@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 {912, title = {Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.}, journal = {Ann Intern Med}, volume = {145}, year = {2006}, month = {2006 Aug 15}, pages = {237-46}, abstract = {

BACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).

OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.

DESIGN: Cohort study.

SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.

PARTICIPANTS: 4663 elderly persons.

MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).

RESULTS: At baseline, 78\% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95\% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.

LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.

CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Creatinine, Cystatin C, Cystatins, Glomerular Filtration Rate, Humans, Kidney, Longitudinal Studies, Prognosis, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors}, issn = {1539-3704}, doi = {10.7326/0003-4819-145-4-200608150-00003}, author = {Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Stehman-Breen, Catherine and Seliger, Stephen L and Kestenbaum, Brian and Psaty, Bruce and Tracy, Russell P and Siscovick, David S} } @article {1012, title = {Cystatin C concentration as a predictor of systolic and diastolic heart failure.}, journal = {J Card Fail}, volume = {14}, year = {2008}, month = {2008 Feb}, pages = {19-26}, abstract = {

BACKGROUND: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study.

METHODS AND RESULTS: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF > or = 50\%) or SHF (EF < 50\%). We compared the association of cystatin C with the risk for DHF and SHF, after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHF. After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95\% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]).

CONCLUSIONS: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Confidence Intervals, Cystatin C, Cystatins, Echocardiography, Female, Heart Failure, Diastolic, Heart Failure, Systolic, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Probability, Proportional Hazards Models, Risk Assessment, Sensitivity and Specificity, Stroke Volume, Survival Analysis}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2007.09.002}, author = {Moran, Andrew and Katz, Ronit and Smith, Nicolas L and Fried, Linda F and Sarnak, Mark J and Seliger, Stephen L and Psaty, Bruce and Siscovick, David S and Gottdiener, John S and Shlipak, Michael G} } @article {9320, title = {Cardiac Mechanics and Kidney Function Decline in the Cardiovascular Health Study.}, journal = {Kidney360}, year = {2023}, month = {2023 Mar 08}, abstract = {

BACKGROUND: Clinical heart failure frequently coexists with chronic kidney disease (CKD) and may precipitate kidney function decline. However, whether earlier-stage myocardial dysfunction assessable by speckle tracking echocardiography is a contributor to kidney function decline remains unknown.

METHODS: We studied 2135 Cardiovascular Health Study (CHS) participants who were free of clinical heart failure and had Year 2-baseline 2D speckle tracking echocardiography and two measurements of estimated glomerular filtration rate (eGFR) (Year 2 and Year 9). "Archival" speckle tracking of digitized echocardiogram videotapes was utilized to measure left ventricular longitudinal strain (LVLS), LV early diastolic strain rate (EDSR), left atrial reservoir strain (LARS), right ventricular free wall strain (RVFWS), and mitral annular velocity (e{\textquoteright}). Multivariable Poisson regression models that adjusted for demographics and cardiovascular risk factors were used to investigate the independent associations of cardiac mechanics indices and decline in kidney function defined as a 30\% decline in eGFR over 7 years.

RESULTS: In risk factor (RF) models LVLS, EDSR, RVFWS, and e{\textquoteright} were all significantly associated with the prevalence of kidney disease. After multivariable adjustment, left atrial dysfunction (RR 1.18 [95\% CI 1.01, 1.38] per SD lower LARS] and left ventricular diastolic dysfunction (RR 1.21 [95\% CI 1.04, 1.41] per SD lower EDSR) were each significantly associated with 30\% decline in eGFR.

CONCLUSIONS: Subclinical myocardial dysfunction suggesting abnormal diastolic function detected by 2D speckle-tracking echocardiography was independently associated with decline in kidney function over time. Further studies are needed to understand the mechanisms of these associations and to test whether interventions that may improve subclinical myocardial dysfunction can prevent decline of kidney function.

}, issn = {2641-7650}, doi = {10.34067/KID.0000000000000100}, author = {Mehta, Rupal and B{\r u}zkov{\'a}, Petra and Patel, Harnish and Cheng, Jeanette and Kizer, Jorge R and Gottdiener, John S and Psaty, Bruce and Khan, Sadiya S and Ix, Joachim H and Isakova, Tamara and Shlipak, Michael G and Bansal, Nisha and Shah, Sanjiv J} }