| 41. |
- Mirza, Majd A. I., et al.
(författare)
-
Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 207:2, s. 546-551
-
Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Serum FGF23 is elevated in chronic kidney disease (CKD) and is a prognostic marker of poor outcomes, such as faster CKD progression and increased mortality in hemodialysis patients. Despite the high prevalence of cardiovascular disease in CKD, the relation between circulating FGF23 and cardiovascular risk factors, both in CKD and in the community, has not been studied in detail. We evaluated the relation between FGF23, left ventricular mass index (LVMI), hypertrophy (LVH) and LV geometry, employing the community-based PIVUS cohort. In total, 795 Swedish men and women aged 70 were included of which 164 had an age-adjusted diminished renal function (estimated glomerular filtration rate<60mL/min/1.73m(2)). FGF23 was positively associated with LVMI (beta=0.11, CI 0.01-0.18), with increased odds for the presence of LVH (OR 1.28, CI 1.09-1.51) and for concentric hypertrophy (OR 1.45, CI 1.19-1.77) in the whole population. All associations were stronger in subjects with eGFR<60mL/min/1.73m(2) (beta=0.30, CI 0.15-0.46 for LVMI; OR 1.86, CI 1.30-2.67 for the presence of LVH; OR 1.83, CI 1.17-2.85 and OR 1.87, CI 1.08-3.22 for concentric and eccentric hypertrophy, respectively). The results were essentially unaltered in multivariate models. In summary, elevated serum FGF23 levels, even within the normal range, are associated with increased LVMI and increased risk for the presence of LVH in elderly subjects. Additional longitudinal studies that evaluate the predictive power of FGF23 and whether FGF23 has additional clinical applications are needed.
|
|
| 42. |
- Ticinesi, Andrea, et al.
(författare)
-
Uric acid and endothelial function in elderly community-dwelling subjects
- 2017
-
Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 89, s. 57-63
-
Tidskriftsartikel (refereegranskat)abstract
- The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β±SE males -0.39±0.17, p=0.03; females -0.57±0.19, p=0.003) and log(EIDV) (males -0.23±0.12, p=0.05; females -0.49±0.15, p=0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (-0.32±0.16, p=0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF.
|
|
| 43. |
- Benedict, Christian, et al.
(författare)
-
Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults
- 2014
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:11, s. 3955-3959
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. Using cross-sectional data from 985 older people (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]). Linear regression analyses controlling for sex, selfreported physical activity level, fasting plasma glucose, and BMI were used. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005; relative plasma ghrelin difference between CC and AA carriers = similar to 9%). In contrast, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin difference between CC and AA carriers = similar to 11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin.
|
|
| 44. |
|
|
| 45. |
- Jayasinghe, Saroj, et al.
(författare)
-
High serum levels of p,p'-DDE are associated with an accelerated decline in GFR during 10 years follow-up
- 2018
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 644, s. 371-374
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 20 years, the global incidence of chronic kidney disease (CKD) has been increasing and organochlorine pesticides (such as DDT) is a suspected etiological factor. The present study examines the associations between low level background exposure to p,p'-DDE (1-dichloro-2,2-bis (p-chlorophenyl) ethylene), the main DDT metabolite, and kidney function during a 10-year follow-up. Data was analysed from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1016, 50% women, all aged 70 years). Serum levels of p,p'-DDE was measured by gas chromatography coupled to high-resolution mass spectrometry (GC/HRMS) at baseline (i.e. age of 70 years). Glomerular filtration rate (GFR) was estimated using serum creatinine and cystatin C at 70, 75 and 80 years of age. A significant decline in GFR was seen during the 10-year follow-up (-24 ml/min/1.73 m2, p < 0.0001). A significant negative interaction was seen between baseline p,p'-DDE levels and change in GFR over time (p < 0.0001) following adjustment for sex, systolic blood pressure, diabetes, BMI, smoking and education level at age 70. Subjects with the lowest levels of p,p'-DDE levels at age 70 showed the lowest decline in GFR over 10 years, while subjects with the highest p,p'-DDE levels showed the greatest decline.Baseline levels of p,p'-DDE were related to an accelerated reduction in GFR over 10 years suggesting a nephrotoxic effect of DDT/p,p'-DDE. These findings support a potential role for DDT in the epidemic of CKD of unknown etiology (CKDu) in agricultural communities of Sri Lanka and Central America where DDT was previously used.
|
|
| 46. |
- Jobs, Elisabeth, et al.
(författare)
-
Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men
- 2012
-
Ingår i: Diabetes Care. - : American diabetes association. - 0149-5992 .- 1935-5548. ; 36:1, s. 163-165
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
|
|
| 47. |
- Lind, Lars, et al.
(författare)
-
On the association between body fat and left ventricular mass
- 2019
-
Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 37:8, s. 1699-1704
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: As intervention studies have shown a reduction in body weight to be paralleled with a reduction in left ventricular mass (LVM), we quantified a hypothesized causal relationship between fat mass and LVM, and how much of these effects that was mediated by blood pressure (BP), diabetes and adipokines. Also visceral and subcutaneous adipose tissue (VAT and SAT) were explored in the same fashion.Methods: In the Prospective Study of the Vasculature in Uppsala Seniors study (n = 1016, 50% women, all aged 70 years), LVM was measured by echocardiography (indexed for lean mass, LVMI), fat and lean mass by dual-energy X-ray. VAT and SAT were measured by abdominal MRI (in n = 275).Results: In a structural equation model adjusting for sex, the total effect of fat mass on LVMI was large (standardized coefficient 0.280, P = 3.2 × 10−15, 95% confidence interval 0.210–0.349). Out of the total effect of fat mass on LVMI, 29.0% was mediated by BP and glucose (P = 2.4 × 10−12). The BP pathway was most important, mediating 24.4% of the total effect of fat mass on LVMI (P = 4.6 × 10−7), while the glucose pathway accounted for 4.6% (P = 0.033). The association of VAT with LVMI (0.202, P = 2.4 × 10−4) was slightly weaker than that of SAT with LVMI (0.283, P = 1.0 × 10−6). Of several measured adipokines, leptin was a significant mediator of the effect of fat mass on LVMI (P = 3.0 × 10−3).Conclusion: One-third of the hypothesized association between body fat and LVMI was mediated by BP and glucose in this population-based cohort. Leptin was also an important mediator. Visceral adipose tissue was not more closely related to LVMI than subcutaneous abdominal fat.
|
|
| 48. |
- Lind, Monica, et al.
(författare)
-
Circulating levels of perfluoroalkyl substances and biomarkers of liver function in a large population based sample of elderly men and women from Sweden
- 2015
-
Ingår i: Toxicology Letters. - : Elsevier. - 0378-4274 .- 1879-3169. ; 238:2, s. S91-S91
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Since perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), have been shown to accumulate in the liver in experimental studies, we investigated the relationships between PFAS and biomarkers of liver function in the general population.Methods: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFAS were detected in almost all participants era by liquid chromatograph/tandem mass spectrometry. Several biomarkers of liver function were measured in parallel.Results: Bilirubin levels were significantly related to several of the PFAS, like perfluoroheptanoic acid (PFHpA), perfluorooctanoicacid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA). Of those, PFHpA, PFOA, PFDA, and PFNA were also related to Alanine Aminotransferase (ALT) levels. PFNA and PFUnDA were inversely related to alkaline phosphatases, while only PFHpA levels were significantly related to gamma-glutamyl transferase (GGT) levels. All associations were adjusted for life-style factors, like smoking, education, exercise habits, energy and alcohol intake.Conclusion: Circulating level of PFAS were related to biomarkers of liver function in this population-based sample, suggesting that PFAS could have a negative effect on liver function also in humans.
|
|
| 49. |
- Mahajan, Anubha, et al.
(författare)
-
Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity
- 2016
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:3, s. 636-646
-
Tidskriftsartikel (refereegranskat)abstract
- We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.
|
|
| 50. |
- Nerpin, Elisabet, et al.
(författare)
-
The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly
- 2014
-
Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 29:11, s. 2069-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.
|
|
