Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.

Effects of short-term bisoprolol on perioperative myocardial injury in patients undergoing non-cardiac surgery: a randomized control study

The protective role of preoperative beta-blocker in patients undergoing non-cardiac surgery is unknown. We aimed to evaluate the effects of beta-blocker on perioperative myocardial injury in patients undergoing non-cardiac surgery. We consecutively enrolled 112 patients undergoing non-cardiac surgery. They were randomly allocated to receive bisoprolol or placebo given at least 2 days preoperatively and continued until 30 days after surgery. The primary outcome was incidence of perioperative myocardial injury defined by a rise of high-sensitive troponin-T (hs-TnT) more than 99th percentile of upper reference limit or a rise of hs-TnT more than 20% if baseline level is abnormal. Baseline characteristics were comparable between bisoprolol and placebo in randomized cohort Mean age was 62.5 ± 11.8 years and 76 (67.8%) of 112 patients were male. Among 112 patients, 49 (43.8%) underwent vascular surgery and 63 (56.2%) underwent thoracic surgery. The median duration of assigned treatment prior to surgery was 4 days (2–6 days). We did not demonstrate the significant difference in the incidence of perioperative myocardial injury [52.6% (30 of 57 patients) vs. 49.1% (27 of 55 patients), P = 0.706]. In addition, the incidence of intraoperative hypotension was higher in bisoprolol group than placebo group in patients undergoing non-cardiac surgery [70.2% (40 of 57 patients) vs. 47.3% (26 of 55 patients), P = 0.017]. We demonstrated that there was no statistically significant difference in perioperative myocardial injury observed between patients receiving bisoprolol and placebo who had undergone non-cardiac surgery.

Evaluation of plasma N-terminal pro-B-type natriuretic peptide levels in healthy North American Salukis with normal echocardiographic measurements.

Measurement of N‐terminal pro‐B‐type natriuretic peptide (NT-proBNP) levels has been shown to have clinical significance for diagnosis and management of heart disease in dogs. Evaluation of current reference limits for specific breeds is necessary to ensure the test can accurately distinguish between healthy and diseased animals. The objective of this study is to evaluate the adequacy of currently established NT-proBNP reference limits for clinical use in healthy Salukis. Cardiac health of 33 clinically healthy Salukis was evaluated via echocardiography using available breed standards. Plasma concentrations of NT-proBNP were measured using a commercially available assay. A one-sided 97.5% upper reference limit for the NT-proBNP concentrations was calculated using non-parametric percentile method. The 97.5% upper reference limit was 769 pmol/L (90% CI, 547-1214 pmol/L) for the study dogs. This upper reference limit was within the currently established non-breed specific NT-proBNP upper reference limit of 900 pmol/L. No relationship between sex, age, or body weight on plasma levels of NT-proBNP was noted. Results of this study supports the use of currently available non-breed specific NT-proBNP cut-off values for clinical evaluation of healthy Salukis.

Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.DesignA cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg).SettingStudy population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.ParticipantsA random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.ResultsAmong the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea <60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.ConclusionIn the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.

Prevalence and Prognostic Value of Myocardial Injury in the Initial Presentation of SARS-CoV-2 Infection among Older Adults

Myocardial involvement during SARS-CoV-2 infection has been reported in many prior publications. We aim to study the prevalence and the clinical implications of acute myocardial injury (MIN) during SARS-CoV-2 infection, particularly in older patients. The method includes a longitudinal observational study with all consecutive adult patients admitted to a COVID-19 unit between March–April 2020. Those aged ≥65 were considered as older adult group. MIN was defined as at least 1 high-sensitive troponin (hs-TnT) concentration above the 99th percentile upper reference limit with different sex-cutoff. Results. Among the 634 patients admitted during the period of observation, 365 (58%) had evidence of MIN, and, of them, 224 (61%) were older adults. Among older adults, MIN was associated with longer time to recovery compared to those without MIN (13 days (IQR 6-21) versus 9 days (IQR 5-17); p < 0.001, respectively. In-hospital mortality was significantly higher in older adults with MIN at admission versus those without it (71 (31%) versus 11 (12%); p < 0.001). In a logistic regression model adjusting by age, sex, severity, and Charlson Comorbidity Index, the OR for in-hospital mortality was 2.1 (95% CI: 1.02–4.42; p = 0.043) among those older adults with MIN at admission. Older adults with acute myocardial injury had greater time to clinical recovery, as well as higher odds of in-hospital mortality.

Cerebrospinal Fluid Protein Concentration in Healthy Older Japanese Volunteers

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.

Gelatinization or Pasting? The Impact of Different Temperature Levels on the Saccharification Efficiency of Barley Malt Starch

Efficient enzymatic hydrolysis of cereal starches requires a proper hydrothermal pre-treatment. For malted barley, however, the exact initial temperature is presently unknown. Therefore, samples were micro-mashed according to accurately determined gelatinization and pasting temperatures. The impact on starch morphology, mash viscometry and sugar yields was recorded in the presence and absence of an amylase inhibitor to differentiate between morphological and enzymatic effects. Mashing at gelatinization onset temperatures (54.5–57.1 °C) led to negligible morphological and viscometric changes, whereas mashing at pasting onset temperatures (57.5–59.8 °C) induced significant starch granule swelling and degradation resulting in increased sugar yields (61.7% of upper reference limit). Complete hydrolysis of A-type and partial hydrolysis of B-type granules was achieved within only 10 min of mashing at higher temperatures (61.4–64.5 °C), resulting in a sugar yield of 97.5% as compared to the reference laboratory method mashing procedure (65 °C for 60 min). The results indicate that the beginning of starch pasting was correctly identified and point out the potential of an adapted process temperature control.

Prevalence of Macroprolactinemia in People Detected to Have Hyperprolactinemia

Background Macroprolactinemia is an analytic laboma encountered as a part of prolactin assay. No data are available on the burden of macroprolactinemia in Indians. This study aimed to determine the prevalence and predictors of macroprolactinemia among people with hyperprolactinemia. Methods Consecutive patients detected to have serum prolactin > 18 ng/mL as per the upper reference limit were further screened for macroprolactin by post-polyethylene-glycol (PEG)-precipitation test. Macroprolactinemia was defined as post-PEG recovery of prolactin < 40%. Results The four most common underlying etiologies for the testing of hyperprolactinemia were polycystic ovary syndrome (n = 402; 32.71%), pituitary adenomas (n = 318; 25.87%), drug-induced hyperprolactinemia (n = 224; 18.23%), and infertility (n = 126; 10.25%). A total of 1,229 patients (male:female = 191:1038) having mean age 30.46 ± 10.14 years had hyperprolactinemia, of which 168 (13.7%) were diagnosed to have macroprolactinemia. Macroprolactinemia was significantly higher in females than males (15.03 vs. 6.28%; p < 0.001). Age quartile-based analysis revealed no difference in occurrence of macroprolactinemia. Only 34 patients (2.76%) with macroprolactinemia (< 40% recovery of prolactin post-PEG precipitation) had raised prolactin levels after recovery. These patients primarily had underlying pituitary pathology. Conclusion Macroprolactinemia is not uncommon in people being tested for hyperprolactinemia. We should not hesitate to screen for macroprolactinemia in patients who have incidentally been detected to have hyperprolactinemia.

Cerebrospinal Fluid Protein Concentration in Japanese Healthy Older Volunteers

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in Japanese healthy older volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥ 65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL).