Plasma osteocalcin levels as a predictor of cardiovascular disease in older men and women: a population-based cohort study

Holvik, Kristin; Schoor, Natasja M. van; Eekhoff, Elisabeth M. W.; Heijer, Martin den; Deeg, Dorly J. H.; Lips, Paul; Jongh, Renate de

doi:10.1530/eje-13-1044

Cited by 31 publications

(27 citation statements)

References 40 publications

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“…Variables in the regression model included: L1‐L4 BMD, E1G AUC, and osteocalcin. Osteocalcin levels are positively associated with cardiovascular disease risk in older estrogen‐deficient women . Using this model, CBF was predicted by L1‐L4 BMD, osteocalcin, and E1G AUC (see Table ), explaining ~63% of the variance (adjusted R 2 = 0.633, F = 14.827, P < 0.001).…”

Section: Resultsmentioning

confidence: 99%

Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density

O’Donnell

Scheid²,

West

et al. 2019

Scandinavian Med Sci Sports

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In estrogen‐deficient post‐menopausal women, osteoporosis shares a common link with cardiovascular disease risk, including endothelial dysfunction. The current study sought to examine associations between bone mineral density (BMD) and endothelial function in estrogen‐deficient premenopausal women with exercise‐associated menstrual disturbances. Recreationally trained women (24.3 ± 0.8 years; overall mean ± SEM) who were estrogen deficient (amenorrheic or eumenorrheic anovulatory cycles; E2Def; n = 13) or estrogen replete (eumenorrheic ovulatory cycles; E2Rep; n = 14) were studied. Total body and lumbar BMD (L1‐L4) were determined using dual‐energy X‐ray absorptiometry. Serum markers of oxidative stress (oxidized low‐density lipoprotein; OxLDL), energy deficiency (triiodothyronine), and bone turnover (osteocalcin, c‐telopeptide X, P1NP) were assessed. Estrogen exposure was determined by assessing daily urinary estrone‐3‐glucuronide (E1G) across a monitoring period. Calf blood flow (CBF), an index of endothelial function, was measured using strain‐gauge plethysmography. CBF, total body and L1‐L4 BMD, triiodothyronine and E1G were lower (P < 0.05), and c‐telopeptide crosslinks higher (P < 0.05) in E2Def. Osteocalcin and OxLDL did not differ (P > 0.05) between groups. L1‐L4 BMD, osteocalcin, and E1G were the strongest predictors of CBF (R2=0.615, P < 0.001). CBF was the strongest predictor of L1‐L4 BMD (R2=0.478, P < 0.001). L1‐L4 (r = 0.558, P = 0.008) and CBF (r = 0.534, P = 0.004) were independently correlated with E1G. In young recreationally trained premenopausal women with anovulatory menstrual disturbances, low CBF predicts decreased lumbar BMD, suggesting impaired peripheral endothelial function may predict early unfavorable changes in bone metabolism. This finding may be of relevance in the early detection of cardiovascular and bone health decrements in otherwise healthy estrogen‐deficient premenopausal women.

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Section: Resultsmentioning

confidence: 99%

Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density

O’Donnell

Scheid²,

West

et al. 2019

Scandinavian Med Sci Sports

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show abstract

“…Thus, a follow-up study of 1290 Korean men found that the serum osteocalcin level was not associated with the development of CVD, even after adjustment for other risk factors for CVD [29]. Another 4.1-year follow-up study also reported no association between plasma osteocalcin level and CVD in younger-old subjects (65–74 years) [13]. A positive correlation between serum osteocalcin level and atherosclerosis was found in a study of 78 patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…For example, population-based longitudinal study by Holvik et al found that there was no association between plasma osteocalcin level and cardiovascular diseases (CVD) in younger-old subjects (65–74 years), but a higher plasma osteocalcin concentration was associated with a reduced risk of CVD in older-old men (≥75 years) while with an increased risk of CVD in older-old women (≥75 years) [13]. However, other research by Reyes-Garcia et al observed that subjects with CAD had significantly higher serum osteocalcin level than those without CAD, and that serum osteocalcin level in women was positively correlated with C-IMT [14].…”

Section: Introductionmentioning

confidence: 99%

Relationship between serum osteocalcin level and carotid intima-media thickness in a metabolically healthy Chinese population

Luo

Hao

et al. 2015

Cardiovasc Diabetol

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BackgroundThe relationship between osteocalcin and atherosclerosis remains unclear. This might be due to different degrees of confounding from factors that are associated with serum osteocalcin level, such as metabolic-related variables. This study aimed to investigate the relationship between serum osteocalcin level and carotid intima-media thickness (C-IMT) in a metabolically healthy population.MethodsA total of 476 subjects with normal values for weight, glucose tolerance, blood pressure, and lipids (age range, 20–75 years; 155 men, 201 premenopausal women, 120 postmenopausal women) from the Shanghai Obesity Study were recruited for this cross-sectional study. Subjects with a history of cardiovascular disease or carotid plaque were excluded. C-IMT was measured by ultrasonography. Serum osteocalcin level was assessed by an electrochemiluminescence immunoassay.ResultsMedian C-IMT in the entire study population was 0.55 mm with an interquartile range of 0.50–0.60 mm. C-IMT in premenopausal women was significantly lower than that in men and postmenopausal women (all P < 0.001). The median (interquartile range) of serum osteocalcin level in the entire population was 17.02 (13.31–21.47) ng/mL. Serum osteocalcin level in postmenopausal women was significantly higher than that in men and premenopausal women (all P < 0.001), while the level of serum osteocalcin in men was also significantly higher than that in premenopausal women (P < 0.001). No significant correlation was found between C-IMT and serum osteocalcin level in either men or postmenopausal women. There was a significant, inverse correlations between C-IMT and serum osteocalcin level in premenopausal women after adjustment of age, but this association was eliminated after adjustment for other confounding factors.ConclusionsSerum osteocalcin level was not independently associated with C-IMT in a metabolically healthy Chinese population.

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“…Ethnicity may also play a role in generating inconsistent results; among Chinese postmenopausal women, plasma phylloquinone was significantly higher and plasma ucOC was significantly lower than among British or Gambian women, while only among British women was plasma phylloquinone inversely associated with ucOC 49 . Among healthy women, serum phylloquinone and MK7, but not serum MK4, were generally inversely correlated with ucOC and the ucOC/OC ratio 67 , while there appears to be a gender difference with respect to the meaning of high plasma OC; in those aged >/=75, but not younger, higher plasma OC was associated with reduced CVD risk in men but with increased risk in women 68 .…”

Section: Bonementioning

confidence: 88%

Cardiovascular Calcification and Bone: A Comparison of the Effects of Dietary and Serum Vitamin K and its Dependent Proteins

Nicoll¹,

Howard²,

Henein³

2015

ICFJ

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This review compares the effect of vitamin K on cardiovascular (CV) calcification and bone health and shows that, in principal, the γ-carboxylation of the vitamin K-dependent proteins matrix Gla protein (MGP) and its bone equivalent osteocalcin (OC), generally ensures that hydroxyapatite is kept out of the CV system and is deposited in bone. This is an important finding, since there is currently no reliable treatment for CV calcification.Vitamin K2 (menaquinone) may be more effective in the arteries, while vitamin K1 (phylloquinone) is more active in bone. Nevertheless, there remains considerable uncertainty over the precise scope of the functions of MGP and OC, and their carboxylated and under-carboxylated forms, as well as the newly discovered vitamin K-dependent proteins. Although a diet high in vegetables could deliver adequate phylloquinone, supplementation of menaquinone may be necessary for those at risk of CV calcification. Several animal studies and one human study have demonstrated that arterial calcification could be reduced with vitamin K supplementation and there are further trials in progress. Patients on warfarin are particularly prone to CV calcification but there has been concern that supplementation would either counter warfarin treatment or destabilise INR. In fact, studies suggest that low dose phylloquinone did not increase coagulation and may improve the stability of anticoagulant therapy. Furthermore, use of oral anticoagulants which do not affect vitamin K metabolism, such as ximelagatran, could be used when there is a need for vitamin K supplementation for artery or bone health.

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Plasma osteocalcin levels as a predictor of cardiovascular disease in older men and women: a population-based cohort study

Cited by 31 publications

References 40 publications

Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density

Impaired vascular function in exercising anovulatory premenopausal women is associated with low bone mineral density

Relationship between serum osteocalcin level and carotid intima-media thickness in a metabolically healthy Chinese population

Cardiovascular Calcification and Bone: A Comparison of the Effects of Dietary and Serum Vitamin K and its Dependent Proteins

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