Top-fenestrating technique in stentgrafting of aortic diseases with mid-term follow-up.

AIM: As a consequence of the rapid growth of thoracic and abdominal endovascular aneurysm repair management of aortic branches has come into focus. The top-fenestrating technique can be used where one or two of the renal arteries, the left carotid artery or the left subclavian artery, have deliberately been covered by a stent-graft and immediately reopened by a preplaced stent. The aim of this study is to evaluate whether this technique is feasible and durable. METHODS: Registry study on 24 patients endovascular repaired with the top-fenestrating technique between September 2004 and January 2008. Elective operations were performed in 15 patients and acute procedures in nine. The median neck length for the patients having a carotid stent was 0 mm, range -18-15, related to the left subclavian artery and median 11 mm, range 0-31 mm, for those having a renal stent. Altogether 25 stents were used. RESULTS: There were two postoperative deaths. One patient died from a cardiac infarction and the other, a ruptured thoracic aortic aneurysm, had a major stroke. Median follow-up time was 17 months (range 1-40 months). Two patients died during follow-up from no-aneurysm related reasons. One type I endoleak was solved with a secondary intervention. Two patients had type II endoleak, which was not treated. After 12 months, 71% of the aneurysms had significantly decreased in size. None of the aneurysms had increased. There were no stent-graft migrations in the entire group. None of the stented branches was lost during follow-up. CONCLUSION: The top-fenestrating technique is feasible in short aortic necks and results are durable in a mid-term follow-up perspective.

Influence of physical activity on urinary leakage in primiparous women.

The impact of physical activity on urinary leakage (UL) has previously been considered, but not in relation to first pregnancy and delivery. The aim of this study was to describe physical activity and urinary leakage before, during and after the first childbirth. The subjects who were invited to participate in the study were taken consecutively from nine maternity clinics in the northwest part of Stockholm County, and the study group included 665 primiparous women. The mean age of the women was 28 (range 17-43) years. The women answered one questionnaire during the 36th gestation week and another 1 year post partum. Physical activity/exercises were classified according to their impact on the pelvic floor, and the women were divided into three groups: high-impact exercise (n=327), low-impact exercise (n=84) and the inactive group (n=254). The results showed a high intensity and frequency of physical activity in the participating primiparous women. Risk factors for UL were symptoms of a dysfunctional pelvic floor and connective tissue disorders and high-impact physical activity before pregnancy, while low-impact activity seemed to promote continence. If urinary leakage was present before pregnancy, it persisted in most women during pregnancy and 1 year post partum.

Prevalence of urinary leakage in nulliparous women with respect to physical activity and micturition habits.

In order to survey the influence of physical activity and micturition habits on urinary leakage (UL) in women before their first pregnancy, a study including 725 women attending nine maternity clinics in the northwest area of Stockholm was performed. During the 36th gestational week the women answered a questionnaire regarding the pre-pregnancy situation regarding UL, micturition habits and physical activity. Thirty-nine percent of the women, mean age of 28 (range 17-43) years, had experienced occasional UL. Of these, the majority (79%) had symptoms of stress urinary leakage and 21% had urge symptoms. Two percent were incontinent according to the definition of the International Continence Society (ICS). In a multivariate analysis age, inability to interrupt the urine flow and high-impact physical activity turned out to be independent risk factors for UL and thus should be observed together with traditional factors concerning UL in nulliparous women.

Prevalence of stress incontinence in nulliparous elite trampolinists.

During trampoline jumping the pelvic floor is exposed to high forces. There has been a general belief that physically fit women have a strong pelvic floor as a result of their regular training, thus preventing urinary incontinence. The aim of this study was to survey the prevalence of stress urinary incontinence in female elite trampolinists. The prevalence of urinary incontinence was assessed by a questionnaire, sent to all 35 elite trampolinists (mean age 15, range 12-22 years) in Sweden. Eighty percent of the trampolinists reported involuntary urinary leakage, but only during trampoline training. The leakage started after 2.5 (range 1-4) years of training. Age (P < 0.001), duration of training (P = 0.04), and training frequency (P = 0.01) were significantly associated with leakage. All women above 15 years of age (n = 23) reported urinary leakage (P < 0.001). Eighteen incontinent women continued the study and their leakage was verified by a pad test. The leakage averaged 28 g during a jump session. The muscle strength was measured with perineometry in 10 women and showed good strength in the pelvic floor muscles.

The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension.

The objective of the study was to examine the influence of angiotensin converting enzyme (ACE) inhibition on circulatory responses to standardized stress tests in primary mild to moderate hypertension. Patients (n = 28) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design, followed by 6 months of open ramipril treatment. Mental stress (a 20-min Stroop's color word conflict test) and a cold pressor test were performed at the end of each of the three study periods. Noninvasive blood pressure and heart rate were recorded. Ramipril reduced systolic and diastolic blood pressure levels at rest (from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks, and 136+/-4/91+/-3 mm Hg at 6 months, in the laboratory) and during mental stress. Resting heart rates were unchanged by ramipril. Ramipril reduced systolic blood pressure and heart rate responses during mental stress; diastolic blood pressure responses were unchanged. Ramipril reduced cardiac workload (systolic blood pressure x heart rate) levels and responses. Treatment effects at 6 months were generally greater than at 6 weeks. During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril, but responses were unchanged. Heart rate responses, however, were reduced. Thus, ramipril reduced cardiac workload levels and responses also during the cold pressor test. These findings show that ACE inhibitors can reduce cardiac workload during stressful situations. If confirmed, this would seem to offer an advantage in the treatment of hypertension.

Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog.

The chronic and acute roles of hyperglucagonemia in sustaining the increased glucose production observed in the conscious infected dog were examined. Three groups of dogs were studied: a sham group (SHAM; n = 10), an infected group (INFXN; n = 11), and a sham group in which the chronic (42-h) increase in glucagon observed in INFXN was simulated (SimGGN; n = 5). INFXN and SimGGN were studied in the presence of hyperglucagonemia. In addition, glucagon was selectively decreased for 180 min in INFXN by use of somatostatin with basal intraportal insulin replacement and in SimGGN by discontinuing the exogenous glucagon infusion. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism and gluconeogenesis. Whereas the rate of glucose appearance (Ra) was increased by 30% (3.3 +/- 0.1 vs. 2.5 +/- 0.1 mg.kg-1.min-1) in INFXN vs. SHAM, Ra did not increase in SimGGN (2.4 +/- 0.2 mg.kg-1.min-1). In addition, the 30% increase in net hepatic gluconeogenic precursor uptake seen in INFXN did not occur in SimGGN despite an augmented net hepatic alanine fractional extraction (0.62 +/- 0.03 vs. 0.47 +/- 0.05, SimGGN vs. INFXN). With acute removal of hyperglucagonemia, endogenous Ra decreased in SimGGN and INFXN by 1.0 +/- 0.2 and 1.4 +/- 0.3 mg.kg-1.min-1, respectively. Net hepatic alanine fractional extraction in INFXN, leading to a greater rise in arterial blood alanine levels. In summary, chronic hyperglucagonemia alone cannot explain the increase in Ra observed during an infection. The marked hyperglucagonemia seen during infection plays an essential role in sustaining normal net hepatic fractional alanine extraction to compensate for an impairment in glucagon-stimulated hepatic amino acid transport activation.

A dietary fibre supplement in the treatment of mild hypertension. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effects of a dietary fibre supplement given as monotherapy upon blood pressure in mildly hypertensive patients. DESIGN: The investigation was performed as a prospective randomized, double-blind, placebo-controlled trial for 3 months. SETTING: Patients attending an outpatient hypertension clinic in a hospital. PATIENTS: Hypertensive patients with a minimum of two diastolic blood pressure (DBP) readings greater than 90 mmHg during a 2-week run-in period were included. Of the 65 patients enrolled, 63 were randomized (32 fibre, 31 placebo). Six patients did not complete the trial. INTERVENTION: Patients were treated with either fibre (7 g/day) or matching placebo. MAIN OUTCOME MEASURE: Based on previous studies, the a priori hypothesis was that dietary fibre supplementation could reduce blood pressure in hypertensive patients. RESULTS: Body weight was significantly reduced in the fibre group. Dietary fibre significantly reduced DBP and fasting serum insulin. However, no correlation between changes in body weight and systolic blood pressure or DBP was found. CONCLUSION: A dietary fibre supplement can lower DBP in mildly hypertensive patients independent of changes in body weight.

Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study.

The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown.

Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study.

In a randomized primary prevention trial including 3,234 men with mild to moderate uncomplicated hypertension, the effect of the beta-blocker metoprolol or a thiazide diuretic as an initial antihypertensive therapy was compared regarding the risk of sudden cardiovascular death during a follow-up ranging from 2.3 to 10.8 years (median of 4.2 years). Only men aged 40 to 64 years were included in the study. The randomization of patients into the metoprolol (n = 1,609) or diuretic group (n = 1,625) was performed after stratification for age, smoking habits, serum cholesterol, and systolic blood pressure. At baseline the two treatment groups were well matched. Metoprolol was given in a mean dose of 174 mg daily and the mean dose of thiazide diuretic was either 46 mg hydrochlorothiazide daily or 4.4 mg bendroflumethiazide daily. Identical blood pressure control was achieved using the fixed therapeutic schedule. Total and cardiovascular mortality were significantly lower for metoprolol than for diuretics, owing to fewer deaths from coronary heart disease and stroke. Of the cardiovascular deaths, 78% were classified as sudden cardiovascular deaths (occurred within 24 h after the onset of symptoms). There were significantly fewer sudden cardiovascular deaths in the metoprolol group compared to the diuretic group (32 v 45, P = .017). The present results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of sudden cardiovascular deaths than initial diuretic treatment in uncomplicated hypertension.

Decreased coronary heart disease in hypertensive smokers. Mortality results from the MAPHY study.

The present primary prevention study aimed at investigating whether metoprolol given as initial antihypertensive treatment would lower cardiovascular complications of high blood pressure to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1,609, 8,110 patient-years) or a thiazide diuretic (n = 1,625, 8,070 patient-years). At randomization, 535 patients in the metoprolol group and 524 patients in the diuretic group were classified as smokers. Blood pressure control during follow-up was equally effective regardless of smoking habits at randomization. Cardiovascular and coronary heart disease mortality was three to four times higher in smokers than in nonsmokers, underlining the importance of smoking as a risk factor. Total and cardiovascular mortality were significantly lower for the metoprolol group than for the thiazide diuretic group in the whole study population (p = 0.028 and p = 0.012), as well as in smokers (p = 0.013 and p = 0.016). Coronary heart disease mortality was significantly lower for patients on metoprolol than for patients on diuretics in the whole study population (p = 0.048) as well as in smokers (p = 0.021). The results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of total, cardiovascular, and coronary heart disease mortality as compared with initial diuretic treatment, both in the whole study population and in smokers. The favorable effect of metoprolol must be mediated via mechanisms other than the blood pressure-lowering effect of metoprolol because equal blood pressure control was achieved with both types of medication, irrespective of smoking habits at randomization.

Melatonin secretion related to side-effects of beta-blockers from the central nervous system.

In two studies of hypertensive patients the relationship between beta-blocker-induced CNS side-effects and the nightly urinary secretion of melatonin was analysed. In one group (n = 10) placebo, atenolol (mean dose 86 mg/day) or propranolol (mean dose 305 mg/day) were given in a double-blind, randomised design. In the other (n = 13) 100-400 mg metoprolol was given daily (mean dose 197 mg). After 4 weeks of treatment all beta-blockers reduced melatonin excretion, but the effect was significant only for metoprolol. Sleep disturbance records revealed more disturbed nights in the metoprolol group compared with the propranolol and the atenolol groups, even when the difference in age between the groups was controlled for. In the metoprolol group a significant relationship (p less than 0.05) was found between the fall in melatonin and the percentage of disturbed nights. Severe CNS side-effects, such as nightmares, occurred only in patients treated with metoprolol (21%), which in all cases were accompanied by low levels of melatonin. Our data suggest that the CNS side-effects during beta-blockade are related to a reduction of melatonin levels.

Responses to mental stress and physical provocations before and during long term treatment of hypertensive patients with beta-adrenoceptor blockers or hydrochlorothiazide.

1 Cardiovascular and sympatho-adrenal responsiveness to mental stress (CWT; a colour word test), orthostatic testing (ORT) and a cold pressor test (CPT) were examined in three groups of hypertensive patients (n = 14-16) before and after 6 months treatment with metoprolol (243 +/- 26 mg daily), propranolol (149 +/- 16 mg daily) or hydrochlorothiazide (50 +/- 8 mg daily) in an open trial design. 2 Treatment reduced outpatient blood pressures in the three groups similarly (from approximately 155/102 to 135/90 mm Hg). During treatment resting blood pressures in the laboratory were clearly reduced by beta-adrenoceptor blockade but not by thiazide treatment. Metoprolol and propranolol caused similar reductions of basal heart rates and plasma glycerol levels, whereas only propranolol reduced cyclic AMP concentrations in plasma. 3 Before treatment CWT and CPT increased systolic and diastolic blood pressures by about 30%. Heart rate increased by about 30 beats min-1 during CWT and 10-15 beats min-1 during CPT and ORT. Small venous plasma adrenaline responses were evoked by all tests, whereas noradrenaline was elevated mainly by CPT and ORT. Dopamine levels did not change. 4 Heart rate responses to all stressors were markedly and similarly reduced, whereas blood pressure responses were essentially unchanged during metoprolol or propranolol treatment. In the thiazide group circulatory responses to CWT were slightly attenuated, whereas responses to ORT and CPT were unchanged. 5 The systolic blood pressure levels were reduced throughout the test session in all three groups, although less so in the hydrochlorothiazide group. Both beta-adrenoceptor antagonists clearly reduced diastolic blood pressure and heart rate levels at rest and during stress, whereas thiazide treatment caused no significant changes in these respects. 6 The rate pressure product, which increased by 80-100% in response to CWT before treatment, was more markedly reduced by beta-adrenoceptor blockade than by thiazide treatment both at rest and during stress. 7 Self ratings (visual analogue scales) of stress and irritation were increased by CWT in a similar fashion before and during treatment in all groups. beta-adrenoceptor blockade was associated with higher subjective ratings of tiredness at rest, but not after CWT. Performance in the CWT increased slightly more in the thiazide group. The physiological responses to CWT were not correlated to the subjective responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of hydrochlorothiazide and slow release furosemide as adjuvant therapy to beta-blockers in the treatment of moderate hypertension.

Fifty hypertensive patients on beta-blocker therapy with supine blood pressure greater than or equal to 95 mmHg were included in a parallel group, double-blind study for 12 weeks to compare blood pressures, metabolic and adverse effects of additional treatment with diuretics. Hydrochlorothiazide (HCT) 25 mg daily was added to one group and furosemide 30 mg daily in a slow-release preparation, Lasix Retard (LR), to the other. Blood pressure decreased significantly and similarly in both groups from about 155/101 to about 144/95 mmHg (p less than 0.01). Diastolic blood pressure was lowered to less than or equal to 90 mmHg in 29% of the HCT patients and in 59% of the LR patients. Serum potassium decreased significantly from 4.05 mmol/l to 3.62 mmol/l on HCT, while the decrease on LR from 4.13 mmol/l to 4.05 mmol/l was not significant. Serum urate increased significantly, although within the normal range, on HCT. No change in fasting blood glucose or HbA1C was observed in any group. The patients were asked to report 40 different possible side-effects on a visual analogue scale at every visit. The side-effects already observed on beta-blockers did not change consistently on additional therapy with either HCT or LR. Thus, additional treatment with HCT or LR to patients already treated with beta-blockers results in an equal further blood pressure reduction, but in contrast to treatment with HCT, addition of LR does not affect serum potassium concentrations.

Reactivity to mental stress and cold provocation during long-term treatment with metoprolol, propranolol or hydrochlorothiazide.

In a study aimed at comparing the effects of beta-blockers and thiazide diuretics on responses to stressful provocations, 45 essential hypertensives (WHO I-II) were treated with either the selective beta-blocker metoprolol (METO), the non-selective beta-blocker propranolol (PROP) or hydrochlorothiazide (HTZ) for 6 months. Blood pressure, heart rate and plasma catecholamines were measured in connection with a mental stress test and a cold pressor test before and during therapy. All drugs reduced outpatient blood pressure similarly, but beta-blockade reduced blood pressure and heart rate levels more efficiently at rest and during stress in the laboratory. Heart rate reactivity to stress was reduced mostly by beta-blockade during mental stress. Blood pressure and sympatho-adrenal reactivity were unchanged by therapy. Stress reactivity failed to predict antihypertensive responses. The results suggest that beta-blockade may be more effective than diuretic treatment in reducing blood pressure levels and cardiac workload as assessed by the rate pressure product in stressful situations.