state usually set at a cardiac index at least two standard deviations above the normal mean. A bivariate analysis of our data (268 normotensive and 186 patients with borderline hypertension) suggests that there indeed are two different populations in this data set. Based on this commingling analysis, the occurrence of a hyperkinetic state was five-fold as frequent in patients with borderline hypertension than in the normotensive population. This, in turn, suggests that the hyperkinetic state is an abnormal state of circulation uniquely characteristic of patients with borderline hypertension.