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Associations between vitamin K status and haemostatic and inflammatory biomarkers in community-dwelling adults. The Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: Vitamin K is integral to haemostatic function, and in vitro and animal experiments suggest that vitamin K can suppress production of inflammatory cytokines. To test the hypothesis that higher vitamin K status is associated with lower haemostatic activation and inflammation in community-dwelling adults, we analysed the cross-sectional association between serum phylloquinone (vitamin K1) with haemostatic and inflammatory biomarkers in 662 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) [mean (SD) age=62 (10) years; 46% female; 37% Caucasian, 25% African-American, 25% Hispanic, 13% Chinese-American]. Following adjustment for demographic and lifestyle characteristics, medication use, triglycerides and body mass index, those in the highest quartile of serum phylloquinone had significantly lower circulating interleukin-6 [adjusted mean (SEM) pmol/l: quartile 4 (Q4)=1.22 (0.07), quartile 1 (Q1)=1.45 (0.07); p-trend<0.01], C-reactive protein [adjusted mean (SEM) mg/dl: Q4=1.57 (0.11), Q1=2.08 (0.18); p-trend=0.02], soluble intercellular adhesion molecule-1 [adjusted mean (SEM) ng/ml: Q4=247 (11), Q1=288 (11); p-trend=0.02], and plasmin-antiplasmin complex [adjusted mean (SEM) nmol/l: Q4=4.02 (0.1), Q1=4.31 (0.1), p-trend=0.04]. We detected an interaction between age and serum phylloquinone with respect to factor VIII and D-dimer (interaction p-values=0.03 and 0.09, respectively). Among participants ?70 years, serum phylloquinone was inversely associated with factor VIII activity (p-trend=0.06) and positively associated with D-dimer (p-trend=0.01), but was not associated with either marker among participants <70 years (both p?0.38). In contrast, dietary phylloquinone intake was not associated with any inflammatory or haemostatic biomarker evaluated (all p-trend>0.11). These findings are consistent with laboratory-based studies that suggest a possible anti-inflammatory role for vitamin K. Whether or not these associations predict clinical outcomes linked to elevated inflammation or haemostatic activation remains to be determined.

SUBMITTER: Shea MK

PROVIDER: S-EPMC4152396 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Associations between vitamin K status and haemostatic and inflammatory biomarkers in community-dwelling adults. The Multi-Ethnic Study of Atherosclerosis.

Shea M K MK Cushman M M Booth S L SL Burke G L GL Chen H H Kritchevsky S B SB

Thrombosis and haemostasis 20140522 3

Vitamin K is integral to haemostatic function, and in vitro and animal experiments suggest that vitamin K can suppress production of inflammatory cytokines. To test the hypothesis that higher vitamin K status is associated with lower haemostatic activation and inflammation in community-dwelling adults, we analysed the cross-sectional association between serum phylloquinone (vitamin K1) with haemostatic and inflammatory biomarkers in 662 participants in the Multi-Ethnic Study of Atherosclerosis ( ...[more]

PMID: 24849546

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Project description:BACKGROUND:Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited. OBJECTIVE:We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design. DESIGN:Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial. RESULTS:The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01]. CONCLUSIONS:Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Project description:Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH2)D3), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000-2002. Volumetric trabecular lumbar BMD was measured from computed tomography scans performed in 2002-2005 expressed as g/cm(3). We used linear regression and graphical methods to compare associations of vitamin D metabolite and PTH concentrations with BMD as the outcomes measure among White (n=714), Black (n=353), Chinese (n=249), and Hispanic (n=457) participants. Serum 25(OH)D and 24,25(OH2)D3 concentrations were highest among Whites and lowest among Blacks. BMD was greatest among Black participants. Higher serum 25(OH)D was only associated with higher BMD among Whites and Chinese participants (P-for-interaction=0.054). Comparing the lowest category of 25(OH)D (<20 ng/ml) to the highest (?30 ng/ml), the adjusted mean difference in BMD was -8.1g/cm3 (95% CI -14.8, -1.4) for Whites; -10.2g/cm3 (-20.4, 0.0) for Chinese vs. 8.8 g/cm3 (-2.8, 20.5) for Black and -1.1g/cm3 (-8.3, 6.2) for Hispanic. Similar results were observed for serum 24,25(OH2)D3. Serum PTH was not associated with BMD. In a multi-ethnic population, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Further studies are needed to determine optimal biomarkers for bone health for multiple ethnic groups.

Project description:OBJECTIVES:Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status. SETTING:We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age. PARTICIPANTS:The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed). OUTCOME MEASURES:Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD. RESULTS:We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10?mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction <0.01). We found a similar pattern among black adults. Poor precision among the estimates for Hispanic or Chinese participants limited the findings in these groups. The attenuated associations were consistent across both multiplicative and additive scales, though physical limitations showed clearer patterns than age on an additive scale. CONCLUSION:Attenuated associations between high blood pressure and incident CVD were observed for blacks and whites with poor function, though small sample sizes remain a limitation for identifying differences among Hispanic or Chinese participants. Identifying the characteristics that distinguish those in whom higher SBP is associated with less risk of morbidity or mortality may inform our understanding of the consequences of hypertension among older adults.

Dataset Information

Associations between vitamin K status and haemostatic and inflammatory biomarkers in community-dwelling adults. The Multi-Ethnic Study of Atherosclerosis.

Publications

Associations between vitamin K status and haemostatic and inflammatory biomarkers in community-dwelling adults. The Multi-Ethnic Study of Atherosclerosis.

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