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The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men
Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.ORCID-id: 0000-0003-3880-2132
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2011 (Engelska)Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 9, s. 2820-2827Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73 m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73 m(2) significantly improved IDI (0.047, P < 0.001).

CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

Ort, förlag, år, upplaga, sidor
2011. Vol. 26, nr 9, s. 2820-2827
Nyckelord [en]
Albuminuria, eGFR and cardiovascular risk
Nationell ämneskategori
Klinisk medicin
Forskningsämne
Hälsa och välfärd
Identifikatorer
URN: urn:nbn:se:du-10427DOI: 10.1093/ndt/gfq848ISI: 000295231600017PubMedID: 21335440OAI: oai:DiVA.org:du-10427DiVA, id: diva2:542721
Tillgänglig från: 2012-08-03 Skapad: 2012-08-03 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Ingår i avhandling
1. The kidney in different stages of the cardiovascular continuum
Öppna denna publikation i ny flik eller fönster >>The kidney in different stages of the cardiovascular continuum
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2013. s. 72
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206; 946 ; 946
Nyckelord
epidemiology, chronic kidney disease, cystatin C, glomerular filtration rate, albuminuria, euglycemic hyperinsulinemic clamp, insulin sensitivity, inflammation, oxidative stress, endothelial dysfunction and left ventricular dysfunction
Nationell ämneskategori
Kardiologi Urologi och njurmedicin Gerontologi, medicinsk/hälsovetenskaplig inriktning
Forskningsämne
Hälsa och välfärd, Nedsatt njurfunktion, insulinresistens, oxidativ stress och utvecklingen av hjärt-kärlsjukdomar
Identifikatorer
urn:nbn:se:du-13489 (URN)978-91-554-8792-8 (ISBN)
Disputation
2013-12-05, Universitetshuset Sal IX, Uppsala, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2013-12-12 Skapad: 2013-12-10 Senast uppdaterad: 2018-01-11Bibliografiskt granskad

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