Early menarche and other endocrine disrupting effects of per- and polyfluoroalkyl substances (PFAS) in adolescents from Northern Norway. The Fit Futures study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large group of chemicals that are ubiquitous in the environment and include recognized persistent organic pollutants. The aim of this cross-sectional study was to investigate possible endocrine disrupting effects of different PFAS in adolescents. METHODS: Serum concentrations of PFAS, thyroid, parathyroid and steroid hormones were measured in 921 adolescents aged 15-19 years in the Fit Futures study, Northern Norway. The questionnaire included data on self-reported age at menarche and puberty development score (PDS). Multiple linear and logistic regression analyses and principle component analyses (PCA) were used to assess associations of PFAS with hormones concentrations and puberty indices. RESULTS: In girls, total PFAS (∑PFAS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) were positively associated with dehydroepiandrosterone sulfate (DHEAS) and negatively associated with 11-deoxycorticosterone (11-DOC)/DHEAS ratio. In boys, the associations with 11-DOC/DHEAS ratio were positive for ∑PFAS, perfluoroheptanoate (PFHpA), perfluoroheptane sulfonate (PFHpS), PFOA, and PFOS. Perfluoroundecanoate (PFUnDA) was negatively associated with free thyroxine (fT4) and free triiodothyronine (fT3) in boys. PFNA and PFDA were also negatively associated with fT3 in boys. Serum parathyroid hormone concentration (PTH) was negatively associated with ∑PFAS and perfluorohexane sulfonate (PFHxS) in girls, and with PFOS in boys. PFDA and PFUnDA were positively associated with early menarche, while ∑PFAS and PFOA were positively associated with PDS in boys. No associations of PFAS with serum testosterone, follicle-stimulating hormone, or luteinizing hormone were found in either sex. In girls, PFOA was positively associated with free testosterone index (FTI). In boys, PFOA was positively associated with androstendione and 17-OH-progesterone, while PFHpA was positively associated with estradiol. CONCLUSIONS: Serum concentrations of several PFAS were associated with parathyroid and steroid hormones in both sexes, and with thyroid hormones in boys, as well as with early menarche in girls and higher PDS in boys.

Impaired gross motor development in infants with higher PFAS concentrations.

Industrial produced perfluoroalkyl substances (PFAS) are environmentally persistent and found in humans around the globe. PFAS is transferred from mother to child during pregnancy and lactation and PFAS concentrations are high in infants. PFAS exposure in early life has been linked to a range of negative health effects. In the present study we have investigated PFAS concentrations in mothers (pregnancy week 18, 28 and 36 and six weeks, four and six months postpartum, n = 114) and in infants at six months age (n = 94), and studied the effects of PFAS status on infant gross motor development by Alberta Infant Motor Scale (AIMS) at age six months. PFAS concentrations declined in the mothers during pregnancy and postpartum period, and the highest concentrations were seen in infants aged six months. Parity was a strong negative predictor and fish intake a strong positive predictor of maternal PFAS status, while maternal concentrations of PFAS in pregnancy week 18 and months of exclusive breastfeeding determined the PFAS concentrations in infants at six months. Infants who scored below the median on gross motor development had higher PFAS concentrations than infants with a better gross motor development. Ninety percent of the women reported having fish for dinner at least once a week, with fatty fish as the most popular choice (72%). A higher maternal fish intake in pregnancy week 18 was associated with a poorer gross motor development in the infants at six months. Infant gross motor development is a marker of later cognitive outcome and our findings indicate that higher PFAS concentrations in young infants and maternal fatty fish intake may impair neurodevelopment.

Longitudinal changes in concentrations of persistent organic pollutants (1986-2016) and their associations with type 2 diabetes mellitus.

BACKGROUND: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality. OBJECTIVES: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases. METHODS: We conducted a longitudinal, nested case-control study (1986-2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points. RESULTS: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p'-DDE, and p,p'-DDT declined more slowly in cases than controls, whereas ß-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide. DISCUSSION: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.

Comparing prevalence of chronic kidney disease and its risk factors between population-based surveys in Russia and Norway.

BACKGROUND: Little data exists on the prevalence of chronic kidney disease (CKD) in the Russian population. We aimed to estimate the prevalence of CKD in a population-based study in Russia, compare with a similar study in Norway, and investigate whether differences in risk factors explained between-study differences in CKD. METHODS: We compared age- and sex-standardised prevalence of reduced eGFR (< 60 ml/min/1.73m2 CKD-EPI creatinine equation), albuminuria and or a composite indicator of CKD (one measure of either reduced eGFR or albuminuria) between participants aged 40-69 in the population-based Know Your Heart (KYH) study, Russia (2015-2018 N = 4607) and the seventh Tromsø Study (Tromsø7), Norway (2015-2016 N = 17,646). We assessed the contribution of established CKD risk factors (low education, diabetes, hypertension, antihypertensive use, smoking, obesity) to between-study differences using logistic regression. RESULTS: Prevalence of reduced eGFR or albuminuria was 6.5% (95% Confidence Interval (CI) 5.4, 7.7) in KYH and 4.6% (95% CI 4.0, 5.2) in Tromsø7 standardised for sex and age. Odds of both clinical outcomes were higher in KYH than Tromsø7 (reduced eGFR OR 2.06 95% CI 1.67, 2.54; albuminuria OR 1.54 95% CI 1.16, 2.03) adjusted for sex and age. Risk factor adjustment explained the observed between-study difference in albuminuria (OR 0.92 95% CI 0.68, 1.25) but only partially reduced eGFR (OR 1.42 95% CI 1.11, 1.82). The strongest explanatory factors for the between-study difference was higher use of antihypertensives (Russian sample) for reduced eGFR and mean diastolic blood pressure for albuminuria. CONCLUSIONS: We found evidence of a higher burden of CKD within the sample from the population in Arkhangelsk and Novosibirsk compared to Tromsø, partly explained by between-study population differences in established risk factors. In particular hypertension defined by medication use was an important factor associated with the higher CKD prevalence in the Russian sample.

Exposure to perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in adolescents. The Fit Futures study.

BACKGROUND: Prevalence of obesity, hypertension and dyslipidemia has been increasing in children and adolescents worldwide. Exposure to environmental pollutants may contribute to this development. Our aim was to study associations between perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in a population-based sample of adolescents. METHODS: Serum PFAS concentrations were measured in 940 adolescents, mean age 16.4 (SD 1.3) years, from the cross-sectional Fit Futures study by the UHPLC-MS/MS method. The following endpoints were used: hypertension (systolic blood pressure over 130 mmHg and/or diastolic blood pressure over 80 mmHg); obesity (body mass index over 2 z-score, WHO charts for adolescents); dyslipidemia (total cholesterol ≥ 5.17 mmol/L, and/or LDL-cholesterol ≥ 3.36 mmol/l, and/or apolipoprotein B ≥ 1.10 g/L). RESULTS: Perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnDA) serum concentrations were positively associated with apolipoprotein B, total- and LDL cholesterol. The highest vs. lowest quartiles of total PFAS (∑PFAS), PFNA and PFDA concentrations were positively associated with the risk of dyslipidemia: OR 2.24 (95% CI 1.10-4.54), OR 2.30 (95% CI 1.16-4.57) and 2.36 (95% CI 1.08-5.16), respectively. The highest vs. lowest quartiles of ∑PFAS, perfluorohexane sulfonate (PFHxS), PFOS, perfluorooctanoate (PFOA) concentrations were positively associated with the risk of hypertension: OR 1.91 (95% CI 1.12-3.26), OR 2.06 (95% CI 1.16-3.65), 1.86 (95% CI 1.08-3.19) and 2.08 (95% CI 1.17-3.69) respectively. PFHxS and perfluoroheptane sulfonate (PFHpS) concentrations were positively associated with obesity. CONCLUSIONS: This cross-sectional study showed a possible link between several PFAS and dyslipidemia, hypertension and obesity in Norwegian adolescents.

Chronic iron deficiency and anaemia were highly prevalent in a population-based longitudinal study among adolescent girls.

AIM: The combination of iron deficiency and anaemia is a major health problem, and adolescents are an at-risk group. The main aim of this study was to explore the magnitude of these conditions among adolescents aged 15-19 and identify possible associated risk factors. METHODS: This population-based longitudinal study of adolescents in North Norway was conducted in 2010-2011, with a follow-up two years later. Repeated measurements of iron deficiency and anaemia and its possible risk factors were studied in 309 girls and 273 boys. RESULTS: Iron deficiency and anaemia were found in 18.1% and 19.9% of girls and 1.6% and 2.9% of boys in the first study and about half of the cases were chronic two years later. Most girls had moderate iron deficiency (14.5%) and mild anaemia (16.0%). Daily milk consumption was associated with increased iron deficiency in girls (odds ratio 2.3, 95% confidence interval 1.1-4.9), and the most physically active girls had the lowest levels of iron deficiency (odds ratio 0.4, 95% confidence intervaI 0.2-0.9). Iron deficiency was the most important risk factor for chronic anaemia in girls. CONCLUSION: The results of this study highlight the importance of iron deficiency screening and treatment for adolescent girls.

Environmental pollutants in blood donors: The multicentre Norwegian donor study.

OBJECTIVES: The aim of this study was to measure blood concentrations of environmental pollutants in Norwegian donors and evaluate the risk of pollutant exposure through blood transfusions. BACKGROUND: Transfused blood may be a potential source of exposure to heavy metals and organic pollutants and presents a risk to vulnerable patient groups such as premature infants. METHODS/MATERIALS: Donors were randomly recruited from three Norwegian blood banks: in Bergen, Tromsø and Kirkenes. Selected heavy metals were measured in whole blood using inductively coupled plasma mass spectrometry (ICP-MS), and perfluoroalkyl substances (PFAS) were measured in serum by ultrahigh-pressure liquid chromatography coupled with a triple-quadrupole mass spectrometer (UHPLC-MS/MS). RESULTS: Almost 18% of blood donors had lead concentrations over the limit suggested for transfusions in premature infants (0.09 µmol/L). About 11% of all donors had mercury concentrations over the suggested limit of 23.7 nmol/L. Cadmium was higher than the limit, 16 nmol/L, in 4% of donors. Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) concentrations were over the suggested limit of 0.91 ng/mL in 68% and 100% of the donors, respectively. PFAS concentrations and heavy metal concentrations increased with donor's age. CONCLUSION: A considerable percentage of donors had lead, PFOS and PFOA concentrations over the suggested limits. In addition, at each study site, there were donors with high mercury and cadmium concentrations. Selecting young donors for transfusions or measurements of pollutants in donor blood may be a feasible approach to avoid exposure through blood transfusions to vulnerable groups of patients such as premature infants.

Serum perfluoroalkyl substances (PFAS) and risk of asthma and various allergies in adolescents. The Tromsø study Fit Futures in Northern Norway.

BACKGROUND: Exposure to environmental pollutants may contribute to the development of asthma and other allergies. The aim of this study was to investigate possible associations between asthma and other allergies with exposure to perfluoroalkyl substances (PFASs) in adolescents from the Arctic region of Norway. METHODS: The Tromsø study Fit Futures 1 (TFF1) and 3-year follow-up Fit Futures 2 study (TFF2) included 675 adolescents that completed a questionnaire about health conditions and underwent a clinical examination with blood tests and fractional nitric oxide (FeNO) measurement. Serum concentrations of 18 PFASs were measured by UHPLC-MS/MS method. RESULTS: Total PFASs (ΣPFAS) serum concentration over 4th quartile was positively associated with asthma in the TFF1 (OR 3.35 (95% CI 1.54-7.29), p = 0.002). Total perfluorooctane sulfonate (ΣPFOS), linear PFOS (linPFOS), linear perfluorohexane sulfonate (linPFHxS) concentrations over 4th quartiles were associated with 2 times higher odds of asthma in the TFF1. The positive associations between ΣPFAS, ΣPFOS, linPFOS and asthma remained statistically significant in the TFF2. ΣPFAS and linPFHxS concentrations over 3rd tertiles were associated with positive marker of eosinophilic airways inflammation FeNO> 25 ppb. Concentrations of ΣPFOS and linPFOS over 3rd quartiles were positively associated with self-reported nickel allergy (OR 2.25 (95% CI 1.17-4.35) p = 0.016 and OR 2.53 (95% CI 1.30-4.90) p = 0.006, respectively). Allergic rhinitis, self-reported pollen allergy, food allergy and atopic eczema were not associated with PFASs concentrations. CONCLUSIONS: This study of Norwegian adolescents showed a positive association between several PFASs and asthma, as well as between PFOS and nickel allergy.

The individual systematic difference between CoaguChek and STA-SPA.

Using CoaguChek to measure PT-INR and comparing the results with those from the hospital laboratory, some patients get consistent results while others do not. The extent of this problem is unknown. Our study aimed to quantify the between-subject variation of the systematic PT-INR difference between CoaguChek and a hospital laboratory method. We used register data with PT-INR results from both CoaguChek and a hospital laboratory method (STA-SPA+) in samples taken simultaneously from 108 patients. After excluding five patients with outlying results, we used mixed-effects models to estimate individual slopes and intercepts to describe the systematic relationship between the two methods for each patient, and calculated the fraction of patients having a systematic difference greater than 0.3 INR units. The included 103 patients had from 3 to 16, median seven data pairs measured over a time span from 15 to 2319, median 234 days. The mean of individual slopes was 1.113, with a standard deviation of 0.137. Corresponding values for the intercept were -0.151 and 0.208, respectively. Adjusted for the average systematic difference, the proportion of patients with a systematic difference greater than 0.3 INR units increased from 15% at a PT-INR level of 2.5 to 50% at a PT-INR level of 4. The systematic difference between CoaguChek and STA-SPA + varies considerably between patients. This precludes using a single, common formula to make the CoaguChek results directly comparable to the results from the hospital laboratory.

Should we eat more fish - or less? / Bør vi spise mer fisk ­ eller mindre?

All food contains environmental toxins. The EU has set a new threshold for the level of environmental toxins that can be considered safe in the body. In Norway, the average intake exceeds this threshold, and fatty fish is the main source. Nevertheless, the Norwegian authorities recommend that all age groups eat more fish.

Characterization of a human platelet antigen-1a-specific monoclonal antibody derived from a B cell from a woman alloimmunized in pregnancy.

Human platelet Ag (HPA)-1a, located on integrin ß3, is the main target for alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia (FNAIT) in the white population. There are ongoing efforts to develop an Ab prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific for HPA-1a, named 26.4, was derived from an immortalized B cell from an alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a-specific human mAb with naturally paired H and L chains. Specific binding of mAb 26.4, both native and recombinant forms, to platelets and to purified integrins αIIbß3 (from platelets) and αVß3 (from trophoblasts) from HPA-1a(+) donors was demonstrated by flow cytometry and surface plasmon resonance technology, respectively. No binding to HPA-1a(-) platelets or integrins was detected. Moreover, the Ab binds with higher affinity to integrin αVß3 compared with a second HPA-1a-specific human mAb, B2G1. Further in vitro experimentation demonstrated that mAb 26.4 can opsonize HPA-1a(+) platelets for enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti-HPA-1a Abs, and weakly inhibit aggregation of HPA-1a-heterozygous platelets, the latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific for HPA-1a and could potentially be explored for use as a prophylactic or therapeutic reagent for FNAIT intervention and as a phenotyping reagent to identify women at risk for immunization.

High level of heavy metals in crab meat. / Høyt nivå av tungmetaller i krabbe.

Crab meat is a popular seafood, but it sometimes contains large amounts of environmental toxins. The content is so high in many places in Norway that consumption of brown crab meat should generally be discouraged.

Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study.

AIM: We aimed to investigate changes in pre-diagnostic concentrations of classic and 11-oxygenated androgens in type 2 diabetes (T2DM) cases and healthy controls, associations between androgen concentrations and T2DM, and the potential for androgens to improve the prediction of T2DM when considered in combination with established risk factors. METHODS: Androgen concentrations were analysed in serum samples from 116 T2DM cases and 138 controls at 3, pre-diagnostic time-points: 1986/87 (T1), 1994/95 (T2), and 2001 (T3). Generalised estimating equations were used to longitudinally examine androgen concentrations, and logistic regression models were used to estimate the odds ratios (OR) of T2DM at each time-point. Logistic regression models were also used to calculate area under the receiver operating characteristics curve (AROC) from models including established risk factors alone (ERF model) and established risk factors plus each androgen, respectively, which were compared to identify improvements in predictive ability. RESULTS: For women, no significant associations were observed between any of the investigated androgens and T2DM after adjusting for confounders. For men, after adjusting for confounders, concentrations of all investigated 11-oxygenated androgens were higher in cases than controls at one or several time-points. We observed associations between T2DM and concentrations of 11-ketoandrostenedione (OR: 1.59) and 11-ketotestosterone (OR: 1.62) at T1; and 11-hydroxyandrostenedione (OR: 2.00), 11-hydroxytestosterone (OR: 1.76), 11-ketoandrostenedione (OR: 1.84), 11-ketotestosterone (OR: 1.78) and testosterone (OR: 0.45) at T3 in men. The addition of these androgens (including 11-hydroxytestosterone at T2) to the ERF model resulted in an improved ability to predict T2DM in men (AROC: 0.79-0.82). We did not observe significant differences in changes in androgen concentrations over time between cases and controls in either sex. CONCLUSION: Our results demonstrate that testosterone and 11-oxygenated androgens are associated with T2DM in men before diagnosis and may be potential biomarkers in T2DM risk assessment.

Polybrominated diphenyl ethers in type 2 diabetes mellitus cases and controls: Repeated measurements prior to and after diagnosis.

BACKGROUND: Previous studies have reported associations between certain persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM). Polybrominated diphenyl ethers (PBDEs) are a class of POPs that are found in increasing concentrations in humans. Although obesity is a known risk factor for T2DM and PBDEs are fat-soluble, very few studies have investigated associations between PBDEs and T2DM. No longitudinal studies have assessed associations between repeated measurements of PBDE and T2DM in the same individuals and compared time trends of PBDEs in T2DM cases and controls. OBJECTIVES: To investigate associations between pre- and post-diagnostic measurements of PBDEs and T2DM and to compare time trends of PBDEs in T2DM cases and controls. METHODS: Questionnaire data and serum samples from participants in the Tromsø Study were used to conduct a longitudinal nested case-control study among 116 T2DM cases and 139 controls. All included study participants had three pre-diagnostic blood samples (collected before T2DM diagnosis in cases), and up to two post-diagnostic samples after T2DM diagnosis. We used logistic regression models to investigate pre- and post-diagnostic associations between PBDEs and T2DM, and linear mixed-effect models to assess time trends of PBDEs in T2DM cases and controls. RESULTS: We observed no substantial pre- or post-diagnostic associations between any of the PBDEs and T2DM, except for BDE-154 at one of the post-diagnostic time-points (OR = 1.65, 95% CI: 1.00, 2.71). The overall time trends of PBDE concentrations were similar for cases and controls. DISCUSSION: The study did not support PBDEs increasing the odds of T2DM, prior to or after T2DM diagnosis. T2DM status did not influence the time trends of PBDE concentrations.

Longitudinal changes in vitamin D concentrations and the association with type 2 diabetes mellitus: the Tromsø Study.

AIM: We aimed to investigate the relationship between pre- and post-diagnostic 25-hydroxyvitamin D (25(OH)D) concentrations and type 2 diabetes (T2DM) over a period of 30 years in individuals who developed T2DM compared to healthy controls. METHODS: This case-control study included 254 participants with blood samples collected at five different time-points (T1-T5) between 1986 and 2016. Of the 254 participants, 116 were diagnosed with T2DM between T3 and T4, and were considered cases; the remaining 138 were controls. Linear mixed regression models were used to examine pre- and post-diagnostic changes in 25(OH)D concentrations, and logistic regression was used to examine associations between these concentrations and T2DM at each time-point. RESULTS: 25(OH)D concentrations at different time-points and the longitudinal change in concentrations differed between cases and controls, and by sex. For women, each 5-nmol/l increase in 25(OH)D concentrations was inversely associated with T2DM at T3 (odds-ratio, OR, 0.79), whereas for men, this same increase was positively associated with T2DM at T1 (OR 1.12). Cases experienced a significant decrease in pre-diagnostic 25(OH)D concentrations (p value < 0.01 for women, p value = 0.02 for men) and a significant increase in post-diagnostic 25(OH)D concentrations (p value < 0.01 for women, p value = 0.01 for men). As such, each 1-unit increase in month-specific z-score change between T1 and T3 was significantly inversely associated with T2DM (OR 0.51 for women, OR 0.52 for men), and each such increase between T3 and T5 was significantly positively associated with T2DM in women (OR 2.48). CONCLUSIONS: 25(OH)D concentrations seem to be affected by disease progression and type 2 diabetes diagnosis.

NT-ProBNP and high-sensitivity troponin T as screening tests for subclinical chronic heart failure in a general population.

AIMS: The aim of this study was to establish age-specific and sex-specific cut-off values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-troponin T) in healthy subjects and assess cardiac biomarkers as screening tools for subclinical heart failure (HF) in a general population. METHODS AND RESULTS: Altogether, 1936 participants were randomly selected from the general population Tromsø 7 study in Northern Norway. Diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) of cardiac markers for echocardiographically defined subclinical HF was evaluated. The receiver-operating characteristic analysis showed that areas under the curve were relatively low (under 0.75) for both NT-proBNP and hs-troponin T, suggesting that the diagnostic accuracy of these biomarkers for subclinical HF was not excellent, especially for mild forms of HF and younger age group 40-49 years. Sex-specific and age-specific cut-offs for hs-troponin T (99th percentiles) and NT-proBNP (97.5th percentiles) were established in healthy subjects from the same general population. The sex-specific and age-specific cut-offs for NT-proBNP had higher specificity for subclinical HF compared with the previously established single cut-off 125 pg/mL. Age-specific cut-off for hs-troponin T (18 ng/L) for men ≥60 years had also higher specificity than the single cut-off 14 ng/L. These cut-offs had high specificity, but low sensitivity, that makes hs-troponin T and NT-proBNP good biomarkers to rule in HF in case of a positive test, but not good enough to rule out all unrecognized HF due to false negative results. CONCLUSIONS: N-terminal pro-brain natriuretic peptide and hs-troponin T are suboptimal screening tools for subclinical HF in a general population due to low sensitivity.