@article {795, title = {Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.}, journal = {J Am Soc Nephrol}, volume = {15}, year = {2004}, month = {2004 Jul}, pages = {1904-11}, abstract = {

Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37\% increased risk of dementia (95\% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26\% increased risk (95\% CI = 1.02 to 1.60). These associations were present only among the 84\% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.

}, keywords = {Aged, Alzheimer Disease, Cardiovascular Diseases, Creatinine, Dementia, Dementia, Vascular, Female, Humans, Kidney, Kidney Diseases, Male, Muscles, Proportional Hazards Models}, issn = {1046-6673}, doi = {10.1097/01.asn.0000131529.60019.fa}, author = {Seliger, Stephen L and Siscovick, David S and Stehman-Breen, Catherine O and Gillen, Daniel L and Fitzpatrick, Annette and Bleyer, Anthony and Kuller, Lew H} } @article {831, title = {Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors.}, journal = {JAMA}, volume = {293}, year = {2005}, month = {2005 Apr 13}, pages = {1737-45}, abstract = {

CONTEXT: Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.

OBJECTIVE: To compare traditional and novel risk factors as predictors of cardiovascular mortality.

DESIGN, SETTING, AND PATIENTS: A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.

MAIN OUTCOME MEASURES: Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.

RESULTS: Among the participants, 1249 (22\%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95\% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95\% confidence interval, 0.71-0.78; P for difference = .15).

CONCLUSIONS: Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.

}, keywords = {Aged, Cardiovascular Diseases, Chronic Disease, Humans, Kidney Diseases, Longitudinal Studies, Risk Factors}, issn = {1538-3598}, doi = {10.1001/jama.293.14.1737}, author = {Shlipak, Michael G and Fried, Linda F and Cushman, Mary and Manolio, Teri A and Peterson, Do and Stehman-Breen, Catherine and Bleyer, Anthony and Newman, Anne and Siscovick, David and Psaty, Bruce} } @article {862, title = {Cystatin C and subclinical brain infarction.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3721-7}, abstract = {

Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7\%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95\% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95\% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Brain Infarction, Confidence Intervals, Creatinine, Cross-Sectional Studies, Cystatin C, Cystatins, Disease Progression, Female, Geriatric Assessment, Humans, Incidence, Ischemic Attack, Transient, Magnetic Resonance Imaging, Male, Odds Ratio, Predictive Value of Tests, Prognosis, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Sex Factors, Survival Analysis}, issn = {1046-6673}, doi = {10.1681/ASN.2005010006}, author = {Seliger, Stephen L and Longstreth, W T and Katz, Ronit and Manolio, Teri and Fried, Linda F and Shlipak, Michael and Stehman-Breen, Catherine O and Newman, Anne and Sarnak, Mark and Gillen, Daniel L and Bleyer, Anthony and Siscovick, David S} }