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Background: Only scarce data exist on the association between obesity and disability in the oldest old. The purpose of this prospective study is to examine if body mass index and waist circumference (WC) are associated with incident mobility and activities of daily living (ADL) disability in nonagenarians.Methods: We used longitudinal data from the Vitality 90+ Study, which is a population-based study conducted at the area of Tampere, Finland. Altogether 291 women and 134 men, aged 90-91 years, had measured data on body mass index and/or WC and did not have self-reported mobility or ADL disability at baseline. Incident mobility and ADL disability was followed-up on median 3.6 years (range 0.6-7.8 years). Mortality was also followed-up. Multinomial logistic regression models were used for the analyses, as death was treated as an alternative outcome. The follow-up time was taken into account in the analyses.Results: Neither low or high body mass index, nor low or high WC, were associated with incident mobility disability. In women, the lowest WC tertile (<82 cm) was associated with an increased probability of incident ADL disability when compared to the middle WC tertile (odds ratio 3.98, 95% CI 1.35-11.77).Conclusions: Obesity is not associated with incident mobility or ADL disability in nonagenarians. Instead, low WC is associated with an increased risk of developing ADL disability in nonagenarian women. [ABSTRACT FROM AUTHOR]

Background: Low socioeconomic status is associated both with poorer functioning and elevated levels of inflammatory and cardiometabolic biomarkers; however, knowledge of such relations for the oldest old is limited. Our aim was to study whether education is associated with cardiometabolic (cholesterol levels, body mass index, and leptin) and inflammatory (C-reactive protein, interleukin-6, interleukin-1Ra) biomarkers for the 90-year-olds who participated in the Vitality 90+ study. In addition, we investigated whether these biomarkers explain educational inequalities in functioning.Methods: All persons in Tampere, Finland, who were born in 1909 or 1910, were invited to participate, irrespective of their health status or dwelling place. The sample consisted of 262 participants who went through the home interview and blood tests. The socioeconomic status indicator used was the highest education, and physical functioning was assessed using the Barthel index. The association of education with individual and combined biomarker scores, and with functioning, was analyzed cross-sectionally applying generalized linear models.Results: The low- and mid-level-educated participants had greater odds of belonging to the high risk group in cardiometabolic biomarkers than did the high-educated. Differences were statistically significant in three individual biomarkers (high-density lipoprotein-cholesterol, leptin, and body mass index) and in a cardiometabolic score. There were no educational differences in inflammatory biomarkers. When all biomarkers were combined, they mediated educational differences in functioning on an average of 23%. After controlling for smoking, alcohol use and diseases, biomarkers mediated part of the differences between the mid-level- and high-educated.Conclusions: High education was associated with better cardiometabolic biomarkers and functioning among the 90-year-olds. In part, educational inequalities in functioning were explained by cardiometabolic biomarkers. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (9): 951-957 Abstract Background Increased levels of C-reactive protein (CRP) and serum amyloid A (SAA) are associated with an increased risk of cardiovascular disease. It is hypothesized that dysregulation of the autonomic nervous system (ANS) leads to increased inflammation via the cholinergic anti-inflammatory pathway. Heart rate variability (HRV) is a marker of ANS function. HRV has been shown to be associated with CRP levels. Currently, there are no studies addressing the relationship between HRV and SAA. Design The purpose of this study was to compare the associations between HRV, CRP and SAA in healthy young adults. CRP and SAA concentrations and short-term HRV indices [high frequency (HF), low frequency (LF), total spectral component of HRV, root mean square differences of successive R-R intervals, the standard deviation of all R-R intervals and ratio between LF and HF) were measured in 1601 men and women aged 24-39 taking part in the Cardiovascular Risk in Young Finns study. Results A significant inverse correlation ( P < 0·05) between HRV indices and inflammatory markers was observed. However, in linear regression analyses, only inverse association between HRV indices and CRP levels remained significant ( P < 0·05), while association between HRV indices and SAA levels was attenuated to the null ( P > 0·05) after adjusting for age, sex, body mass index, cholesterol levels, leptin and other common traditional cardiovascular risk factors. Conclusions Reduced HRV indices are independently associated with increased CRP levels, but not with SAA levels. This association supports the hypothesis that dysregulation of the ANS may lead to increased inflammation early in adulthood. [ABSTRACT FROM AUTHOR]

Abstract: Ageing is characterized by chronic low-grade inflammation and the expected lifespan may be affected by several immunological and inflammatory mediators. In this study, we investigated whether the functional Tyr402His polymorphism (rs1061170) on complement factor H (CFH) gene, which is a key inflammatory downregulator, modulates the longevity of 491 nonagenarians in the Vitality 90+ study. Logistic regression analysis and Kaplan–Meier method with the log rank test were used to examine the effect of the CFH Tyr402His polymorphism on 4-year mortality. After follow-up, we observed that risk factor-adjusted mortality was significantly higher among the carriers of CFH 402His allele compared to non-carriers (OR 1.78, 95% CI 1.19–2.67, p =0.005) and that the survival curves of CFH 402His carriers and non-carriers deviated significantly (p =0.016). We propose that the increased mortality is inflammation-related and mediated by aberrant complement regulation by the CFH 402His variant. [Copyright &y& Elsevier]

Cell-free circulating DNA (cf-DNA) has recently arisen as a promising biomarker in acute cardiovascular pathologies and as a mortality predictor in myocardial infarction. We wanted to investigate whether the baseline cf-DNA concentration could serve as an indicator of increased cardiovascular risk and early atherosclerosis. The study population consisted of 1337 participants (aged 46-77 years) in the Health 2000 Survey. cf-DNA was quantified directly in plasma using the fluorescence-based Quant-iT™ high-sensitivity DNA assay kit. Increased cf-DNA levels paralleled a cluster of cardiometabolic risk factors, such as high blood pressure, unfavorable lipid metabolism profile and systemic inflammation in both sexes. In addition, higher cf-DNA levels indicated decreased arterial elasticity and glucose intolerance in women not using hormonal replacement therapy (HRT). The cf-DNA level was also observed to be an independent determinant for Young's elastic modulus but not for carotid artery compliance or beta stiffness index in the women not using HRT. Hence, we conclude that cf-DNA could serve as an auxiliary biomarker in cardiometabolic risk assessment and as an indicator of arterial stiffness in women not using HRT., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Among patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. We evaluated the prognostic value of plasma cf-DNA in patients with Staphylococcus aureus bacteraemia (SAB) treated in the ICU or in the general ward., Methods: 418 adult patients with positive blood culture for S. aureus were prospectively followed for 90 days. SAB patients were grouped according to ICU treatment: 99 patients were treated in ICU within 7 days of documented SAB whereas 319 patients were managed outside ICU. Pitt bacteraemia scores were assessed at hospital arrival and cf-DNA was measured at days 3 and 5 from positive blood culture., Results: SAB patients with high Pitt bacteraemia scores and ICU treatment presented higher cf-DNA values as compared to SAB patients with low Pitt bacteraemia scores and non-ICU treatment at both days 3 and 5. Among ICU patients cf-DNA >1.99 µg/ml at day 3 predicted death with a sensitivity of 67% and a specificity of 77% and had an AUC in receiver operating characteristic analysis of 0.71 (p<0.01). The cut-off cf-DNA >1.99 µg/ml value demonstrated a strong association to high Pitt bacteraemia scores (≥ 4 points) (p<0.000). After controlling for all prognostic markers, Pitt bacteraemia scores ≥ 4 points at hospital admission (OR 4.47, p<0.000) and day 3 cf-DNA (OR 3.56, p<0.001) were the strongest factors significantly predicting outcome in ICU patients. cf-DNA at day 5 did not predict fatal outcome., Conclusion: High cf-DNA concentrations were observed among patients with high Pitt bacteraemia scores and ICU treatment. Pitt bacteraemia scores (≥ 4 points) and cf-DNA at day 3 from positive blood culture predicted death among SAB patients in ICU and were found to be independent prognostic markers. cf-DNA had no prognostic value among non-ICU patients.

Puumala virus (PUUV) causes an acute hemorrhagic fever with renal syndrome (HFRS), a zoonosis also called nephropathia epidemica (NE). The reservoir host of PUUV is the bank vole (Myodes glareolus). Herein we review the main clinical manifestations of NE, acute kidney injury, increased vascular permeability, coagulation abnormalities as well as pulmonary, cardiac, central nervous system and ocular manifestations of the disease. Several biomarkers of disease severity have recently been discovered: interleukin-6, pentraxin-3, C-reactive protein, indoleamine 2,3-dioxygenase, cell-free DNA, soluble urokinase-type plasminogen activator, GATA-3 and Mac-2 binding protein. The role of cytokines, vascular endothelial growth hormone, complement, bradykinin, cellular immune response and other mechanisms in the pathogenesis of NE as well as host genetic factors will be discussed. Finally therapeutic aspects and directions for further research will be handled., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aging is characteristically accompanied by a low-grade inflammatory state and increased cellular death. In this study, we analyzed the associations between the plasma cell-free DNA (cf-DNA) level and immunoinflammatory factors and 4-year mortality. The distribution of qualitative cf-DNA patterns in relation to the total cf-DNA concentration and the antinuclear antibody (ANA) serostatus was also evaluated. The study population consisted of n=258 nonagenarians who were participants in the Vitality 90+ Study. Cf-DNA levels were positively correlated with the C-reactive protein (CRP) level, the interleukin-1 receptor antagonist (IL-1ra) level, the serum amyloid A (SAA) level and the indoleamine 2,3-dioxygenase enzyme activity (IDO), weight and chair-stand test time and inversely correlated with the HDL cholesterol level. The total cf-DNA concentration also remained as an independent predictor of 4-year all-cause mortality. A predominance of low-molecular-weight cf-DNA was observed in ANA-seropositive subjects but this cf-DNA pattern was not associated with mortality. The cf-DNA concentration could thus represent a novel biomarker for systemic inflammation and mortality in the elderly., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Circulating cell-free DNA (cf-DNA) is a useful indicator of cell death, and it can also be used to predict outcomes in various clinical disorders. Several innate immune mechanisms are known to be involved in eliminating DNA and chromatin-related material as part of the inhibition of potentially harmful autoimmune responses. However, the exact molecular mechanism underlying the clearance of circulating cf-DNA is currently unclear., Methods: To examine the mechanisms controlling serum levels of cf-DNA, we carried out a genome-wide association analysis (GWA) in a cohort of young adults (aged 24-39 years; n = 1841; 1018 women and 823 men) participating in the Cardiovascular Risk in Young Finns Study. Genotyping was performed with a custom-built Illumina Human 670 k BeadChip. The Quant-iT(TM) high sensitivity DNA assay was used to measure cf-DNA directly from serum., Results: The results revealed that 110 single nucleotide polymorphisms (SNPs) were associated with serum cf-DNA with genome-wide significance (p<5×10(-8)). All of these significant SNPs were localised to chromosome 2q37, near the UDP-glucuronosyltransferase 1 (UGT1) family locus, and the most significant SNPs localised within the UGT1 polypeptide A1 (UGT1A1) gene region., Conclusion: The UGT1A1 enzyme catalyses the detoxification of several drugs and the turnover of many xenobiotic and endogenous compounds by glucuronidating its substrates. These data indicate that UGT1A1-associated processes are also involved in the regulation of serum cf-DNA concentrations.