RESUMO
PURPOSE: Fibroblast growth factor-23 (FGF23) is critical for phosphate homeostasis. Considering the high prevalence of vitamin D deficiency and the association of FGF23 with adverse outcomes, we investigated effects of vitamin D3 supplementation on FGF23 concentrations. METHODS: This is a post-hoc analysis of the Styrian Vitamin D Hypertension trial, a single-center, double-blind, randomized, placebo-controlled trial, conducted from 2011 to 2014 at the Medical University of Graz, Austria. Two hundred subjects with 25(OH)D concentrations < 30 ng/mL and arterial hypertension were randomized to receive either 2800 IU of vitamin D3 daily or placebo over 8 weeks. Primary outcome was the between-group difference in FGF23 levels at study end while adjusting for baseline values. RESULTS: Overall, 181 participants (mean ± standard deviation age, 60.1 ± 11.3; 48% women) with available c-term FGF23 concentrations were considered for the present analysis. Mean treatment duration was 54 ± 10 days in the vitamin D3 group and 54 ± 9 days in the placebo group. At baseline, FGF23 was significantly correlated with serum phosphate (r = 0.135; p = 0.002). Vitamin D3 supplementation had no significant effect on FGF23 in the entire cohort (mean treatment effect 0.374 pmol/L; 95% confidence interval - 0.024 to 0.772 pmol/L; p = 0.065), but increased FGF23 concentrations in subgroups with baseline 25(OH)D concentrations below 20 ng/mL (n = 70; mean treatment effect 0.973 pmol/L; 95% confidence interval - 0.032 to 1.979 pmol/L; p = 0.019) and 16 ng/mL (n = 40; mean treatment effect 0.593 pmol/L; 95% confidence interval 0.076 to 1.109; p = 0.022). CONCLUSIONS: Vitamin D3 supplementation had no significant effect on FGF23 in the entire study cohort. We did, however, observe an increase of FGF23 concentrations in subgroups with low baseline 25(OH)D.
Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/sangue , Suplementos Nutricionais , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/efeitos dos fármacos , Áustria , Estudos de Coortes , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.
Assuntos
Transtornos Cerebrovasculares/sangue , Metabolismo Energético , Insuficiência Cardíaca/sangue , Homoarginina/sangue , Nefropatias/sangue , Amidinotransferases/metabolismo , Animais , Biomarcadores/sangue , Transtornos Cerebrovasculares/mortalidade , Glicina/análogos & derivados , Glicina/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Nefropatias/mortalidade , Óxido Nítrico/sangueRESUMO
BACKGROUND: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA). METHODS: Plasma MBG concentrations (mean: 0.51±0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women). RESULTS: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68±0.12 versus 0.35±0.24 nmol/l; p<0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at >0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at >3.32 ng/dl/µU/ml. CONCLUSIONS: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA.
Assuntos
Bufanolídeos/farmacocinética , Hiperaldosteronismo/tratamento farmacológico , Hipertensão/tratamento farmacológico , Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Bufanolídeos/uso terapêutico , Espessura Intima-Media Carotídea , Hipertensão Essencial , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/fisiopatologia , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Renina/sangue , Estudos Retrospectivos , Resultado do Tratamento , Vasoconstritores/farmacocinética , Vasoconstritores/uso terapêuticoRESUMO
BACKGROUND: Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and homoarginine are considered to modulate nitric oxide synthesis. We evaluated whether ADMA, SDMA, and homoarginine are associated with diastolic dysfunction. METHODS AND RESULTS: We investigated primary care patients at cardiovascular risk with preserved left ventricular ejection fraction from the multicenter DIAST-CHF study. We measured serum concentrations of ADMA, SDMA, and homoarginine and performed standardized echocardiographic examinations. Among 1,396 patients (mean age 65.3 ± 8.3 y, 54.6% women), diastolic dysfunction was ruled out in 261 patients (18.7%). Mild and moderate/severe grades of diastolic dysfunction were present in 900 (64.5%) and 235 (16.8%) study participants, respectively. After adjustments for cardiovascular risk factors, ADMA and SDMA were positively and homoarginine negatively associated with N-terminal pro-B-type natriuretic peptide and midregional pro-adrenomedullin (P < .05 for all). Lower homoarginine levels were associated with diastolic dysfunction, and higher ADMA and SDMA levels were associated with the severity of diastolic dysfunction (P < .05 for all). CONCLUSIONS: Higher levels of ADMA and SDMA and lower levels of homoarginine are associated with an adverse cardiovascular risk profile and diastolic dysfunction. Further studies should clarify the potential of these amino acid derivatives for the therapy of cardiovascular diseases.
Assuntos
Arginina/análogos & derivados , Insuficiência Cardíaca Diastólica/sangue , Homoarginina/sangue , Volume Sistólico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Valores de Referência , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
The high worldwide prevalence of vitamin D deficiency is largely the result of low sunlight exposure with subsequently limited cutaneous vitamin D production. Classic manifestations of vitamin D deficiency are linked to disturbances in bone and mineral metabolism, but the identification of the vitamin D receptor in almost every human cell suggests a broader role of vitamin D for overall and cardiovascular health. The various cardiovascular protective actions of vitamin D such as anti-diabetic and anti-hypertensive effects including renin suppression as well as protection against atherosclerosis and heart diseases are well defined in previous experimental studies. In line with this, large epidemiological studies have highlighted vitamin D deficiency as a marker of cardiovascular risk. However, randomized controlled trials (RCTs) on vitamin D have largely failed to show its beneficial effects on cardiovascular diseases and its conventional risk factors. While most prior vitamin D RCTs were not designed to assess cardiovascular outcomes, some large RCTs have been initiated to evaluate the efficacy of vitamin D supplementation on cardiovascular events in the general population. When considering the history of previous disappointing vitamin RCTs in general populations, more emphasis should be placed on RCTs among severely vitamin D-deficient populations who would most likely benefit from vitamin D treatment. At present, vitamin D deficiency can only be considered a cardiovascular risk marker, as vitamin D supplementation with doses recommended for osteoporosis treatment is neither proven to be beneficial nor harmful in cardiovascular diseases.
Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/fisiologia , Animais , Aterosclerose/epidemiologia , Aterosclerose/genética , Aterosclerose/metabolismo , Cálcio/metabolismo , Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/genética , Transtornos Cerebrovasculares/metabolismo , Suplementos Nutricionais , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Humanos , Prevalência , Fatores de Risco , Luz Solar , Vitamina D/genética , Vitamina D/metabolismo , Vitamina D/toxicidade , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genética , Vitaminas/metabolismo , Vitaminas/toxicidadeRESUMO
BACKGROUND: Inappropriate utilization of laboratory resources is an increasing concern especially in high-throughput facilities. Until now, no reliable information has been published addressing to which extent laboratory results are actually used for clinical decision-making. Therefore, we aimed to close this gap using a novel retrospective approach including a survey of clinicians and nurses. METHODS: We retrospectively evaluated the number of re-orders for potassium (K), lactate dehydrogenase (LD), aspartate-aminotransferase (AST), activated partial thromboplastin-time (APTT) and prothrombin-time/INR (PT/INR), after the initial order had to be cancelled due to preanalytical non-conformities. We analyzed subgroups regarding time to re-order, ward and sample priority (urgent vs. routine). Subsequently, we surveyed clinicians and nurses, asking for their estimate of the amount of failed re-orders as well as for possible reasons. RESULTS: From initially cancelled tests, only ~20% of K, LD, AST and ~30% of APTT and PT/INR tests were re-ordered within 24â¯h. 70% of the investigated clinical chemistry and 60% of coagulation tests were re-ordered one week after cancellation or not at all. Survey participants quite accurately estimated these numbers. Routine laboratory panels, short stay of out-patients, obsolete test results and avoiding additional phlebotomies were the main reasons for not re-ordering cancelled tests. CONCLUSIONS: Overall, 60-70% of test results in the investigated assays ordered in a high throughput laboratory are potentially inappropriate or of doubtful clinically importance. Although clinicians and nurses are aware of this situation, it is the duty of laboratory specialists to overcome overutilization in close collaboration with all involved healthcare workers.
Assuntos
Análise Química do Sangue , Hospitais , Uso Excessivo dos Serviços de Saúde , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Vitamin D deficiency is associated with an unfavorable lipid profile, but whether and how vitamin D supplementation affects lipid metabolism is unclear. OBJECTIVE: To examine the effects of vitamin D supplementation on lipid and lipoprotein parameters. METHODS: This is a post hoc analysis of the single-center, double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011-2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D concentrations of <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for 8 weeks. RESULTS: One hundred sixty-three participants (62.2 [53.1-68.4] years of age; 46% women) had available lipid data and were included in this analysis. Vitamin D supplementation significantly increased total cholesterol, triglycerides, very-low-density lipoprotein (VLDL) triglycerides, low-density lipoprotein (LDL) triglycerides, high-density lipoprotein (HDL) triglycerides, apolipoprotein B (ApoB), LDL-ApoB, ApoCII, ApoCIII, phospholipids, and ApoE (P < .05 for all). Except for ApoCII and ApoCIII and HDL-triglycerides, all other treatment effects remained statistically significant after adjustment for multiple testing with the Benjamini and Hochberg false discovery rate method. There was a nonsignificant increase in LDL cholesterol. Furthermore, no significant effects were seen on free fatty acids, lipoprotein (a), ApoAI, ApoAII, VLDL cholesterol, VLDL-ApoB, HDL cholesterol, LDL diameter, and VLDL diameter. CONCLUSIONS: The effects of vitamin D on lipid metabolism are potentially unfavorable. They require further investigation in view of the wide use of vitamin D testing and treatment.
Assuntos
Suplementos Nutricionais , Lipoproteínas/metabolismo , Vitamina D/farmacologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive. Objective: The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs. Design: Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied. Results: Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified. Conclusions: For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.
Assuntos
Calcifediol/farmacologia , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Adulto , Calcifediol/administração & dosagem , Cálcio/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Hemoglobinas Glicadas , Humanos , Hormônio Paratireóideo/sangueRESUMO
Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from ≥25 to ≥50 nmol/L (≥10-≥20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 µg (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations <30 nmol/L (12 ng/mL) and <50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.
RESUMO
BACKGROUND: A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation. METHODS AND FINDINGS: We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses. CONCLUSIONS: Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels.
Assuntos
Suplementos Nutricionais/efeitos adversos , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Neoplasias/dietoterapia , Neoplasias/epidemiologia , Neoplasias/patologia , Terapia Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Vitamina D/efeitos adversos , Redução de Peso/efeitos dos fármacosRESUMO
Increasing evidence suggests a possible interaction between vitamin D and insulin-like growth factor-1 (IGF-1). We aimed to investigate effects of vitamin D supplementation on IGF-1 (primary outcome) and calcitriol (1,25(OH)2D) concentrations (secondary outcome). This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial-a single-center, double-blind, randomized, placebo-controlled trial (RCT) conducted from 2011 to 2014 at the Medical University of Graz, Austria. Two-hundred subjects with arterial hypertension and 25(OH)D concentrations <30 ng/mL were randomized to either receive 2800 IU of vitamin D daily or placebo for eight weeks. A total of 175 participants (mean ± standard deviation age, 60 ± 11 years; 49% women) with available IGF-1 concentrations were included in the present analysis. At baseline, IGF-1 concentrations were significantly correlated with 1,25(OH)2D (r = 0.21; p = 0.005) but not with 25(OH)D (r = -0.008; p = 0.91). In the RCT, vitamin D had no significant effect on IGF-1 (mean treatment effect 3.1; 95% confidence interval -5.6 to 11.9 ng/mL; p = 0.48), but it increased 1,25(OH)2D concentrations (mean treatment effect 9.2; 95% confidence interval 4.4 to 13.9 pg/mL; p ≤ 0.001). In this RCT, in hypertensive patients with low 25(OH)D concentrations, there was no significant effect of vitamin D supplementation on IGF-1 concentrations. However, we observed a cross-sectional correlation between 1,25(OH)2D and IGF-1 and an increase of 1,25(OH)2D after vitamin D supplementation.
Assuntos
Calcitriol/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Vitamina D/administração & dosagem , Vitamina D/farmacologia , Idoso , Calcitriol/metabolismo , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Bone turnover markers (BTMs) are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP), osteocalcin (OC), C-terminal telopeptide (CTX), and procollagen type 1 N-terminal propeptide (P1NP). This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT) performed at the Medical University of Graz, Austria (2011-2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D) levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women) were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE) 0.013, 95% CI -0.029 to 0.056 µg/L; p = 0.533), CTX (MTE 0.024, 95% CI -0.163 to 0.210 ng/mL, p = 0.802), OC (MTE 0.020, 95% CI -0.062 to 0.103 ng/mL, p = 0.626), or P1NP (MTE -0.021, 95% CI -0.099 to 0.057 ng/mL, p = 0.597). Analyzing patients with 25(OH)D levels <50 nmol/L separately (n = 74) left results largely unchanged. In hypertensive patients with low 25(OH)D levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Vitamina D/administração & dosagem , Vitamina D/farmacologia , Idoso , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina/genética , Osteocalcina/metabolismo , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/genética , Pró-Colágeno/metabolismo , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
BACKGROUND: Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. METHODS: In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. FINDINGS: We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00-1.29), 1.33 (1.16-1.51), and 1.67 (1.44-1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. INTERPRETATION: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.
Assuntos
Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Idoso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Padrões de Referência , Taxa de Sobrevida , Vitamina D/administração & dosagem , Vitamina D/normas , Deficiência de Vitamina D/prevenção & controleRESUMO
Aside from its well-known effects on bone and mineral metabolism, vitamin D may also play an important role in extra-skeletal processes like immunologic diseases, cancer, or cardiovascular diseases. Even though meta-analyses showed that vitamin D supplementation reduces fractures, falls, and overall mortality, its potential benefits did not find universal acclaim. Several health care authorities published Recommended Dietary Allowances (RDAs) for vitamin D, most of them ranging from 600 to 800 international units (IU) per day, corresponding to a serum level of 25-hydroxyvitamin D of at least 20 ng/mL (50 nmol/L). However, studies conducted in the general population revealed a much lower overall intake of vitamin D than the proposed RDAs. Thus, strategies to increase the vitamin D intake in the general population, e.g., food fortification or vitamin D supplementation, are needed to match the existing evidence and recommendations. Therefore, several currently ongoing projects aim to investigate the effect of vitamin D supplementation in the general population and try to establish food-based solutions to improve vitamin D status.
Assuntos
Raios Ultravioleta , Vitamina D/análogos & derivados , Acidentes por Quedas , Osso e Ossos , Suplementos Nutricionais , Alimentos Fortificados , Humanos , Vitamina D/metabolismo , Vitamina D/efeitos da radiação , Deficiência de Vitamina D/sangueRESUMO
Epidemiological evidence suggests that circulating 25-hydroxyvitamin D (25OHD) levels are inversely associated with hemoglobin (Hb) levels and anemia risk. We evaluated whether vitamin D supplementation improves Hb levels and reduces anemia risk in hypertensive patients. Two hundred patients with 25OHD levels <75 nmol/L who attended the Styrian Vitamin D Hypertension Trial were included, of whom 188 completed the trial. Patients randomly received 2800 IU vitamin D3 daily or a matching placebo for eight weeks. Initially, the prevalence of anemic status (Hb levels <12.5 g/dL) and deficient 25OHD levels (<30 nmol/L) was 6.5% and 7.5%, respectively. All anemic patients had 25OHD levels >50 nmol/L. The mean (95% confidence interval) vitamin D effect on Hb levels was 0.04 (-0.14 to 0.22) g/dL (P = 0.661). Moreover, vitamin D treatment did not influence anemic status significantly (P > 0.999). Likewise, vitamin D had no significant effect on Hb levels in the subgroups of anemic patients or in patients with initial 25OHD levels <30 nmol/L. In conclusion, a daily vitamin D supplement of 2800 IU for eight weeks did not improve Hb levels or anemic status in hypertensive patients. Future trials should focus on anemic patients with deficient 25OHD levels (e.g., <30 nmol/L). This trial is registered with clinicaltrials.gov [NCT02136771].
RESUMO
In this narrative review, we aim to summarize and discuss the current evidence linking vitamin D and mortality. Low 25-hydroxyvitamin D [25(OH)D] concentrations are associated with an increased risk of mortality. This has been shown in different cohort studies including general populations, as well as various patient cohorts. Some single-study results and meta-analyses indicate that the shape of the relationship between 25(OH)D and mortality follows a U- or a reverse J-shaped curve. Interassay and laboratory differences are, however, a limitation of most previous surveys, and standardization of 25(OH)D measurements is needed for future investigations. Apart from observational data, it has been documented in meta-analyses of randomized controlled trials that vitamin D3 supplementation is associated with a moderate, yet statistically significant, reduction in mortality. This latter finding must be interpreted in light of some limitations such as incomplete follow-up data, but such a reduction of mortality with vitamin D3 supplementation as the finding of meta-analyses of randomized controlled trials strongly argues for the benefits and, importantly, also the safety of vitamin D.
Assuntos
Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Estudos de Coortes , Suplementos Nutricionais , Humanos , Metanálise como Assunto , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/uso terapêuticoRESUMO
BACKGROUND: The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH). METHODS: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks. RESULTS: Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome. CONCLUSIONS: In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients.
Assuntos
Cirrose Hepática/sangue , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Cirrose Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Vitamina D/sangueRESUMO
Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2â±â10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128â±â12.8/77.1â±â9.2âmmHg and with a median of 2 (IQR: 1-3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3â±â42.0âmilliseconds for males and 434.7â±â38.3âmilliseconds for females. Mean 24H-HR and 24H-HRV was 71.9â±â9.8 and 10.0â±â3.6âbpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (meanâ=â426â±â42.4âmilliseconds; ß-coefficientâ=â0.121; Pâ=â0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (medianâ=â9.67 [IQRâ=â7.38-12.22âbpm]; ß-coefficientâ=â-0.133; Pâ=â0.01).In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.
Assuntos
Aldosterona/sangue , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Hipertensão/fisiopatologia , Renina/sangue , Adulto , Idoso , Áustria , Doenças do Sistema Nervoso Autônomo , Monitorização Ambulatorial da Pressão Arterial , Eletrocardiografia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RadioimunoensaioRESUMO
Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone. The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration (PAC) in patients with hypertension and 25-hydroxyvitamin D[25(OH)D] insufficiency. The Styrian Vitamin D Hypertension Trial was a single-center, double-blind, placebo-controlled randomized clinical trial conducted from 2011 to 2014. Two hundred patients with arterial hypertension and 25(OH)D levels <30 ng/mL were enrolled. Study participants were randomized to receive either 2800 IU of vitamin D3 or placebo. The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences. A total of 188 participants (mean±standard deviation age, 60.1±11.3 years; 47% women; 25(OH)D, 21.2±5.6 ng/mL) completed the trial. Mean differences between baseline and follow-up PAC in the control and intervention arm were +3.3 ng/dL and +0.9 ng/dL, respectively (P=.04). The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency.
Assuntos
Aldosterona/sangue , Hipertensão/complicações , Renina/sangue , Deficiência de Vitamina D/dietoterapia , Vitamina D/administração & dosagem , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vitamina D/farmacologia , Deficiência de Vitamina D/metabolismoRESUMO
High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24-hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross-sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39-61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH-modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted ß-coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies.