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Sökning: swepub > Larsson Anders > Tidskriftsartikel > Lind Lars

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1.
  • 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
  • 2013
  • Ingår i: Diabetes Care. - 0149-5992. ; 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 (euglycemic-hyperinsulinemic 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.
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2.
  • 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. - 0931-0509.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: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).METHODS: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.RESULTS: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).CONCLUSIONS:Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.
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3.
  • Carlsson, Axel C, et al. (författare)
  • Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage
  • 2013
  • Ingår i: Hypertension. - 0194-911X. ; 62:6, s. 1146-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.
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4.
  • Ärnlöv, Johan, et al. (författare)
  • Serum endostatin and risk of mortality in the elderly : findings from 2 community-based cohorts
  • 2013
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642. ; 33:11, s. 2689-2695
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk.APPROACH AND RESULTS:Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]).CONCLUSIONS:High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.
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5.
  • Carlsson, Axel C, et al. (författare)
  • Kidney injury molecule (KIM)-1 is associated with insulin resistance : Results from two community-based studies of elderly individuals
  • 2014
  • Ingår i: Diabetes Research and Clinical Practice. - 0168-8227. ; 103:3, s. 516-521
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
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6.
  • Carlsson, Axel C, et al. (författare)
  • Soluble TNF Receptors and Kidney Dysfunction in the Elderly
  • 2014
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 25:6, s. 1313-1320
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
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7.
  • Carlsson, Axel C, et al. (författare)
  • Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes : Findings from two community based cohorts of elderly
  • 2014
  • Ingår i: Atherosclerosis. - 0021-9150. ; 237:1, s. 236-242
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
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8.
  • Carlsson, Axel C, et al. (författare)
  • Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
  • 2013
  • Ingår i: European Journal of Heart Failure. - 1388-9842. ; 15:4, s. 441-446
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS:There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.METHODS AND RESULTS:This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).CONCLUSION:Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
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9.
  • Carlsson, Axel C, et al. (författare)
  • Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men
  • 2014
  • Ingår i: Clinical journal of the American Society of Nephrology : CJASN. - 1555-905X. ; 9:8, s. 1393-1401
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objectivesKidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.Design, setting, participants, & measurementsThis was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).ResultsDuring follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m2), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m2), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).ConclusionsThese findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
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10.
  • Fall, Tove, et al. (författare)
  • Relations of circulating vitamin D concentrations with left ventricular geometry and function
  • 2012
  • Ingår i: European Journal of Heart Failure. - 1388-9842. ; 14:9, s. 985-991
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study. In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52 women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (, 0.42 mm, P 0.03; , 0.70, P 0.03; and , 0.91 P 0.01, respectively), per 1 SD increase in 25-OH D (SD 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.
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