Study of the association between ischemic heart disease and use of alpha-blockers and finasteride indicated for the treatment of benign prostatic hyperplasia.

OBJECTIVE: Given the high possibility of co-occurrence of benign prostatic hyperplasia (BPH) and cardiovascular disease, we evaluated whether patients using BPH drugs are at an increased risk of acute hospital admission for ischemic heart disease (IHD). METHODS: A nested case control study within a cohort of 4414 men (aged > or =30 years) who had a history of using BPH products between 1992 and 1998 was conducted. Cases were defined as men with a first record of an acute hospital admission for IHD during the study period; three controls were matched to each case on year of birth, pharmacy and calendar time (index date). RESULTS: The study population comprised 220 cases and 515 controls. Current use of alpha-blockers (adjusted odds ratio 1.0, 95% confidence interval: 0.5-2.2) or finasteride (adjusted odds ratio 0.3, 95% CI: 0.1-1.4) was not associated with hospital admission for IHD. Furthermore, current use of BPH drugs was not associated with IHD in patient subgroups (age, history of cardiovascular disease, diabetes), nor with duration of use prior to hospitalization. CONCLUSION: Although the power of the study was low, we found no evidence for an association between current use of BPH drugs and hospital admission for IHD. Therefore, our study seems to confirm the good cardiovascular safety profile of modern BPH drugs.

Evaluating adverse cardiovascular effects of drug treatment for benign prostatic hyperplasia (BPH): methodological considerations.

When studying the effects of drug exposure in diseases with a long asymptomatic clinical course, exposure classification may be biased by the gradually developing "visibility" of the disease. Benign prostatic hyperplasia (BPH) is such a disease. We found that cardiovascular morbidity is two times more prevalent in patients starting drug treatment for BPH when compared to age-matched population controls. This resulted in a difference of cardiovascular prognostic factors between the exposed and non-exposed. This feature can jeopardize the validity of non-randomized comparisons of drug effects. Moreover, the existence of non-treatment strategies, disease under-reporting, and an elderly population with a high baseline risk of experiencing (cardiovascular) outcome events were encountered as methodological problems. When studying adverse cardiovascular effects in patients using BPH products in a non-randomized fashion, an important question is whether we can measure in the database all relevant prognostic factors and use the information for statistical adjustment. This question is an important challenge to observational research and once again stresses the need for control of possible biases in choosing an appropriate study design.

Stent placement for renal arterial stenosis: where do we stand? A meta-analysis.

PURPOSE: To perform a meta-analysis of renal arterial stent placement in comparison with renal percutaneous transluminal angioplasty (PTA) in patients with renal arterial stenosis. MATERIALS AND METHODS: Studies dealing with renal arterial stent placement (14 articles; 678 patients) and renal PTA (10 articles; 644 patients) published up to August 1998 were selected. A random-effects model was used to pool the data. RESULTS: Renal arterial stent placement proved highly successful, with an initial adequate performance in 98% and major complications in 11%. The overall cure rate for hypertension was 20%, whereas hypertension was improved in 49%. Renal function improved in 30% and stabilized in 38% of patients. The restenosis rate at follow-up of 6-29 months was 17%. Stent placement had a higher technical success rate and a lower restenosis rate than did renal PTA (98% vs 77% and 17% vs 26%, respectively; P <.001). The complication rate was not different between the two treatments. The cure rate for hypertension was higher and the improvement rate for renal function was lower after stent placement than after renal PTA (20% vs 10% and 30% vs 38%, respectively; P <.001). CONCLUSION: Renal arterial stent placement is technically superior and clinically comparable to renal PTA alone.

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group.

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.

Contribution of adverse drug reactions to hospital admission of older patients.

OBJECTIVE: To describe the severity of adverse drug reactions as a factor in hospital admission of older patients, and to identify risk indicators for severe adverse drug reactions in these patients. DESIGN: Observational cross-sectional study. SETTING: Five wards in a university hospital in The Netherlands. SUBJECTS: Patients aged 70 and over admitted to general medical wards. METHODS: Use of statistical comparison and Kramer's algorithm. RESULTS: A severe adverse drug reaction was present in 25 (24%) of 106 patients. Thirteen patients (12%; 95% confidence interval 6.1-18.6%) were admitted probably because of an adverse drug reaction. Risk indicators for a severe adverse drug reaction were a fall before admission (odds ratio 51.3, P = 0.006), gastrointestinal bleeding or haematuria (odds ratio 19.8, P < 0.001) and the use of three or more drugs (odds ratio 9.8, P = 0.04). CONCLUSION: Adverse drug reactions are an important cause of hospital admissions in older people. A fall before admission may indicate a severe adverse drug reaction.

Do older hospital patients recognize adverse drug reactions?

OBJECTIVE: To establish the relationship between subjective complaints of side effects of drugs and the objective presence of adverse drug reactions in older patients. DESIGN: Observational cross-sectional study. SETTING: Five medical wards at the University Hospital Rotterdam Dijkzigt. SUBJECTS: Patients aged 70 and over admitted to the general medical wards over a 3-month period. METHODS: Statistical comparison and Kramer's algorithm. RESULTS: Of 106 patients, 102 used medication, and 93 of these were able to report whether they believed they were experiencing drug side effects. Thirty-six [39% (95% confidence interval 28.8-48.6)] believed that they were experiencing side effects and the number of diagnoses per patient and the proportion of patients with chronic obstructive pulmonary disease was higher in these 36 'complainers' than in the group of the 'non-complainers'. We found a correct opinion (true positive and negative) about the objective presence or absence of mild or severe adverse drug reactions in 79% (95% confidence interval 70.2-86.8). Asking the patient about side effects of drugs had a sensitivity of 0.70 and a specificity of 0.85 patients. The severe adverse drug reactions in 21 patients were not recognized by 14 of them. CONCLUSION: At hospital admission, older patients should be asked about drug side effects because they are often correct in recognizing them. However, severe adverse drug reactions are not easily recognized.

Assessment of body position to quantify its effect on nocturnal blood pressure under ambulatory conditions.

BACKGROUND: Nocturnal blood pressure readings may be influenced by body position because of variation in the vertical distance between heart and cuff level. OBJECTIVES: To quantify the effect of body position on nocturnal blood pressure and to assess whether this effect influences the reproducibility of nocturnal blood pressure. PATIENTS AND METHODS: In 16 individuals (three normotensive and 13 hypertensive) 24 h ambulatory measurement of blood pressure and body position was performed twice, separated by an interval of 2-6 weeks. Body position was measured with five acceleration sensors, which were mounted on the trunk and legs. RESULTS: During the first night, 43 +/- 31% of blood pressure values were measured while participants were in the supine position, 29 +/- 28% when they were lying on their side with the cuffed arm down and 28 +/- 29% when they were lying on their side with the cuffed arm up. During the second night these percentages were 40 +/- 29%, 32 +/- 29% and 28 +/- 25% respectively. Blood pressure readings obtained while individuals were lying with the cuffed arm up were about 10 mmHg lower than those obtained with the individual in either the supine position or lying with the cuffed arm down. After correction for the underestimation attributable to 'cuff-up' readings, nocturnal blood pressure increased by 3 mmHg and the number of non-dippers increased from two to four. Correction did not affect the reproducibility of nocturnal blood pressure measurements (standard deviation of the differences 8.3 mmHg for systolic and 6.0 mmHg for diastolic blood pressure after correction). Dipping status was reproduced in 88% of individuals before correction, and in 87% after correction. CONCLUSIONS: Under ambulatory conditions, a highly variable but sometimes substantial number of blood pressure readings are taken with the cuffed arm above heart level. These readings result in underestimation of nocturnal blood pressure and hence influence dipper-non-dipper classification. However, body position does not seem to have an important influence on the reproducibility of nocturnal blood pressure or dipping status.

Cardiac evaluation in hypotension-prone and hypotension-resistant hemodialysis patients.

BACKGROUND: Hypotension during hemodialysis occurs frequently, but the precise mechanism remains unclear. In this study, the presence of myocardial ischemia and myocardial contractile reserve during infusions of the beta-adrenergic receptor agonist dobutamine was assessed by means of dobutamine-atropine stress echocardiography (DSE) in hypotension-prone (HP) and hypotension-resistant (HR) hemodialysis patients. METHODS: Eighteen HP patients (age 53 +/- 6 years) were compared with 18 HR patients (age 53 +/- 3 years), matched with respect to the duration of hemodialysis and cardiovascular history. New wall abnormalities during dobutamine stress reflect the presence of myocardial ischemia, whereas the increase in stroke index and cardiac index reflects myocardial contractile reserve. RESULTS: Wall motion score at rest (1.42 +/- 0.53 vs. 1.44 +/- 0.57) and dobutamine-induced new wall motion abnormalities (4 vs. 3 patients) between HP and HR patients were similar, but responses of cardiac index, stroke index, and systolic blood pressure to do butamine between the two groups were different. Not withstanding a similar cardiac index at rest (2.4 +/- 1.1 liter/min/m2 in HP and 2.8 +/- 1.2 liter/min/m2 in HR patients), dobutamine-induced increments in the cardiac index were considerably smaller in the former (0.8 +/- 1.3 liter/min/m2) than in the latter patients (2.3 +/- 1.6 liter/min/m2, P = 0.002), predominantly because of a progressive decrease in the stroke index in the HP patients. CONCLUSION: Impaired myocardial contractile reserve rather than ischemia is predominant in HP patients. This impaired myocardial contractile reserve may play a role in the development of hemodialysis-induced hypotension.

Stroke volume changes during dobutamine-atropine stress echocardiography: the influence of heart rate and ischaemia.

BACKGROUND: A decrease in stroke volume during dobutamine-atropine stress echocardiography heralds ischaemia and possible hypotension. Hypotension results from worsening of LV-function (as a result of ischaemia) left ventricular outflow tract obstruction or hypovolemia, while an increase of stroke volume indicates the preservation of myocardial contractile reserve. OBJECTIVE: To assess stroke volume changes during dobutamine stress echocardiography in relation to heart rate and occurrence of ischaemia and to validate a new automated cardiac output measurement device. METHODS: In fifty patients, the stroke volume was assessed using the echocardiographic biplane discs method during a stress echocardiography. These data were reference values for the validation of a new automated cardiac output measurement using the first method as a reference. RESULTS: Stroke volume measured by the biplane discs method and automated cardiac output device decreased from rest to peak stress, respectively, from 54+/-16 to 34+/-9 (63%) ml and 63+/-17 to 38+/-15 (60%) ml (p < 0.001). Stroke volume decreased with increased heart rate and stress-induced ischaemia when assessed by the biplane discs method, but with the automated device it decreased only with increased heart rate. CONCLUSIONS: Both increased heart rate and myocardial ischaemia during dobutamine stress echocardiography cause a reduction of stroke volume. However, the automated device did not detect the effects of stress-induced ischaemia on stroke volume. It appears that the biplane discs method is more sensitive for evaluating the effect of ischaemia.

Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice.

AIMS: Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide. METHODS AND RESULTS: Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). CONCLUSIONS: Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide.

Sensitive and specific method for the simultaneous determination of natural and synthetic catecholamines and 3,4-dihydroxyphenylglycol in microdialysis samples.

The relatively new technique of microdialysis provides new possibilities for investigating in vivo the functioning of the sympathetic nervous system. The small sample volumes obtained, however, are a great challenge for analytical chemists. We report here a HPLC method for measuring in one run both natural and synthetic catecholamines [dopamine, (nor)epinephrine, alpha-methylnorepinephrine, isoproterenol and epinine] and the intraneuronal metabolite 3,4-dihydroxyphenylglycol in small microdialysis samples after derivatization with the fluorogenic agent 1,2-diphenylethylenediamine. No prior clean-up step is necessary. N-Ethylmaleimide is necessary for preventing an inhibitory action on derivatization occurring in in vivo microdialysis samples. The method can handle large numbers of samples, is sensitive (on-column detection limits 30 to 200 fg) and reproducible (RSD 1 to 7%). Recovery characteristics of the commercial microdialysis probe used (CMA/20) were extensively investigated both in vitro and in vivo at various perfusion rates; for practical purposes a rate of 2 microl/min and sampling at 10-min intervals was found to be workable and to give good and reproducible recoveries (50 to 70%).

Role of sympathetic nervous system in cyclosporine-induced rise in blood pressure.

To clarify the role of the sympathetic nervous system in the development of cyclosporine A (CsA)-induced rise in blood pressure (BP), the effects of CsA on 24-hour ambulatory BP (ABP) were studied in patients with familial amyloid polyneuropathy (FAP) who underwent a liver transplantation. On the basis of autonomic function tests, patients with absent or mild-to-moderate sympathetic damage (Group A, n=11, age 29 to 43 years, disease duration 2 to 6 years) and patients with severe sympathetic damage (Group B, n=9, age 27 to 38 years, disease duration 3 to 9 years) were identified. Both groups were followed for 1 year. The daily doses of CsA and the CsA whole blood trough levels between the groups did not differ. Pretransplantation values of daytime and nighttime ABP were, respectively, 117+/-8/76+/-7 mm Hg and 108+/-12/68+/-9 mm Hg in group A and 107+/-6/66+/-4 mm Hg (P<0.05 group A versus group B) and 102+/-6/62+/-4 mm Hg in group B. In response to CsA, BP increased in all patients, but more so in patients of group B than in patients of group A. One year after transplantation, daytime and nighttime ABP had increased by 6+/-9/3+/-11% and 12+/-10/14+/-14% in group A and by 12+/-6/13+/-10% (P<0.05) and 21+/-11/27+/-21% (P<0.01) in group B. In both groups, the increase in nighttime ABP was greater than the increase in daytime ABP, which resulted in an attenuation or, even, a reversal of the diurnal BP rhythm. Because the rise in BP was greater in patients with more advanced sympathetic dysfunction, the sympathetic nervous system appears to counteract the CsA-induced rise in BP rather than causing it. This implies involvement of factors other than sympathetic activation in the pathogenesis of CsA-induced rise in BP in patients with familial amyloid polyneuropathy.

Cardiovascular control and plasma catecholamines during rest and mental stress: effects of posture.

In order to understand the complex autonomic adjustments that occur during the psychological challenges of normal daily life, autonomic responses to psychological stress were studied by evaluating the effects of body posture on various indices of sympathetic and parasympathetic regulation during performance of a psychological task. Twelve male subjects were studied in various postures (supine, sitting and standing), and during performance of the Colour Word Test (CWT) when sitting and then when standing. This procedure was subsequently repeated in reverse order (first standing and then sitting) after 15 min of supine rest. Blood samples for assay of plasma catecholamines were obtained before and during each CWT. Spectral analysis of beat-to-beat variations of heart rate (HR) and blood pressure (BP) was applied in order to obtain non-invasive indices of sympathetic and parasympathetic regulation. HR, diastolic BP, mid-frequency band power (0.07-0.14 Hz) of HR and systolic BP, and plasma adrenaline and noradrenaline concentrations showed significant increases when changing from supine to sitting to standing posture, whereas high-frequency band power (0.15-0.50 Hz) of HR decreased in a posture-dependent fashion. In the sitting position, the CWT caused significant increases in HR, BP and plasma adrenaline levels, and decreased HR and BP variability indices. In the standing posture, the CWT responses differed significantly from those during sitting for HR (a mild decrease during standing), high-frequency band power of HR (decreased more while sitting), high-frequency band power of BP (decreased more while standing), and plasma adrenaline responses (larger during sitting). Posture-related differential effects were observed on indices of sympatho-adrenomedullary activation during performance of a psychological challenge, whereas indices of parasympathetic activity indicated primarily less vagolytic effects when the task was performed in the standing posture. Our findings therefore underline the complexity of the adjustments that occur in neurohumoral and haemodynamic parameters during the psychological challenges of daily life.

In-vitro validation, with histology, of intravascular ultrasound in renal arteries.

OBJECTIVE: To investigate the feasibility of using intravascular ultrasound to characterize normal and diseased renal arteries. MATERIALS AND METHODS: Forty-four renal artery specimens from 21 humans, removed at autopsy, were studied with intravascular ultrasound in vitro. From each vascular specimen, two to four sets of corresponding intravascular ultrasound images and histologic sections were subjected to qualitative analysis. The renal arterial wall was considered normal by intravascular ultrasound when the wall thickness (intima and media) was 0.5 mm or less. On intravascular ultrasound imaging, a distinction was made between bright lesions with or without peripheral shadowing (i.e. calcification). Histological sections were examined and fibromuscular lesions were scored with or without calcifications. Quantitative analysis of a multitude of intravascular ultrasound cross-sections (interval 5 mm) included assessment of the lumen area, vessel area, plaque area and percentage area obstructed. The target site (smallest lumen area) was compared with a reference site (largest lumen area before the first major side branch). RESULTS: Of the 130 corresponding intravascular ultrasound images and histologic sections analysed, 55 were normal and 75 presented a bright lesion on ultrasound; in 31 lesions, peripheral shadowing was involved. The sensitivity of the intravascular ultrasound in detecting calcifications was 87%, and the specificity was 89%. Lumen area reduction at the target site was associated with vessel and plaque area enlargement in eight specimens, with plaque area enlargement in 12 specimens and with a vessel area reduction in 21 specimens. CONCLUSIONS: Intravascular ultrasound is a reliable technique for distinguishing renal arteries with or without a lesion. Both plaque development and local vessel narrowing may result in renal artery stenosis.

Circulating semicarbazide-sensitive amine oxidase is raised both in type I (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and even in childhood type I diabetes at first clinical diagnosis.

Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 +/- 300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins.

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure.

BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. AIMS: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. METHODS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. CONCLUSION: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function.

Inter-observer variability in the angiographic assessment of renal artery stenosis. DRASTIC study group. Dutch Renal Artery Stenosis Intervention Cooperative.

OBJECTIVE: To assess inter-observer agreement in the interpretation of renal angiograms. DESIGN: Comparison of the assessment of renal angiograms by three experienced radiologists, who evaluated the number of renal arteries and the presence, location, aspect and severity of a renal artery stenosis. SETTING: General hospital and university hospital serving urban and rural populations. PATIENTS: Patients with difficult-to-treat hypertension referred for diagnostic work-up; 312 angiograms with the intra-arterial digital subtraction technique were obtained from 289 consecutive patients. MAIN OUTCOME MEASURES: Inter-observer agreement was tested for the following parameters: number of arteries per kidney, presence of stenosis, location of stenosis (truncal, ostial), aspect of stenosis (concentric, eccentric, post-stenotic dilatation), severity of stenosis (reduction of lumen diameter in categories of 30%, 40%, etc. to 100%), and overall quality of the angiographic images. Kappa (kappa) values and weighted kappa between the three pairs of radiologists were used as estimates of inter-observer agreement RESULTS: Agreement about the number of renal arteries was reasonable (kappa = 0.50-0.72), as was agreement about the presence of stenosis (kappa = 0.68-0.86). Agreement about stenosis location and aspect was poor (kappa = 0.26-0.47 and kappa = 0.15-0.26, respectively). There was general agreement about the severity of stenosis (weighted kappa = 0.65-0.70), but it was not possible to distinguish between 50 and 60% stenosis or between 60 and 70% stenosis (kappa < 0.40). No correlation was found between agreement on severity of stenosis and the quality of the images. CONCLUSIONS: It is not realistic to make statements about what degree of renal artery stenosis is clinically significant, as long as the intra-arterial angiogram with digital subtraction remains the gold standard. It is likewise risky to rely too strongly on stenosis morphology as visualized by renal angiography in choosing between balloon angioplasty and stent deployment.

Stent placement for treatment of renal artery stenosis guided by intravascular ultrasound.

PURPOSE: To study the impact of intravascular ultrasound (IVUS) during renal artery stent placement. MATERIALS AND METHODS: Patients (n = 22) with atherosclerotic renal artery stenosis were studied with IVUS after predilation and after angiographically successful stent deployment (diameter stenosis < 10%). After predilation, IVUS was used to assess whether the balloon size selected angiographically was correct (discrepancy balloon-reference lumen diameter < 20%). After stent placement, IVUS images were assessed for (i) complete stent-vessel wall apposition; (ii) complete stent expansion (discrepancy stent-reference lumen diameter < 20%), and (iii) complete lesion covering by the stent. Modification based on IVUS included selection of a larger balloon, additional dilation, and placement of a second stent. Clinical outcome was based on blood pressure, amount of antihypertensive drugs, and glomerular filtration rate during follow-up of 3 months. RESULTS: Stent placement and ultrasound imaging were completed successfully in 18 patients. After predilation, IVUS warranted the use of a larger balloon in five patients. After stent placement, incomplete stent apposition (n = 1), discrepancy between stent and reference lumen diameter (n = 3), and lesion distal to the stent (n = 2) seen on IVUS were treated with additional dilation in five patients and with a second stent in one patient. A larger balloon was used in three patients. Mean blood pressure and amount of antihypertensive drugs decreased (P < .05). CONCLUSIONS: In a number of patients, IVUS monitoring during renal artery stent placement resulted in additional lumen enlargement not considered necessary at angiography.

High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.

OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.

Primary Sjögren's syndrome presenting as autonomic neuropathy. Case report.

Abnormalities of the autonomic nervous system have been described in several connective tissue diseases, but the relation with primary Sjögren's syndrome is unclear. This report describes a patient with primary Sjögren's syndrome who presented with severe autonomic failure. The present knowledge on dysfunction of the autonomic nervous system in primary Sjögren's syndrome and other connective tissue diseases is shortly reviewed.