Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Association between foetal sex and adverse neonatal outcomes in women with gestational diabetes.

AIMS: Foetal male sex is associated with adverse perinatal outcomes. However, studies evaluating the impact of foetal sex on perinatal outcomes in women with gestational diabetes (GDM) are scarce. We studied whether male new-born sex is associated with neonatal outcomes, in women with GDM. METHODS: This is a retrospective study based on the national Portuguese register of GDM. All women with live-born singleton pregnancies between 2012 and 2017 were eligible for study inclusion. Primary endpoints under analysis were neonatal hypoglycaemia, neonatal macrosomia, respiratory distress syndrome (RDS) and neonatal intensive care unit (NICU) admission. We excluded women with missing data on the primary endpoint. Pregnancy data and neonatal outcomes between female and male new-borns were compared. Multivariate logistic regression models were built. RESULTS: We studied 10,768 new-borns in mothers with GDM, 5635 (52.3%) male, 438 (4.1%) had neonatal hypoglycaemia, 406 (3.8%) were macrosomic, 671 (6.2%) had RDS, and 671 (6.2%) needed NICU admission. Male new-borns were more frequently small or large for gestational age. No differences were observed on maternal age, body mass index, glycated haemoglobin, anti-hyperglycaemic treatment, pregnancy complications or gestational age at delivery. In the multivariate regression analysis, male sex was independently associated with neonatal hypoglycaemia [OR 1.26 (IC 95%: 1.04-1.54), p = 0.02], neonatal macrosomia [1.94 (1.56-2.41), p < 0.001], NICU admission [1.29 (1.07-1.56), p = 0.009], and RDS [1.35 (1.05-1.73, p = 0.02]. CONCLUSIONS: Male new-borns have an independent 26% higher risk of neonatal hypoglycaemia, 29% higher risk of NICU admission, 35% higher risk of RDS, and almost twofold higher risk of macrosomia, compared to female new-borns.

Low stress hyperglycemia ratio predicts worse prognosis in diabetic acute heart failure patients.

INTRODUCTION: Acute blood glucose but not glycated hemoglobin (HbA1c) predicts poor outcome in acute heart failure (HF). The stress hyperglycemia ratio (SHR) has been proposed as a prognostic predictor in various clinical settings. OBJECTIVES: We assessed the prognostic implications of the SHR in acute HF patients with and without diabetes. METHODS: We performed a retrospective analysis of an acute HF registry conducted between 2009 and 2010. Estimated average glucose (eAG) was calculated as (28.7×HbA1c)-46.7 and SHR as acute blood glucose divided by eAG. The primary endpoint was all-cause mortality. Follow-up was three months. Patients were grouped by SHR tertiles (≤0.88, 0.89-1.16, and >1.16). Cox regression analysis was used to test the association of SHR (cut-off 0.88) with all-cause mortality. Analysis was stratified according to the presence of diabetes. Multivariate models were built accounting for acute blood glucose and for eAG (models 1 and 2, respectively). RESULTS: We studied 599 patients, mean age 76±12 years, of whom 62.1% had reduced ejection fraction and 50.9% had diabetes. Median acute blood glucose, eAG and SHR were 136 (107-182) mg/dl, 131 (117-151) mg/dl, and 1.02 (0.20-3.34), respectively. During follow-up 102 (17.0%) died. In patients with diabetes, those in the lowest SHR tertile had a hazard ratio (HR) of 2.24 (95% CI: 1.05-5.22) (model 1) and 2.34 (1.25-4.38) (model 2). In patients without diabetes, the HR of three-month death in the lowest SHR tertile was 0.71 (95% CI: 0.36-1.39) and 1.02 (0.58-1.81). Significant interaction was observed between diabetes and SHR. CONCLUSIONS: In HF patients with diabetes, a SHR ≤0.88 was associated with a more than twofold higher three-month mortality risk. No such association was found in non-diabetic patients. The presence of diabetes influences the association of the SHR with mortality.

Maternal height as a predictor of glucose intolerance in the postpartum and its relationship with maternal pre-gestational weight.

PURPOSE: Short stature predicts higher risk of developing type 2 diabetes. We studied the association between height and glucose intolerance in women with gestational diabetes mellitus (GDM) and whether this association differed according to body mass index (BMI). METHODS: Retrospective study of the Portuguese GDM registry. EXCLUSION CRITERIA: missing data on postpartum oral glucose tolerance test (OGTT) or BMI. ENDPOINT: postpartum glucose intolerance (diabetes mellitus or prediabetes on the 6-8 weeks postpartum OGTT). Women were divided by mean height and compared. A multivariate logistic regression was used, and the analysis was stratified by BMI (cut-off: 30 kg/m2) and interaction was tested. RESULTS: We included 7402 women; mean height was 161.9 ± 6.2 cm. Taller women had lower BMI and lower rates of glucose intolerance (6.8 vs. 8.8%, p = 0.002). Women with BMI < 30 kg/m2 were taller than those with obesity. Height associated with glucose intolerance. The multivariate adjusted OR of glucose intolerance was 0.98 (95% CI 0.96-0.99), p = 0.001, per 1 cm increase in height. This association was only observed in women with BMI < 30 kg/m2: OR 0.97 (95% CI 0.95-0.99), < 0.001. There was no such association in women with BMI ≥ 30 kg/m2: OR 0.99 (95% CI 0.97-1.02), p = 0.65. P for interaction between BMI and height was 0.09. CONCLUSIONS: In non-obese pre-gestational women, height is inversely associated with postpartum glucose intolerance. Per 1 cm increase in height, women present a 3% decrease in the risk of developing diabetes mellitus or prediabetes.

CA-125 variation in acute heart failure: a single-centre analysis.

AIMS: A decrease in carbohydrate antigen 125 (CA-125) predicts survival advantage in chronic heart failure (HF); the impact of its variation in acute HF is unknown. We studied the association of CA-125 decrease with prognosis in acute HF. METHODS AND RESULTS: We studied acute hospitalized HF patients. Predictors of admission and discharge CA-125 were determined by linear regression. Follow-up was 1 year; endpoint was all-cause death. The association of admission and discharge CA-125 with mortality was assessed using a Cox-regression analysis. A Cox-regression analysis was also used to assess the prognostic impact of CA-125 decrease during hospitalization. Analysis was stratified by length of hospital stay (LOS). We studied 363 patients, 51.5% male, mean age 75 ± 12 years, 51.5% ischaemic, 30.0% with preserved ejection fraction, and 57.3% with reduced ejection fraction; patients presented elevated comorbidity burden. Median LOS was 7 (5-11) days. In the subgroup of 262 patients with CA-125 measured both at admission and at discharge, we reported a significant increase in its levels: 56.0 (26.0-160.7) U/mL to 74.0 (32.3-195.0) U/mL. Independent predictors of admission CA-125 were higher BNP and lower creatinine. Predictors of discharge CA-125 were higher discharge BNP, lower discharge albumin, and younger age. Both admission and discharge CA-125 predicted mortality. During follow-up, 75 (31.8%) patients died. A decrease in CA-125 predicted a 68% reduction in the 1 year death risk only in patients with LOS > 10 days. CONCLUSIONS: Our results suggest that an early re-evaluation (>10 days) with CA-125 measurement after an acute HF hospitalization may be of interest in patient management.

First trimester fasting glucose and glycated haemoglobin cut-offs associated with abnormal glucose homeostasis in the post-partum reclassification in women with hyperglycaemia in pregnancy.

Hyperglycaemia first detected during pregnancy is either gestational diabetes mellitus (GDM) or previous undiagnosed diabetes. We aimed to study if there were a first trimester fasting glycaemia (FTG) and a glycated haemoglobin (HbA1c) cut-off values associated with type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis (AGH) at the post-partum oral glucose tolerance test (OGTT) reclassification. We retrospectively studied a group of pregnant women from the Portuguese National Registry of GDM. Receiver-operating characteristic (ROC) curves were used to determine the best FTG and HbA1c cut-offs to predict T2DM and AGH. We studied 4068 women. The area under the ROC curves (AUC) for the association with T2DM was 0.85 (0.80-0.90) for FTG and 0.85 (0.80-0.91) for HbA1c. The best FTG cut-off for association with T2DM was 99 mg/dL: sensitivity 77.4%, specificity 74.3%, positive predictive value (PPV) 4.8%, and negative predictive value (NPV) 99.5%. The best HbA1c cut-off for association with T2DM was 5.4%: sensitivity 79.0%, specificity 80.1%, PPV 5.7%, and NPV 99.6%. The AUC for the association of FTG and HbA1c with AGH were 0.73 (0.70-0.76) and 0.71 (0.67-0.74), respectively. The best FTG cut-off for predicting AGH was 99 mg/dL: sensitivity 59.4%, specificity 76.2%, PPV 17.0%, and NPV 95.8%. The best HbA1c cut-off was 5.4%: sensitivity 48.7%, specificity 81.5%, PPV 17.8%, and NPV 95.1%. We suggest an FTG of 99 mg/dL and an HbA1c of 5.4% as the best cut-offs below which T2DM is unlikely to be present. Almost all patients with FTG < 99 mg/dL and HbA1c < 5.4% did not reclassify as T2DM. These early pregnancy cut-offs might alert the physician for the possibility of a previous undiagnosed diabetes and alert them to the importance of testing for it after delivery.

The prognostic impact of magnesium in acute heart failure is different according to the presence of diabetes mellitus.

Background: Hypermagnesemia predicts mortality in chronic heart failure (HF); however, in acute HF, magnesium does not seem to be outcome-associated. Diabetes mellitus (DM) frequently associates with altered magnesium status. We hypothesized that DM might influence the prognostic impact of magnesium in acute HF. Methods: This is a retrospective cohort study of hospitalized patients with acute HF. Patients without data on admission serum magnesium were excluded. Follow-up: 1 year from hospital admission. Primary end point: all-cause mortality. Patients were divided according to median serum magnesium (1.64 mEq/L). The Kaplan-Meier survival method was used to determine survival curves according to magnesium levels. The analysis was stratified according to the presence of DM. A multivariable Cox regression analysis was used to study the prognostic impact of magnesium. Results: We studied 606 patients. The mean age was 76 ± 12 years, 44.1% were male, 50.7% had DM, and 232 (38.3%) died during follow-up. Median magnesium was 1.64 (1.48-1.79) mEq/L. Patients with magnesium ≥1.64 mEq/L had higher 1-year mortality [141 (46.4%) vs 91 (30.1%), P < .001]. After adjustments for age, sex, history of atrial fibrillation, systolic blood pressure, heart rate, ischemic etiology, B-type natriuretic peptide, estimated glomerular filtration rate, alcohol consumption, antihyperglycaemic agents or glycated hemoglobin, admission glycemia, New York Heart Association class IV, and severe left ventricle systolic dysfunction, serum magnesium ≥1.64 mEq/L was associated with higher mortality only in patients with DM: HR 1.89 (95% confidence interval: 1.19-3.00), P = .007, and 1.27 (95% confidence interval: 0.83-1.94) and P = .26 for non-DM patients. The results were similar if magnesium was analyzed as a continuous variable. Per 0.1 mEq/L increase in magnesium levels, patients with DM had 13% increased risk of 1-year mortality. Conclusions: Higher magnesium levels were associated with worse prognosis only in HF patients with DM.

The prognostic impact of uric acid in acute heart failure according to coexistence of diabetes mellitus.

BACKGROUND AND AIMS: Increased uric acid levels predict higher mortality in heart failure (HF) patients. Patients with diabetes mellitus (DM) appear to have increased xanthine oxidase activity. We aimed to study if the association between uric acid and mortality in acute HF was different according to the coexistence of DM. METHODS AND RESULTS: We studied a cohort of patients hospitalized due to acute HF in 2009-2010. Patients with no uric acid measurement upon admission were excluded from the analysis. FOLLOW-UP: 2 years; endpoint: all-cause mortality. Patients with elevated uric acid (>80.0 mg/L) were compared with those with lower values. We used a multivariate Cox-regression analysis to assess the prognostic impact of uric acid (both continuous and categorical variable: cut-off 80.0 mg/L). The analysis was stratified according to coexistence of DM. We studied 569 acute HF patients, 44.6%male, mean age 76 years, 290 were diabetic. Median admission uric acid: 81.2 mg/L and 52.2%had uric acid >80.0 mg/L. Elevated uric acid predicted all-cause mortality in acute HF only in patients with DM. The multivariate-adjusted HR of 2-year mortality was 1.68 (95 % CI: 1.15-2.46) for diabetic HF patients with uric acid>80.0 mg/L compared to those with lower levels (p = 0.008) and 1.10 (95 % CI: 1.03-1.18) per each 10 mg/L increase in uric acid (p = 0.007). In non-diabetic HF patients, uric acid was not associated with mortality. CONCLUSIONS: Increased uric acid predicts ominous outcome in acute HF patients with diabetes, however, it is not prognostic associated in non-diabetics. Uric acid may play a different role in acute HF depending on DM status.

Dynamics of growth differentiation factor 15 in acute heart failure.

AIMS: Risk stratification in acute heart failure (HF) patients can help to decide therapies and time for discharge. The potential of growth differentiation factor 15 (GDF-15) in HF has been previously shown. We aimed to study the importance of GDF-15-level variations in acute HF patients. METHODS AND RESULTS: We retrospectively evaluated a cohort of patients hospitalized due to acute HF. GDF-15 was measured both at admission and on the discharge day. Patients were followed-up during a 3 year period. The endpoint under analysis was all-cause mortality. GDF-15 variation is equal to [(admission GDF-15 - discharge GDF-15)∕admission GDF-15] × 100. Variation was categorized in levels of increase or decrease of GDF-15. Patients were cross-classified according to admission and discharge GDF-15 cut-off points. A Cox regression analysis was used to assess the prognostic impact of GDF-15 variation and the impact of both admission and discharge GDF-15 according to the cross-classification. We studied a group of 249 patients with high co-morbidity burden. Eighty-one patients died at 1 year and 147 within 3 years. There was a modest decrease in GDF-15 during hospitalization from a median value of 4087 to 3671 ng/mL (P = 0.02). No association existed between GDF-15 variation and mortality. In multivariate analysis, patients with admission GDF-15 ≥ 3500 ng/mL and discharge GDF-15 ≥ 3000 ng/mL had a significantly higher 1 year death risk when compared with the remaining-hazard ratio = 2.59 (95% confidence interval: 1.41-4.76)-and a 3 year 1.76 (95% confidence interval: 1.08-2.87) higher death risk compared with those with both values below the cut-off. CONCLUSIONS: Growth differentiation factor 15 decreased during an acute HF hospitalization, but its variation had no prognostic implications. The knowledge of both admission and discharge GDF-15 added meaningful information to patients' risk stratification.

The utility of prolactin serial sampling and the best prolactin cut-offs associated with persistent hyperprolactinemia.

BACKGROUND: A single prolactin sampling is recommended for the diagnosis of hyperprolactinemia. We aimed to study the utility of the prolactin serial sampling and to determine the best cut-offs associated with persistent hyperprolactinemia. METHODS: Retrospective study of hyperprolactinemic patients [referral prolactin (rPRL)] that underwent prolactin serial samplings. Prolactin at 0 minutes (PRL0'), 20 to 30, and 40 to 60 minutes. The lowest of these last 2 was defined as nadir prolactin (nPRL). Persistent hyperprolactinemia was defined as nPRL above normal. We excluded patients under dopamine receptor agonists. Receiver-operating characteristic (ROC) curves were used to determine the best rPRL and PRL0' cut-offs predicting persistent hyperprolactinemia. RESULTS: We studied 53 patients (3 males). Median rPRL 48.0 ng/mL (39.5-72.5), PRL0' 34.3 ng/mL (18.0-50.8) and nPRL 29.5 ng/mL (11.4-44.4). PRL0' was elevated in 35 (66.0%) patients and in 7 of them a normal nPRL was reached; therefore 28 (52.8%) had persistent hyperprolactinemia. The area under curve (AUC) for the association between rPRL and persistent hyperprolactinemia was 0.70 (95%CI: 0.56-0.84); best cut-off: 53.4 ng/mL [sensitivity 53.6%, specificity 80.0%, positive predictive value (PPV) 75.0%, and negative predictive value (NPV) 60.6%]. In the 35 patients with elevated PRL0', the AUC was 0.92 (95%CI: 0.81-1.00); best cut-off: 35.2 ng/mL (sensitivity 85.7%, specificity 85.7%, PPV 60.0%, and NPV 96.0%). CONCLUSIONS: Approximately 1/3 of the patients reached a normal PRL0'. In an additional 20%, prolactin normalized after serial samplings. Patients with rPRL >53.4 ng/mL had 75% probability of having persistent hyperprolactinemia and those with PRL0' <35.2 ng/mL had a 96% probability of not having persistent hyperprolactinemia.

Glucose variability predicts 6-month mortality in patients hospitalized with acute heart failure.

In diabetes mellitus (DM), glycaemic fluctuations associate with higher oxidative stress than sustained chronic hyperglycaemia and glucose variability increases the risk of chronic diabetic complications. Our hypothesis was that higher glucose variability would associate with mortality after an acute heart failure (HF) episode. We retrospectively analysed patients with DM hospitalized with acute HF between 2009 and 2010. Patients with < 2 point-of-care glucose values/day were excluded. Glucose coefficient of variation (GCV) was defined as (glucose standard deviation/mean glucose) × 100. Patients were categorized according GCV ≤ 30.0 and > 30.0%. Follow-up: 6-months. Endpoint: all-cause mortality. A Cox-regression analysis was used to study the association of glucose variability with 6-month mortality. We studied 214 diabetic patients with acute HF, 49.1% male, mean age 76 years. Mean glycaemia during hospitalization was 187 ± 50 mg/dL, hypoglycaemia (< 70 mg/dL) was reported in 21 patients and mean GCV was 28.3 ± 7.6%. Patients with GCV > 30.0% had higher mean glycaemia, more hypoglycaemic episodes and higher HbA1c; they were also more often treated with insulin. Patients were similar concerning age, gender, comorbidities, left ventricular systolic dysfunction and ischemic heart disease. During the 6-month follow-up, 38 (17.8%) patients died. Patients with GCV > 30.0% had a HR of 6-month mortality of 2.21 (95% CI: 1.16-4.21), p = 0.02. This association with more than twofold higher short-term mortality was independent of main confounders. Elevated glycaemic variability in acute HF admissions of patients with DM predicts short-term mortality. Patients with GCV > 30.0% have an independent more than twofold higher risk of 6-month death after an acute HF hospitalization.

Diabetic patients need higher furosemide doses: a report on acute and chronic heart failure patients.

INTRODUCTION: Diuretics are first-line drugs in symptomatic heart failure treatment. Diabetes mellitus has been suggested as a determinant of diuretic resistance. Studies comparing the dose and efficacy of diuretics in patients with and without diabetes are lacking. We aimed to study if furosemide dose differed according to diabetes status. METHODS: We studied two cohorts of heart failure patients: a cohort of acute heart failure patients consecutively hospitalized with the primary diagnosis of heart failure and another of stable and optimized patients followed in a heart failure clinic. Data on comorbidities and medication were abstracted from patients' files. Use and doses of furosemide were compared between diabetic and nondiabetic patients. Regression analysis was used to determine the association of variables with diuretic dose. The independent association of diabetes with furosemide dose was assessed using multivariate models. RESULTS: We studied 865 heart failure patients: 601 acute heart failure patients and 264 chronic stable heart failure patients. Acute heart failure patients with diabetes were more likely to need intravenous diuretic therapy and they were also more often discharged under higher doses of furosemide. They needed extra 6-mg furosemide at discharge in comparison with their nondiabetics counterparts and had an independent 26% higher odds of being discharged with at least 80-mg furosemide. Chronic patients were also more frequently prescribed with furosemide and on higher doses, although, diabetes was not independently associated with the use of higher furosemide doses. CONCLUSION: Diabetic patients are more intensively treated with the loop diuretic furosemide. In acute heart failure, diabetes is an independent predictor of furosemide dose.

The cholesterol paradox may be attenuated in heart failure patients with diabetes.

BACKGROUND: In heart failure (HF) patients, a lower total cholesterol (TC) appears to portend an ominous prognosis. We studied if the prognostic impact of TC was different according to diabetes mellitus (DM) status in a chronic HF population. METHODS: Patients with systolic HF under optimized and stable evidence-based therapy were prospectively recruited from our HF clinic. We excluded patients on renal replacement therapy and those hospitalized in the previous 2 months. A venous blood sample was collected. Patients were followed for up to 5 years and all-cause mortality was the endpoint under analysis. The prognostic impact of TC was analyzed using a Cox-regression analysis. Analysis was stratified according to coexistence of DM. RESULTS: We studied 262 chronic HF patients, 182 males, mean age 69 years, 98 (37.4%) diabetic and 62.2% with severe left ventricular systolic dysfunction. Median B-type natriuretic peptide: 237.8 pg/mL; median TC: 169 mg/dL. During follow-up 121 (46.2%) patients died. Patients with TC>200 mg/dL had better survival than those with lower TC; however, this protective effect was mostly observed in non-diabetic HF patients. In non-diabetics the multivariate adjusted 5-year mortality hazard ratio (HR) was 0.36 (95% CI: 0.16-0.79) for those with TC>200 mg/dL. In diabetic HF patients, there was a non-significant survival benefit of TC>200 mg/dL; HR 0.51 (95% CI: 0.20-1.30). CONCLUSIONS: Non-diabetic chronic HF patients with TC>200 mg/dL have a 64% lower risk of 5-year death. In diabetics, there is a non-significant 49% protective effect of elevated TC. The cholesterol paradox may be attenuated in diabetic HF patients.

Natriuretic Peptide System Activation in Acute Heart Failure Patients with Diabetes.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) is a hallmark in heart failure (HF). Diabetic patients with chronic HF seem to have higher BNP than nondiabetics. We studied, in acute HF, if BNP levels are different between diabetics and nondiabetics. METHODS: From a prospectively recruited population of acute HF patients, we selected a convenience sample. In pair-matched analysis, each diabetic patient was matched with a nondiabetic of the same age (±1 year), gender, and according to left ventricular systolic dysfunction. Diabetics and nondiabetics were compared. Cox-regression analysis was used to analyse the prognostic impact of diabetes. RESULTS: We studied 328 patients, mean age: 78 years, 44.5% male. Diabetics were more often hypertensive and had ischemic HF; they had higher body mass index, lower haemoglobin, and worse renal function. Diabetics were more often discharged on ACE inhibitors/ARB, antiplatelet therapy, and statins. Neither admission nor discharge BNP values differed between diabetics and pair-matched nondiabetics. One-year mortality was also nondifferent between pairs of diabetics and nondiabetics: 44 (26.8%) and 46 (28.0%), respectively. HR for 1-year mortality in diabetics was 1.00 (95% CI: 0.82-1.24) compared with nondiabetics. CONCLUSIONS: HF patients with diabetes have similar neurohumoral activation when compared with nondiabetics. One-year mortality is also nondifferent after matching for age, gender, and systolic function.

Prognostic prediction in acute heart failure patients with extreme BNP values.

BACKGROUND: Some patients have good prognosis despite elevated B-type natriuretic peptide (BNP), while others have ominous outcome with low BNP. We aimed at characterising these groups of patients. METHODS: We analysed patients prospectively included in an acute HF registry. Vital status within 1-year post discharge was ascertained. A receiver-operating characteristic curve was used to define discharge BNP cut-offs for 1-year death prediction. Among survivors, we compared patients with low and not-low BNP (cut-off 400 pg/mL); and among non-survivors those with high vs not-high BNP (cut-off 2000 pg/mL). In the specific subgroups of patients with low and high BNP, mortality predictors were assessed with multivariate Cox-regression analysis. RESULTS: We studied 584 patients, median age 78 years, 62.5% had HF with reduced ejection fraction; and 199 (34.1%) died during the first year. Non-survivors were very homogeneous irrespective of BNP, survivors were substantially different. In patients discharged with BNP <400 pg/mL, increasing age independently predicted death; when BNP ≥2000 pg/mL death predictors were higher NYHA class, and non-use of evidence-based therapy. BNP was outcome associated in both groups. CONCLUSIONS: Different prognostic predictors may play a role in different BNP levels. We suggest that risk stratification in HF would probably be more accurate if made on top of BNP knowledge.

Insulin treatment may not be associated with worse prognosis in acute heart failure diabetic patients.

BACKGROUND: Diabetic patients with heart failure (HF) treated with insulin appear to have a worse prognosis compared to oral anti-diabetic (OAD) agents. Whether insulin is a risk factor or a marker of disease severity is unknown. We studied the prognostic impact of insulin treatment in an acute HF diabetic population. METHODS: From a prospectively recruited population of hospital-admitted acute HF patients we retrospectively selected a convenience sample. Pair-matched analysis: each insulin-treated patient was matched with a diabetic patient with similar glycated hemoglobin (HbA1c±0.2%) under OAD. End-point: all-cause death. FOLLOW-UP: 5 years. Insulin-treated and OAD-treated patients were compared. Multivariate Cox-regression analysis was used to analyze the prognostic impact of insulin. RESULTS: We studied 92 patients: 46 insulin-treated and 46 HbA1c-matched under OAD. Mean age: 74±9 years, 46.7% male and 63.5% had HF with reduced ejection fraction. HbA1c was 7.8±1.5% in both groups. In the subgroup under OAD: 87.0% metformin, 41.3% sulphonylurea, 28.3% dipeptidyl peptidase-4 inhibitors and 4.3% other agents. Insulin-treated patients had lower hemoglobin, higher creatinine and discharged B-type natriuretic peptide (BNP) levels (816.6 [289.2-1805.8] vs. 613.3 [205.6-1110.8]; P=0.02). Seventy three patients died. There were no differences in mortality up to 5 years. After multivariate adjustment accounting for hemoglobin, creatinine and discharge BNP, HR for 1-, 2-, 3-, and 5-year all-cause death in insulin-treated patients were 1.48 (0.62-3.54); P=0.38, 1.11 (0.55-2.25); P=0.77, 1.08 (0.56-2.08); P=0.28 and 1.24 (0.70-2.19); P=0.46, respectively. CONCLUSIONS: Insulin-treated diabetic patients with HF and HbA1c-matched patients treated with OAD have similarly ominous prognosis. Our results favor insulin as a marker of poor health condition.

Effect of different bariatric surgery type on the leukocyte formula.

BACKGROUND: Obesity is associated with higher leukocyte counts, whereas weight loss decreases these counts. It is unknown if different bariatric surgery (BS) types have different effects on leukocytes. OBJECTIVES: The aim of the study was to determine predictors of leukocyte and their subset count variation in patients submitted to BS. SETTING: Tertiary care university hospital, Porto, Portugal. METHODS: This was a retrospective analysis of patients submitted to Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), or sleeve gastrectomy (SG). Leukocyte and subset counts were compared between baseline and 1-year postsurgery and between BS types. A multivariate linear regression model was built to study determinants of leukocyte and subset variation. RESULTS: We analyzed 764 patients: 238 submitted to LAGB; 452 to RYGB, and 74 to SG. Mean age was 42 years and 86.6% were women. All BS types were associated with a decrease in leukocyte and neutrophil counts but the variation in body mass index and homeostatic model assessment (HOMA-IR) were the only variables independently associated with a decrease 1-year postsurgery. Monocytes increased in patients submitted to LAGB and decreased in those who underwent RYGB and SG. The BS type was independently associated with monocyte variation. Patients who underwent RYGB and SG had a decrease in monocyte counts of 77/µL and 62/µL, respectively, compared with LAGB. CONCLUSION: Weight and insulin resistance are the main predictors of leukocyte and neutrophil variation after BS. The specific type of BS is a determinant of monocyte count variation independent of the amount of weight loss or the degree of insulin resistance improvement.

The Effect of Bariatric Surgery Type on Lipid Profile: An Age, Sex, Body Mass Index and Excess Weight Loss Matched Study.

BACKGROUND: Bariatric surgery improves lipid profile. A still unanswered question is whether this improvement is merely weight-dependent or also results from factors inherent to specificities of the bariatric procedure. We aimed to study lipid profile 1 year after bariatric surgery and compare its changes between the different procedures in patients matched for initial weight and weight loss. METHODS: We retrospectively analysed patients submitted to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB) or sleeve gastrectomy (SG) between 2010 and 2013. Patients were matched for age (±5 years), sex, pre-surgery body mass index (BMI) (±2 Kg/m(2)) and excess weight loss (EWL) (±5%). Baseline and 1-year lipid profile, its variation and percentage of variation was compared between surgeries. RESULTS: We analysed 229 patients: 72 pairs RYGB-AGB, 47 pairs RYGB-SG and 33 pairs AGB-SG. The median age was 41 (35-52) years and 11.8% were male. Pre-operative BMI was 44.0 ± 4.6 and 32.1 ± 4.4 Kg/m(2) at 1 year. EWL at 1 year was 64.2 ± 18.9%. There were no differences in baseline lipid profile between patients submitted to different types of bariatric surgery. At 1 year, high-density lipoprotein cholesterol (HDL) and triglycerides (TG) improved similarly with all surgeries. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) at 1 year decreased significantly more in patients submitted to RYGB than in weight-matched patients undergoing AGB or SG. CONCLUSIONS: RYGB is the only bariatric surgery that reduces TC and LDL in age-, sex-, BMI- and EWL-matched patients. All three procedures improved TG and HDL similarly when the confounding effect of weight loss is eliminated.

Is there a heart rate paradox in acute heart failure?

BACKGROUND: Higher heart rate predicts higher mortality in chronic heart failure (HF). We studied the prognostic impact of admission heart rate in acute HF and analysed the importance of its change during hospitalization. METHODS: Acute HF patients were studied. Endpoint was all-cause death. Patients were followed-up for 12 months from hospital admission. Cox-regression analysis was used to study the association of heart rate (both as a continuous and as a categorical variable) with mortality. Analysis was stratified according to admission rhythm and to systolic dysfunction. Multivariate models were built. Patients surviving hospitalization were additionally cross-classified attending to admission and discharge heart rates ­ cut-offs: 100 and 80 beats per minute (bpm), respectively. RESULTS: We analysed 564 patients. Median age was 78 years and median admission heart rate 87 bpm. In a 12-month period 205 patients died, 23 in-hospital. Mortality increased steadily with heart rate decrease. Patients with heart rate ≥ 100 bpm had a multivariate-adjusted HR of 12-month death of 0.57 (95%CI: 0.39-0.81), and the HR was 0.92 (0.85-0.98) per 10 bpm increase in heart rate. Association of heart rate with mortality was stronger in patients in sinus rhythm (SR) and in those with systolic dysfunction. Eighty-seven patients had admission heart rate ≥ 100 and discharge heart rate < 80 bpm. In them, death rate was 14.9%; in the remaining patients it was 37.7%. CONCLUSIONS: Higher admission heart rate predicted survival advantage in acute HF. Patients presenting with tachycardia and discharged with a controlled heart rate had better outcome than those admitted non-tachycardic or discharged with a non-controlled heart rate.