Cardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68–102: The cardiovascular Health Study

Cao, Jie J; Biggs, Mary L.; Barzilay, Joshua I.; Konen, Joseph C.; Psaty, Bruce M.; Kuller, Lewis H.; Bleyer, Anthony J.; Olson, Jean L.; Wexler, Jason A.; Summerson, John H.; Cushman, Mary

doi:10.1016/j.atherosclerosis.2007.07.029

Cited by 41 publications

(34 citation statements)

References 23 publications

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“…For example, elevated urinary albumin excretion was associated with a doubling of risk of CVD and allcause mortality in a study of elderly persons. This study also showed an inverse correlation between urinary levels of albumin and plasma levels of HDL-C. 38 Similarly, patients with chronic renal failure have decreased plasma HDL concentration. 39 Furthermore, a missense cubilin variant is associated with albuminuria in both the general population and individuals with diabetes.…”

Section: Discussionsupporting

confidence: 59%

Cubilin Maintains Blood Levels of HDL and Albumin

Aseem

Smith

Cooley

et al. 2014

Journal of the American Society of Nephrology

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Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL 3 particles (density.1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL 2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.

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Section: Discussionsupporting

confidence: 59%

Cubilin Maintains Blood Levels of HDL and Albumin

Aseem

Smith

Cooley

et al. 2014

Journal of the American Society of Nephrology

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“…30 The specific age limitations of the FRS have been addressed by other groups who have studied elderly cohorts, such as the Australian community-based Dubbo Study of the elderly (the Dubbo equation) and those using participants included in other hypertension treatment outcome trials 15,16 (the Pocock equation). Other proposed solutions to the limitations of the FRS as a predictor of outcome in older people include the addition of new biomarkers, such as C-reactive protein 31 and albuminuria, 32 to improve predictive power.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Cardiovascular Events in Subjects in the Second Australian National Blood Pressure Study

et al. 2010

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Abstract-Estimating absolute risk rather than measurement of blood pressure alone is considered the best way to identify those who would most likely benefit from medical intervention. Risk calculators used to estimate risk in those without previous cardiovascular disease (CVD) events are based on the Framingham Heart Study, which had no person Ͼ74 years of age at baseline. This needs to be addressed, because age is the most important determinant of risk. We estimated the predictive value of 3 risk equations for CVD end points in the Second Australian National Blood Pressure study cohort (mean age: 71.9 years at baseline). Observed and predicted 5-year incidence rates, 2 goodness-of-fit tests, and Harrell C statistic and area under the receiver operator characteristic curve were used to assess the ability of the equations to predict CVD outcomes over 5 years. A recalibration analysis was undertaken. Significant (PϽ0.05) 2 goodness-of-fit statistics were observed using each of the risk equations for myocardial infarction, coronary heart disease, stroke, or CVD morbidity or mortality across age groups and both sex. All of the overall C statistics or the area under the receiver operator characteristic curve indicated modest discrimination of the algorithms for prediction of the outcomes for coronary heart disease and CVD morbidity and mortality, myocardial infarction, or stroke (Framingham); cardiac death (Pocock); and CVD events (Dubbo). Recalibration analyses showed that it would be inappropriate to apply the risk equations to the Second Australian National Blood Pressure study population. New risk equations for CVD events in the hypertensive aged are needed. (Hypertension. 2010;56:44-48.)

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“…Standard CVD risk factors are associated with microalbuminuria. 174,175 Microalbuminuria is associated with incident hypertension, progression to a higher blood pressure category, and incident diabetes. 176,177 Microalbuminuria and diabetes each appear to influence the other's progression.…”

Section: General Descriptionmentioning

confidence: 99%

“…166,184 -186 In studies examining the incremental yield of adding urinary albumin excretion in the microalbuminuria range to standard CVD risk factors for CVD risk prediction, the Framingham Heart Study and the Cardiovascular Health Study observed only minor improvements in the C statistic. 175,187 However, the Cardiovascular Health Study observed that the urinary albumin-to-creatinine ratio did assist with risk reclassification. Persons at intermediate risk (predicted 5-year Framingham risk of 5% to 10%) with a urinary albumin-to-creatinine ratio Ն30 mg/g had a substantially higher 5-year risk of CHD than those with a ratio of Ͻ30 mg/g (20.1% versus 6.3%, respectively).…”

Section: Association With Cardiovascular Riskmentioning

confidence: 99%