Copeptin levels associate with cardiovascular events in patients with ESRD and type 2 diabetes mellitus.

In ESRD, the neurohormone arginine vasopressin (AVP) may act primarily through V1a and V1b receptors, which promote vasoconstriction, myocardial hypertrophy, and release of adrenocorticotropic hormone. The preanalytical instability of AVP limits the investigation of whether this hormone associates with cardiovascular events, but the stable glycopeptide copeptin may serve as a surrogate because it is co-secreted with AVP from the posterior pituitary. Here, we studied whether copeptin predicts cardiovascular risk and mortality in ESRD. We measured copeptin at baseline in 1241 hemodialysis patients with type 2 diabetes participating in the German Diabetes and Dialysis Study. The median copeptin level was 81 pmol/L (interquartile range, 81 to 122 pmol/L). In Cox regression analyses, compared with patients with copeptin levels in the lowest quartile (≤51 pmol/L), patients with copeptin levels in the highest quartile (>122 pmol/L) had a 3.5-fold increased risk for stroke (HR, 3.48; 95% CI: 1.71 to 7.09), a 73% higher risk for sudden death (HR, 1.73; 95% CI: 1.01 to 2.95), a 42% higher risk for combined cardiovascular events (HR, 1.42; 95% CI: 1.06 to 1.90), and a 48% higher risk for all-cause mortality (HR, 1.48; 95% CI: 1.15 to 1.90). In contrast, we did not detect significant associations between copeptin levels and risks for myocardial infarction or death caused by congestive heart failure. In conclusion, copeptin levels strongly associate with stroke, sudden death, combined cardiovascular events, and mortality in hemodialysis patients with type 2 diabetes. Whether vasopressin receptor antagonists will improve these outcomes requires further studies.

Association of LDL cholesterol and inflammation with cardiovascular events and mortality in hemodialysis patients with type 2 diabetes mellitus.

BACKGROUND: In the general population, C-reactive protein (CRP) in addition to low-density lipoprotein (LDL) cholesterol level is useful in predicting cardiovascular events. In hemodialysis patients, the additive value is unknown. The association between LDL cholesterol level and outcome previously was suggested to be inverse and confounded by inflammation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,255 hemodialysis patients with type 2 diabetes mellitus randomly assigned to atorvastatin versus placebo in the German Diabetes Dialysis Study. PREDICTORS: Baseline LDL cholesterol level. OUTCOMES & MEASUREMENTS: Combined vascular end point (cardiac death, myocardial infarction, and stroke), mortality, myocardial infarction, sudden death, and stroke. RESULTS: During 4 years, 465 combined vascular events, 612 deaths, 160 sudden deaths, 200 myocardial infarctions, and 99 strokes occurred. Median LDL cholesterol level was 123 mg/dL. LDL cholesterol level (millimoles per liter and quartiles) was not predictive of outcome. This was analyzed further in patients with and without inflammation. In patients with inflammation (CRP level > 5 mg/L), the adjusted relative risk of combined vascular events was 29% greater compared with those without inflammation and a low LDL cholesterol level (LDL cholesterol < or = 123 mg/dL). This was irrespective of whether LDL cholesterol level was low or high (hazard ratio [HR] for LDL < 123 mg/dL [HR (for LDL< or =123 mg/dL)], 1.29, with 95% confidence interval [CI], 0.98 to 1.70; HR(LDL>123 mg/dL), 1.29, with 95% CI, 0.99 to 1.69). Similar results were found for all-cause death (HR(LDL< or =123 mg/dL), 1.47 [95% CI, 1.16 to 1.86]; HR(LDL>123 mg/dL), 1.48 [95% CI, 1.16 to 1.88]), sudden death (HR(LDL< or =123 mg/dL), 1.98 [95% CI, 1.23 to 3.20]; HR(LDL>123 mg/dL), 1.66 [95% CI, 1.01 to 2.75]), and myocardial infarction (HR(LDL< or =123 mg/dL), 1.74 [95% CI, 1.14 to 2.66]; HR(LDL>123 mg/dL), 1.54 [95% CI, 0.99 to 2.38]). In patients without inflammation, the respective risks did not differ significantly between patients with varying LDL cholesterol levels. However, there was a trend toward an increased risk of myocardial infarction (HR(LDL>123 mg/dL), 1.45 [95% CI, 0.95 to 2.21]) in patients with high compared with low LDL cholesterol levels. P values for the interaction between CRP and LDL cholesterol levels were 0.9 (composite vascular end point), 0.5 (mortality), 0.9 (sudden death), 0.09 (stroke), and 0.2 (myocardial infarction). LIMITATIONS: Selected patient cohort, post hoc analysis. CONCLUSION: Because CRP level more than LDL cholesterol level determined outcome, the value of regular LDL cholesterol measurements in long-term hemodialysis patients with type 2 diabetes needs reassessment.

Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death, stroke, myocardial infarction, and all-cause mortality in diabetic dialysis patients.

AIMS: N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are altered in renal failure. This study examined the effect of baseline and change from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis patients. METHODS AND RESULTS: On the basis of the German Diabetes and Dialysis Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM) haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on pre-specified, adjudicated endpoints was investigated: sudden death (SD; n = 160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612). Patients with baseline NT-pro-BNP ≥ 9252 pg/mL (fourth quartile) exhibited a more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.0-8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2-3.3), CVE (HR 2.0; 95% CI 1.5-2.7), and mortality (HR 2.1; 95% CI 1.6-2.7) compared with patients with baseline NT-pro-BNP ≤ 1433 pg/mL (first quartile). Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality. Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1-2.0). Neither baseline nor change in NT-pro-BNP was significantly associated with MI. CONCLUSION: Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves outcome needs to be evaluated prospectively.

Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus on hemodialysis.

Statins have multiple effects, including anti-inflammatory actions, lowering C-reactive protein levels, and reducing coronary events. We performed a post hoc analysis of the randomized placebo-controlled 4D Study that had evaluated the efficacy and safety of atorvastatin in 1255 patients with type 2 diabetes mellitus who were on maintenance hemodialysis. Here we determined the relationship between atorvastatin treatment, C-reactive protein, and the outcome of patients who had pre-specified and adjudicated endpoints of all-cause mortality, composite vascular endpoint, myocardial infarction, sudden death, and stroke. Atorvastatin had no significant effect on the risk of composite vascular endpoint or death relative to placebo in any quartile of baseline C-reactive protein. These baseline levels were not significantly different between the treated and placebo group and remained stable at 6 months on atorvastatin but significantly increased in those patients on placebo. All of the patients with baseline C-reactive protein in the fourth quartile had a significantly increased risk of deaths and in composite vascular endpoint compared to patients in the first quartile. The mean value of two consecutive C-reactive protein measurements was associated with significant increases in the risk of sudden death, stroke, all-cause mortality and composite vascular endpoint. Our results show that C-reactive protein was highly predictive of outcome, but atorvastatin treatment was not associated with reduced relative risks in the composite vascular endpoint or mortality in patients on hemodialysis with or without inflammation.

Antibodies to platelet factor 4-heparin complex and outcome in hemodialysis patients with diabetes.

BACKGROUND AND OBJECTIVES: Hemodialysis patients with type 2 diabetes exhibit an excessive cardiovascular risk and regularly receive heparin. We tested whether antibodies to the platelet factor 4-heparin complex (PF4-H-AB) contribute to outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 1255 hemodialysis patients with type 2 diabetes, the German Diabetes Dialysis Study evaluated the effect of atorvastatin (20 mg/d) versus placebo. In a post hoc analysis, the association among PF4-H-ABs, biochemistry, and prespecified, centrally adjudicated end points (combined cardiovascular end point [CVE], all-cause mortality, sudden death, myocardial infarction, stroke) was investigated. RESULTS: During 4 years, 460 patients reached the CVE; 605 died, 159 of sudden death. Myocardial infarction and stroke occurred in 199 and 97 patients, respectively. Positive PF4-H-AB status was found in 231 (18.7%) of 1236 tested patients and was associated with lower albumin, higher C-reactive protein, and arrhythmia. In a multivariate model adjusted for demographics, comorbidities, and biochemistry, PF4-H-ABs were associated with sudden death. No significant association between PF4-H-ABs and all-cause mortality, myocardial infarction, stroke, or the CVE was observed. Detecting an interaction between acetylsalicylic acid and PF4-H-ABs regarding sudden death and mortality, we found that the association between PF4-H-ABs and outcomes was restricted to patients with acetylsalicylic acid use, most likely because of indication bias. CONCLUSIONS: In hemodialysis patients who have type 2 diabetes and are treated with acetylsalicylic acid, PF4-H-ABs are associated with sudden and all-cause death. Further studies are needed to elucidate this association.

Electrocardiography and outcome in patients with diabetes mellitus on maintenance hemodialysis.

BACKGROUND AND OBJECTIVES: In hemodialysis, applicable guidelines recommend regular electrocardiogram (ECG) recordings. However, respective systematic evaluations are absent. Thus, the authors investigated whether routine ECG findings add prognostic information to standard risk assessment in hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The relationship between nine common baseline ECG variables and a combined cardiovascular endpoint (CVE; cardiac death, myocardial infarction, stroke), sudden death, stroke, MI, and all-cause death in 1253 patients from the German Diabetes and Dialysis Study was evaluated. All patients were on maintenance hemodialysis, had type 2 diabetes mellitus, and received randomized treatment with atorvastatin or placebo. RESULTS: During 4 yr of follow-up (March 1998 to March 2004), 469 patients reached the CVE, and 617 died. After adjustment for demographics, comorbidities, and biomarkers in multivariate analysis, patients presenting without sinus rhythm were 89% more likely to die, and the risk of CVE and stroke increased by 75% and 164%, respectively, compared with patients with preserved sinus rhythm. Left ventricular hypertrophy was associated with >2-fold increase in the risk of stroke and a 60% increase in the risk of sudden death. CONCLUSIONS: In hemodialysis patients with type 2 diabetes mellitus, the absence of sinus rhythm is a risk indicator for CVE, stroke, and all-cause death, and left ventricular hypertrophy is associated with stroke and sudden death. Thus, routine ECG recording adds prognostic information to standard risk assessment.

Biodegradable implants versus standard metal fixation for displaced radial head fractures. A prospective, randomized, multicenter study.

This multicenter, prospective, randomized study compares the use of biodegradable polylactide pins with standard metal mini-fragment implants for the treatment of displaced radial head fractures. It compares complication rates and clinical outcomes of both treatment methods. At 2 years, 135 (82%) of 164 patients were available for evaluation. Equivalence of treatment method was defined as a difference of 10% or less in the number of complication-free patients. Functional status was assessed by using the Broberg and Morrey Elbow Score and compared by an unpaired t test. Good or excellent clinical results were achieved by 92% (56/61) of the control patients and 96% (71/74) of the polylactide patients. The incidence of complication-free patients was 3.7% less in the polylactide group than in the control group. The 1-sided 95% confidence interval for the treatment difference between the 2 groups was more than -6.1%. Biodegradable polylactide pins have at least comparable outcomes as standard metal implants for the internal fixation of reconstructable displaced radial head fractures.

Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Results from a prospective randomized study.

AIMS: Despite the high prevalence of atrial fibrillation (AF), there are only limited data on quality of life (QoL) stemming from prospective trials comparing rate versus rhythm control. This prospective study evaluated QoL in patients with symptomatic persistent AF randomized to therapy aiming at rate versus rhythm control. METHODS AND RESULTS: Patients with symptomatic persistent AF (7 to 360 days duration) were prospectively randomized to ventricular rate control (n=125) or to cardioversion and maintenance of sinus rhythm (n=127). QoL was assessed by the Medical Outcomes Study Short Form health survey (SF-36) at baseline and during 1 year of follow-up. Changes in QoL were compared on an intent-to-treat basis, and subsequently between patients in sinus rhythm versus AF. At baseline, all SF-36 scales were reduced compared to healthy controls. At 1 year, six of eight items had improved significantly in patients assigned to rate control, and five of eight items on rhythm control (p=ns). The physical component summary showed a comparable increase with both treatment strategies (rate control: p=0.004; rhythm control: p<0.001) whereas no significant changes were found for the mental component summary. At 1 year, 55% of patients reported a positive health transition with no inter-group differences. There were no significant differences in QoL in patients in sinus rhythm or AF at the end of the observation period. CONCLUSION: In patients with symptomatic persistent AF, the two treatment strategies of rate versus rhythm control are associated with similar improvements in QoL.