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Reduced glomerular filtration rate and its association with clinical outcome in older patients at risk of vascular events: secondary analysis.
Ford, Ian Bezlyak, Vladimir Stott, David J Sattar, Naveed Packard, Chris J Perry, Ivan Buckley, Brendan M Jukema, J Wouter de Craen, Anton J M Westendorp, Rudi G J
Ford, Ian
Bezlyak, Vladimir
Stott, David J
Sattar, Naveed
Packard, Chris J
Perry, Ivan
Buckley, Brendan M
Jukema, J Wouter
de Craen, Anton J M
Westendorp, Rudi G J
Advisors
Editors
Other Contributors
Date
2009-01-20
Date Submitted
Keywords
Other Subjects
Subject Mesh
Aged
Aged, 80 and over
Cardiovascular Diseases
Female
Glomerular Filtration Rate
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Kidney Diseases
Male
Pravastatin
Prospective Studies
Risk Factors
Treatment Outcome
Vascular Diseases
Aged, 80 and over
Cardiovascular Diseases
Female
Glomerular Filtration Rate
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Kidney Diseases
Male
Pravastatin
Prospective Studies
Risk Factors
Treatment Outcome
Vascular Diseases
Planned Date
Start Date
Collaborators
Principal Investigators
Files
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pmed.1000016.pdf
Adobe PDF, 110.62 KB
Alternative Titles
Publisher
Abstract
Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20-40], [40-50], [50-60]) >or= 60 ml/min/1.73 m(2). Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m(2) relative to eGFR >or= 60 ml/min/1.73m(2) respectively 2.04 (1.48-2.80), 2.37 (1.53-3.67), 3.52 (1.78-6.96), 1.64 (1.18-2.27), 3.31 (2.03-5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.
We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.
Glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation and was categorized in the ranges ([20-40], [40-50], [50-60]) >or= 60 ml/min/1.73 m(2). Baseline risk factors were analysed by category of eGFR, with and without adjustment for other risk factors. The associations between baseline eGFR and morbidity and mortality outcomes, accrued after an average of 3.2 y, were investigated using Cox proportional hazard models adjusting for traditional risk factors. We tested for evidence of an interaction between the benefit of statin treatment and baseline eGFR status. Age, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index, fasting glucose, female sex, histories of hypertension and vascular disease were associated with eGFR (p = 0.001 or less) after adjustment for other risk factors. Low eGFR was independently associated with risk of all cause mortality, vascular mortality, and other noncancer mortality and with fatal and nonfatal coronary and heart failure events (hazard ratios adjusted for CRP and other risk factors (95% confidence intervals [CIs]) for eGFR < 40 ml/min/1.73m(2) relative to eGFR >or= 60 ml/min/1.73m(2) respectively 2.04 (1.48-2.80), 2.37 (1.53-3.67), 3.52 (1.78-6.96), 1.64 (1.18-2.27), 3.31 (2.03-5.41). There were no nominally statistically significant interactions (p < 0.05) between randomized treatment allocation and eGFR for clinical outcomes, with the exception of the outcome of coronary heart disease death or nonfatal myocardial infarction (p = 0.021), with the interaction suggesting increased benefit of statin treatment in subjects with impaired GFRs.
We have established that, in an elderly population over the age of 70 y, impaired GFR is associated with female sex, with presence of vascular disease, and with levels of other risk factors that would be associated with increased risk of vascular disease. Further, impaired GFR is independently associated with significant levels of increased risk of all cause mortality and fatal vascular events and with composite fatal and nonfatal coronary and heart failure outcomes. Our analyses of the benefits of statin treatment in relation to baseline GFR suggest that there is no reason to exclude elderly patients with impaired renal function from treatment with a statin.
Language
en
ISSN
1549-1676
eISSN
ISBN
DOI
10.1371/journal.pmed.1000016
PMID
19166266