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  • Author: Natasja M van Schoor x
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Christa C van Bunderen, Mirjam M Oosterwerff, Natasja M van Schoor, Dorly J H Deeg, Paul Lips and Madeleine L Drent

Objective

High as well as low levels of IGF1 have been associated with cardiovascular diseases (CVD). The relationship of IGF1 with (components of) the metabolic syndrome could help to clarify this controversy. The aims of this study were: i) to investigate the association of IGF1 concentration with prevalent (components of) the metabolic syndrome; and ii) to examine the role of (components of) the metabolic syndrome in the relationship between IGF1 and incident CVD during 11 years of follow-up.

Methods

Data were used from the Longitudinal Aging Study Amsterdam, a cohort study in a representative sample of the Dutch older population (≥65 years). Data were available in 1258 subjects. Metabolic syndrome was determined using the definition of the US National Cholesterol Education Program Adult Treatment Panel III. CVD were ascertained by self-reports and mortality data.

Results

Levels of IGF1 in the fourth quintile were associated with prevalent metabolic syndrome compared with the lowest quintile (odds ratio: 1.59, 95% confidence interval (CI) 1.09–2.33). The middle up to the highest quintile of IGF1 was positively associated with high triglycerides in women. Metabolic syndrome was not a mediator in the U-shaped relationship of IGF1 with CVD. Both subjects without the metabolic syndrome and low IGF1 levels (hazard ratio (HR) 1.75, 95% CI 1.12–2.71) and subjects with the metabolic syndrome and high IGF1 levels (HR 2.28, 95% CI 1.21–4.28) demonstrated increased risks of CVD.

Conclusions

In older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Furthermore, this study suggests the presence of different pathomechanisms for both low and high IGF1 levels and incident CVD.

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Nathalie E Heima, E Marelise W Eekhoff, Mirjam M Oosterwerff, Paul T A Lips, Natasja M van Schoor and Suat Simsek

Background

Studies suggest an association between a high TSH and (individual components of) the metabolic syndrome. Only a few studies have been performed in the general older population.

Objective

This study investigates the association between serum TSH and the metabolic syndrome in a representative sample of older persons in The Netherlands.

Design and patients

Data of the Longitudinal Aging Study Amsterdam were used, which is an ongoing cohort study in a representative sample of Dutch older persons. A total of 1187 subjects (590 men and 597 women) between the ages of 65 and 88 years participated in the study.

Measurements

Metabolic syndrome (US National Cholesterol Education Program definition) and its individual components were assessed, as well as serum TSH levels.

Results

Among the participants, the prevalence of the metabolic syndrome was 34.2%. The mean serum TSH was 1.9 mU/l. Subjects in the upper quartile with a serum TSH level above 2.28 mU/l (odds ratio (OR)=1.68; 95% confidence interval (CI) 1.19–2.37) had a significantly increased prevalence of metabolic syndrome compared with subjects in the lowest quartile with a serum TSH below 1.04 mU/l. After adjustment for confounders, age, sex, alcohol use, total physical activity, and smoking, the OR was 1.62 (95% CI 1.15–2.32).

Conclusions

Subjects with a serum TSH in the upper quartile have a higher prevalence of metabolic syndrome as compared with subjects with a serum TSH in the lowest quartile.

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Renate T de Jongh, Paul Lips, Kelly J Rijs, Natasja M van Schoor, Mark H H Kramer, Jan P Vandenbroucke and Olaf M Dekkers

Context

Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality.

Objective

To investigate the associations between VDR gene variants and mortality among older people.

Design

The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (≥65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms.

Results

During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2 GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01–1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2 GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copies=reference, HR, 95% CI: 1 copy 2.01, 0.99–4.07 and 2 copies 1.81, 0.87–4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2 GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83–1.41).

Conclusions

The Cdx2 GATA haplotype 1 allele was related to increased mortality risk, which may be partly explained by osteoporotic fractures. As the biological mechanism is uncertain and this study size is limited, our results should be interpreted as hypothesis generating.

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

Objective

The role of osteocalcin (OC) in cardiovascular disease (CVD) is unresolved. We aimed to study the association between plasma OC concentrations and the risk of non-fatal and fatal CVDs. We also aimed to investigate whether such an association, if present, would be mediated by established metabolic risk factors.

Design

A population-based longitudinal cohort study.

Methods

In 1995/1996, OC was determined in blood samples drawn from 1319 subjects aged 65–88 years participating in the Longitudinal Aging Study Amsterdam in 1995/1996. The self-reported CVD events were collected every 3 years until 2005/2006, and CVD deaths until 1st January 2007. Cox proportional hazards regression was performed, considering potential confounders (smoking, physical activity, and BMI) and mediators (blood pressure, plasma triglycerides, total and HDL cholesterol, fructosamine, and aortic calcification).

Results

During the median 4.1 years follow-up, 709 subjects (53.8%) suffered a CVD event. There was no overall association between OC and CVD: hazard ratio (HR) was 0.97 (95% CI 0.90–1.04) per nmol/l higher plasma OC, adjusted for age and sex. There was a statistical interaction between plasma OC, age, and sex on CVD (P=0.014). In those subjects aged ≥75 years, age-adjusted HRs (95% CI) were 0.86 (0.75–0.99) in men and 1.16 (1.03–1.31) in women per nmol/l higher plasma OC. Adjustment for covariates only slightly attenuated the association in older-old men, but did not affect the association in older-old women.

Conclusion

A higher plasma OC concentration was associated with a reduced risk of CVD in older-old men and with an increased risk of CVD in older-old women. We found no evidence that this was mediated by arterial calcification or metabolic risk factors.

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Liset E M Elstgeest, Elisa J de Koning, Ingeborg A Brouwer, Natasja M van Schoor, Brenda W J H Penninx and Marjolein Visser

Objective

Previous prospective studies on the association between vitamin D status and depression used a single 25-hydroxyvitamin D (25(OH)D) measurement. We investigated the association between change in serum 25(OH)D and parallel change in depressive symptoms over time in Dutch older adults.

Design

A population-based, prospective study in two cohorts of older men and women from the Longitudinal Aging Study Amsterdam.

Methods

Serum 25(OH)D concentrations were determined at two time points: in 1995/1996 and 13 years later in the older cohort (aged 65–88y, n = 173) and in 2002/2003 and 6 years later in the younger cohort (55–65 years, n = 450). At these time points, depressive symptoms were measured with the Center for Epidemiologic Studies Depression scale (CES-D). Associations were tested by multiple linear regression analyses.

Results

During follow-up, serum 25(OH)D concentrations increased in 32.4% of the older cohort and in 69.8% of the younger cohort. In the older cohort, change in 25(OH)D was not associated with change in CES-D score. In the younger cohort, no associations were observed in participants with higher baseline 25(OH)D concentrations (>58.6 nmol/L), but in those with lower baseline 25(OH)D concentrations, an increase in 25(OH)D was associated with a decrease in CES-D score (adjusted B per 10 nmol/L 25(OH)D increase: −0.62 (95% CI: −1.17, −0.07)).

Conclusions

Our study suggests that over 6 years, an increase in serum 25(OH)D is associated with a small decrease in depressive symptoms in young older adults with lower baseline 25(OH)D. Well-designed intervention trials are required to determine causality.

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Renate T de Jongh, Paul Lips, Natasja M van Schoor, Kelly J Rijs, Dorly J H Deeg, Hannie C Comijs, Mark H H Kramer, Jan P Vandenbroucke and Olaf M Dekkers

Objective

To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate.

Design

A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam.

Methods

TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal)

Results

Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22–0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59–1.35 and 0.69, 95% CI 0.40–1.20 respectively).

Conclusions

This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population.