@article {697, title = {Cardiovascular disease risk status in elderly persons with renal insufficiency.}, journal = {Kidney Int}, volume = {62}, year = {2002}, month = {2002 Sep}, pages = {997-1004}, abstract = {

BACKGROUND: Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency.

METHODS: This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors.

RESULTS: Among the 5808 participants with creatinine levels measured at entry, 15.9\% of men (N = 394), and 7.6\% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64\% in persons with renal insufficiency compared with 43\% in those without it [odds ratio (OR) 2.34; 95\% confidence interval (95\% CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95\% CI, 1.18, 1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk>20\% by the Framingham equations, 78\% of men and 61\% of women with renal insufficiency had elevated cardiovascular risk status.

CONCLUSIONS: Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults.

}, keywords = {Age Distribution, Aged, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Creatinine, Cross-Sectional Studies, Female, Humans, Kidney Failure, Chronic, Male, Prevalence, Prospective Studies, Risk Factors}, issn = {0085-2538}, doi = {10.1046/j.1523-1755.2002.00522.x}, author = {Shlipak, Michael G and Fried, Linda F and Crump, Casey and Bleyer, Anthony J and Manolio, Teri A and Tracy, Russell P and Furberg, Curt D and Psaty, Bruce M} } @article {719, title = {Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Jan 07}, pages = {87-92}, abstract = {

BACKGROUND: Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease.

METHODS AND RESULTS: The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11\%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar.

CONCLUSION: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.

}, keywords = {Aged, alpha-2-Antiplasmin, Biomarkers, Blood Coagulation Factors, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Creatinine, Cross-Sectional Studies, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Fibrinolysin, Humans, Inflammation, Interleukin-6, Male, Prospective Studies, Renal Insufficiency, Risk Factors}, issn = {1524-4539}, doi = {10.1161/01.cir.0000042700.48769.59}, author = {Shlipak, Michael G and Fried, Linda F and Crump, Casey and Bleyer, Anthony J and Manolio, Teri A and Tracy, Russell P and Furberg, Curt D and Psaty, Bruce M} } @article {737, title = {Relationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study.}, journal = {Am J Kidney Dis}, volume = {41}, year = {2003}, month = {2003 May}, pages = {990-6}, abstract = {

BACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS).

METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination.

RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63\%], 309 men [37\%], 194 African Americans [23\%], and 635 Caucasians [76\%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8\%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72\% versus 50\%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16\% versus 8\%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95\% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95\% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041).

CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.

}, keywords = {Aged, Blood Pressure, Female, Humans, Hypertension, Kidney, Kidney Diseases, Male, Prospective Studies, Ultrasonography, Doppler, Duplex, Vascular Diseases}, issn = {1523-6838}, doi = {10.1016/s0272-6386(03)00196-3}, author = {Edwards, Matthew S and Hansen, Kimberley J and Craven, Timothy E and Cherr, Gregory S and Bleyer, Anthony J and Burke, Gregory L and Dean, Richard H} } @article {735, title = {Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals.}, journal = {J Am Coll Cardiol}, volume = {41}, year = {2003}, month = {2003 Apr 16}, pages = {1364-72}, abstract = {

OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.

BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.

METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women.

RESULTS: An elevated creatinine level was present in 648 (11.2\%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.

CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.

}, keywords = {Aged, Cardiovascular Diseases, Confidence Intervals, Creatinine, Female, Heart Failure, Humans, Intermittent Claudication, Kidney Failure, Chronic, Male, Odds Ratio, Predictive Value of Tests, Survival Analysis}, issn = {0735-1097}, doi = {10.1016/s0735-1097(03)00163-3}, author = {Fried, Linda F and Shlipak, Michael G and Crump, Casey and Bleyer, Anthony J and Gottdiener, John S and Kronmal, Richard A and Kuller, Lewis H and Newman, Anne B} } @article {765, title = {Associations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study.}, journal = {Vasc Endovascular Surg}, volume = {38}, year = {2004}, month = {2004 Jan-Feb}, pages = {25-35}, abstract = {

Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity >/= 1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63\%], 309 men [37\%], 194 African-Americans [23\%], and 635 Caucasians [76\%]) with a mean age of 77.2 +/-4.9 years underwent RDS examination. RVD was present in 57 participants (6.8\%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3\%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p = 0.002), previous myocardial infarction (p < 0.001), >/= 25\% diameter-reducing internal carotid artery stenosis (p = 0.010), increased carotid intimal medial thickness (p = 0.003), and major electrocardiographic abnormalities (p = 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.

}, keywords = {Aged, Arteriosclerosis, Cardiovascular Diseases, Cohort Studies, Humans, Hypertension, Renovascular, Longitudinal Studies, Male, Multivariate Analysis, Prevalence, Prospective Studies, Renal Artery Obstruction, Ultrasonography, United States}, issn = {1538-5744}, doi = {10.1177/153857440403800103}, author = {Edwards, Matthew S and Hansen, Kimberley J and Craven, Timothy E and Bleyer, Anthony J and Burke, Gregory L and Levy, Pavel J and Dean, Richard H} } @article {813, title = {Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals.}, journal = {J Am Soc Nephrol}, volume = {15}, year = {2004}, month = {2004 Dec}, pages = {3184-91}, abstract = {

Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7\%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Creatinine, Factor VII, Female, Fibrinogen, Follow-Up Studies, Glomerular Filtration Rate, Hemoglobins, Humans, Leukocyte Count, Linear Models, Longitudinal Studies, Male, Predictive Value of Tests, Prospective Studies, Renal Insufficiency, Serum Albumin, Thrombosis}, issn = {1046-6673}, doi = {10.1097/01.ASN.0000146422.45434.35}, author = {Fried, Linda and Solomon, Cam and Shlipak, Michael and Seliger, Stephen and Stehman-Breen, Catherine and Bleyer, Anthony J and Chaves, Paolo and Furberg, Curt and Kuller, Lewis and Newman, Anne} } @article {865, title = {Kidney function as a predictor of noncardiovascular mortality.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3728-35}, abstract = {

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95\% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Cohort Studies, Confidence Intervals, Creatinine, Cystatin C, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Longitudinal Studies, Male, Probability, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Survival Analysis, United States}, issn = {1046-6673}, doi = {10.1681/ASN.2005040384}, author = {Fried, Linda F and Katz, Ronit and Sarnak, Mark J and Shlipak, Michael G and Chaves, Paulo H M and Jenny, Nancy Swords and Stehman-Breen, Catherine and Gillen, Dan and Bleyer, Anthony J and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {863, title = {The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {187}, year = {2006}, month = {2006 Aug}, pages = {372-7}, abstract = {

PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events.

METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33\%), those with hypertension (52\%) and those with diabetes, with or without hypertension (15\%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass.

RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95\% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95\% CI 1.08, 2.30]) or diabetes (OR 2.51 [95\% CI 1.27, 4.94]).

CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Atherosclerosis, Cardiovascular Diseases, Coronary Disease, Diabetes Mellitus, Female, Humans, Hypertension, Male, Peripheral Vascular Diseases, Prevalence, Risk Factors, Stroke, United States}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2005.09.015}, author = {Cao, Jie J and Barzilay, Joshua I and Peterson, Do and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis and Wexler, Jason and Bleyer, Anthony J and Cushman, Mary} } @article {983, title = {Cardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68-102: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {197}, year = {2008}, month = {2008 Apr}, pages = {806-13}, abstract = {

BACKGROUND: Elevated urinary albumin excretion (UAE) is associated with the risk of cardiovascular disease (CVD) and all-cause mortality. We tested the hypothesis that elevated UAE improves cardiovascular risk stratification in an elderly cohort aged 68-102 years.

METHODS: We evaluated UAE in 3112 participants of the Cardiovascular Health Study who attended the 1996-1997 examination and had median follow up of 5.4 years. Elevated UAE was defined as urinary albumin to creatinine ratio > or =30 microg/mg. Microalbuminuria and macroalbuminuria were defined as urinary albumin to creatinine ratio 30-300 microg/mg and >300 microg/mg, respectively. Outcomes included CVD (myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox proportional hazards models were used to assess the risk of outcomes associated with elevated UAE.

RESULTS: The prevalence of elevated UAE was 14.3\%, 17.1\% and 26.9\% in those aged 68-74, 75-84 and 85-102 years, respectively. CVD incidence and all-cause mortality were doubled (7.2\% and 8.1\% per year) in those with microalbuminuria and tripled (11.1\% and 12.3\% per year) in those with macroalbuminuria compared to those with normal UAE (3.3\% and 3.8\% per year). The increased CVD and mortality risks were observed in all age groups after adjustment for conventional risk factors. The adjusted population attributable risk percent of CVD and all-cause mortality for elevated UAE was 11\% and 12\%, respectively. When participants were cross-classified by UAE and Framingham Risk Score categories, the 5-year cumulative incidence of coronary heart disease among participants with elevated UAE and a 5-year predicted risk of 5-10\% was 20\%, substantially higher than 6.3\% in those with UAE <30m microg/mg.

CONCLUSION: Elevated UAE was associated with an increased risk of CVD and all-cause mortality in all age groups from 68 to 102 years. Combining elevated UAE with the Framingham risk scores may improve risk stratification for CVD in the elderly.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Biomarkers, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Female, Health Surveys, Humans, Male, Predictive Value of Tests, Risk}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2007.07.029}, author = {Cao, Jie J and Biggs, Mary L and Barzilay, Joshua and Konen, Joseph and Psaty, Bruce M and Kuller, Lewis and Bleyer, Anthony J and Olson, Jean and Wexler, Jason and Summerson, John and Cushman, Mary} }