Kidney dysfunction and fatal cardiovascular disease - an association independent of atherosclerotic events: Results from the Health, Aging, and Body Composition (Health ABC) study

Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD, USA.
American heart journal (Impact Factor: 4.46). 01/2008; 155(1):62-8. DOI: 10.1016/j.ahj.2007.08.012
Source: PubMed


Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events.
The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death, and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (> or = 1.19 mg/L); serum creatinine (cutoff value of > or = 1.3 in women and > or = 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m2) were dichotomized.
During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events.
Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease.

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    • "Several observational studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease [21–23]. It was difficult to conclude whether kidney dysfunction is an independent predictor of sudden cardiac death. "
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    ABSTRACT: Sudden cardiac death continues to be a major public health problem. Ventricular arrhythmia is a main cause of sudden cardiac death. The present review addresses the links between renal function tests, several laboratory markers, and ventricular arrhythmia risk in patients with renal disease, undergoing or not hemodialysis or renal transplant, focusing on recent clinical studies. Therapy of hypokalemia, hypocalcemia, and hypomagnesemia should be an emergency and performed simultaneously under electrocardiographic monitoring in patients with renal failure. Serum phosphates and iron, PTH level, renal function, hemoglobin and hematocrit, pH, inflammatory markers, proteinuria and microalbuminuria, and osmolarity should be monitored, besides standard 12-lead ECG, in order to prevent ventricular arrhythmia and sudden cardiac death.
    BioMed Research International 05/2014; 2014. DOI:10.1155/2014/509204 · 2.71 Impact Factor
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    • "Defined by cystatin C, CKD [7, 29] has been shown to predict cardiovascular events and mortality in several studies. Ix et al. [7] studied 990 participants in the Heart and Soul Study and demonstrated that compared to participants in the lowest cystatin C quartile, those in the highest quartile (those with CKD) were at increased risk of cardiovascular events (HR, 2.0; 95% CI, 1.0–3.8). "
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    ABSTRACT: Background. There is an association between chronic kidney disease (CKD) and metabolic syndrome (MetS). We examined the joint association of CKD and MetS with incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African-Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C estimated glomerular filtration rate ≤ 60 mL/min/1.73 m(2) and MetS was defined by NCEP criteria. Cox proportional regression adjusting for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol was performed to assess the joint association of CKD and MetS with incident CVD events. Participants were divided into four groups by presence of CKD and/or MetS and compared to the group without CKD and MetS (CKD(-)/MetS(-)). Tests for additive and multiplicative interactions between CKD and MetS and prediction of incident CVD were performed. Results. During follow-up period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression analysis demonstrated that CKD and MetS were independent predictors of CVD (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared to the CKD(-)/MetS(-) group, adjusted HR for the CKD(+)/MetS(+) group was 5.56 (95% CI 3.72-8.12). There was no multiplicative interaction between CKD and MetS (P = 0.2); however, there was presence of additive interaction. The relative excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the attributable portion (AP) was 0.49 (0.24-0.74). Conclusion. Our findings illustrate that the combination of CKD and MetS is a strong predictor of incident clinical cardiovascular events due to presence of additive interaction between CKD and MetS.
    Cardiology Research and Practice 01/2012; 2012(1):806102. DOI:10.1155/2012/806102
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    • "Chronic kidney disease (CKD) is associated with accelerated atherosclerosis, hypertension and increased incidence of death from myocardial infarction, stroke, and heart failure [2]. Several factors contribute to the pathogenesis of CKD-induced atherosclerosis and cardiovascular disease; these include oxidative stress, inflammation, dyslipidemia and hypertension [3], [4], [5], [6]. "
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    ABSTRACT: Dysregulation of phosphate homeostasis as occurs in chronic kidney disease is associated with cardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease. The molecular mechanisms by which high or low serum phosphate levels adversely affect cardiovascular function are poorly understood. The purpose of this study was to explore the mechanisms of endothelial dysfunction in the presence of non-physiologic phosphate levels. We studied the effects of simulated hyper- and hypophosphatemia in human umbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C β2 (PKCβ2), reduced cell viability, and increased apoptosis. While simulated hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios, NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance. This is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and increased PKCβ2. Hyperphosphatemia also appears to reduce eNOS transcription via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the other hand, hypophosphatemia appears to activate these pathways. Our data provides the basis for further studies to elucidate the relationship between altered phosphate homeostasis and cardiovascular disease. As a corollary, our data suggests that the level of phosphate in the culture media, if not in the physiologic range, may inadvertently affect experimental results.
    PLoS ONE 08/2011; 6(8):e23268. DOI:10.1371/journal.pone.0023268 · 3.23 Impact Factor
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