Association of Polypharmacy with Kidney Disease Progression in Adults with CKD

Author(s):  
Hiroshi Kimura ◽  
Kenichi Tanaka ◽  
Hirotaka Saito ◽  
Tsuyoshi Iwasaki ◽  
Akira Oda ◽  
...  

Background and objectivePolypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT.Design, setting, participants, and measurementsWe retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5–9 and ≥10 medications per day, respectively.ResultsThe median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality.ConclusionsThe use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

Author(s):  
Christopher E. Clark ◽  
Fiona C. Warren ◽  
Kate Boddy ◽  
Sinead T.J. McDonagh ◽  
Sarah F. Moore ◽  
...  

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02–1.08) and 1.06 (95% CI, 1.02–1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01–1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00–1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01–1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06–1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227


Author(s):  
Qin Wang ◽  
Yu Wang ◽  
Jinwei Wang ◽  
Luxia Zhang ◽  
Ming-Hui Zhao ◽  
...  

Background and objectivesNocturnal hypertension is associated with adverse outcomes in patients with CKD. However, the individual association of entities of nocturnal hypertension according to achievement of systolic and/or diastolic BP goals with kidney failure and cardiovascular outcomes of CKD is not clear.Design, setting, participants, & measurementsOur study analyzed data from participants in the Chinese Cohort Study of Chronic Kidney Disease. Nocturnal hypertension was categorized into three entities: isolated nocturnal diastolic hypertension with diastolic BP ≥70 mm Hg and systolic BP <120 mm Hg, isolated nocturnal systolic hypertension with systolic BP ≥120 mm Hg and diastolic BP <70 mm Hg, and nocturnal systolic-diastolic hypertension with both systolic BP ≥120 mm Hg and diastolic BP ≥70 mm Hg. Associations of nocturnal hypertension entities with kidney failure and cardiovascular outcomes were evaluated by Cox regression.ResultsIn total, 2024 patients with CKD stages 1–4 were included in our analysis (mean age, 49±14 years; 57% men; eGFR=51±29 ml/min per 1.73 m2; proteinuria: 0.9 [0.4–2.1] g/d). Among them, 1484 (73%) patients had nocturnal hypertension, with the proportions of 26%, 8%, and 66% for isolated nocturnal diastolic hypertension, isolated nocturnal systolic hypertension, and nocturnal systolic-diastolic hypertension, respectively. Three hundred twenty kidney events and 148 cardiovascular events were recorded during median follow-up intervals of 4.8 and 5.0 years for kidney and cardiovascular events, respectively. After adjustment, isolated nocturnal systolic hypertension was associated with a higher risk for cardiovascular events (hazard ratio, 3.17; 95% confidence interval, 1.61 to 6.23). Nocturnal systolic-diastolic hypertension showed a higher risk for both kidney failure (hazard ratio, 1.71; 95% confidence interval, 1.17 to 2.49) and cardiovascular outcomes (hazard ratio, 2.19; 95% confidence interval, 1.24 to 3.86). No association was observed between isolated nocturnal diastolic hypertension with either kidney failure or cardiovascular events.ConclusionsNocturnal systolic hypertension, either alone or in combination with diastolic hypertension, is associated with higher risks for adverse outcomes in patients with CKD.


Author(s):  
Hae Hyuk Jung

ABSTRACT Background The treatment BP target in CKD remains unclear, and whether the benefit of intensive BP-lowering is comparable between CKD and non-CKD patients is debated. Methods Using the Korean National Health Information Database, 359,492 CKD patients who had received antihypertensives regularly were identified from 12.1 million participants of nationwide health screening. The composite risk of major cardiovascular events, kidney failure, and all-cause mortality was assessed according to timely-averaged, on-treatment systolic BP. Results Over 9-year follow-up, the composite outcome noted in 18.4% of 239,700 participants with eGFR &lt;60 ml/min/1.73 m2 and 18.9% of 155,004 with dipstick albuminuria. The thresholds of systolic BP, above which the composite risk increased significantly, in the reduced eGFR and the proteinuric population were 135 mm Hg and 125 mm Hg, respectively. For all-cause mortality, the respective thresholds were 145 mm Hg and 135 mm Hg. When comparing the composite risk between propensity score-matched groups, the hazard ratios of on-treatment BP of systolic 135–144 mm Hg (reference, 115–124 mm Hg) in the reduced eGFR and non-CKD pairs were 1.18 and 0.98, respectively (P = 0.13 for interaction), and those in the proteinuria and non-CKD pairs were 1.30 and 1.01, respectively (P = 0.003 for interaction). Conclusions The findings support the recommendation that, based on office BP, the systolic target in CKD with proteinuria is ≤ 130 mm Hg, and the target in CKD with no proteinuria is ≤ 140 mm Hg. The benefit of intensive BP-lowering may be greater in CKD patients particularly with proteinuria than in their non-CKD counterparts.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8987
Author(s):  
Cheng-Chun Wei ◽  
Pei-Chun Chen ◽  
Hsiu-Ching Hsu ◽  
Ta-Chen Su ◽  
Hung-Ju Lin ◽  
...  

Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18–2.76]) and 1.45 (95% CI [0.67–3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.


2016 ◽  
Vol 6 (3) ◽  
pp. 251-259
Author(s):  
Masaru Matsui ◽  
Ken-ichi Samejima ◽  
Yukiji Takeda ◽  
Katsuhiko Morimoto ◽  
Miho Tagawa ◽  
...  

Background: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family that acts as a pleiotropic cytokine capable of stimulating angiogenesis and accelerating atherogenesis. Soluble fms-like tyrosine kinase-1 (sFlt-1) antagonizes PlGF action. Higher levels of PlGF and sFlt-1 have been associated with cardiovascular events in patients with chronic kidney disease, yet little is known about their relationship with adverse outcomes in patients on peritoneal dialysis (PD). The aim of this study was to investigate the association of PlGF and sFlt-1 with technique survival and cardiovascular events. Methods: We measured serum levels of PlGF and plasma levels of sFlt-1 in 40 PD patients at Nara Medical University. Results: PlGF and sFlt-1 levels were significantly correlated with the dialysate-to-plasma ratio of creatinine (r = 0.342, p = 0.04 and r = 0.554, p < 0.001) although PlGF and sFlt-1 levels were not correlated with total creatinine clearance and total Kt/V. Additionally, both PlGF and sFlt-1 levels were significantly higher in patients with high transport membranes compared to those without (p = 0.039 and p < 0.001, respectively). Patients with PlGF levels above the median had lower technique survival and higher incidence of cardiovascular events than patients with levels below the median, with hazard ratios of 11.9 and 7.7, respectively, in univariate Cox regression analysis. However, sFlt-1 levels were not associated with technique survival or cardiovascular events (p = 0.11 and p = 0.10, respectively). Conclusion: Elevated PlGF and sFlt-1 are significantly associated with high transport membrane status. PlGF may be a useful predictor of technique survival and cardiovascular events in PD patients.


2016 ◽  
Vol 62 (4) ◽  
pp. 631-638 ◽  
Author(s):  
Yader Sandoval ◽  
Charles A Herzog ◽  
Sara A Love ◽  
Jing Cao ◽  
Yan Hu ◽  
...  

Abstract INTRODUCTION Serial changes in cardiac troponin in hemodialysis (HD) patients have uncertain clinical implications. We evaluated associations of adverse outcomes in HD patients with reference change value (RCV) data and tertile concentrations for cardiac troponin I (cTnI) and cTnT measured by high-sensitivity (hs) assays. METHODS RCV data and tertiles for hs-cTnI and hs-cTnT were determined from plasma samples collected 3 months apart in 677 stable outpatient HD patients and assessed for their associations with adverse outcomes using adjusted Cox models. Primary outcomes were all-cause mortality and sudden cardiac death (SCD). RESULTS During a median follow-up of 23 months, 18.6% of patients died. RCVs were: hs-cTnI +37% and −30%; hs-cTnT +25% and −20%. Patients with serial hs-cTnI and hs-cTnT changes &gt;RCV (increase or decrease) had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with changes ≤RCV [adjusted hazard ratios (aHRs): 1.9, P = 0.0003 and 1.7, P = 0.0066), respectively]. Only hs-cTnI changes &gt;RCV were predictive of SCD (aHR 2.6, P = 0.005). hs–Cardiac troponin changes &gt;RCV improved all-cause mortality prognostication compared to changes ≤RCV in tertile 2: hs-cTnI aHR, 2.70 (P = 0.003); hs-cTnT aHR, 1.98 (P = 0.043). The aHR of changes in hs-cTnI in tertile 2 &gt;RCV for SCD was 5.62 (P = 0.039). CONCLUSIONS Changes over 3 months in hs-cTnI and hs-cTnT of &gt;RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes &gt;RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality.


Author(s):  
Amanda R Moraska ◽  
Alanna M Chamberlain ◽  
Nilay D Shah ◽  
Kristin S Vickers ◽  
Shannon M Dunlay ◽  
...  

Background: The increasing prevalence of heart failure (HF) and high associated costs has spurred investigation of factors related to adverse outcomes in these patients. Reports to date present discrepant evidence regarding the link between depression and HF outcomes, and only scarce data related to healthcare utilization in the form of emergency department (ED) visits are available. Purpose: To evaluate the relationship of depression with healthcare utilization and death among HF patients in the community. Methods: Residents of Olmsted, Dodge, and Fillmore, MN counties with HF were prospectively recruited between October 2007 and December 2010, and completed a 9-item Patient Health Questionnaire (PHQ-9) for depression categorized as: none-minimal (PHQ-9 score 0-4), mild (5-9), or moderate-severe (≥10). Anderson-Gill models were used to determine if depression predicted hospitalizations and ED visits while proportional hazards regression estimated hazard ratios for death. Results: Among 411 HF patients (mean age 73±13, 58% male), 15% had moderate-severe depression, 27% mild, and 58% none-minimal. Over a mean follow-up of 1.5 years, 613 hospitalizations, 786 ED visits, and 75 deaths occurred. The risk of all adverse outcomes increased stepwise with increasing severity of depression (Table). After adjustment for key clinical characteristics, moderate-severe depression was associated with nearly a 2-fold increased risk of hospitalization and ED visits, and almost a 4-fold increased risk of death. These results are independent of coexisting comorbidities. Conclusions: Depression is frequent among HF patients in the community and independently predicts a significant increase in the use of healthcare resources and mortality. Greater attention to the recognition and management of depression in HF may improve clinical outcomes and decrease healthcare utilization and expenditures in these patients. Hazard Ratios (95%CI) for Hospitalizations and All-Cause Mortality by Severity of Depression None-Minimal Mild Moderate-Severe P for trend Hospitalizations Crude 1.00 (ref) 1.23 (0.91-1.66) 2.01 (1.39-2.89) <0.001 Fully-Adjusted * 1.00 (ref) 1.15 (0.86-1.54) 1.93 (1.37-2.71) 0.001 Emergency Department Visits Crude 1.00 (ref) 1.42 (1.03-1.96) 1.99 (1.42-2.79) <0.001 Fully-Adjusted * 1.00 (ref) 1.39 (1.00-1.93) 1.98 (1.40-2.79) <0.001 All-Cause Mortality Crude 1.00 (ref) 1.53 (0.87-2.68) 3.33 (1.95-5.70) <0.001 Fully-Adjusted * 1.00 (ref) 1.55 (0.88-2.74) 3.84 (2.21-6.68) <0.001 * Adjusted for age, sex, and Charlson comorbidity index


Author(s):  
Claudia R.L. Cardoso ◽  
Gil F. Salles

Home blood pressure (HBP) monitoring has been increasingly used in hypertension management. We aimed to evaluate the prognostic importance of HBP parameters in patients with resistant hypertension in relation to office and ambulatory blood pressures (BPs). Three hundred thirty-three patients with resistant hypertension performed 24-hour ambulatory and HBP monitoring at baseline and were followed up for a median of 5.6 years. Primary outcomes were total cardiovascular events, major adverse cardiovascular events, and all-cause and cardiovascular mortality. Associations between HBPs (total mean, morning and evening BPs, analyzed as continuous and as dichotomical variables) and outcomes were assessed by multivariable-adjusted Cox analyses. Improvement in risk discrimination with HBP was evaluated by C statistics and the Integrated Discrimination Improvement index. During follow-up, there were 48 cardiovascular events (42 major adverse cardiovascular events) and 43 all-cause deaths (26 cardiovascular). Continuous HBP parameters were associated with significantly higher risks of all adverse outcomes, with hazard ratios varying from 1.7 to 2.1, after adjustments for office and ambulatory BPs. In dichotomical analyses, uncontrolled HBP was associated with significantly higher risks of all outcomes, except for the evening HBP. Morning HBP was associated with the highest risks. HBP parameters improved risk discrimination, with increases in C statistics of up to 0.044 and relative Integrated Discrimination Improvements up to 42%, equivalent to those obtained from ambulatory BPs, except for all-cause and cardiovascular mortalities, in which ambulatory BPs provided greater improvements than HBPs. In conclusion, higher/uncontrolled HBP levels are predictive of adverse cardiovascular outcomes and mortality and improve risk discrimination in patients with resistant hypertension.


2013 ◽  
Vol 203 (2) ◽  
pp. 90-102 ◽  
Author(s):  
A. Meijer ◽  
H. J. Conradi ◽  
E. H. Bos ◽  
M. Anselmino ◽  
R. M. Carney ◽  
...  

BackgroundThe association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity.AimsTo combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity.MethodAn individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses.ResultsSixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26–1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14–1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively.ConclusionsThe association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.


2020 ◽  
Vol 15 (11) ◽  
pp. 1576-1586 ◽  
Author(s):  
Qi Chen ◽  
Zi Wang ◽  
Jingwei Zhou ◽  
Zhenjie Chen ◽  
Yan Li ◽  
...  

Background and objectivesSeveral clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR.Design, setting, participants, & measurementsWe systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis.ResultsWe identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m2 per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, −3.45 mm Hg; 95% confidence interval, −6.10 to −0.80; diastolic BP: weighted mean difference, −2.02 mm Hg; 95% confidence interval, −3.25 to −0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group.ConclusionsUrate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.


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