The risk of cardiovascular death in elderly patients with possible heart failure. Results from a 6-year follow-up of a Swedish primary care population.

UNLABELLED: Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure. AIM: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients. METHODS: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction<40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality. CONCLUSION: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction<40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population.

UNLABELLED: Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. METHODS: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. CONCLUSION: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations.

Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy.

AIM: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). METHODS: Blood samples for plasma P-BNP and P-ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non-parametric. RESULTS: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P-BNP and P-ANP were higher, 263 ng l(-1) (range 47.5-1300) and 303 ng l(-1) (range 168-466), than in those without CSHF, 12.3 ng l(-1) (range 4.8-30.8) and 42.9 ng l(-1) (range 13.7-189), respectively (p < 0.001, Mann-Whitney U-test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD. CONCLUSION: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.

Urinary iodine and thyroid volume in a Swedish population.

OBJECTIVE: To evaluate the present efficacy of an iodine supplementation programme working in Sweden since 1936 by studying the iodine excretion in urine and determining the thyroid volume in a population in a semi-rural community. DESIGN: A cross-sectional population screening comprising three age groups with randomly selected individuals: group 1 (children): 7-9 years, n = 61 (invited 70); group 2 (teenagers): 15-17 years, n = 61 (invited 63), and group 3 (adults): 60-65 years; n = 57 (invited 73). MAIN MEASUREMENTS: Urinary iodine was measured spectrophotometrically; thyroid volume by ultrasonography. RESULTS: The median values for urinary iodine concentration in the three age groups were 194 microg L(-1), 246 microg L(-1) and 190 microg L(-1), respectively, indicating an adequate iodine intake. In the 7-9 year olds, the median value of the thyroid volume was 4.7 mL, which coincides with the recently established upper limit of normal children of that age, 4.0-4.8 mL (ICCIDD, International Council for control iodine deficiency disorders). One eight-year-old boy had a pronounced goiter. Four teenagers and one adult were found to have an enlarged thyroid gland according to earlier established reference volumes (15 years >16 mL; adults > 25 mL). CONCLUSION: We conclude that the iodine intake in our region is sufficient in age groups ranging from young children to pre-retirement adults.

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial.

OBJECTIVES: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. DESIGN: Double-blind placebo-controlled intervention study. SETTING: Outpatient clinic. SUBJECTS: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. INTERVENTION: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). RESULTS: High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. CONCLUSIONS: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.

Smoking and use of smokeless tobacco in treated hypertensive men at high coronary risk: utility of urinary cotinine determination.

Guidelines for the treatment of hypertension underline the central importance of strenuous efforts to reduce the prevalence of smoking, as epidemiological studies consistently have demonstrated that smoking increases the risk of cardiovascular disease and death by some two- or three-fold. Accuracy of a questionnaire is examined against the ability of urinary cotinine determination to distinguish between men exposed to tobacco (94 smokers [25%], 30 snuff users [8%]) and men not exposed (n = 257), all of whom where treated hypertensives and were associated with at least one of the following factors: smoking, diabetes mellitus, serum cholesterol > or = 6.5 mmol/L. Main outcome variables in this cross-sectional study of 381 men were cotinine concentration and cotinine:creatinine ratio in overnight urine samples (decision limits: 2 mumol/L and 1.0 mmol/mol, respectively); tobacco use according to questionnaire; and follow-up examination by questionnaire of alleged non-smokers with high urinary cotinine levels. Questionnaire sensitivity was 85%, whereas the urinary cotinine assay showed 98% sensitivity and 99% specificity. Fourteen (15%) out of 94 patients may have used tobacco without reporting it in the questionnaire. In conclusion, cotinine measurement substantially improved the discrimination between smokers and non-smokers in men with multiple risk factors for cardiovascular disease.

Radioiodine ablation and therapy in differentiated thyroid cancer under stimulation with recombinant human thyroid-stimulating hormone.

We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.

[Better treatment of heart failure by measurements of natriuretic peptides. There are still remaining problems when it comes to the interpretation of measurement levels]. / Bättre behandling av hjärtsvikt med mätning av natriuretiska peptider. Tolkningen av mätvärdena bereder dock fortfarande problem.

The heart is increasingly being recognised as a major endocrine organ involved in haemodynamic homeostasis. Natriuretic peptides, i.e. atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), affect renal, adrenal and central nervous system functions as well as vessel tonus and permeability thus causing decreased preload and afterload. Natriuretic peptides, BNP in particular, are independent risk factors for morbidity and mortality. They also have high negative predictive values for cardiac insufficiency indicating high diagnostic sensitivity for heart failure in outpatient practice. Monitoring of therapy for heart failure may be improved if BNP measurement is used in conjunction with clinical assessment. However, several problems remain to be solved, such as optimal decision limits in relation to sex and age for the assessment of heart failure.

Screening for thyroid disease of 15-17-year-old schoolchildren in an area with normal iodine intake.

OBJECTIVE: The prevalence of thyroid disease in Swedish schoolchildren is today insufficiently known. The aim of the study was therefore to determine the prevalence of abnormal thyroid function and thyroid autoimmunity in teen-age schoolchildren and to compare the findings with a healthy control group of 60-65-year-old inhabitants from the same community. SETTING: A semirural community of approximately 15,000 inhabitants. DESIGN: Cross-sectional study. MAIN OUTCOME MEASURES: Thyroid volume and serum concentrations of serum thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3'-triiodothyronine (T3), and antithyroperoxidase antibodies (TPOAb). RESULTS: Four schoolchildren (7%, 59 screened) had elevated TPOAb concentration, three of the subjects being girls (8%). One girl with a goitre was overtly hypothyroid and one girl showed borderline-high serum TSH concentration suggesting subclinical autoimmune thyroid disease. One euthyroid boy had a goitre and high concentration of TPOAb. The serum free T3 concentration was significantly higher in 15-17-year-old than 60-65-year-old (7.4 vs. 6.4 pmol L(-1), P < 0.001). The concentrations of other thyroid hormones and of TSH in 15-17-year-old did not differ from those of the 60-65-year-old. CONCLUSIONS: We found three cases of thyroid disease in need of immediate attention or later follow-up. The prevalence of autoimmune thyroid disease was high as indicated from TPOAb measurements. Thyroid tests including TPOAb measurement should be performed on wide indications when teenagers seek medical advice. The reference intervals for teen-age children for commonly used first line tests (TSH and free T4) do not differ from those for adults.

Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men.

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.

The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.

Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.

Erosive oral lichen planus and salivary cortisol.

Patients with oral lichen planus (OLP) often relate the onset and aggravation of oral symptoms to increased levels of stress. Under normal conditions, stress induces increased cortisol secretion that counteracts inflammatory reactions. The objective of the present study was to assess whether patients with OLP have an impaired capacity to elevate their cortisol concentrations as a response to stress. Saliva samples were collected for cortisol analysis from 10 OLP patients once every 15 min during a 2-h test period. In order to induce stress during a part of this test period, the patients were confronted with a computerised device specifically developed for the induction of transient stress. A visual analogue scale (VAS) and a mood adjective check list (MACL) were used to estimate the degree of permanent stress. A control group of patients was matched for age and sex. The OLP patients did not present with different stress scores when a psychometric test (MACL) was used. No statistically significant correlation between cortisol concentration and stress level was observed. Thus, no support for an impaired capacity of OLP patients to suppress an immune response through cortisol induction in conjunction with experimental stress was revealed.

[Increased procalcitonin level in bacteriogenic metabolic disturbances. A new possibility for diagnosis and treatment monitoring in sepsis]. / Prokalcitoninökning vid bakteriellt betingade metabola störningar. Ny möjlighet vid diagnostik och behandlingsuppföljning av sepsis.

Earlier observations of increased plasma concentrations of immunoreactive calcitonin (32 amino acids) in sepsis and other non-tumorous conditions may be explained by increased secretion of procalcitonin, the 116-amino acid prohormone. At present, the site(s) of origin of procalcitonin in sepsis, the factors regulating its biosynthesis and release, the route(s) of its elimination from blood as well as its biological function(s) are unknown. The rapid increase in procalcitonin concentration in sepsis--in some patients earlier than that of C-reactive protein--and decrease upon successful chemotherapy makes procalcitonin a potentially important biomarker in monitoring patients with suspected or confirmed sepsis.

[Laboratory diagnosis of gastrinoma. Nordic collaboration can improve the quality]. / Laboratoriediagnostik av gastrinom. Nordiskt samarbete kan ge ökad säkerhet.

Measurement of gastrin in serum or plasma in patients with gastrinoma may be complicated by the presence of circulating biosynthetic intermediates which may not be detected by commonly available immunoassays. In contrast, the "processing-independent analysis" of gastrins developed by professor Jens Rehfeld et al in Copenhagen detects gastrin forms irrespective of their size. The authors review gastrinoma pathophysiology, the biochemistry of gastrin and other biomarkers of gastrinoma, the differential diagnosis of hypergastrinemia as well as other methods currently employed in the workup of gastrinoma patients, and illustrate with a clinical case.