Personalized Intervention Based on Early Detection of Atherosclerosis: JACC State-of-the-Art Review.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required-moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health.

Association between transfusion of blood products and acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a serious complication following cardiac surgery associated with increased mortality. Red blood cell transfusion enhances the risk of developing AKI. However, the impact of other blood products on AKI is virtually unexplored. The aim of this study was to explore if transfusion of red blood cells, fresh frozen plasma and platelets alone or in combination were associated with postoperative AKI. METHODS: Patients undergoing elective on-pump cardiac surgery were included (n = 1960) between 2012 to 2014. Transfusion data were collected intraoperatively and until the first postoperative day. AKI was classified according to the KDIGO criteria. Data were analysed using univariate and stepwise multiple logistic regression with adjustment for clinical risk factors and complementary blood products. RESULTS: AKI was observed in 542 patients (27.7%). In univariate analysis and following adjustment for clinical risk factors, administration of red blood cells, freshfrozen plasma and platelets were all independently associated with KDIGO stage 2-3. Following additional adjustment for complementary blood products, only red blood cell transfusion remained significantly associated with AKI. A dose-dependent association between volume of red blood cells and degree of AKI severity was observed. CONCLUSION: Transfusion of all blood products in a dose-dependent manner increased the risk for AKI. However, in multivariate analysis combining all blood products, only red blood cell transfusion remained significantly associated with AKI development.

Duration of critically low oxygen delivery is associated with acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury is a serious complication following cardiac surgery associated with mortality. Restricted oxygen delivery is a potential risk factor for acute kidney injury. The aim of this study was to investigate the impact of the duration of low oxygen delivery (<272 mL  min-1  m-2 ), during cardiopulmonary bypass on kidney function. METHODS: Patients undergoing coronary artery bypass graft surgery ± valve repair were included n = 1968. Oxygen delivery was monitored during cardiopulmonary bypass. Data were explored using multiple regression analyses regarding association between low oxygen delivery and renal replacement therapy (RRT), acute kidney injury (AKI) and post-operative peak serum creatinine (PPSC). RESULTS: Post-operative peak serum creatinine, incidence of acute kidney injury, and need for dialysis increased in a dose-dependent manner in relation to duration of a mean oxygen delivery <272 mL  min-1  m-2 . Using multiple regression analyses, only exposure for at least 30 minutes was independently associated with increased PPSC and AKI. In contrast, both short (1-5 min, OR: 2.58 [1.20, 5.54]; P = .015) and at least 30-minute (OR: 2.85 [1.27-6.41]; P = .011) exposure to low DO2 were both independently associated with the need for RRT. CONCLUSION: A low oxygen delivery during cardiopulmonary bypass was in a dose-dependent manner associated with an increased risk of renal injury.

The Gly16 Allele of the G16R Single Nucleotide Polymorphism in the ß 2 -Adrenergic Receptor Gene Augments the Glycemic Response to Adrenaline in Humans.

Cerebral non-oxidative carbohydrate consumption may be driven by a ß2-adrenergic mechanism. This study tested whether the 46G > A (G16R) single nucleotide polymorphism of the ß2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Forty healthy Caucasian men were included from a group of genotyped individuals. Cardio- and cerebrovascular variables at baseline and during a 60-min adrenaline infusion (0.06 µg kg-1 min-1) were measured by Model flow, near-infrared spectroscopy and transcranial Doppler sonography. Blood samples were obtained from an artery and a retrograde catheter in the right internal jugular vein. The ADRB2 G16R variation had no effect on baseline arterial glucose, but during adrenaline infusion plasma glucose was up to 1.2 mM (CI95: 0.36-2.1, P < 0.026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. The extrapolated steady-state levels of plasma glucose was 1.9 mM (CI95: 1.0 -2.9, PNLME < 0.0026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. There was no change in the cerebral oxygen glucose index and the oxygen carbohydrate index during adrenaline infusion and the two indexes were not affected by G16R polymorphism. No difference between genotype groups was found in cardiac output at baseline or during adrenaline infusion. The metabolic response of glucose during adrenergic stimulation with adrenaline is associated to the G16R polymorphism of ADRB2, although without effect on cerebral metabolism. The differences in adrenaline-induced blood glucose increase between genotypes suggest an elevated ß2-adrenergic response in the Gly16 homozygotes with increased adrenaline-induced glycolysis compared to Arg16 homozygotes.

Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery: a randomized, blinded, placebo-controlled trial.

Glucocorticoids have attracted increasing attention as adjuvants in the treatment of acute postoperative pain. Furthermore, anecdotal reports may support glucocorticoids for preventing sustained postoperative pain. We explored preoperative dexamethasone combined with paracetamol and ibuprofen on acute and sustained pain after lumbar disk surgery. In this blinded study, 160 patients undergoing lumbar disk surgery were randomly assigned to 16 mg IV dexamethasone or placebo. All patients received perioperative paracetamol and ibuprofen, and postoperative IV patient-controlled analgesia with morphine. Primary outcome was pain during mobilization (visual analog scale) 2 to 24 hours postoperatively. Secondary outcomes were acute pain at rest, morphine consumption, nausea, vomiting, ondansetron consumption, sedation, and quality of sleep. Patients were followed up by written questionnaire 3 months postoperatively. Acute pain during mobilization (weighted average area under the curve, 2-24 hours) was significantly reduced in the dexamethasone group: 33 (22) mm vs placebo 43 (18) mm, (95% confidence interval [CI] 3-16) P = 0.005. Vomiting 0 to 24 hours postoperatively was reduced in the dexamethasone group (17 episodes) vs placebo (51 episodes) P = 0.036. No other differences were observed. However, 6.5% (95% CI 2-15) in the dexamethasone group vs placebo 0% had an antibiotically treated wound infection (P = 0.13). Sixteen percent (95% CI 7-26) vs 8% (95% CI 0-17) reported new weakness/paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively.