Serum Levels of Dihomo-Gamma (γ)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction

Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid (PUFA) derived from linoleic acid (LA). The LA:DGLA ratio reflects conversion from LA to DGLA. Low levels of DGLA in serum have been related to poor outcome in myocardial infarction (MI) patients. Aims: To assess the association of DGLA and LA:DGLA with total death as a primary aim and incident cardiovascular events as a secondary objective. Methods: Baseline samples from 1002 patients, aged 70 to 82 years, included 2–8 weeks after an MI and followed for 2 years, were used. Major adverse clinical events (MACE) consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. Cox regression analysis was used to relate serum n-6 PUFA phospholipid levels (%wt) to the risk of MACE, adjusting for the following: (1) age, sex and body mass index (BMI); (2) adding baseline cod liver oil supplementation; (3) adding prevalent hypertension, chronic kidney disease and diabetes mellitus. Results: Median DGLA level in serum phospholipids was 2.89 (Q1–Q3 2.43–3.38) %wt. DGLA was inversely related to LA and LA:DGLA ratio. There were 208 incident cases of MACE and 55 deaths. In the multivariable analysis, the hazard ratio (HR) for the total death in the three higher quartiles (Q2–4) of DGLA as compared to Q1 was 0.54 (0.31–0.95), with p = 0.03 (Model-1), 0.50 (0.28–0.91), with p = 0.02 (Model-2), and 0.47 (0.26–0.84), with p = 0.012 (Model-3), and non-significant for MACE. Risk of MACE (Model 3) approached borderline significance for LA:DGLA in Q2–4 vs. Q1 [HR 1.42 (1.00–2.04), p = 0.052]. Conclusions: Low levels of DGLA were related to a high LA:DGLA ratio and risk of total death in elderly patients with recent MI.publishedVersio

Very long chain marine n-3 polyunsaturated fatty acids in atherothrombotic heart disease. A brief review, with a focus on metabolic effects

The global burden of atherothrombotic heart disease should be considered as a life-style disorder where differences in dietary habits and related risk factors like limited physical activity and adiposity together play important roles. Related metabolic changes have been scientifically elucidated in recent decades, and the role of the very-long-chain marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been much focused on, especially their possible effects on processes like inflammation and thrombosis. In the present brief review of related metabolic mechanisms, the effects of these fatty acids in a clinical setting have been referred to, including some of the authors’ work on this topic. The main focus is the divergent results in the field and the important differences between the study population, the type of supplements and fresh marine sources, the proportion of EPA versus DHA dosages, and the duration of supplementation in clinical trials. We conclude that daily intake of at least 1 g of EPA + DHA may improve a dysmetabolic state in the population. The potential to reduce the risk and progression of atherothrombotic heart disease is still a matter of debate

Novel biomarkers of cardiovascular disease: Applications in clinical practice

Measurement of biomarkers has revolutionized the work-up of patients with suspected cardiovascular disease. The most widely used contemporary cardiovascular biomarkers are the natriuretic peptides in the diagnosis and prognosis of heart failure and cardiac troponins in the diagnosis of acute myocardial infarction. Numerous other biomarkers pertaining to diagnosis, prognosis, and risk prediction have been identified, but few have made their way to clinical practice. In this review, we will initially describe the fundamental approach to evaluate a novel biomarker. Before implementation of a biomarker into clinical practice, several stringent criteria related to its clinical utility are required. Essential statistical metrics such as discrimination, calibration, and reclassification are required to properly evaluate prediction models. We will then discuss the biomarkers according to main groups of cardiovascular pathology:1.  myocardial injury (cardiac troponins, heart-type fatty acid-binding protein, cardiac myosin binding protein-C);2.  myocardial stress (A-type and B-type natriuretic peptides, mid-regional pro-adrenomedullin, copeptin); 3.  inflammation (C-reactive protein, interleukin 6, growth differentiation factor 15, soluble suppressor of tumorigenicity 2, galectin-3);4.  platelet activation (soluble CD40 ligand, P-selectin);5.  plaque instability (lipoprotein-associated phospholipase A2, matrix metalloproteinase-9);6.  systemic stress (catecholamines, granin proteins);7.  calcium homeostasis (secretoneurin). Finally, we will discuss novel applications of cardiovascular biomarkers, more specifically prediction of ventricular arrhythmias, and the use of biomarkers in composite risk prediction models

Cardiac imaging and circulating biomarkers for primary prevention in the era ofprecision medicine

Introduction: Current primary prevention guidelines do not strongly support the use of cardiovascular imaging and circulating biomarkers in risk assessment. Still, an increasing body of evidence suggests that important prognostic information can be obtained from imaging and biomarker measurements. Areas covered: In this review, we describe the most important imaging modalities (coronary computed tomography, myocardial perfusion imaging, carotid intima media thickness, echocardiography and cardiac magnetic resonance imaging) and circulating biomarkers (cardiac troponins, B-type natriuretic peptides and C-reactive protein) for risk prediction in people without known cardiovascular disease. We discuss both the prognostic performance and clinical utility of these biomarkers in the era of primary prevention with increased focus on precision medicine. Finally, we comment on the use of cardiac biomarkers in screening for additional work-up with cardiac imaging and the combination of the entities in risk prediction. Expert opinion: We believe future primary prevention should, to a larger extent, integrate measurements of cardiovascular biomarkers and non-invasive imaging to enhance the precision of subclinical disease detection and risk stratification. The use of cardiovascular biomarkers as a screening tool for further testing with non-invasive imaging may be a cost-effective strategy

Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise

Background We aimed to assess the associations between cardiac troponin (cTn) T and I concentrations, physical exercise and the presence and severity of angiographic coronary artery disease (CAD) in patients evaluated for suspected chronic coronary syndrome (CCS). Methods and results All patients performed an exercise stress test on a bicycle ergometer and underwent invasive coronary angiography with weighted anatomical evaluation using the Gensini score. Blood samples were collected before and after exercise and analysed with high-sensitivity (hs) cTnT and cTnI assays. Of 297 patients (median age 62 (Quartile [Q]1–3 56–69) years, 35% female), 46% were categorized as “severe CAD” (Gensini score ≥ 20). Resting hs-cTnT and hs-cTnI concentrations were detectable in 88% and 100% of patients, with medians of 6 (Q1-3 4–9) ng/L and 1.5 (0.9–2.4) ng/L, respectively. In adjusted normalized linear regression analyses, higher resting concentrations were associated with increasing Gensini score (hs-cTnT: B 0.19, 95% Confidence Interval [CI] [0.09–0.41], p < 0.001; hs-cTnI: B 0.18, [0.06–0.30], p = 0.002). The area under the receiver operating characteristics curve for predicting severe CAD was 0.72 (95% CI [0.66–0.78]) and 0.68 (0.62–0.74) for resting hs-cTnT and hs-cTnI, p = 0.11 for difference. The median (Q1-3) relative increase in hs-cTnT and hs-cTnI concentrations were 5 (0–12) % and 13 (3–27) %, respectively, with no significant associations with CAD severity. Conclusions In patients with suspected CCS, higher hs-cTn concentrations at rest were associated with increasing angiographic severity of CAD, without any significant differences between the troponin isotypes. Post-exercise hs-cTn concentrations did not have discriminatory power for CAD

Galectin-3, a marker of cardiac remodeling, is inversely related to serum Levels of marine omega-3 fatty acids. A cross-sectional study

Objective: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. Setting: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2–8 weeks after the index acute myocardial infarction. Results: Gal-3 was inversely correlated to eicosapentaenoic acid (r = −.120, p = .039) and docosahexaenoic acid (r = −.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). Conclusions: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction

A single‐centre, prospective cohort study of COVID‐19 patients admitted to ICU for mechanical ventilatory support

Background Mortality rates in COVID‐19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID‐19 patients from a resource‐rich, publicly financed healthcare system. Methods Prospective study from a tertiary hospital. Consecutive SARS‐CoV‐2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High‐dose dalteparin was adjusted by D‐dimer. Demographics, treatments and high‐resolution physiological variables were collected. Outcomes were 30‐day and hospital mortality. Data are medians (quartiles). Results Of the 1484 persons in the hospital catchment area testing positive for SARS‐CoV‐2, 201 (13.5%) were hospitalized. Thirty‐eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53‐70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8‐23). D‐dimer peaked at 3.8 mg/L (2.1‐5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000‐15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. Conclusion In a prospective cohort study of mechanically ventilated COVID‐19 patients treated in a resource‐rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies

Cardiac troponin I and T for ruling out coronary artery disease in suspected chronic coronary syndrome

To compare the performance of high-sensitivity cardiac troponin I and T (hs-cTnI; hs-cTnT) in diagnosing obstructive coronary artery disease (CAD50) in patients with suspected chronic coronary syndrome (CCS). A total of 706 patients with suspected CCS, referred for Coronary Computed Tomography Angiography, were included. cTn concentrations were measured using the Singulex hs-cTnI (limit of detection [LoD] 0.08 ng/L) and Roche hs-cTnT (LoD 3 ng/L) assays. Obstructive coronary artery disease (CAD50) was defned as ≥ 50% coronary stenosis. Cardiovascular risk was determined by the NORRISK2-score. Median age of the patients was 65 (range 28–87) years, 35% were women. All patients had hs-cTnI concentrations above the LoD (median 1.9 [Q1-3 1.2–3.6] ng/L), 72% had hs-cTnT above the LoD (median 5 [Q1-3 2–11] ng/L). There was a graded relationship between hs-cTn concentrations and coronary artery calcium. Only hs-cTnI remained associated with CAD50 in adjusted analyses (OR 1.20 95% Confdence Interval [1.05–1.38]), p = 0.009). The C-statistics for hs-cTnI and hs-cTnT were 0.65 (95% CI [0.60–0.69]) and 0.60 (0.56–0.64). The highest specifcity and negative predictive values for CAD50 were in the lowest NORRISK2-tertile. hs-cTn concentrations provide diagnostic information in patients with suspected CCS, with superior performance of hs-cTnI compared to hs-cTnT in regard to CAD50. The diagnostic performance appeared best in those with low cardiovascular risk

Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19

Objective Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. Methods We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. Results Concentrations of sST2 at baseline was median 48 (IQR 37–67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36–59) ng/mL; ICU 67 (39–104) ng/mL and non-survivors 107 (72–116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . Conclusions sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19