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Prime mover or fellow traveller: 25-hydroxy vitamin D's seasonal variation, cardiovascular disease and death in the Scottish Heart Health Extended Cohort (SHHEC).

ABSTRACT: Theoretical links between seasonal lack of sunlight, hypovitaminosis D and excess cardiovascular disease and death prompted our adding novel to conventional cohort analyses.We tested three postulates on 13,224 Scottish Heart Health Extended Cohort participants, assayed for 25-hydroxyvitamin D (25OHD) and followed for 22 years. (i) Endpoints enumerated by month of occurrence mirror annual seasonal oscillation in 25OHD. (ii) Endpoint seasonality is increased in people with below median 25OHD. (iii) Low 25OHD predicts endpoints independently of major risk factors.Baseline median 25OHD level was 36.4 (other quartiles 26.7, 51.7) nmol/l. The March trough was half the August peak, both well after seasonal solstices. (i) There was no demonstrable monthly variation in First Cardiovascular Event (n = 3307). Peaks and troughs for All Death and Cardiovascular Death (n = 2987, 1350) were near the solstices, earlier than extremes of 25OHD. (ii) Endpoint variability showed no difference between those above and below median 25OHD. (iii) Cox model hazard ratios (HR), by decreasing 25OHD, increased modestly and nonspecifically for all endpoints examined, with no threshold, the gradients diminishing by ? : 60% following multiple adjustment. For Cardiovascular Disease, HR, by 20 (? SD) nmol/l decrease, =1.224 (1.175, 1.275) adjusted for age and sex; additionally adjusted for family history, deprivation index, smoking, systolic blood pressure, total and HDL cholesterol, =1.093 (1.048, 1.139); All Deaths = 1.238 (1.048, 1.139) and 1.098 (1.050, 1.149). 25OHD made no independent contribution to cardiovascular discrimination and reclassification.Our analyses challenge vitamin D's alleged role as major prime mover in cardiovascular disease and mortality.

SUBMITTER: Tunstall-Pedoe H

PROVIDER: S-EPMC4681106 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Prime mover or fellow traveller: 25-hydroxy vitamin D's seasonal variation, cardiovascular disease and death in the Scottish Heart Health Extended Cohort (SHHEC).

Tunstall-Pedoe Hugh H Woodward Mark M Hughes Maria M Anderson Annie A Kennedy Gwen G Belch Jill J Kuulasmaa Kari K

International journal of epidemiology 20150621 5

<h4>Background</h4>Theoretical links between seasonal lack of sunlight, hypovitaminosis D and excess cardiovascular disease and death prompted our adding novel to conventional cohort analyses.<h4>Methods</h4>We tested three postulates on 13,224 Scottish Heart Health Extended Cohort participants, assayed for 25-hydroxyvitamin D (25OHD) and followed for 22 years. (i) Endpoints enumerated by month of occurrence mirror annual seasonal oscillation in 25OHD. (ii) Endpoint seasonality is increased in p ...[more]

PMID: 26095374

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Project description:Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1?-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts. 50-1000 nM 25(OH) and 0.05-10 nM 1,25(OH)2 metabolites were used. At high concentrations, 25(OH)D2/D3 and 1,25(OH)2D2/D3 suppressed cell number in both human and mouse cells. The suppression was greater with cholecalciferol (D3) metabolites than with those of ergocalciferol (D2). In both cell types, 25(OH)D2 and 25(OH)D3 increased the expression of osteopontin, osteocalcin, collagen-1, receptor activator of nuclear factor kappa-B ligand, vitamin D receptor, CYP24A1 and CYP27B1 genes. Whereas there was little or no difference between the effects of 25(OH)D2 and 25(OH)D3 in hBMSCs, differences were observed in the magnitude of the effects of these metabolites on the expression of most studied genes in 2T3 cells. Alkaline phosphatase (ALP) activity was increased by 25(OH)D2/D3 and 1,25(OH)2D2/D3 in hBMSC and 2T3 cells, and the increase was greater with the D3 metabolites at high concentrations. In hBMSCs, mineralisation was also increased by 25(OH)D2/D3 and 1,25(OH)2D2/D3 at high concentrations, with D3 metabolites exerting a greater influence. In 2T3 cells, the effects of these compounds on mineralisation were stimulatory at low concentrations and inhibitory when high concentrations were used. The suppression at high concentrations was greater with the D3 metabolites. These findings suggest that there are differences in the effects of 25-hydroxy and 1?,25(OH)2 metabolites of D3 and D2 on human preosteoblasts and mouse osteoblasts, with the D3 metabolites being more potent in suppressing cell number, increasing ALP activity and influencing mineralisation.

Dataset Information

Prime mover or fellow traveller: 25-hydroxy vitamin D's seasonal variation, cardiovascular disease and death in the Scottish Heart Health Extended Cohort (SHHEC).

Publications

Prime mover or fellow traveller: 25-hydroxy vitamin D's seasonal variation, cardiovascular disease and death in the Scottish Heart Health Extended Cohort (SHHEC).

Similar Datasets

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