Cardiovascular Outcomes In Dialysis Patients Research Articles

Evaluation of the effect of statins on cardiovascular outcomes in dialysis patients.

Evaluation of the effect of statins on cardiovascular outcomes in dialysis patients.

Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor.

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): A randomized trial.

This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy with forearm autografting (PTx) on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced SHPT. In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between-groups or within-groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P=0.008) but the difference became insignificant after adjusting for baseline difference in heart failure (P=0.43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P=0.005). No significant changes were observed in HRQOL measures in either group. Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, arterial stiffness or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients.

Abstract 9607: Sex Differences in Cardiovascular Outcomes in Dialysis Patients

Background: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared to the general population. Little is known about sex differences in cardiovascular outcomes in dialysis patients which precludes sex-specific therapies. Methods: We evaluated 508,822 patients who initiated dialysis between 1/1/2005 and 12/31/2014 using the United States Renal Data System with linked Medicare claims. We determined rates of hospitalizations for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with the outcome of cardiovascular events, cardiovascular death, and all-cause death, using adjusted time-to-event models. Results: The mean age of patients in the study cohort was 70±12 years, and 44.7% were women. The cardiovascular event rate was 232 PTPY (95% CI, 231-233), with a higher rate in women than in men (248 PTPY; 95% CI, 247-250 vs. 219 PTPY; 95% CI, 217-220). Women had a 13% higher risk of cardiovascular events than did men (HR, 1.13; 95% CI, 1.11-1.14). Women had a 15% higher risk of heart failure (HR, 1.15; 95% CI, 1.13-1.16), a 29% higher risk of stroke (HR, 1.29; 95% CI, 1.26-1.32), and no difference in risk of acute coronary syndrome (HR, 0.99; 95% CI, 0.97-1.01). Women had a lower risk of cardiovascular death (HR, 0.84; 95% CI, 0.83-0.85), and a lower risk of all-cause death, as compared to men (OR, 0.92; 95% CI, 0.91-0.93). Conclusion: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality. Further studies are needed to better understand the factors associated with sex differences in cardiovascular outcomes in patients with kidney failure.

Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on cardiovascular outcomes in dialysis patients: a systematic review and meta-analysis.

Angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) are recommended by guidelines as first-line antihypertensive therapies in the general population or in patients with earlier stages of kidney disease. However, the cardioprotective benefit of these agents among patients on dialysis remains uncertain. We searched the MEDLINE, PubMed and Cochrane databases from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis. RCTs were eligible if they assessed fatal or non-fatal cardiovascular events as a primary efficacy endpoint. We identified five RCTs involving 1582 dialysis patients. Compared with placebo or no add-on treatment, the use of ACEIs/ARBs was not associated with a significantly lower risk of cardiovascular events {risk ratio [RR] 0.79 [95% confidence interval (CI) 0.57-1.11]}. Furthermore, there was no benefit in cardiovascular mortality [RR 0.82 (95% CI 0.59-1.14)] and all-cause mortality [RR 0.86 (95% CI 0.64-1.15)]. These results were consistent when the included RCTs were stratified by subgroups, including hypertension, ethnicity, sample size, duration of follow-up and quality. The present meta-analysis showed that among patients on dialysis, the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality as compared with placebo or no add-on treatment.

Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study.

Given the cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs), it is essential to identify the relationship between NSAIDs and cardiovascular outcomes in dialysis patients who have elevated cardiovascular risk. A case-crossover study was conducted to assess the association of NSAIDs with major adverse cardiac and cerebrovascular events (MACCEs) and mortality using the Korean Health Insurance dataset. The case period was defined as 1-30 days prior to the event date and the control periods were defined as 61-90 days and 91-120 days prior to the event date. There were 3433 and 8524 incident dialysis patients who experienced MACCEs and mortality, respectively, after exposure to NSAIDs within 120 days before each event. NSAIDs significantly increased the risk of MACCEs {adjusted odds ratio [aOR] 1.37 [95% confidence interval (CI) 1.26-1.50]} and mortality [aOR 1.29 (95% CI 1.22-1.36)]. Nonselective NSAIDs, but not selective cyclooxygenase-2 inhibitors, significantly increased the risk of MACCEs and mortality. However, the MACCE and mortality risk did not increase in a dose-dependent manner in the analysis according to the cumulative defined daily dosage of NSAIDs. The incidence of MACCEs in the case period tended to be more common in patients who had recent exposure to NSAIDs than in patients who did not have recent exposure to NSAIDs. Clinicians should be particularly cautious when prescribing NSAIDs to dialysis patients considering the associations of NSAIDs with cardiovascular outcomes and mortality, which might occur independent of the dose and duration of exposure.

Cardiovascular outcomes in dialysis patients: one size does not fit all.

Cardiovascular outcomes in dialysis patients: one size does not fit all.

P-cresol sulfate and indoxyl sulfate: some clouds are gathering in the uremic toxin sky

An increasing body of experimental and clinical evidence suggests that p-cresol sulfate and indoxyl sulfate contribute to the high cardiovascular burden in patients with chronic kidney disease. In a post hoc analysis on the HEMO trial, Shafi etal. failed to confirm an association between total p-cresol sulfate and indoxyl sulfate and cardiovascular outcomes in dialysis patients. Analytical issues and case-mix may explain the discrepant findings.

The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

BackgroundThere is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD).MethodsFollowing a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up.Main resultsAt baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80–4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85–2.66, p = 0.159), according to the modality of dialysis.ConclusionDialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Moderate to high intensity statin in dialysis patients after acute myocardial infarction: A national cohort study in Asia

Background and aimsStatin is not beneficial for dialysis patients but moderate to high intensity statin is beneficial for patients after acute myocardial infarction (MI). The aim of this study was to evaluate the effect of moderate to high intensity statin on mortality, cardiovascular outcomes in dialysis patients after acute MI. MethodsData on dialysis patients were retrieved from the National Health Insurance Research Database in Taiwan. Dialysis patients admitted for MI were selected and divided into two groups according to statin prescription or not after MI. All-cause mortality and cardiovascular outcomes after a 4-year follow-up were analyzed after propensity score matching (PSM). ResultsWe identified 790 patients who received moderate to high intensity statin therapy and 1788 patients who did not receive any statins after acute MI and clinical outcomes were analyzed after 1:1 PSM. The benefit of statin on mortality therapy appeared from 1 year to the end of the 4-year follow-up period after hospitalization (statin group versus non-statin group: 22.9% vs. 31.1% at 1 year (HR: 0.70; 95% CI: 0.58–0.85); 48.0% vs. 55.1% at the end of the 4 years (HR: 0.76; 95% CI: 0.67–0.88)). In addition, the impact of statin therapy was stronger in patients with shock at admission (p = 0.035). There were no differences in any individual cardiovascular outcome or adverse event. ConclusionsModerate to high intensity statin therapy might lower all-cause mortality in dialysis patients after acute MI, especially those with shock, but not influence cardiovascular outcomes and any adverse events.

Circulating Wnt/β-catenin signalling inhibitors and uraemic vascular calcifications.

The process of vascular calcification has been associated with the canonical Wnt/β-catenin signalling pathway in cell cultures and animal studies. The relationship between circulating Wnt/β-catenin inhibitors and vascular calcification in dialysis patients is unknown. The aim of this study was to investigate the associations between serum dickkopf-1 (Dkk-1) and sclerostin, two circulating inhibitors of the Wnt/β-catenin signalling pathway, and the severity of aortic calcification (AoC) and cardiovascular outcomes in dialysis patients. This was a prospective observational cohort study. One hundred and twenty-five patients on maintenance haemodialysis participated in the study. Serum levels of Dkk-1 and sclerostin were measured. AoC scores were calculated from plain films of both posterior-anterior and lateral views. The patients were followed up for 2 years or until death or withdrawal. The circulating sclerostin level was inversely associated with the severity of AoC (P = 0.035) and indicators of the bone turnover rate including serum alkaline phosphatase (ALP) (r = -0.235, P = 0.008) and intact parathyroid hormone (r = -0.523, P < 0.001). Furthermore, Cox regression analysis indicated that the patients with high circulating sclerostin levels were less likely to experience future cardiovascular events [1 pmol/L sclerostin increase, hazard ratio 0.982 (95% CI, 0.967-0.996), P = 0.015] after adjusting for a propensity score. In contrast, serum Dkk-1 was not associated with AoC and clinical outcomes. In long-term haemodialysis patients, circulating sclerostin but not Dkk-1 is inversely associated with AoCs and future cardiovascular events. Our findings suggest that sclerostin, as a bone-related protein, might act as a communicator between uraemic bone and vasculature.

Tissue Advanced Glycation End Product Deposition after Kidney Transplantation

Background: Tissue advanced glycation end products (AGEs) accumulate in chronic kidney disease (CKD) and are a measure of cumulative metabolic stress. Measurement of tissue AGEs by skin autofluorescence (SAF) correlates well with cardiovascular outcomes in dialysis patients. SAF levels in transplant recipients relative to CKD and dialysis patients have not been previously studied, and the impact of transplantation on SAF levels in dialysis patients is unknown. Methods: SAF was measured using an AGE reader in 66 patients who had received a kidney transplant. Values were compared to those obtained in 1,707 patients with CKD stage 3 and in 115 patients on dialysis. Results: Mean SAF in transplant recipients [2.81 ± 0.64 arbitrary units (AU)] was significantly lower than in patients on haemodialysis (3.73 ± 0.88 AU) and peritoneal dialysis (3.57 ± 0.75 AU; p < 0.001), but was no different from CKD stage 3 (2.79 ± 0.66 AU; p = 0.42). In the transplant group, SAF correlated most strongly with age (r = 0.316). There was no correlation between SAF and estimated glomerular filtration rate or renal replacement therapy vintage. A small cohort of patients with SAF recorded on dialysis and following transplantation showed a drop in SAF over a mean time of 16 months after transplantation. Discussion: Tissue AGE values in kidney transplant recipients are significantly lower than in patients receiving dialysis and similar to those in patients with CKD stage 3. Our data suggest that transplantation may be associated with a reduction in tissue AGEs, and this might be an important component of the observed reduction in cardiovascular risk in transplant recipients compared to patients on dialysis.

678 Ace inhibitor and angiotensin receptor blocker use and cardiovascular outcomes in dialysis patients: A population-based cohort study in Ontario, Canada

impact on mortality of improved utilization on CHD quality indicators from 2005 levels to recommend benchmark utilization of 90%. Eight CHD disease subgroups were evaluated, including in-patients with acute myocardial infarction (AMI), acute coronary syndromes and heart failure, in addition to ambulatory patients who were post-AMI survivors, or had heart failure, chronic stable angina, hypertension or hyperlipidemia. The primary outcome was the predicted mortality reduction associated with meeting quality indicator targets for each CHD subgroup-treatment combination. In 2005, there were 10,060 CHD deaths in Ontario, representing an age-adjusted CHD mortality of 191 per 100,000 people. By meeting quality indicator utilization benchmarks, mortality could be potentially reduced by approximately 20% (95% confidence interval 18.1-21.4), representing approximately 1990 avoidable deaths. The bulk of this potential benefit was in ambulatory patients with chronic stable angina (35% of reduction) and heart failure (30% of reduction). The biggest drivers were optimizing ACE inhibitor use in chronic stable angina patients (approximately 440 avoidable deaths) and -blocker use in heart failure (approximately 400 avoidable deaths). CONCLUSIONS: These findings reinforce the importance of quality indicators and could aid policy makers in prioritizing strategies to meet the goals outlined in the Canadian Heart Health Strategy and Action Plan (CHHS-AP) for reducing cardiovascular mortality.

Beta-blockers and cardiovascular outcomes in dialysis patients: a cohort study in Ontario, Canada

Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy. We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged≥66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization. There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92-1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29-0.88). We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Is There a Reversal of Reverse Epidemiology in Renal Transplant Recipients?

AbstractSimilar to the general population, cardiovascular disease is the leading cause of death in patients with a functioning renal graft. Recent studies have shown an inverse relationship between cardiovascular risk factors and outcomes in dialysis patients. Low blood pressure, low body mass index (BMI) and low serum cholesterol levels are correlated with a higher risk of adverse cardiovascular outcomes in dialysis patients. The explanation for these observations is unclear. In renal transplant recipients (RTR), these parameters are correlated with a lower risk of cardiovascular adverse outcomes, a phenomenon labeled as “reversal of reverse epidemiology.” The aims of this review are: (1) to explore the association between cardiovascular risk factors and outcomes in RTR; (2) to assess whether these effects are reversal of the reverse epidemiology in dialysis predecessors; and (3) to determine the strategies for minimizing cardiovascular risk in RTR. This article also compares the determinants of cardiovascular risk factors among the general population, maintenance dialysis patients and RTR. Because definitive evidence on optimal intervention is lacking, population‐specific clinical trials are needed to define optimum targets for treatment of these risk factors in maintenance dialysis patients and RTR separately.

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Hypertension Is Harmful to Dialysis Patients and Should Be Controlled

AbstractManaging hypertension is among the commonest and most challenging features of end‐stage renal disease and many clinical trials have shown the benefit of treating hypertension in the general population. If associations between blood pressure levels and cardiovascular outcomes in dialysis patients mirrored those seen in general population studies, one could argue that dialysis population‐specific antihypertensive trials are unnecessary. Associations between blood pressure levels and outcomes are complex in this population. Naturally, comparisons of observational and experimental findings within intervention in patients with chronic kidney disease often show a surprising degree of disparity. In addition, the possibility of serious unmeasured co‐morbid illnesses masking the true causal relationship between blood pressure and outcomes in this population looms large. Unfortunately, therefore, observational studies appear to be highly unreliable guides to identifying the truth regarding optimal management of hypertension. It appears, then, that controlled trials, alone, can inform appropriate treatment. Of late, intervention trials of antihypertensives in dialysis patients have begun to emerge. Though mostly small, less than definitive, and heterogeneous regarding patient selection, interventions and outcomes, several suggest net benefit and none suggests net harm. As dialysis patients are at vast cardiovascular risk, these findings suggest that aggressive treatment of hypertension should be the default approach, until large clinical trials show otherwise.

Left Atrial Volume is a Relevant Predictor of Cardiovascular Outcomes in Dialysis Patients

Left Atrial Volume is a Relevant Predictor of Cardiovascular Outcomes in Dialysis Patients

Smoking and cardiovascular outcomes in dialysis patients: The United States Renal Data System Wave 2 Study ,

Smoking has received surprisingly little research attention in dialysis populations, a group at monumental cardiovascular risk. Medicare claims data were used to study associations between smoking and new-onset cardiovascular outcomes, and death in the prospective, inception Wave 2 cohort (N = 4024), assembled in 1996 and 1997. Of the participants, 56.4% were lifetime nonsmokers, 3.6% were smokers with unknown current status, 20.0% had quit for more than 1 year, 5.8% had quit less than 1 year ago, and 14.2% were current smokers. Subjects with cardiovascular disease at baseline were more likely to be former smokers, less likely never to have smoked and less likely to be current smokers (P < 0.001). Patients were followed until December 31, 1998. When adjustment was made for baseline age, demographic variables, mode of dialysis therapy, and comorbidity, smoking status was associated with new-onset congestive heart failure (adjusted hazards ratio 1.59 comparing current to nonsmokers, P = 0.004), new-onset peripheral vascular disease (adjusted hazards ratio 1.68, P < 0.001), and mortality (adjusted hazards ratio 1.37, P < 0.001). Former smokers, in contrast, had adjusted event risks similar to lifelong nonsmokers. Smoking is a major, modifiable, cardiovascular risk factor in patients starting dialysis therapy.