Clinical predictors of sleep apnoea in heart failure outpatients.

BACKGROUND: Sleep-disordered breathing (SDB) is common in heart failure patients. Many of them still remain undiagnosed. The aim of this study was to detect clinical predictors of sleep apnoea which may help to identify patients with SDB at a heart failure clinic. METHODS: We performed an in-home sleep study on 115 consecutive patients from our heart failure clinic. Clinical characteristics, blood samples, daytime sleepiness and quality of life were registered. RESULTS: Among 115 patients, 52% had moderate to severe SDB. Body Mass Index (BMI) ≥ 30 kg/m² was the only independent predictor of moderate to severe SDB [Odds ratio (OR) = 3.62, 95% Confidence interval (CI) 1.40-9.36, p = 0.008]. Quality of life and level of sleepiness were not significantly associated with SDB. Patients with mild to moderate chronic obstructive pulmonary disease (COPD) were unlikely to have SDB compared with patients without COPD (OR = 0.10, 95% CI 0.02-0.43, p = 0.002). Hypertension was a predictor of having obstructive sleep apnoea (OR = 2.78, 95% CI 1.15-6.75, p = 0.02), while haemoglobin ≥ 15 g/dl was associated with central sleep apnoea (OR = 6.71, 95% CI 1.96-22.99, p = 0.002). CONCLUSION: BMI ≥ 30 kg/m(2) is associated with moderate to severe SDB, both obstructive and central sleep apnoea. Thus, BMI may be used as one of the selection criteria for referral of heart failure patients to a sleep specialist.

Plasma leptin in postmenopausal women with coronary artery disease: effect of transdermal 17beta-estradiol and intermittent medroxyprogesterone acetate.

OBJECTIVES: In the present study, the relationship between plasma leptin and other cardiovascular risk factors in high-risk postmenopausal women was assessed, as well as the effect of transdermal 17beta-estradiol unopposed or in combination with intermittent medroxyprogesterone acetate (MPA) on plasma leptin. METHODS: Postmenopausal women (n = 118) with coronary artery disease (CAD) were consecutively recruited from women admitted to hospital for coronary angiography. They were randomized to estradiol plus intermittent MPA or to a control group, and investigated at study inclusion, and after 3 and 12 months. RESULTS: A strong relationship was found between leptin and body mass index (r = 0.69, p < 0.001). Leptin was related to lipid fractions (high-density lipoprotein cholesterol: r = -0.33, p < 0.001; apolipoprotein A: r = -0.28, p = 0.004; and triglycerides: r = 0.27, p = 0.003) and indices of glucose metabolism (C-peptide: r = 0.47, p < 0.001; fasting insulin: r = 0.42, p < 0.001; glucose: r = 0.25, p = 0.008; insulin resistance: r = 0.45, p < 0.001; and insulin secretion: r = 0.36, p < 0.001). In a multiple regression model, only body mass index (p < 0.001) and C-peptide (p = 0.002) remained as independent factors for leptin levels. Despite the association with sex hormone-binding globulin (r = 0.30, p = 0.001), no effect on leptin levels was observed with either unopposed transdermal estradiol or estradiol combined with MPA. CONCLUSION: Plasma leptin is related to other cardiovascular risk factors in postmenopausal women with CAD, but seems to be unaffected by transdermal 17beta-estradiol administration.

Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and beta-cell function.

OBJECTIVES: To investigate possible associations between smoking habits and other coronary risk factors in postmenopausal women with known coronary heart disease (CHD). SETTING: The study was conducted at a university clinic. SUBJECTS: A total of 118 postmenopausal women with CHD verified with angiography, consecutively recruited. INTERVENTIONS: Conventional treatment for CHD. The women were randomized to hormone replacement therapy (HRT) with transdermal 17-beta oestradiol and medroxyprogesterone acetate, or to a control group. RESULTS: Smokers were younger (P = 0.005), had lower body mass index (P = 0.04) and lipoprotein Lp(a) levels (P = 0.02) compared with nonsmokers. Smokers had reduced beta-cell function (homeostasis model assessment, P = 0.006), whereas whole blood viscosity (WBV) was higher at all shear rates. WBV was not affected by HRT over a 12-month period. Oestrone levels were higher in smokers. CONCLUSIONS: Smoking adversely affects insulin secretion (beta-cell function) and WBV in postmenopausal women with established CHD, which could be of importance as a mechanism for the increased risk of CHD in smokers. The importance of smoking as a risk factor, overrides the effect of Lp(a), which is lower in smokers compared with nonsmokers.

Blood pressure levels in treated hypertensive patients in general practice in Norway.

The aim of this study was to examine the blood pressure (BP) levels in patients treated for essential hypertension in 1816 patients in general practice in Norway. The study was based on an optical readable questionnaire filled out by the physician including information about systolic (S) and diastolic (D) BP, gender, age, body weight, smoking habits and all pharmaceutical treatment given. Sixty-four per cent of the patients were treated with one antihypertensive drug. Only 22.3% of the women and 30.7% of the men (p < 0.05) had BP < or = 140/90 mmHg. When BP < 160/95 was used as criterion for BP control, the fraction of patients was 50%. The fraction of patients with DBP < or = 80 mmHg was 26% in the whole group of patients. DBP < or = 90 mmHg was achieved in 74% and SBP < or = 140 mmHg in 30% of the patients. The BP control was less in women and in patients above 60 years of age. Patients on combination therapy were no better controlled than those on monotherapy. Based on our results, the proportion of hypertensive patients on drug treatment with insufficient BP control is too high. Efforts should be made to improve the medical treatment of hypertension in general practice in Norway.

[Prescription patterns of antihypertensive agents in general practice in 1995]. / Forskrivningsmønster av blodtrykksmedisiner i allmennpraksis i 1995.

BACKGROUND: Hypertension represents a risk factor in the development of cardiovascular disease. MATERIAL AND METHODS: The prescription of antihypertensive drugs and the daily doses used were examined in a questionnaire-based survey among 2,586 drug-treated hypertensive patients who attended a general practitioner for clinical control in November 1995. RESULTS: The proportion of patients treated with one antihypertensive drug only was 63%. ACE inhibitors, alpha blockers and angiotensin-II antagonists constituted 22.7%, 6.6% and 4.4%, and betablockers, calcium channel blockers and diuretics 21.7%, 23.7% and 16.3% of the prescriptions respectively. Women were more often prescribed diuretics than men, and older individuals more often than younger persons. No striking difference in the prescription of antihypertensive drugs were observed between the five health regions of Norway. There was no reduction in the prescribed daily doses of antihypertensives used in combination therapy compared with monotherapy. In approximately one quarter of the prescriptions there was a positive correlation between the prescribed daily dose and the patient's weight. The number of antihypertensives prescribed did positively correlate with the patient's weight. INTERPRETATION: This survey shows that antihypertensives without any documented effect on morbidity and mortality were frequently prescribed for hypertension in general practice. Except for the low proportion of diuretic users among elderly patients, our results is in accordance with the Guidelines from the Norwegian Society of General Practitioners.

The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins.

OBJECTIVES: To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. SETTING: In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. SUBJECTS: Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. INTERVENTIONS: The women were randomized to HRT, i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. MAIN OUTCOMES: Effects on lipids and lipoproteins. RESULTS: After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. CONCLUSIONS: In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

Increased plasma concentrations of TGF-beta1 after hormone replacement therapy.

OBJECTIVES AND DESIGN: Hormone replacement therapy (HRT) in postmenopausal women may reduce the cardiovascular risk. A dominant protective role of transforming growth factor beta (TGF-beta1) on coronary arteries has been proposed. Lp(a) lipoprotein may block the activation of latent TGF-beta1. Given this background, we examined the effects of HRT on TGF-beta1 and Lp(a) lipoprotein in 99 postmenopausal women. The women had angiographically documented coronary heart disease (CHD) and were randomized to either sequential transdermal 17beta-oestradiol for 14 weeks and then medroxyprogesterone (MPA) for 14 days (HRT) or to a control group (C). RESULTS: Serum levels of TGF-beta1 were increased in the HRT group compared with the C group after 3 months' treatment and this effect was sustained after 12 months. There was a significant reduction in Lp(a) lipoprotein serum levels after 3 months' treatment in the HRT group compared with the C group. However, after 12 months, no significant difference in changes in Lp(a) lipoprotein serum levels was detected between the two groups. CONCLUSION: The novel observation that transdermal 17beta-oestradiol in postmenopausal women increases levels of TGF-beta1 and lowers the concentration of Lp(a) lipoprotein suggests yet another possible mechanism for the cardioprotective effect of HRT. Whereas combination therapy of oestradiol and MPA preserves the beneficial effect on TGF-beta1, it reduces the unopposed oestradiol effects on Lp(a) lipoprotein.

How well are patients with atherosclerotic disease treated? Secondary prevention in primary care.

OBJECTIVE: To examine changing trends in the field of secondary prevention of atherosclerotic disease in Norwegian general practice. DESIGN: A multipractice survey of consecutive patients with atherosclerotic disease consulting general practitioners in 1994/95 compared with a similar survey in 1996/97. SETTING: Primary health care. SUBJECTS: 707 patients attending 31 general practitioners in 1994/95 and 1353 patients attending 63 general practitioners in 1996/97. MAIN OUTCOME MEASURES: The patients were examined and interviewed for risk factors and pharmacological treatment. RESULTS: In 1994/95, 18% of the patients had been prescribed a lipid-lowering agent as opposed to 55% in the later survey. Consequently, the average level of LDL cholesterol in the 1996/97 population was 19% lower than in the 1994/95 population (3.8 mmol/l vs 4.7 mmol/l), which may imply a marked risk reduction. Aspirin and beta-blockers were prescribed to approximately 50% of the patients in both surveys. Diabetic patients had the same drug prescription rate and lipid profile as non-diabetics. In both surveys, about 25% of the patients were smokers. CONCLUSION: Secondary prevention in the majority of patients with atherosclerotic disease though ameliorating is still unsatisfactory. More attention is needed to achieve and sustain treatment goals.

[Chronic heart failure--suggestion to a management program]. / Kronisk hjertesvikt--forslag til handlingsprogram.

In 1994, a Norwegian programme for diagnosis and treatment of chronic heart failure was published. Recently the American College of Cardiology, the American Heart Association and the Task Force on Heart Failure of the European Society of Cardiology have published similar guidelines. In this article, the Working Group on Heart Failure of the Norwegian Society of Cardiology presents an updated programme for evaluation and management of patients with chronic heart failure.

Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure.

OBJECTIVES: The study aimed to assess the hemodynamic and neuroendocrine effects of candoxatril and frusemide compared with placebo in patients with mild chronic heart failure. BACKGROUND: Candoxatril is an atriopeptidase inhibitor. It increases circulating levels of atrial natriuretic peptide leading to natriuresis and diuresis, which alleviate the symptoms of a failing heart. METHODS: This was a multicenter, randomized, double-blind study. Forty-seven patients with mild stable chronic heart failure received candoxatril 400 mg/day, frusemide 40 mg/day or placebo for up to six weeks. Cardiac indices were determined at rest and during exercise, and blood samples were taken for laboratory analysis. Assessments were performed at baseline (day 0) and after six weeks (day 42). RESULTS: In comparison with placebo, both drugs significantly reduced mean pulmonary capillary wedge pressure following the first dose administration. Only candoxatril significantly reduced pulmonary capillary wedge pressure during exercise on day 0, while both drugs significantly reduced this parameter on day 42. Changes in the remaining hemodynamic parameters were comparable for both drugs relative to placebo. Frusemide significantly increased mean plasma renin activity (days 0 and 42), and the mean aldosterone concentration (day 42) in comparison with placebo, whereas candoxatril caused no significant changes in any of the hormonal parameters assessed. CONCLUSIONS: These results show that candoxatril, 400 mg/day, has a similar hemodynamic profile to frusemide, 40 mg/day, but it does not induce adverse neuroendocrine effects. Candoxatril therefore appears to offer a clinically significant advantage over frusemide, providing an alternative therapeutic approach to the treatment of patients with mild stable chronic heart failure.

Adverse drug reactions in current antihypertensive therapy: a general practice survey of 2586 patients in Norway.

The objective of this study was to determine the frequency and profile of adverse reactions to antihypertensive drugs in an unselected group of drug-treated hypertensive patients. A questionnaire-based survey was carried out among 2586 drug-treated hypertensive patients who attended a general practitioner for clinical control. Adverse drug reactions reported spontaneously, upon general inquiry, upon specific questioning and as evaluated by a physician were used as the main outcome measures. The study shows that the percentage of patients who reported adverse drug reactions spontaneously, upon general inquiry and upon specific questioning were 16%, 24% and 62% respectively. Users of diuretics reported the lowest frequency of adverse reactions, whereas users of beta-blockers reported the highest frequency. In 7% of the patients, the adverse drug reactions were of such a nature that the physicians considered discontinuing the treatment. As a conclusion, the reported frequency of adverse drug reactions in antihypertensive treatment is high, but with significant differences between the various drug groups. Monotherapy is connected with far fewer adverse drug reactions than combination therapy.

[An overview of hypertension studies with calcium antagonists]. / Oversikt over hypertensjonsstudier med kalsiumantagonister. ASCOT. Anglo-Scandinavian Cardiac Outcomes Trial.

Calcium antagonists are widely used in the treatment of hypertension. However, few endpoint studies with calcium antagonists have been done to prove reduction in hypertensive complications. Results of the STONE, SYST-EUR and SYST-CHINA studies show that long-acting calcium antagonists are effective compared to placebo, especially in patients with isolated systolic hypertension and diabetes. Ongoing prospective and randomized trials like STOP II, INSIGHT, NORDIL, ALLHAT and ASCOT will clarify whether calcium antagonists are more effective than well-proven diuretics and betablockers. ASCOT will test the hypothesis that amlodipine is more efficacious than atenolol in preventing cardiac complications in 18,000 hypertensive patients with high coronary risk including diabetes (among them, 2,000 in Norway). The study is also randomizing the patients in a factorial design to either atorvastatin or placebo, testing the so-called lipid hypothesis.

[How well are patients with atherosclerosis treated in general practice? Risk factors and intervention surveyed in 1996-97 as compared to two previous years]. / Hvor godt behandles pasienter med aterosklerotisk sykdom i allmennpraksis? Risikofaktorer og intervensjon kartlagt i 1996-97 sammenliknet med to år tidligere.

In 1996 and 97, a total of 1,353 patients with coronary heart disease and peripheral arterial disease were screened in 63 general practices for their specific risk factors and treatment. 63% of the patients were males and 25% were smokers. 55% of the patients had been prescribed a lipid lowering agent, in most cases by their general practitioner, as opposed to 18% in a similar screening in 1994 and 95. This corresponds with a general increase in the number of prescriptions for this kind of drug. The majority of patients treated were 75 years of age and under. The recommended level of LDL-cholesterol in secondary prevention is 2.6 mmol/l or less. 83% of the patients had values above this level. Neither the treatment with antithrombotic agents and beta-blockers, nor the reduction in the systolic blood pressure in hypertensive patients was found to be satisfactory. The same lipid profile and frequency with which drugs were prescribed was seen in both diabetic and non-diabetic patients. We found that lipid lowering agents were prescribed more frequently and aspirin less frequently than in comparable European surveys. It is essential to develop effective intervention strategies and for general practitioners and specialists to collaborate closely to implement these strategies for patients with atherosclerotic disease.

Arterial and venous plasma catecholamines during submaximal steady-state exercise.

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0.81, 95% CI 0.71-0.87), as were systolic blood pressure and heart rate (r = 0.78, 95% CI 0.71-0.87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.

Evidence of excess hereditary predisposition in women with angiographically documented coronary artery disease.

In a hospital-based case-control study including women and men with angiographically documented coronary artery disease (CAD) admitted to a university hospital during a 6-month period, we observed an excessive hereditary predisposition in women. Clustering of risk factors was more pronounced in women than in men. Thus, the results suggest that hereditary factors as well as multiple risk factors are essential when CAD is expressed in women.

[Calcium channel blockers in heart failure]. / Kalsiumkanalblokkarar ved hjartesvikt.

Patients with heart failure are particularly susceptible to the negative effects of calcium channel blockers because the failing heart demonstrates a defect in the delivery of calcium to the contractile proteins, and an attenuation of the normal sympathetic reflexes. Currently these drugs have no place in the treatment of heart failure caused by systolic dysfunction of the left ventricle. Calcium channel blockers should probably not be described for patients with coronary artery disease and left ventricular dysfunction. When the patient needs additional treatment for angina and beta-blockers or nitrates have not given satisfactory results, it may be appropriate to prescribe amlodipine or felodipine.

[Treatment of heart failure with beta-blockaders]. / Betablokkerbehandling av hjertesviktpasienter.

Since 1975 several studies have indicated that treatment with beta-adrenergic blocking drugs has a positive effect on prognosis in patients with left ventricular dysfunction. After myocardial infarction, treatment with timolol and propranolol improves prognosis in patients with symptoms of cardiomegaly and heart failure. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol improves the left ventricular ejection fraction and symptoms of heart failure, and may have a positive effect on prognosis. Recent studies of patients with chronic congestive heart failure also indicate that carvedilol has a positive effect on mortality and morbidity. The authors review some relevant studies, to stimulate the use of beta-adrenergic blocking drugs to treat certain types of heart failure.

[Secondary prevention in coronary disease. A questionnaire study in Norwegian departments of internal medicine with emphasis on non-pharmacological intervention]. / Sekundaerprofylakse ved koronarsykdom. Spørreundersøkelse til norske indremedisinske avdelinger med spesiell vekt på ikke-farmakologisk intervensjon.

Research has shown that lifestyle intervention has a promising effect in patients with coronary heart disease, but little is known about the practice of such intervention. To explore this issue a questionnaire was sent to all departments of internal medicine in Norway (N = 67). 58 hospitals responded. The results showed that most hospitals offered physical training (49 hospitals) and dietary intervention programmes (51 hospitals) to patients with coronary heart disease, but only six hospitals offered a smoking cessation programme. The hospitals expressed a desire to expand the existing programmes (especially dietary intervention) and establish new ones (in particular smoking cessation), but claimed that lack of personnel and funds limited their activity. Only a few hospitals record in the medical journal that a patient has been informed about the significance of changes in lifestyle.

[Risk factors and intervention in cardiovascular diseases in general practice]. / Risikofaktorer og intervensjon ved hjerteog karsykdommer i allmennpraksis.

The authors conducted a cross-sectional study including 707 patients with chronic ischaemic heart disease or obstructive peripheral atherosclerotic disease. The patients were monitored by 31 general practitioners in different parts of Norway, from October 1994 to April 1995. 67% of the patients were male and 33% were female. 28% were smokers. In this study the majority of the patients were being adequately treated for hypertension, and the prevalence of antithrombotic treatment with either warfarin or acetylsalicylic acid was comparable with the results from recent intervention trials, for instance the Scandinavian Simvastatin Survival Study (4S). More than 90% of the patients had levels of total cholesterol and LDL-cholesterol which, based on today's international consensus, implied giving dietary advice and treatment with statin-type drugs in order to increase survival and reduce morbidity once atherosclerotic disease has been diagnosed. In this study less than 20% received statins, and only a minority of those treated had reached the established goals for treatment. Based on this study we recommend that much stronger emphasis is placed on serum-cholesterol level reduction in patients with established atherosclerotic disease, both by specialists and in primary health care.