Martin J. Holzmann

Minimal Changes in Postoperative Creatinine Values and Early and Late Mortality and Cardiovascular Events After Coronary Artery Bypass Grafting

Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with adverse outcomes. This study investigated if already a minimal change of 0 to 0.3 mg/dl in postoperative serum creatinine values was associated with early death and long-term cardiovascular outcomes and death. From the SWEDEHEART registry, we included 25,686 patients who underwent elective, isolated, primary CABG in Sweden from 2000 to 2008. AKI was categorized according to increases in postoperative creatinine values: group 1, 0 to 0.3 mg/dl; group 2, 0.3 to 0.5 mg/dl; and group 3, >0.5 mg/dl. The primary outcome measure was death from any cause. During a mean follow-up of 6 years, there were 4,350 deaths (17%) and 7,095 hospitalizations (28%) for myocardial infarction, stroke, heart failure, or death (secondary outcome). The adjusted odds ratios (95% confidence interval [CI]) for early mortality in AKI groups 1 to 3 were 1.37 (0.84 to 2.21), 3.64 (2.07 to 6.38), and 15.4 (9.98 to 23.9), respectively. For long-term mortality, the corresponding hazard ratios (95% CI) were 1.07 (1.00 to 1.15), 1.33 (1.19 to 1.48), and 2.11 (1.92 to 2.32), respectively. There was a significant association between each AKI group and the composite outcome (HR 1.09, 95% CI 1.03 to 1.15; HR 1.39, 95% CI 1.27 to 1.52; and HR 1.99, 95% CI 1.84 to 2.16, respectively). In conclusion, already a minimal increase in the postoperative serum creatinine level after CABG was independently associated with long-term all-cause mortality and cardiovascular outcomes, regardless of preoperative renal function.

Acute kidney injury after coronary artery bypass grafting and long-term risk of end-stage renal disease.

Background— Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG) and is associated with adverse outcomes. However, the relationship between AKI after CABG and the long-term risk of end-stage renal disease (ESRD) is unknown. Methods and Results— This study included 29 330 patients who underwent primary isolated CABG in Sweden between 2000 and 2008. AKI was classified according to the Acute Kidney Injury Network (AKIN) classification: stage 1, >0.3 mg/dL (>26 &mgr;mol/L) or 50% to 100% increase; stage 2, 100% to 200% increase; and stage 3, >200% increase from the preoperative to postoperative serum creatinine level. Cox proportional hazards regression analysis was used to calculate hazard ratios with 95% confidence intervals for ESRD in AKIN stage 1 and stage 2 to 3. Postoperative AKI occurred in 13% of patients. During a mean follow-up of 4.3±2.4 years, 123 patients (0.4%) developed ESRD, including 50 (1.6%) in AKIN stage 1, 29 (5.2%) in AKIN stage 2 to 3, and 44 (0.2%) without AKI after CABG. After multivariable adjustment, the hazard ratio for ESRD was 2.92 (95% confidence interval, 1.87–4.55) for AKIN stage 1 and 3.81 (95% confidence interval, 2.14–6.79) for AKIN stage 2 to 3. Conclusions— This nationwide study of patients who underwent CABG found that a small increase in the postoperative serum creatinine level was associated with an almost 3-fold increase in the long-term risk of ESRD after adjustment for a number of confounders, including preoperative renal function.

Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50–69 years

AIMS The objective was to investigate the long-term all-cause mortality in patients aged 50-69 years after aortic valve replacement (AVR) with bioprosthetic or mechanical valves. METHODS AND RESULTS All patients aged 50-69 years who had undergone AVR in Sweden 1997-2013 were identified from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register. Subsequent patient-level record linkage with national health-data registers provided patient characteristics, vital status, and clinical outcomes. Of the 4545 patients, 60% (2713/4545) had received mechanical valves and 40% (1832/4545) bioprostheses. In 1099 propensity score-matched patient pairs, 16% (180/1099) had died in the mechanical valve group and 20% (217/1099) in the bioprosthetic group; mean follow-up 6.6 (maximum 17.2) years. Survival was higher in the mechanical than in the bioprosthetic group: 5-, 10-, and 15-year survival 92, 79, and 59% vs. 89, 75, and 50%; hazard ratio 1.34; 95% confidence interval (CI) 1.09-1.66; P = 0.006. There was no difference in stroke [subdistribution hazard ratio (sHR) 1.04; 95% CI 0.72-1.50, P = 0.848]; however, the risk for aortic valve reoperation was higher (sHR 2.36; 95% CI 1.42-3.94, P = 0.001), and for major bleeding lower (sHR 0.49; 95% CI 0.34-0.70, P < 0.001), in patients who had received bioprostheses than in those with mechanical valves. CONCLUSION Patients aged 50-69 years who received mechanical valves had better long-term survival after AVR than those with bioprostheses. The risk of stroke was similar; however, patients with bioprostheses had a higher risk of aortic valve reoperation and a lower risk of major bleeding. CLINICAL TRIAL REGISTRATION http://clinicaltrials.gov/show/NCT02276950. CLINICALTRIALSGOV IDENTIFIER NCT02276950.

Acute Kidney Injury Following Coronary Artery Bypass Surgery and Long-term Risk of Heart Failure

Background— Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is common and increases the risk of postoperative complications and mortality. There is little information on the association between AKI after CABG and long-term risk of incident heart failure (HF). Methods and Results— All patients (n=24 018) undergoing primary, isolated CABG in Sweden between 2000 and 2008 with complete information on pre- and postoperative serum creatinine values, and no prior hospitalization for HF were included. The postoperative increase in serum creatinine was used to define different stages of AKI: stage 1, 0.3 to 0.5 mg/dL; stage 2, 0.5 to 1 mg/dL; stage 3, >1 mg/dL. Hazard ratios with 95% confidence intervals were calculated for first hospitalization for HF for each stage of AKI using Cox proportional hazards regression. Twelve percent of the study population developed AKI. During a mean follow-up of 4.1 years, there were 1325 cases (5.5%) of incident HF. Hazard ratios with 95% confidence interval for HF in AKI stage 1, 2, and 3 were 1.60 (1.34–1.92), 1.87 (1.54–2.27), and 1.98 (1.53–2.57), respectively, after multivariable adjustment for age, sex, diabetes mellitus, estimated glomerular filtration rate, left ventricular ejection fraction, and myocardial infarction before surgery or during follow-up. Conclusions— AKI is associated with increased long-term risk of HF after CABG. Patients with AKI after CABG should be followed closely to detect early changes in cardiac function.

Preoperative Estimates of Glomerular Filtration Rate as Predictors of Outcome after Surgery: A Systematic Review and Meta-analysis

Background:Kidney dysfunction is a strong determinant of prognosis in many settings. Methods:A systematic review and meta-analysis was undertaken to explore the relationship between estimated glomerular filtration rate (eGFR) and adverse outcomes after surgery. Cohort studies reporting the relationship between eGFR and major outcomes, including all-cause mortality, major adverse cardiovascular events, and acute kidney injury after cardiac or noncardiac surgery, were included. Results:Forty-six studies were included, of which 44 focused exclusively on cardiac and vascular surgery. Within 30 days of surgery, eGFR less than 60 ml·min·1.73 m−2 was associated with a threefold increased risk of death (multivariable adjusted relative risk [RR] 2.98; 95% confidence interval [CI] 1.95–4.96) and acute kidney injury (adjusted RR 3.13; 95% CI 2.22–4.41). An eGFR less than 60 ml·min·1.73 m−2 was associated with an increased risk of all-cause mortality (adjusted RR 1.61; 95% CI 1.38–1.87) and major adverse cardiovascular events (adjusted RR 1.49; 95% CI 1.32–1.67) during long-term follow-up. There was a nonlinear association between eGFR and the risk of early mortality such that, compared with patients having an eGFR more than 90 ml·min·1.73 m−2 the pooled RR for death at 30 days in those with an eGFR between 30 and 60 ml·min·1.73 m−2 was 1.62 (95% CI 1.43–1.80), rising to 2.85 (95% CI 2.49–3.27) in patients with an eGFR less than 30 ml·min·1.73 m−2 and 3.75 (95% CI 3.44–4.08) in those with an eGFR less than 15 ml·min·1.73 m−2. Conclusion:There is a powerful relationship between eGFR, and both short- and long-term prognosis after, predominantly cardiac and vascular, surgery.

Renal dysfunction increases the risk of ischemic and hemorrhagic stroke in the general population.

Abstract Aims. The association between chronic kidney disease (CKD) and different subtypes of stroke is unclear, and previous studies have yielded conflicting results. We aimed to assess the impact of CKD on the risk of fatal or non-fatal ischemic and hemorrhagic stroke in both men and women. Methods. In 539,287 Swedish men and women, mainly undergoing health controls, with mean age 45 years, and no previous stroke or myocardial infarction, hazard ratios for stroke were calculated to assess the association between renal dysfunction and incidence of stroke. We estimated glomerular filtration rates (GFR) using the Mayo (GFR-Mayo) formula. Glomerular filtration rate 60–90, 30–60, and 15–30 mL per minute per 1.73 m2 was defined as mildly, moderately, and severely decreased GFR, respectively. Results. There were 17,678 strokes, of which 72% were ischemic, 15% hemorrhagic, and 12% unspecified, during 12 years of follow-up. Hazard ratios (95% confidence intervals) for ischemic stroke were 1.09 (1.04–1.14) for mildly, 1.24 (1.10–1.39) for moderately, and 2.27 (1.63–3.17) for severely decreased GFR-Mayo. The corresponding figures for hemorrhagic stroke were 1.04 (0.93–1.15), 1.26 (0.96–1.64), and 2.31 (1.10–4.87). Ischemic stroke was related to all levels of decreased GFR-Mayo in both genders (P < 0.0003). Hemorrhagic stroke was only related to renal dysfunction among women; hazard ratios (95% confidence intervals) 1.38 (1.14–1.66) for mildly, 1.70 (1.13–2.57) for moderately, and 3.46 (1.09–10.9) for severely decreased GFR-Mayo. Conclusions. Already mildly decreased GFR-Mayo increases the risk of ischemic fatal or non-fatal stroke and severely decreased GFR-Mayo the risk of hemorrhagic stroke in the general population. In gender-specific analyses ischemic stroke was related to a decreased GFR-Mayo in both genders. Hemorrhagic stroke was only related to renal dysfunction among women.

Acute kidney injury after coronary artery bypass grafting and long-term risk of myocardial infarction and death.

BACKGROUND Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with early mortality. Its impact on the risk of myocardial infarction (MI) over time and long-term mortality has not been well described. METHODS We performed a nationwide population-based cohort study in 27,929 patients who underwent a first isolated CABG between 2000 and 2008 in Sweden. Acute kidney injury was divided into three categories based on the absolute increase in postoperative serum creatinine (sCr) concentration compared with the preoperative baseline: stage 1, sCr increase of 0.3 to 0.5mg/dL; stage 2, sCr increase of >0.5 to 1.0mg/dL and stage 3, sCr increase of ≥ 1.0mg/dL. RESULTS The overall incidence of postoperative AKI was 13%, 6.3% met the criterion for stage 1, 4.3% for stage 2 and 2.3% for stage 3. During a mean follow-up of 5.0 years, there were 2119 (7.6%) MIs and 4679 (17%) deaths. Multivariable adjusted hazard ratios with 95% confidence intervals for MI were 1.35 (1.15 to 1.57), 1.80 (1.53 to 2.13) and 1.63 (1.29 to 2.07), in AKI stages 1, 2 and 3, respectively. The corresponding hazard ratios for all-cause mortality were 1.30 (1.17 to 1.44), 1.65 (1.48 to 1.83) and 2.68 (2.37 to 3.03), respectively. CONCLUSIONS Our results show that AKI after CABG is associated with an increased long-term risk of MI and death.

Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications

Abstract Objectives. To investigate the prognostic importance of acute kidney injury on early mortality, postoperative stroke, and mediastinitis in patients undergoing a first isolated coronary artery bypass grafting. Design. 7594 patients undergoing coronary artery bypass grafting with information on pre- and postoperative serum-creatinine values were included. Patients were classified using the Acute Kidney Injury Network classification. Odds ratios (OR) for mortality and postoperative complications within 60 days of surgery were calculated after adjustment for confounders separately for stage 1 and for stages 2 and 3 together. Results. 1047 (14%) patients developed acute kidney injury. There were 132 (1.7%) deaths, 103 (1.4%) strokes and 118 (1.6%) cases of mediastinitis during follow-up. Among patients in stage 1 the adjusted odds ratio for death was 4.36 (95% confidence interval 2.83–6.71) and for stage 2 plus 3; 21.5 (12.0–38.6) compared to patients without acute kidney injury. Corresponding OR for stroke were 2.34 (1.43–3.82) and 6.52 (2.97–14.3) and for mediastinitis 2.88 (1.84–4.50) and 4.68 (2.07–10.6), respectively. Conclusions. Acute kidney injury following coronary artery bypass grafting is related to postoperative mortality, stroke, and mediastinitis. Patients undergoing coronary artery bypass grafting should be assessed for presence of acute kidney injury postoperatively, in order to predict early prognosis.

Long-term prognosis in patients with type 1 and 2 diabetes mellitus after coronary artery bypass grafting.

BACKGROUND Patients with diabetes mellitus (DM) have an increased risk of adverse outcomes after coronary artery bypass grafting (CABG). Previous studies have reported prognosis in relation to treatment with or without insulin, and not to the type of diabetes. OBJECTIVES This study investigated long-term survival in patients with type 1 DM (T1DM) and type 2 DM (T2DM) following CABG. METHODS We included all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent primary isolated CABG in Sweden during 2003 through 2013. We identified patients with T1DM or T2DM in the Swedish National Diabetes Register. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality in patients with T1DM or T2DM. RESULTS In total, 39,235 patients were included, of whom 725 (1.8%) had T1DM and 8,208 (21%) had T2DM. Patients with TDM1 were younger (59 vs. 67 years), had reduced kidney function (31% vs. 24%), and had peripheral vascular disease (21% vs. 11%) more often than patients with TDM2 or no diabetes. During a mean follow-up of 5.9±3.2 years (230,085 person-years), 6,765 (17%) patients died. Among patients with T1DM, 152 (21%) died, and among patients with T2DM, 1,549 (19%) died. Adjusted hazard ratio (95% confidence interval) for death in patients with T1DM and T2DM, compared with patients without diabetes, were 2.04 (1.72 to 2.42), and 1.11 (1.05 to 1.18), respectively. CONCLUSIONS Patients with T1DM had more than double the long-term risk of death after CABG compared with patients without diabetes. The long-term risk of death in patients with T2DM was only slightly increased.

Renal function assessed by two different formulas and incidence of myocardial infarction and death in middle-aged men and women

Abstract.  Holzmann MJ, Ivert T, Jungner I, Nordqvist T, Walldius G, Östergren J, Hammar N (Karolinska University Hospital, Institute of Environmental Medicine, King Gustaf V Research Institute, Karolinska Institutet; Stockholm; AstraZeneca Sverige AB, Södertälje; AstraZeneca Research & Development, Mölndal, Sweden). Renal function assessed by two different formulas and incidence of myocardial infarction and death in middle‐aged men and women. J Intern Med 2010; 267: 357–369.