Implications of vitamin D levels or status for mortality in rheumatoid arthritis: analysis of 2001-2018 data from the National Health and Nutrition Examination Survey.

Background: Inadequate levels of vitamin D (VitD) have been linked to increased rates of various health conditions and mortality. However, little is known about the relationship between mortality outcomes and 25-hydroxyvitamin D [25(OH)D] levels in individuals with rheumatoid arthritis (RA). This study aimed to examine this association using data from the National Health and Nutrition Examination Survey. Methods: A cohort of 2,290 individuals aged 20 to 85 years with RA was analyzed. Lower 25(OH)D levels were inversely associated with all-cause mortality, with a hazard ratio (HR) of 0.91 (0.87 to 0.96) per 10 nmol/L increase. Comparatively, the HR for the VitD insufficiency group was 0.64 (0.50 to 0.83), and for the VitD sufficiency group, it was 0.60 (0.44 to 0.80), both compared to the VitD deficiency group. Cause-specific analysis showed that higher 25(OH)D levels were associated with reduced mortality from heart disease (HR: 0.88, 0.82 to 0.95) and malignant neoplasms (HR: 0.86, 0.79 to 0.94). No significant correlation was found between 25(OH)D levels and cause-specific mortalities for other conditions. Results: Stratified by gender, the HR for males was 0.92 (0.85 to 0.99) and for females was 0.91 (0.86 to 0.98) per 10 nmol/L increase in 25(OH)D levels. Among individuals aged 20-59 years, no significant correlation was observed, while for those aged 60 years and older, the HR was 0.86 (0.82 to 0.90) per 10 nmol/L increase. Nonlinear analysis identified a sharp increase in HR below 59.95 nmol/L, while HR remained below 1 for 25(OH)D levels above 59.95 nmol/L. Conclusion: This study reveals a strong negative correlation between 25(OH)D levels and overall mortality in individuals with RA. Notably, this association is particularly significant for mortality related to heart disease and malignant neoplasms. Targeted VitD supplementation should be emphasized, especially in individuals aged 60 years and older with RA. The proposed minimum threshold for adequate 25(OH)D levels in the RA population is 60 nmol/L.

Saturation association between serum 25-hydroxyvitamin D levels and mortality in elderly people with hyperlipidemia: a population-based study from the NHANES (2001-2016).

Background: 25-hydroxyvitamin D is the body's main storage form of vitamin D and is internationally recognized as the best indicator of vitamin D status in the human body. There is a scarcity of research investigating the interrelationship between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality among elderly individuals with hyperlipidemia. To address this knowledge gap, we examined the association between serum 25(OH)D levels and mortality in an older hyperlipidemic population from NHANES, while controlling for other influential factors. The study sought to elucidate the correlation between serum 25(OH)D levels and mortality about all-cause mortality, cardiovascular disease (CVD), malignant neoplasms, and mortality from other causes. Methods: The data from NHANES 2001-2016, including 9,271 participants were analyzed to examine the association between serum 25(OH)D levels and mortality. The interrelationship was illustrated using Kaplan-Meier curves and restricted cubic splines, while the Cox proportional hazards model was utilized to estimate the multifactor adjusted hazard ratio (HR). Results: This study included 9,271 participants (43.28% male) with an average age of 69.58 years, and the average duration of participant follow-up was 88.37 months. Kaplan-Meier curves demonstrated that lower serum 25(OH)D levels were associated with increased risks of all-cause mortality, cardiovascular mortality, malignant neoplasm mortality, and mortality from other causes. This negative association was further confirmed by the Cox proportional hazards models. Additionally, restricted cubic splines not only revealed this negative association but also highlighted the saturated serum 25(OH)D levels. Moreover, subgroup analyses indicated that the inverse correlation between serum 25(OH)D levels and all-cause mortality was more pronounced in the non-obese and smoking population. And the inverse correlation with mortality from other causes was even stronger in the non-obese population. Conclusions: In the elderly population with hyperlipidemia, 25(OH)D serum levels were negatively correlated with both cause-specific mortality and all-cause mortality. Moreover, there was a threshold effect in this negative association.

Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia.

BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

On-admission serum 25(OH)D level and mortality within one year in older patients.

BACKGROUND: Mounting evidence suggests that vitamin D deficiency is associated with a higher risk of many chronic non-skeletal, age-associated diseases as well as mortality. AIM: To determine, in older patients aged ≥ 80, the prevalence of vitamin D deficiency and its association with comorbidity, laboratory tests, length of stay and mortality within one year from blood withdrawal on admission to acute geriatrics ward. METHODS: We retrospectively surveyed electronic hospital health records of 830 older patients. The recorded data included patient demographics (e.g., age, sex, stay duration, readmissions number, death within one year from blood withdrawal on admission), medical diagnoses, laboratory results, including 25-hydroxyvitamin D [25(OH)D], and medications. We compared the characteristics of the patients who survived to those who died within one year. RESULTS: On admission, in 53.6% patients, vitamin D levels were lower than 50 nmol/L, and in 32%, the levels were ≤ 35 nmol/L. Persons who died were likely to be older, of male sex, were likely to be admitted for pneumonia or CHF, were likely to have lower level of albumin or hemoglobin, lower level of vitamin D or higher vitamin B12 and higher level of creatinine, were also likely to have had a lengthier hospitalization stay, a greater number of hospitalizations in the last year, a higher number of comorbidities, to have consumption of ≥5 drugs or likely to being treated with insulin, diuretics, antipsychotics, anticoagulants or benzodiazepines. Higher age, male sex, on-admission CHF, higher number of drugs, lower albumin, higher vitamin B12, vitamin D < 50 nmol/L, and consumption of antipsychotics and anticoagulants - were predictors of mortality. CONCLUSION: Hypovitaminosis D is predictive of mortality in older patients within one year from hospitalization in the acute geriatric ward, but a causal relationship cannot be deduced. Nevertheless, older patients in acute care settings, because of their health vulnerability, should be considered for vitamin D testing. In the acutely ill patients, early intervention with vitamin D might improve outcomes. Accurate evaluation of mortality predictors in this age group patients may be more challenging and require variables that were not included in our study.

Serum 25-hydroxyvitamin D levels and risk of all-cause and cause-specific mortality: A 14-year prospective cohort study.

BACKGROUND & AIMS: The circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality. METHODS: This prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005-2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity. RESULTS: The median (interquartile range) of 25(OH)D level was 55.8 (40.8-71.8) nmol/L. During a median follow-up of 14.3 years, 2250 deaths were recorded. Compared with participants with a 25(OH)D level <30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥75 nmol/L) were associated with a lower risk of all-cause mortality: HR (95% CI) of 0.82 (0.69-0.98), 0.74 (0.62-0.88), and 0.69 (0.57-0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI: 0.39-0.77) for a 25(OH)D level ≥75 nmol/L compared with <30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men. CONCLUSIONS: Vitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50-60 nmol/L may contribute to longevity and warrants further investigation.

Association of serum 25-hydroxyvitamin D with cardiovascular and all-cause mortality in patients with chronic kidney disease: NHANES 2007‒2018 results.

BACKGROUND: Vitamin D insufficiency is a prevalent issue in patients suffering from CKD. The purpose of this study was to determine whether serum 25(OH)D levels are associated with all-cause and cardiovascular mortality in patients with CKD. METHODS: To examine the associations between 25(OH)D levels and cardiovascular mortality, this retrospective cohort study used the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007‒2018 database. A total of 2,668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. The associations were assessed using Cox proportional hazards regression, restricted cubic splines, Kaplan-Meier survival curves, and competing risks survival analysis. Furthermore, subgroup and sensitivity analyses were performed. RESULTS: During a median follow-up of 72 months in a weighted population of 11,715,452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause mortality (HR= 0.85, 95 % CI 0.77∼0.94) and cardiovascular mortality (SHR= 0.80, 95 % CI 0.67∼0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile). Compared to group Q1, both group Q3 (HR = 0.71, 95 % CI 0.54‒0.93) and group Q4 (HR = 0.72, 95 % CI 0.55‒0.94) exhibited a significantly reduced mortality risk. Weighted restricted cubic splines revealed an inverse J-shaped linear association between levels of 25(OH) D and all-cause mortality ((PNonliner > 0.05). Subgroup analysis and sensitivity analysis yielded similar findings. CONCLUSIONS: All-cause mortality and cardiovascular disease-related mortality were significantly increased by lower 25(OH)D levels, both as continuous and categorical variables. 25(OH)D has an inverse J-shaped linear association with all-cause and cardiovascular mortality.

Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

The Association between Vitamin D Deficiency and the Risk of Mortality after Hip Fractures: A Systematic Review and Meta-Analysis.

Prevalence of hip fractures is on the rise and is associated with high mortality, especially in aging patients. Vitamin D is routinely recommended for bone health in general population. Our study explores the potential association between low levels (≤20 ng/mL) of vitamin D and mortality in hip fracture patients. Systematic search was done for studies that were published from inception until May 10, 2023, and that report a possible correlation between low vitamin D levels and mortality in patients with hip fractures. A random-effects model was used to assess the effects of normal vitamin D levels on mortality, subgroup analyses were conducted to assess the link between low levels of vitamin D and geographic location of the study and its impact on the recovery process. In 575 identified studies, 18 met the inclusion criteria. A strong connection between low serum levels of vitamin D (<20 ng/mL) and mortality (hazard ratio (HR): 2.29, p<0.001). Further analysis indicated that insufficient (20 to 30 ng/mL) and sufficient (>30 ng/mL) levels of vitamin D levels did not have a significant association with the mortality (HR: 1.10, p=0.12), and (HR: 1.04, p=0.50). As shown by subgroup analysis vitamin D deficiency significantly correlated with mortality in studies conducted in Europe (HR: 2.4). Our results clearly demonstrate that vitamin D deficiency is associated with higher risk of mortality in hip fracture patients. Additional analyses demonstrate that insufficient and sufficient levels of vitamin D were not significantly associated with mortality outcomes in hip fracture patients.

Impact of vitamin D deficiency on mortality in patients with hip fracture: A meta-analysis.

BACKGROUND: Vitamin D deficiency has been linked to numerous health issues, including an increased risk of hip fractures. This meta-analysis aimed to investigate the relationship between vitamin D deficiency and mortality in patients with hip fracture. To assess the impact of different levels of vitamin D deficiency on mortality in patients with hip fractures and examine the influence of potential confounding factors. METHODS: A systematic search of PubMed, EMBASE, Scopus, and Cochrane Collaboration Library was conducted, resulting in nine eligible cohort studies (n = 4409). Patients with hip fractures were categorized based on their vitamin D levels as severe, moderate, or insufficient. Mortality was the primary outcome measure in this study. Subgroup analyses were performed according to the follow-up time. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model in Review Manager 5.4. RESULTS: Nine studies, with a pool of 4409 patients, were included. Vitamin D insufficiency was significantly associated with increased mortality (OR 1.24, 95% CI 1.05-1.46; I2 = 4%). Severe deficiency also led to a significant increase in mortality (OR 2.08, 95% CI 1.09-3.97; I2 = 42%), whereas moderate deficiency did not show a significant effect (OR 1.06, 95% CI 0.79-1.44; I2 = 0%). Subgroup analysis revealed significant associations between vitamin D insufficiency and increased mortality at 1-year (OR 1.37, 95% CI 1.06-1.77) and 2-year follow-ups (OR 1.78, 95% CI 1.01-3.15). After adjusting for potential confounders, no significant increase in the mortality rate was observed. CONCLUSIONS: This meta-analysis suggests that vitamin D insufficiency and severe deficiency are associated with increased mortality in patients with hip fracture. However, after adjusting for confounding factors, this association was not statistically significant. Further research is necessary to understand the role of vitamin D deficiency in this population.

Violation of the Constant Genetic Effect Assumption Can Result in Biased Estimates for Non-Linear Mendelian Randomization.

INTRODUCTION: Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. METHODS: We use the recently developed doubly ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D (25[OH]D) used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. RESULTS: The effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method but not for the doubly ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures and less reasonable for others. If the doubly ranked method indicates that this assumption is violated, then estimates from both the residual and doubly ranked methods can be biased, although bias was smaller on average in the doubly ranked method. CONCLUSION: Analysts wanting to perform non-linear Mendelian randomization should compare results from both the residual and doubly ranked methods, as well as consider transforming the exposure for the residual method to reduce heterogeneity in the genetic effect on the exposure.

Serum vitamin D levels and mortality in Mexicans: results from the Mexican Health and Aging Study.

Introduction: Background: the population in Latin America is aging and elders face several obstacles for good health, including an elevated frequency of vitamin D deficiency. Thus, identification of patients at high risk to develop its negative consequences should be a priority. Objective: the objective of this analysis was to determine if levels of vitamin D lower than 15 ng/ml are associated with high mortality in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). Methods: prospective, population study in Mexico, that included Subjects of 50 years and older who were evaluated for Serum vitamin D levels during the year 2012 (third wave of the study). Serum 25(OH)D levels were categorized into four groups, based on cutoff points used in previous studies on vitamin D and frailty: < 15, 15-< 20, 20-< 30 and ≥ 30 ng/ml. Mortality was evaluated during 2015 (fourth wave of the study). Hazard ratio was calculated (for mortality) through Cox Regression Model, adjusted for covariates. Results: we included 1626 participants, and those with lower levels of vitamin D were older, more often women, required more aid for activities of daily living, reported higher number of chronic diseases, and lower scores on cognition. The relative risk of death was 5.421 (95 % CI 2.465-11.92, p < 0.001) for the participants with vitamin D levels < 15, which after adjusting for covariates, remained statistically significant. Conclusions: levels of vitamin D lower of 15, are associated with an increase in the rate of mortality in community-dwelling senior Mexicans.

Introducción: Introducción: la población en América Latina está envejeciendo y los adultos mayores enfrentan varios obstáculos para gozar de buena salud, incluida una frecuencia elevada de deficiencia de vitamina D. Por lo tanto, la identificación de pacientes con alto riesgo de desarrollar sus consecuencias negativas debe ser una prioridad. Objetivo: el objetivo de este análisis fue determinar si los niveles de vitamina D inferiores a 15 ng/ml están asociados con una alta mortalidad en la población adulta mayor mexicana, a partir de la base de datos del Estudio de Salud y Envejecimiento en México. Métodos: estudio poblacional prospectivo en México, que incluyó Sujetos de 50 años y mayores que fueron evaluados para los niveles de vitamina D en suero durante el año 2012 (tercera ola del estudio). Los niveles séricos de 25(OH)D se clasificaron en cuatro grupos, según los puntos de corte utilizados en estudios previos sobre vitamina D y fragilidad: < 15, 15-< 20, 20-< 30 y ≥ 30 ng/ml. La mortalidad se evaluó durante 2015 (cuarta ola del estudio). Se calculó la razón de riesgo (para la mortalidad) a través del modelo de regresión de Cox, ajustado por covariables. Resultados: incluimos 1626 participantes, y aquellos con niveles más bajos de vitamina D eran mayores, más a menudo mujeres, requerían más ayuda para las actividades de la vida diaria, informaron un mayor número de enfermedades crónicas y puntuaciones más bajas en cognición. El riesgo relativo de muerte fue de 5,421 (IC 95 % 2,465-11,92, p < 0,001) para los participantes con niveles de vitamina D < 15, que después de ajustar por covariables, se mantuvo estadísticamente significativo. Conclusiones: niveles de vitamina D inferiores a 15, se asocian con un aumento en la tasa de mortalidad en adultos mayores mexicanos residentes en la comunidad.

Serum 25-hydroxyvitamin D concentrations are inversely associated with all-cause mortality among Koreans: a nationwide cohort study.

Evidence on the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and all-cause and cause-specific mortality in Asians, especially Koreans, is limited. We hypothesized that high concentrations of 25(OH)D are associated with lower all-cause and cause-specific mortality in the general Korean population. This study included 27,846 adults participating in the Fourth and Fifth Korean National Health and Nutrition Examination Survey 2008-2012, followed up through December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using multivariable-adjusted Cox proportional hazards regression. The weighted mean serum 25(OH)D of study participants was 17.77 ng/mL; 66.5% had vitamin D deficiency (<20 ng/mL) and 94.2% had insufficient vitamin D (<30 ng/mL). During a median follow-up of 9.4 years (interquartile range, 8.1-10.6 years), 1680 deaths were documented, including 362 CVD deaths and 570 cancer deaths. Serum 25(OH)D levels ≥30 ng/mL were inversely associated with all-cause mortality (HR, 0.57; 95% CI, 0.43-0.75) compared with serum 25(OH)D levels <10 ng/mL. Based on the quartile cutoffs of serum 25(OH)D concentration, the highest quartile of serum 25(OH)D concentration (≥21.8 ng/mL) was associated with the lowest all-cause mortality (HR, 0.72; 95% CI, 0.60-0.85; P trend < .001), and CVD mortality (HR, 0.60; 95% CI, 0.42-0.85; P trend = .006). No association with cancer mortality outcome was found. In conclusion, higher serum 25(OH)D levels were associated with lower all-cause mortality in the general Korean population. An additional association was found between higher quartile of serum 25(OH)D and lower CVD mortality.

Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19.

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21-93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.

Serum 25-hydroxyvitamin D, frailty, and mortality among the Chinese oldest old: Results from the CLHLS study.

BACKGROUND AND AIMS: In this study, the aim is to explore whether frailty status modified the associations of serum 25(OH)D levels with all-cause and cause-specific mortality in the oldest old Chinese population. METHODS AND RESULTS: A total of 1411 participants aged at least 80 years were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Information on serum 25(OH)D level, frailty status, and covariates were examined at baseline. All-cause and cause-specific mortality status were ascertained during the follow-up survey conducted in 2017-2018 by using the ICD-10 codes. Cox proportional hazard models with stratified analyses were performed to evaluate potential associations. Over a median follow-up of 3.2 years, 722 (51.2%) participants were deceased, including 202 deaths due to circulatory diseases, and 520 deaths due to noncirculatory causes. After multivariable adjustment, the lowest quartile of serum 25(OH)D levels (Hazard Ratios (95% Confidence Intervals), 1.85 (1.45-2.36), 1.85 (1.45-2.36), 1.73 (1.31-2.29), respectively) and frailty (Odd Ratios (95% Confidence Intervals), 1.91 (1.60-2.29), 2.67 (1.90-3.74), 1.64 (1.31-2.05)) were associated with significantly higher risk of all-cause mortality, circulatory mortality, and noncirculatory mortality, respectively. In addition, we observed significant interactions among 25(OH)D and frailty on the risk of all-cause and cause-specific mortality (all P-interaction < 0.001). Similar results were found in sensitivity analyses by excluding participants who died in the first year of follow-up and using clinical cutoffs of serum 25(OH)D levels. CONCLUSION: Low serum 25(OH)D levels were associated with higher risk of all-cause and cause-specific mortality among the oldest old of the Chinese population, and the associations were significantly stronger in individuals with frailty.

Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.

BACKGROUND: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS: A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS: The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS: Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

Serum 25-hydroxyvitamin D values and risk of incident cardiovascular disease: A population-based retrospective cohort study.

BACKGROUND: Concentrations of serum 25-hydroxyvitamin D [25(OH)D] below 20 ng/mL and above 50 ng/mL have been associated with chronic adverse events including cardiovascular disease. OBJECTIVE: To conduct a comprehensive population-based study in the United States of the relationship of low and high serum 25(OH)D levels with cardiovascular disease. METHODS: We identified all serum 25(OH)D measurements in adults age 18 years and older residing in Olmsted County, MN between January 1, 2005 and December 31, 2011, using the resources of the Rochester Epidemiology Project. Any new diagnosis of cardiovascular disease was the primary outcome, and time zero was 30 days after first 25(OH)D measurement. Patients were followed until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Categories of 25(OH)D values were examined using predetermined ranges of interest: <12, 12-19, 20-50 (reference range), and >50 ng/mL. Multivariable Cox proportional hazards models were adjusted for age, BMI, sex, race, smoking history, season of 25(OH)D measurement, hypertension, hyperlipidemia, socioeconomic status and Charlson comorbidity index at time of 25(OH)D measurement. RESULTS: A total of 11,002 unique persons had a 25(OH)D measurement, with a mean (±SD) value of 30.0 ± 12.9 ng/mL. Mean age was 54.3 ± 17.2 years, and the majority were female (77.1 %) and white (87.6 %). There were 4124 new diagnoses of cardiovascular disease in this cohort after a median overall follow-up of 4.8 years (IQR 3.4-6.2). Adjusted cardiovascular disease hazard ratios (HRs) (95 % confidence interval) for 25(OH)D values <12, 12-19, and >50 ng/mL, compared to the reference range 20-50 ng/mL, were 1.28 (1.12-1.46), 1.19 (1.09-1.31), and 1.10 (0.95-1.26), respectively. CONCLUSION: Values of 25(OH)D <20 ng/mL were associated with development of a new diagnosis of cardiovascular disease. There was no significant association between 25(OH)D values >50 ng/mL and cardiovascular disease.

Association Between Serum 25-hydroxyvitamin D Concentrations and Mortality Among Adults With Prediabetes.

OBJECTIVES: To investigate the association of circulating 25-hydroxyvitamin D [25(OH)D] levels with mortality among adults with prediabetes. METHODS: This retrospective cohort study included 15,195 adults with prediabetes (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2014. Mortality from all causes, cardiovascular disease (CVD), and cancer was linked to National Death Index mortality data. RESULTS: The median (interquartile range) concentration of serum 25(OH)D was 60.5 (45.3, 77.4) nmol/L, and only 23.1% had sufficient vitamin D (≥75 nmol/L). Elevated serum 25(OH)D concentrations were significantly associated with lower levels of insulin, homeostasis model assessment of insulin resistance, triglyceride, and C-reactive protein, and higher levels of high-density lipoprotein at baseline (all Ptrend < 0.05). During a median follow up of 10.7 years, 3765 deaths (including 1080 CVD deaths and 863 cancer deaths) were identified. Compared with participants with 25(OH)D <30 nmol/L, the multivariate-adjusted hazard ratios and 95% confidence intervals for participants with 25(OH)D ≥ 75 nmol/L were 0.66 (0.53, 0.82) for all-cause mortality (Ptrend < 0.001), 0.66 (0.48, 0.89) for CVD mortality (Ptrend = 0.001), and 0.82 (0.49, 1.35) for cancer mortality (Ptrend = 0.32). For per-unit increment in ln-transformed 25(OH)D, there was a 27% lower risk of all-cause mortality and a 34% lower risk of CVD mortality (both P < 0.01). CONCLUSIONS: These findings suggested that higher serum 25(OH)D concentrations were associated with lower all-cause and CVD mortality among individuals with prediabetes.

COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents.

Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D's plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality.