The European Atherosclerosis Society-European Federation of Clinical Chemistry and Laboratory Medicine Consensus Panel aims to provide recommendations to optimize atherogenic lipoprotein ...quantification for cardiovascular risk management.
We critically examined LDL cholesterol, non-HDL cholesterol, apolipoprotein B (apoB), and LDL particle number assays based on key criteria for medical application of biomarkers. (
) Analytical performance: Discordant LDL cholesterol quantification occurs when LDL cholesterol is measured or calculated with different assays, especially in patients with hypertriglyceridemia >175 mg/dL (2 mmol/L) and low LDL cholesterol concentrations <70 mg/dL (1.8 mmol/L). Increased lipoprotein(a) should be excluded in patients not achieving LDL cholesterol goals with treatment. Non-HDL cholesterol includes the atherogenic risk component of remnant cholesterol and can be calculated in a standard nonfasting lipid panel without additional expense. ApoB more accurately reflects LDL particle number. (
) Clinical performance: LDL cholesterol, non-HDL cholesterol, and apoB are comparable predictors of cardiovascular events in prospective population studies and clinical trials; however, discordance analysis of the markers improves risk prediction by adding remnant cholesterol (included in non-HDL cholesterol) and LDL particle number (with apoB) risk components to LDL cholesterol testing. (
) Clinical and cost-effectiveness: There is no consistent evidence yet that non-HDL cholesterol-, apoB-, or LDL particle-targeted treatment reduces the number of cardiovascular events and healthcare-related costs than treatment targeted to LDL cholesterol.
Follow-up of pre- and on-treatment (measured or calculated) LDL cholesterol concentration in a patient should ideally be performed with the same documented test method. Non-HDL cholesterol (or apoB) should be the secondary treatment target in patients with mild to moderate hypertriglyceridemia, in whom LDL cholesterol measurement or calculation is less accurate and often less predictive of cardiovascular risk. Laboratories should report non-HDL cholesterol in all standard lipid panels.
The ceramide- and phospholipid-based cardiovascular risk score (CERT2) has been found to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular mortality. In the present ...study, our aim was to estimate the predictive ability of CERT2 for mortality of CVD, coronary artery disease (CAD), and stroke in the elderly and to compare these results with those of conventional lipids.
We conducted a prospective study with an 18-year follow-up period that included a total of 1260 participants ages ≥64 years. Ceramides and phosphatidylcholines were analyzed using a LC-MS. Total cholesterol and triglycerides were performed by enzymatic methods and HDL cholesterol was determined by a direct enzymatic method. Concentrations of LDL-cholesterol were calculated according to the Friedewald formula.
A higher score of CERT2 was significantly associated with higher CVD, CAD, and stroke mortality during the 18-year follow-up both in unadjusted and adjusted Cox regression models. The unadjusted hazard ratios (HRs) of CERT2 (95% CI) per SD for CVD, CAD, and stroke were 1.72 (1.52-1.96), 1.76 (1.52-2.04), and 1.63 (1.27-2.10), respectively, and the corresponding adjusted HRs (95% CI) per SD for CERT2 were 1.48 (1.29-1.69), 1.50 (1.28-1.75), and 1.41 (1.09-1.83). For conventional lipids, HRs per SD were lower than for CERT2.
The risk score CERT2 associated strongly with CVD, CAD, and stroke mortality in the elderly, while the association between these events and conventional lipids was weak.
Aims
To investigate the incidence, haemodynamic alterations and 90‐day mortality of acute kidney injury (AKI) in patients with cardiogenic shock. We assessed the utility of creatinine, urine output ...(UO) and cystatin C (CysC) definitions of AKI in prognostication.
Methods and results
Cardiogenic shock patients with serial plasma samples (n = 154) from the prospective multicenter CardShock study were included in the analysis. Acute kidney injury was defined and staged according to the KDIGO criteria by creatinine (AKIcrea) and/or UO (AKIUO). CysC‐based AKI (AKICysC) was defined similarly to AKIcrea. Changes in haemodynamic parameters were assessed over time from baseline until 96 h. Mean age of the study population was 66 ± 12 years and 74% were men. Median baseline creatinine was 1.12 interquartile range (IQR) 0.87–1.54 mg/dL and CysC 1.19 (IQR 0.90–1.69) mg/L. The 90‐day mortality was 38%. The incidences for AKI were: AKIcrea 31%, AKIUO 50%, and AKICysc 33%. AKIcrea odds ratio (OR) 12.2, 95% confidence interval (CI) 4.1–36.0 and AKICysC (OR 2.5, 95% CI 1.1–6.1), but not AKIUO, were independent predictors of mortality. However, a stricter UO cut‐off of <0.3 mL/kg/h for 6 h was independently associated with 90‐day mortality (OR 3.6, 95% CI 1.4–9.3). Development of AKI was associated with persistently elevated central venous pressure and decreased cardiac index and mean arterial pressure.
Conclusions
Acute kidney injury is frequent in patients with cardiogenic shock and especially AKIcrea predicts poor outcome. The KDIGO UO criterion seems, however, rather liberal and a stricter AKI definition of UO <0.3 mL/kg/h for at least 6 h seems more useful for mortality risk prediction. Haemodynamic alterations reflecting venous congestion and hypoperfusion were associated with AKI.
Scope
The aim of the study is to examine whether lean fish (LF), fatty fish (FF), and camelina sativa oil (CSO), a plant‐based source of alpha‐linolenic acid (ALA), differ in their metabolic effects ...in subjects with impaired glucose metabolism.
Methods and results
Altogether 79 volunteers with impaired fasting glucose, BMI 25–36 kg m–2, age 43–72 years, participated in a 12‐week randomized controlled trial with four parallel groups, that is, the FF (four fish meals/week), LF (four fish meals/week), CSO (10 g d–1 ALA), and control (limited intakes of fish and sources of ALA) groups. The proportions of eicosapentaenoic acid and DHA increase in plasma lipids in the FF group, and the proportion of ALA increase in the CSO group (p < 0.0001 for all). In the CSO group, total and LDL‐cholesterol (C) concentrations decrease compared with the FF and LF groups; LDL‐C/HDL‐C and ApoB/ApoA‐I ratios decrease compared with the LF group. There are no significant changes in glucose metabolism or markers of low‐grade inflammation.
Conclusions
A diet enriched in CSO improves serum lipid profile as compared with a diet enriched in FF or LF in subjects with impaired fasting glucose, with no differences in glucose metabolism or concentrations of inflammatory markers.
In subjects with impaired glucose metabolism (n = 79), a 12‐week ingestion of camelina sativa oil decreased serum total and LDL‐cholesterol concentrations compared with the ingestion of both fatty fish and lean fish. LDL‐C/HDL‐C and ApoB/ApoA‐I ratios decreased compared with the ingestion of lean fish. There were no significant changes among the diet groups in glucose metabolism assessed by both oral and intravenous glucose tolerance tests, or markers of low‐grade inflammation.
Vitamin D deficiency has been associated with an increased risk of developing a number of diseases. Here we investigated samples from 71 pre-diabetic individuals of the VitDmet study, a 5-month high ...dose vitamin D3 intervention trial during Finnish winter, for their changes in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations and the expression of primary vitamin D target genes in peripheral blood mononuclear cells and adipose tissue. A negative correlation between serum concentrations of parathyroid hormone and 25(OH)D3 suggested an overall normal physiological vitamin D response among the participants. The genes CD14 and thrombomodulin (THBD) are up-regulated primary vitamin D targets and showed to be suitable gene expression markers for vitamin D signaling in both primary tissues. However, in a ranking of the samples concerning their expected response to vitamin D only the top half showed a positive correlation between the changes of CD14 or THBD mRNA and serum 25(OH)D3 concentrations. Interestingly, this categorization allows unmasking a negative correlation between changes in serum concentrations of 25(OH)D3 and the inflammation marker interleukin 6. We propose the genes CD14 and THBD as transcriptomic biomarkers, from which the effects of a vitamin D3 supplementation can be evaluated. These biomarkers allow the classification of subjects into those, who might benefit from a vitamin D3 supplementation, and others who do not.
The prevalence of hypoalbuminemia, early changes of plasma albumin (P-Alb) levels, and their effects on mortality in cardiogenic shock are unknown.
P-Alb was measured from serial blood samples in 178 ...patients from a prospective multinational study on cardiogenic shock. The association of hypoalbuminemia with clinical characteristics and course of hospital stay including treatment and procedures was assessed. The primary outcome was all-cause 90-day mortality.
Hypoalbuminemia (P-Alb < 34g/L) was very frequent (75%) at baseline in patients with cardiogenic shock. Patients with hypoalbuminemia had higher mortality than patients with normal albumin levels (48% vs. 23%, p = 0.004). Odds ratio for death at 90 days was 2.4 95% CI 1.5-4.1 per 10 g/L decrease in baseline P-Alb. The association with increased mortality remained independent in regression models adjusted for clinical risk scores developed for cardiogenic shock (CardShock score adjusted odds ratio 2.0 95% CI 1.1-3.8, IABP-SHOCK II score adjusted odds ratio 2.5 95%CI 1.2-5.0) and variables associated with hypoalbuminemia at baseline (adjusted odds ratio 2.9 95%CI 1.2-7.1). In serial measurements, albumin levels decreased at a similar rate between 0h and 72h in both survivors and nonsurvivors (ΔP-Alb -4.6 g/L vs. 5.4 g/L, p = 0.5). While the decrease was higher for patients with normal P-Alb at baseline (p<0.001 compared to patients with hypoalbuminemia at baseline), the rate of albumin decrease was not associated with outcome.
Hypoalbuminemia was a frequent finding early in cardiogenic shock, and P-Alb levels decreased during hospital stay. Low P-Alb at baseline was associated with mortality independently of other previously described risk factors. Thus, plasma albumin measurement should be part of the initial evaluation in patients with cardiogenic shock.
NCT01374867 at ClinicalTrials.gov.
The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic ...shock.
Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study).
A total of 254 patients with severe sepsis or septic shock.
After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily.
NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis.
NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.
Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and ...hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis.
We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene.
Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents GE/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis.
Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.
Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on ...Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation.
Abstract Aims To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart ...failure. Methods Patients with AHF (n = 620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined. Results The overall mortality was 60.3% (n = 374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p < 0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12 months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4–2.2; p < 0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome. Conclusion The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF.
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