Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients.

OBJECTIVES: The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients. BACKGROUND: Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value of NT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients. METHODS: Our study population comprised 7 ADHF cohorts. We defined absolute (<1,500 ng/l, <3,000 ng/l, <5,000 ng/l, and <15,000 ng/l) and relative NT-proBNP discharge cut-off levels (>30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age ≤75 years). Thereafter, we compared percentages of elderly and young patients attaining NT-proBNP levels (= attainability). RESULTS: A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT-proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levels and a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia at discharge. CONCLUSIONS: In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed to factors other than age.

Quality of life in patients with primary hypothyroidism related to BMI.

OBJECTIVE: Many patients treated for primary hypothyroidism have an unexplained reduced quality of life (QOL). We studied the relation between QOL and various parameters in treated hypothyroid patients. DESIGN AND METHODS: QOL analysis was done in 90 consecutive patients (77.8% females) treated for primary hypothyroidism. QOL was measured by the questionnaires Short-Form 36, Hospital Anxiety and Depression Scale and MFI20. Post hoc analysis was performed on the relation of QOL at baseline and BMI, thyroid hormones and other serum values. QOL in patients was also compared to the general population. RESULTS: QOL was decreased compared to the general population. We found an inverse relationship between QOL and BMI. A relationship between QOL and serum thyroid parameters or auto-antibodies could not be found. Higher sex hormone binding globulin (SHBG) levels corresponded with a better QOL, which is explained by the negative association of SHBG with body weight and BMI. CONCLUSIONS: A decreased QOL in hypothyroid patients on thyroxine treatment is related to a higher body weight (BMI). Weight gain needs more attention in the treatment of hypothyroidism.

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Measurements Until a 30% Reduction Is Attained During Acute Decompensated Heart Failure Admissions and Comparison With Discharge NT-proBNP Levels: Implications for In-Hospital Guidance of Treatment.

BACKGROUND: A >30% N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction at discharge in acute decompensated heart failure (ADHF) predicts a favorable prognosis. To study the feasibility of guiding ADHF treatment by measuring NT-proBNP well before discharge, we assessed at which moment during hospitalization patients attain a NT-proBNP reduction of >30% (target) and whether this target is still attained at discharge. METHODS: Twenty-five consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original cohort). NT-proBNP was measured daily until the target was attained, at clinical stability, and at discharge and was analyzed as percentages of patients on target. For comparison purposes, the same analysis was performed in individual patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in which NT-proBNP was measured from admission to day 3 and at discharge. RESULTS: In the original cohort of 25 patients (median age 70 years, 40% male), the cumulative percentage of patients attaining the target increased gradually during admission to 22 patients (88%) in a median of 3 days (interquartile range 2-5). In the comparison cohorts, a similar course was observed in patients attaining the target before discharge. Compared with levels measured at days 2 and 3, rebound NT-proBNP increases to levels off-target at discharge were seen in up to 33% of patients in the original and comparison cohorts. CONCLUSION: A target >30% NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP increases to levels off-target occur in up to 33% of ADHF patients who initially attained target early during admission.

Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?

AIMS: NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target. METHODS AND RESULTS: Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (∼60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets. CONCLUSION: In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target.

The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial.

BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively. METHODS: We conducted a prospective, randomized, double-blind trial that compared a full starting levothyroxine dose of 1.6 mug/kg with a low starting dose of 25 mug (increased every 4 weeks) in patients with newly diagnosed cardiac asymptomatic hypothyroidism. Safety was studied by documenting cardiac symptoms and events, and efficacy was studied by monitoring thyrotropin and free thyroxine levels and by assessing improvement of signs and symptoms and quality of life. RESULTS: Seventy-five consecutive patients were enrolled, of whom 50 underwent randomization. At baseline, the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8 weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs 20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism and quality of life improved at a comparable rate. CONCLUSION: A full starting dose of levothyroxine in cardiac asymptomatic patients with primary hypothyroidism is safe and may be more convenient and cost-effective than a low starting dose regimen.