High physical fitness is associated with reduction in basal- and exercise-induced inflammation.

C-reactive protein (CRP) increases after strenuous exercise. It has been a concern that prolonged strenuous exercise may be harmful and induce a deleterious inflammatory response. The purpose of this study was to (a) assess and quantify the magnitude of CRP response following an endurance cycling competition in healthy middle-aged recreational cyclists. (b) Identify important determinants of this response. (c) Identify the relationship between CRP, myocardial damage (cardiac Troponin I (cTnI)), and myocardial strain (B-type natriuretic peptide [BNP]). (d) Identify the relationship between CRP and clinical events, defined as utilization of healthcare services or self-reported unusual discomfort. Race time was used as a measure of physical fitness. A total of 97 individuals (43±10 years of age, 74 [76%] males) were assessed prior to and 0, 3, and 24 hours following the 91-km mountain bike race "Nordsjørittet" (Sandnes, Norway, June 2013). There was a highly significant increase in CRP from baseline to 24 hours (0.9 (0.5-1.8) mg/L vs. 11.6 (6.0-17.5) mg/L (median[IQR]), P<.001), with no correlation of CRP to cTnI and BNP at any time-point. CRP was strongly correlated to race time at baseline (r=.38, P<.001) and at 24 hours following the race (r=.43, P<.001), In multivariate models, race time was an independent predictor of CRP both at baseline and at 24 hours (P<.01). There was no relationship between CRP levels and clinical events. In conclusion, high physical fitness was associated with reduction in both basal- and exercise-induced CRP. No adverse relationship was found between high intensity physical exercise, CRP levels, and outcomes.

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure.

BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.

PURPOSE: Topical beta-blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24-hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+/-SD) age of 63 (+/-8) years were randomized and crossed over in a double-masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24-hour heart rate compared with placebo (P < or = .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats/min). Timolol gellan showed a numerically but not significantly smaller reduction in 24-hour heart rate, compared with timolol solution. During the night, the mean 12-hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24-hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta-blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences.

Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure - a substudy to the MERIT-HF trial.

BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity among healthy subjects, while more variable results have been observed in chronic heart failure (CHF), probably related to patients studied, methods and agent used. The effect of metoprolol controlled release/extended release (CR/XL) on peak oxygen uptake (peak VO(2)) in this patient population has not previously been investigated. AIMS: We examined the effect of long-term treatment with the selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24 females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in New York Heart Association (NYHA) functional class II-IV, and with ejection fraction

Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.

BACKGROUND: Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids. DESIGN: Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001). CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids.

Assessing the effect of exercise training in men with heart failure; comparison of maximal, submaximal and endurance exercise protocols.

AIMS: No consensus exists regarding the most appropriate exercise testing protocol for patients with congestive heart failure. This study describes the effect of exercise training on performance using three different protocols (maximal, submaximal and endurance testing) in patients with heart failure. METHODS AND RESULTS: Thirty men (mean age 67+/-8 years) with congestive heart failure in NYHA class III (mean ejection fraction 32+/-5%) were evaluated prior to and following exercise training. A maximal exercise cycle test with gas exchange measurements, a submaximal 6 min walk test and an endurance treadmill test with blood lactate sampling were used to evaluate exercise capacity after 12 weeks of exercise training. There was a 44.6% (P<0.001) increase in work performed during the maximal cycle test, with no significant increase in peak VO(2). The distance covered by the submaximal 6 min walk test increased by 8.1% (P<0.001). Lactate measured as area under the curve during the matched work intensity treadmill endurance test was reduced by 19.5% (P<0.005). CONCLUSION: We demonstrated a significant improvement in maximal, submaximal and endurance exercise capacity following 12 weeks of exercise training in patients with congestive heart failure. Endurance tests may be more sensitive and appropriate when assessing the efficacy of intervention in this population. Specifically, demonstration of reduced lactate production at matched work intensities suggests more efficient work and decreased dependence on anaerobic metabolism following training. Although maximal cycle tests are commonly used in clinical work, submaximal and endurance testing might be preferable for evaluating new treatment regimens in this population as they are easy to perform, are reproducible, and reflect daily tasks better than the maximal cycle test in this population.

The effects of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure.

AIMS: Congestive heart failure (CHF) is characterized by elevated plasma norepinephrine (PNE) associated with a poor prognosis. Moxonidine selectively stimulates medullary imidazoline receptors which centrally inhibit sympathetic outflow and potently suppress levels of circulating PNE. This study was designed to evaluate the effects of central sympathetic inhibition on clinical and neurohumoral status in patients with CHF. METHODS AND RESULTS: This study evaluated 25 patients (age=69+/-7 years, 20 males) with symptomatic CHF (NYHA II-III), stabilized on standard therapy. The mean ejection fraction was 28+/-7% at baseline. Patients were titrated in a double-blind fashion to 11 weeks of oral therapy with placebo (n=9) or sustained-release (SR) moxonidine 0.9 mg bid (n=16). Clinical and neurohumoral status were evaluated at baseline, on chronic therapy at the target dose, and during cessation of therapy. All patients completed the trial and reached the target dose. Dry mouth, symptomatic hypotension, and asthenia were more frequent in the moxonidine SR-treated group. PNE was substantially reduced after 6 weeks at the maximum dose (0.9 mg bid) by 50% vs. placebo (P<0. 0005). A reduction in 24-h mean heart rate (P<0.01) was correlated to the reduction in PNE (r=0.70, P<0.05). A 36% increase in the standard deviation of normal-to-normal intervals (SDNN) was observed in the moxonidine SR group vs. a 2% decrease for placebo (P=0.06); for the root mean square of successive differences (rMSSD), there was a 21% increase for moxonidine SR vs. a 19% decrease for placebo (P<0.05). Abrupt cessation of chronic therapy resulted in substantial increases in PNE, blood pressure, and heart rate. CONCLUSIONS: Chronic therapy with a sustained-release formulation of moxonidine in patients with CHF was well tolerated, with substantial and sustained reductions in PNE. The tachyarrhythmias were attenuated, with evidence of improved autonomic tone. Due to the observed effects following moxonidine discontinuation, tapering of therapy is recommended.

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Elevated plasma norepinephrine (PNE) has been shown to be an important predictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in the medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study evaluated the acute neurohumoral and hemodynamic effects of a single dose of oral moxonidine in 32 patients (22 men, mean +/- SD age 66 +/- 10 years) with CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotensin-converting enzyme inhibitors. The mean PNE concentration was 509 +/- 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring after double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependent, vasodilator response compared with placebo. Analysis of the time-averaged change from baseline over 6 hours demonstrated that moxonidine 0.6 mg caused significant reductions in mean systemic arterial pressure (p <0.0001), mean pulmonary arterial pressure (p <0.005), systemic vascular resistance (p <0.05), pulmonary vascular resistance (p <0.01), and heart rate (p <0.05). Stroke volume was unchanged. PNE was reduced substantially (-180 pg/ml at 4 hours, p <0.005) and the reduction was highly correlated with the baseline level (r = -0.968). Moxonidine was well tolerated in this single-dose study and resulted in a modest, dose-dependent, vasodilator response, with substantial reductions in systemic and pulmonary arterial blood pressure. Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate.

Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia.

Favourable effects of n-3 fatty acids on the atherogenic risk profile were recently demonstrated in subjects with combined (type IIb) hyperlipidaemia, not responding to a therapeutic diet. Re-examination of a previous patient material was performed to assess the influence of n-3 fatty acids on homocysteine and several coagulation factors. Subjects were randomly allocated to receive either a concentrated compound of 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (n = 28), or corn oil (n = 29), in a daily dose of 4g for 12 weeks. The intervention was double-blind. Homocysteine remained unchanged in both groups after 12-week treatment. N-3 fatty acids supplementation did not affect the levels of fibrinogen, coagulation factor VII or tissue factor pathway inhibitor (TFPI), while plasminogen activator inhibitor (PAI) increased significantly (Student's t-test; p <0.05). Total blood platelets were significantly reduced in subjects receiving n-3 fatty acids (Student's t-test; p <0.05), whereas bleeding times increased non-significantly.

Depressed mood and subjective health symptoms as predictors of mortality in patients with congestive heart failure: a two-years follow-up study.

OBJECTIVE: The present study was undertaken in order to evaluate the relationship between depressed mood (depression, emotional distress) and disease-specific subjective health symptoms upon mortality risk among patients with congestive heart failure (CHF). METHODS AND RESULTS: Proportional hazard models were used to evaluate the effects of selected biomedical, subjective health and psychological variables on mortality among 119 clinically stable patients (71.4% men; mean age 65.7 years +/- 9.6) with symptomatic heart failure, recruited from an outpatient cardiology practice. Twenty deaths were registered during the twenty-four-month period of data collection, all from cardiac causes. Results indicated that depressed mood was a significant predictor of mortality with a hazard ratio of 1.9, p .002. In contrast, subjective health was not a significant predictor of mortality in a Cox regression model that included depressed mood. The hazard ratio for a 1-point increase in Zung Depression Scale score was equal to 1.08 based on the multivariate model. CONCLUSIONS: Results indicate that depressed mood is significantly related to increased mortality risk among heart failure patients. This finding is of concern to clinicians and should have implications for treatment of patients with congestive heart failure.

Plasma N-terminal atrial natriuretic peptide predicts hospitalization in patients with heart failure.

The plasma concentration of N-terminal atrial natriuretic peptide (N-ANP) has been shown to be predictive of both clinical status and survival in patients with heart failure. In this analysis the relationship between N-ANP, morbidity and hospitalization time was evaluated in 417 patients with stable, congestive heart failure recruited from an active, outpatient heart failure registry. Hospital admissions along with the duration of stay occurring after the initial N-ANP sampling during the period of data collection were recorded. A total of 755 admissions occurred, accounting for 7917 days' hospitalization. Relative hospitalization times (in-hospital days/observation period) per N-ANP quartiles I-IV were: 1.2 (+/- 2.7)%, 5.5 (+/- 12.2)%, 10.0 (+/- 21.5)% and 20.8 (+/- 34.3)%, respectively. Although N-ANP levels were correlated with age (r = 0.234, p < 0.0001), division by age quartiles did not significantly predict relative hospitalization times. These data indicate that the degree of cardiac endocrine activation and subsequent N-ANP release is related to morbidity in patients with heart failure and that moderate elevation in N-ANP levels is associated with a substantially increased hospitalization time. N-ANP sampling should be of value as a supplement to clinical evaluation in the assessment of the individual patient with this common syndrome.

Functional status and depression among men and women with congestive heart failure.

OBJECTIVE: The study was designed 1) to examine the prevalence of depression in patients with congestive heart failure (CHF); 2) to explore associations between the physician's rating of functional status (NYHA class) and patient's assessment of functional status (physical limitation, dyspnea) with symptoms of depression; and 3) to explore gender related differences in relation to physician's rating and patient's rating of function status, and symptoms of depression. METHOD: A sample of 119 clinically stable heart failure patients (85 males and 34 females) was recruited from an outpatient cardiology hospital practice. The patients underwent a physical examination and completed a set of questionnaires. Prevalence of depressive symptoms and the association of these symptoms with NYHA class and patient's perceived functional status was studied. RESULTS: Findings indicate that depressive symptoms were not predominant among this sample of CHF patients. Path analyses showed non-significant direct associations between NYHA class as well as patient's perception of dyspnea with depression. In contract, the subjective indicator of physical limitations was strongly associated with symptoms of depression among the males, but this relation was not significant among the females. CONCLUSIONS: Results suggest that men and women respond differently to the burden of heart failure. However, interpretation of the results from the present study should be considered as tentative and additional research is required to examine mechanisms that explain gender differences in response to heart failure.

Social support, social disability and their role as predictors of depression among patients with congestive heart failure.

The purpose of this study was to assess the effect of social support variables, personality, clinical variables (New York Heart Associations classification), and social disability upon depression. The sample consisted of 119 clinically stable patients (34 females, 85 males) with symptomatic heart failure, recruited from an outpatient hospital practice. The patients underwent a brief physical examination and completed a set of questionnaires. Descriptive statistics were used to characterise the patients' informal functional network. The analysis revealed that the intimate social network support (spouses) and primary social network support (close family) were rated as most supportive. Results from the path analysis showed that social disability was explained by the two personality factors, neuroticism and extraversion, and by the severity of disease (NYHA). No significant effects of the social support variables upon social disability were detected. Moreover, path-analyses showed that poor intimate network support, social disability and neuroticism were significantly positively associated with depression.

Comparison of the degree of hemodynamic tolerance during intravenous infusion of nitroglycerin versus nicorandil in patients with congestive heart failure.

BACKGROUND: Continuous exposure to organic nitrates is associated with substantial tachyphylaxis. This study compares the development of tolerance during continuous intravenous treatment with nitroglycerin versus nicorandil over a 24-hour period. METHODS AND RESULTS: Twenty patients with congestive heart failure and pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg were randomly assigned to nitroglycerin or nicorandil in a double-blind, crossover study. Doses were titrated to obtain a reduction of PCWP of at least 30% and then maintained. The mean pretreatment PCWP for nitroglycerin was 25.4 +/- 6.7 mm Hg, decreasing to 19.0 +/- 6.8 mm Hg at 24 hours. The values for nicorandil were 24.3 +/- 6.3 mm Hg and 15.6 +/- 4.5 mm Hg, respectively. Between-treatment difference was significant (p < 0.01). The difference between the minimal PCWP value and the 24-hour PCWP value for nitroglycerin was 5.1 mm Hg vs 1.4 mm Hg for nicorandil (p < 0.005). The mean systemic vascular resistance was 1418 +/- 355 dynes.sec.cm-5 before nitroglycerin infusion, decreasing to 1312 +/- 353 dynes.sec.cm-5 at 24 hours. Corresponding values for nicorandil were 1420 +/- 366 dynes.sec.cm-5 and 967 +/- 274 dynes.sec.cm-5. Between-treatment difference was significant (p = 0.005). Tachyphylaxis developed in 12 (60%) patients during nitroglycerin infusion versus three patients (15%) during nicorandil infusion. CONCLUSION: This study demonstrates that intravenous nicorandil administration results in significantly less hemodynamic tolerance over a 24-hour period compared with nitroglycerin. This finding may represent a clinical advantage for nicorandil in the short-term treatment of patients with congestive heart failure.

Plasma N-terminal atrial natriuretic factor: a predictor of survival in patients with congestive heart failure.

BACKGROUND: Congestive heart failure results in biatrial stretch, which stimulates myocyte release of atrial natriuretic factor (1-126). The N-terminal fragment, proatrial natriuretic factor(1-98), (proANF), is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply because of prolonged in vitro stability. Proatrial natriuretic factor has been shown to be predictive of clinical status in patients with congestive heart failure. This retrospective analysis was undertaken to evaluate the relationship between N-terminal atrial natriuretic factor(1-98) and survival in patients with stable congestive heart failure. METHODS AND RESULTS: Proatrial natriuretic factor was sampled from 316 patients (mean age, 68 (+/-) 11 years; 71% men) recruited from an outpatient heart failure clinic. The mean ejection fraction was 34 (+/-) 13%. Seventy-three deaths were registered during the period of data collection (42 months). Deaths per proANF quartile (n = 79) were as follows: 2 (2.5%) in quartile I. 13 (16.5%) in quartile II, 21 (26.6%) in quartile III, and 37 (46.8%) in quartile IV. The odds ratio estimates for death adjusted for age and sex were 7.6, 13.9, and 33.9 for the second, third, and fourth quartiles, respectively. Survival curves constructed according to proANF quartiles demonstrate significant differences in mortality rates. The correlation with death was greater for proANF as compared with left ventricular end-diastolic diameter (P < .001), systolic pulmonary artery pressure (P < .005), or ejection fraction (P < .05). CONCLUSION: These data indicate that the concentration of proANF is related to prognosis in patients with heart failure and that moderate elevation is associated with markedly decreased survival. Analysis should be of practical value in the assessment of prognosis in this heterogeneous population.

[Pro-atrial natriuretic factor is predictive for the clinical status of patients with heart failure]. / Pro-atrial natriuretisk faktor i plasma er prediktiv for klinisk status hos hjertesviktpasienter.

This study was undertaken in order to evaluate the relationship between N-terminal proatrial natriuretic factor [1-98] and routinely available measures of clinical status. Odds ratio estimates demonstrated a much higher risk of presence of left ventricular dysfunction and dilatation, pulmonary hypertension, and New York Heart Association function class III or IV with increasing proANF values. Analysis is simple and can be of practical value as a supplement in the assessment of cardiac status in this heterogeneous population.

Comparison of the effects of aqueous and gellan ophthalmic timolol on peak exercise performance in middle-aged men.

PURPOSE: To compare the effects of 0.5% aqueous timolol and 0.5% timolol gellan on exercise performance in middle-aged men. METHODS: We evaluated the effects of 0.5% aqueous timolol (timolol solution, administered twice daily, and a 0.5% timolol gellan suspension that forms a gel on application to the conjunctiva (timolol gellan), administered once daily, on exercise performance in 42 healthy men with a mean age of 58 years (range, 55 to 65 years). Serum concentrations of timolol were assayed. Subjects exercised maximally on an upright cycle ergometer four times with ten-day intervals. After baseline testing, subjects were randomly assigned and crossed over in a double-masked manner to two and a half days of treatment with placebo, 0.5% timolol solution, and 0.5% timolol gellan. RESULTS: The serum timolol concentrations immediately after testing were 0.91 +/- 0.51 ng/ml for timolol solution compared to 0.71 +/- 0.46 ng/ml for timolol gellan (P < .05). The change from baseline in resting heart rate was -1.8 +/- 9.3 beats/min (P = .23) for placebo, -11.0 +/- 9.6 beats/min (P < .001) for timolol gellan. The change from baseline in peak heart rate was -0.1 +/- 7.3 beats/min (P = .92) for placebo, -15.6 +/- 5.6 beats/min (P < .001) for timolol solution, and -11.9 +/- 8.0 beats/min (P < .001) for timolol solution, and -8.5 +/- 7. 5 beats/min (P<.001) for timolol gellan. Pair-wise comparison demonstrated significantly less reduction in both resting (P < .05) and peak heart rate (P < .01) for timolol gellan vs timolol solution. CONCLUSIONS: Although both treatments caused reductions in testing and peak heart rate, timolol gellan was associated with significantly less reductions. The significant difference in serum concentrations of timolol between the two treatments is strong evidence that the difference in heart rate response was caused by reduced systemic absorption with timolol gellan.

Plasma proatrial natriuretic factor is predictive of clinical status in patients with congestive heart failure.

Atrial stretch results in myocyte release of the prohormone atrial natriuretic factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor (proANF) is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply due to in vitro stability. This study was undertaken to evaluate the relation between proANF and routinely available measures of clinical status. ProANF was sampled from 202 patients (median age 68 years [range 15 to 85], 77% men) recruited from an active outpatient heart failure clinic. Patients were subgrouped according to New York Heart Association functional class, radionuclide ejection fraction (EF), echocardiographic left ventricular (LV) end-diastolic diameter, and Doppler-determined systolic pulmonary arterial pressure. The median proANF (pmol/L) values for patients in New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and 5,172, respectively. The proANF value for the group with EF > 40% was 1,534 versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241 versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01). ProANF correlated better than the other variables with New York Heart Association functional class and was more closely associated with noninvasive measurements than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia.

OBJECTIVES: To investigate the effect of an omega-3 fatty acid concentrate K85 on serum lipids, lipoproteins, insulin metabolism and blood pressure in subjects with combined hyperlipidaemia. DESIGN: After a run-in dietary period of 10 weeks, subjects were randomly allocated to receive either encapsulated K85 (n = 28) or corn oil (n = 29). The intervention was double-blind. SETTING: An outpatient centre in Stavanger, Norway. SUBJECTS: Fifty-seven of 141 individuals, who, after the run-in period continued to meet the inclusion criteria: serum triglycerides of > or = 2.0 mmol L-1 and total serum cholesterol of > or = 6.0 mmol L-1. INTERVENTION: Encapsulated K85, containing 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), or corn oil, both administered in a daily dose of 4 g for 12 weeks. MAIN OUTCOME MEASURES: Change in metabolic and haemodynamic parameters related to intervention. RESULTS: Serum EPA and DHA increased significantly in the K85 group during the treatment period. The body-mass index remained unchanged. A 28% reduction in serum triglycerides was noted in the K85 group from the first 4 weeks. Total serum cholesterol was significantly reduced with both regimens. Serum high-density lipoprotein cholesterol increased significantly during the first 8 weeks in the K85 group. Significant reductions in systolic and diastolic blood pressures were noted in subjects on K85. The treatment did not affect serum glucose, plasma insulin and proinsulin levels. Insulin:glucose and proinsulin:glucose ratios remained unchanged. CONCLUSIONS: The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia, but n-3 fatty acids supplementation did not affect glucose/insulin homeostasis.