McCullough, P. A. et al. Independent components of chronic kidney disease as a cardiovascular risk state: results from the Kidney Early Evaluation Program (KEEP). Arch. Intern. Med. 167, 1122-1129

Department of Medicine, University of Chicago, Chicago, Illinois, United States
Archives of Internal Medicine (Impact Factor: 17.33). 06/2007; 167(11):1122-9. DOI: 10.1001/archinte.167.11.1122
Source: PubMed


The relationships of anemia, microalbuminuria, and estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) and subsequent death are not fully understood. We hypothesized that each of these chronic kidney disease-related measures would have an independent relationship with CVD.
A cohort of 37 153 persons screened in the National Kidney Foundation's Kidney Early Evaluation Program were followed up for a median of 16.0 months (range, 0.2-47.5 months). Participants were volunteers who completed surveys regarding past medical events and who underwent blood pressure and laboratory testing. Estimated glomerular filtration rate was computed using a 4-variable equation. Mortality was ascertained by linkage to national data systems.
Of 37 153 persons, the mean +/- SD age was 52.9 +/- 15.9 years, and 68.7% were female. A total of 1835 (4.9%) had a self-reported history of myocardial infarction, 1336 (3.6%) had a history of stroke, and 2897 (7.8%) had a history of myocardial infarction or stroke. Multivariate analysis controlling for age demonstrated that the following were independently associated with CVD: male sex (odds ratio [OR], 1.64; P<.001), smoking (OR, 1.73; P<.001), body mass index (OR, 1.01; P = .03), diabetes mellitus (OR, 1.66; P<.001), hypertension (OR, 1.77; P<.001), eGFR of 30 to 59 mL/min per 173 m(3) (OR, 1.37; P = .001), hemoglobin level of 12.8 g/dL or less (OR, 1.45; P<.001), and microalbuminuria of greater than 30 mg/L (OR, 1.28; P = .01). Survival analysis found CVD (OR, 3.02; P = .003), chronic kidney disease (OR, 1.98; P = .05), and the combination (OR, 3.80; P<.001) to be independent predictors of mortality. Persons with a combination of all 3 chronic kidney disease measures (anemia, microalbuminuria, and eGFR of <60 mL/min per 1.73 m(2)) had the lowest survival of about 93% by the end of 30 months.
Anemia, eGFR, and microalbuminuria were independently associated with CVD, and when all 3 were present, CVD was common and survival was reduced.

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    • "Particularly, in patients with chronic renal failure (CRF), vitamin D deficiency is uniformly present because the critical conversion of nutritional vitamin D3 (25(OH)D3) to the hormonally active form of vitamin D3 (1,25(OH)2D3) occurs primarily in the kidney by 1α-hydroxylase (1α-OHase)[4]. CRF has been shown to be an independent risk factor for CVD, with 10–20 times greater incidence of cardiovascular disease in CRF patients [5]. Clinical studies have also demonstrated that there is an association between improved survival and decreased cardiovascular mortality in hemodialysis patients treated with an activated vitamin D analog, paricalcitol (PC) [6], [7]. "
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    ABSTRACT: Aim Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood. We examine the mechanism and the role of vitamin D signaling in the development of cardiac dysfunction. Methods and Results We analyzed 1α-hydroxylase (1α-OHase) knockout (1α-OHase−/−) mice, which lack 1α-OH enzymes that convert the inactive form to hormonally active form of vitamin D. 1α-OHase−/− mice showed modest cardiac hypertrophy at baseline. Induction of pressure overload by transverse aortic constriction (TAC) demonstrated exaggerated cardiac dysfunction in 1α-OHase−/− mice compared to their WT littermates with a significant increase in fibrosis and expression of inflammatory cytokines. Analysis of calcium (Ca2+) transient demonstrated profound Ca2+ handling abnormalities in 1α-OHase−/− mouse cardiomyocytes (CMs), and treatment with paricalcitol (PC), an activated vitamin D3 analog, significantly attenuated defective Ca2+ handling in 1α-OHase−/− CMs. We further delineated the effect of vitamin D deficiency condition to TAC by first correcting the vitamin D deficiency in 1α-OHase−/− mice, followed then by either a daily maintenance dose of vitamin D or vehicle (to achieve vitamin D deficiency) at the time of sham or TAC. In mice treated with vitamin D, there was a significant attenuation of TAC-induced cardiac hypertrophy, interstitial fibrosis, inflammatory markers, Ca2+ handling abnormalities and cardiac function compared to the vehicle treated animals. Conclusions Our results provide insight into the mechanism of cardiac dysfunction, which is associated with severely defective Ca2+ handling and defective vitamin D signaling in 1α-OHase−/− mice.
    PLoS ONE 09/2014; 9(9):e108382. DOI:10.1371/journal.pone.0108382 · 3.23 Impact Factor
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    • "Even modest reductions in GFR in patients with acute myocardial infarction (AMI) are associated with a higher mortality rate [3], and the progression from chronic kidney disease to end-stage renal disease is more rapid following an AMI [4] [5]. While the relationship between GFR and mortality is unidirectional, with a stepwise increase in mortality with worsening GFR, the relationship between haemoglobin levels and mortality is that of an inverse-J curve; lower haemoglobin concentrations are an independent predictor of cardiovascular disease and mortality [6], while haemoglobin levels beyond the upper limit of normal are also associated with an increased hazard of adverse cardiovascular outcomes [7] [8]. To date, data from randomized controlled trials have failed to conclusively demonstrate that correcting anaemia with either transfusions or erythropoietic agents [9] [10] reduce mortality, possibly because these trials selected targets for haemoglobin correction that were too aggressive, especially in the context of impaired GFR, or the forms of treatment had cardiovascular toxicities [11] [12]. "
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    ABSTRACT: Background: Impaired renal function and anaemia are common among patients with acute myocardial infarction (AMI). While both conditions are known independent risk factors for increased mortality, their interaction as risk factors for increased mortality in AMI is unclear. Methods: We studied 5395 subjects hospitalized for AMI between January 2000 and December 2005. An estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) was defined as impaired GFR and GFR ≥ 60 mL/min/1.73 m(2) was defined as preserved GFR. Anaemia was defined as <13 g/dL (males) and <12 g/dL (females). The odds ratio (OR) for one-year mortality and its 95% confidence interval (CI) were calculated by logistic regression. Results: We identified 758 (14%) patients with impaired GFR and anaemia, 1105 (20.5%) patients with impaired GFR without anaemia, 465 (8.6%) patients with preserved GFR and anaemia, and 3012 (55.8%) patients with preserved GFR without anaemia; one-year mortality rates were 56.5%, 41.8%, 31.8% and 10.3% respectively in these 4 groups. Among patients with impaired GFR, anaemia was associated with an adjusted OR of 1.47 (95% CI=1.17-1.85) for one-year mortality, while among patients with preserved GFR, anaemia was associated with a higher adjusted OR of 2.07 (95% CI=1.54-2.76) for one-year mortality, interaction P<0.001. Conclusion: The combination of impaired GFR and anaemia confers greater than five-fold increased risk of mortality after AMI. The differential effect of anaemia among patients with impaired and preserved GFR on mortality suggests that in patients with preserved GFR anaemia confers a greater relative hazard than in patients with impaired renal function.
    International journal of cardiology 01/2013; 168(2). DOI:10.1016/j.ijcard.2012.12.017 · 4.04 Impact Factor
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    • "[22]. In contrast, there are community-based studies that demonstrated the independent association of moderate renal insufficiency with increased risk of CVD events and mortality in general population [7,9,22-28]. GO et al. [29] after 2.84 years of follow-up of 1,120,295 participants, reported an independent, graded association between a reduced eGFR and the risk of cardiovascular events, in a large, community-based population. "
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    ABSTRACT: Chronic kidney disease(CKD) has been proposed as a risk factor for cardiovascular disease (CVD). There is conflicting evidence among community based studies regarding the association between CKD and CVD. Furthermore, in order to assess the possible interaction between CKD and BMI, we also examined the association between CKD and CVD, across different BMI categories. The risk of CVD events was evaluated in a large cohort of participants selected from the Tehran Lipid and Glucose Study. Participants(mean age, 47.4 years) free of previous CVD were followed up for 9.1 years. GFR ml/min per 1.73 m(2) was estimated using the MDRD formula. Of the 6,209 participants, 22.2%(1381) had CKD with eGFR ml/min per 1.73 m(2) <60 at baseline. Almost all of them (99%) were in stage 3a. Moderate renal insufficiency only predicted CVD outcomes independently when we adjusted for age and sex. After further adjustment, the presence of moderate CKD lost its statistical significance to confer an independent increased risk of CVD events with a hazard ratio of: HR: 1.14, CI 95% 0.91-1.42. Furthermore, when participants were categorized according to CKD status and BMI groups, after further adjustment, no interaction was found(P = 0.2). CKD was not an independent risk factor for CVD events in a community-based study in a Tehranian population and the higher prevalence of CVD in subjects with mild to moderate renal insufficiency might be due to the co-occurrence of traditional CVD risk factors in this group.
    BMC Nephrology 07/2012; 13(1):59. DOI:10.1186/1471-2369-13-59 · 1.69 Impact Factor
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