| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 2. |
- Baturova, Maria A., et al.
(författare)
-
P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation – The Malmö Preventive Project
- 2024
-
Ingår i: Journal of Electrocardiology. - 0022-0736 .- 1532-8430. ; 82, s. 125-130
-
Tidskriftsartikel (refereegranskat)abstract
- Background: P-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. Methods: Malmö Preventative Project (MPP) participants were reexamined in 2002–2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. Results: During follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95–11.03) and MVP score 4 (HR 6.17 CI 95% 1.76–21.64), both correlated with LA area: Person r − 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02–6.58). Conclusion: P-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition.
|
|
| 3. |
- Berntsson, John, et al.
(författare)
-
Increased vascular endothelial growth factor D is associated with atrial fibrillation and ischaemic stroke
- 2019
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:7, s. 553-558
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular endothelial growth factor D (VEGF-D) has important functions in lymphangiogenesis and angiogenesis. High plasma levels of VEGF-D have been associated with incidence of heart failure. The association of VEGF-D with atrial fibrillation (AF) and stroke is unclear and we hypothesised that VEGF-D could also be associated with incidence of AF and ischaemic stroke. Methods: VEGF-D was measured in fasting blood samples of 4689 subjects (40% men) without a history of AF from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Median age was 58 years (range 46-68). Cox regression analyses, adjusted for multiple risk factors, was used to assess AF and ischaemic stroke risk in relation to VEGF-D levels. Results: During a median follow-up time of 20.6 years, there were 637 cases of incident AF and 322 cases of first ischaemic stroke. After adjustment, VEGF-D was significantly associated with AF (HR 1.13(95% CI 1.04 to 1.23) per 1 SD increase) and ischaemic stroke (HR 1.14(95% CI 1.02 to 1.28) per 1 SD). The association with ischaemic stroke was explained by an increased incidence of AF-related stroke. HRs per 1 SD were 1.34 (95% CI 1.04 to 1.71) for AF-related ischaemic stroke and 1.04 (95% CI 0.90 to 1.19) for ischaemic stroke without AF. Conclusions: Increased VEGF-D concentrations were associated with AF and ischaemic stroke. The relationship with ischaemic stroke was more pronounced in subjects with a diagnosis of AF.
|
|
| 4. |
- Dziubiński, Marek J., et al.
(författare)
-
Diagnostic yield is dependent on monitoring duration. Insights from a full-disclosure mobile cardiac telemetry system
- 2022
-
Ingår i: Kardiologia Polska. - 0022-9032. ; 80:1, s. 56-63
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the advancement of electrocardiogram (ECG) monitoring methods, the most important factor influencing diagnostic yield (DY) may still be monitoring duration. Ambulatory ECG monitoring, typically with 24–48 hours duration, is widely used but may result in underdiagnosis of rare arrhythmias. Aims: This study aimed to examine the relationship between the DY and monitoring duration in a large patient cohort and investigate sex and age differences in the presentation of arrhythmias. Methods: The study population consisted of 25 151 patients (57.8% women; median [interquartile range, IQR], 71 [64–78] years), who were examined with mobile cardiac telemetry during 2017 in the United States, using the PocketECGTM that continuously transmits a signal on a beat-to-beat basis. We investigated the occurrence of atrial fibrillation at a burden of both ≤1% (atrial fibrillation [AF], ≤1%) and ≤10% (AF ≤10%), premature ventricular contractions (PVC; >10 000 per 24 hours), non-sustained ventricular tachycardias (nsVT), sustained ventricular tachycardias (VT ≥30 seconds), atrioventricular blocks (AVB), pauses of >3 seconds duration, and bradycardia (heart rate <40 beats per minute for ≥60 seconds). Results: The median (IQR) recording duration was 15.4, 8.2–28.2) days. The DY increased gradually with monitoring duration for all types of investigated arrhythmias. Compared to DY after up to 30 days of monitoring, a standard 24 hours monitoring resulted in DY for males/females of 20%/18% for AF ≤1%, 29%/28% for AF ≤10%, 45%/40% for PVCs, 17%/11% for nsVT, 17%/11% for VT ≥30 seconds, 49%/42 for AVB, 27%/20% for pauses, 36%/29% for bradycardia. Conclusion: A substantial number of patients suffering from arrhythmias may remain undiagnosed due to insufficient ECG monitoring time.
|
|
| 5. |
- Engström, Gunnar, et al.
(författare)
-
Cardiovagal Function Measured by the Deep Breathing Test : Relationships With Coronary Atherosclerosis
- 2022
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background The cardiovagal function can be assessed by quantification of respiratory sinus arrhythmia (RSA) during a deep breathing test. However, population studies of RSA and coronary atherosclerosis are lacking. This population-based study examined the relationship between RSA during deep breathing and coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Methods and Results SCAPIS (Swedish Cardiopulmonary Bioimage Study) randomly invited men and women aged 50 to 64 years from the general population. CACS was obtained from computed tomography scanning, and deep breathing tests were performed in 4654 individuals. Expiration-inspiration differences (E-Is) of heart rates were calculated, and reduced RSA was defined as E-I in the lowest decile of the population. The relationship between reduced RSA and CACS (CACS≥100 or CACS≥300) was calculated using multivariable-adjusted logistic regression. The proportion of CACS≥100 was 24% in the lowest decile of E-I and 12% in individuals with E-I above the lowest decile (P<0.001), and the proportion of CACS≥300 was 12% and 4.8%, respectively (P<0.001). The adjusted odds ratio (OR) for CACS≥100 was 1.42 (95% CI, 1.10-1.84) and the adjusted OR for CACS≥300 was 1.62 (95% CI, 1.15-2.28), when comparing the lowest E-I decile with deciles 2 to 10. Adjusted ORs per 1 SD lower E-I were 1.17 (P=0.001) for CACS≥100 and 1.28 (P=0.001) for CACS≥300. Conclusions Low RSA during deep breathing is associated with increased coronary atherosclerosis as assessed by CACS, independently of traditional cardiovascular risk factors. Cardiovagal dysfunction could be a prevalent and modifiable risk factor for coronary atherosclerosis in the general population.
|
|
| 6. |
|
|
| 7. |
- Johnson, Linda S.B., et al.
(författare)
-
Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke
- 2018
-
Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 15:6, s. 805-811
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. Objective: The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. Methods: The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. Results: The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06–11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76–57.6; P <.0001, adjusted for age and sex). Conclusion: Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four–hour ECG could identify subjects suitable for primary prevention efforts.
|
|
| 8. |
- Johnson, Linda S.B., et al.
(författare)
-
LVS-HARMED Risk Score for Incident Heart Failure in Patients With Atrial Fibrillation Who Present to the Emergency Department : Data from a World-Wide Registry
- 2021
-
Ingår i: Journal of the American Heart Association. - : Wolters Kluwer. - 2047-9980. ; 10:18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is a common complication to atrial fibrillation (AF), leading to rehospitalization and death. Early identification of patients with AF at risk for HF might improve outcomes. We aimed to derive a score to predict 1-year risk of new-onset HF after an emergency department (ED) visit with AF.Methods and Results: The RE-LY AF (Randomized Evaluation of Long-Term Anticoagulant Therapy) registry enrolled patients with AF presenting to an ED in 47 countries, and followed them for a year. The end point was HF hospitalization and/or HF death. Among 15 400 ED patients, 9765 had no prior HF (mean age, 64.9 +/- 14.9 years). Within 1 year, new-onset HF developed in 6.8% of patients, of whom 21% died of HF. Independent predictors of HF included left ventricular hypertrophy (odds ratio [OR], 1.47; 95% CI, 1.19-1.82), valvular heart disease (OR, 1.55; 95% CI, 1.18-2.04), smoking (OR, 1.42; 95% CI, 1.12-1.78), height (OR, 0.93; 95% CI, 0.90-0.95 per 3 cm), age (OR, 1.11; 95% CI, 1.07-1.15 per 5 years), rheumatic heart disease (OR, 1.77, 95% CI, 1.24-2.51), prior myocardial infarction (OR, 1.85; 95% CI, 1.45-2.36), remaining in AF at ED discharge (OR, 1.86; 95% CI, 1.46-2.36), and diabetes (OR, 1.33; 95% CI, 1.09-1.64). A continuous risk prediction score (LVS-HARMED [left ventricular, valvular heart disease, smoking or other tobacco use, height, age, rheumatic heart disease, myocardial infarction, emergency department discharge rhythm, and diabetes]) had good discrimination (C statistic, 0.735; 95% CI, 0.716-0.755). Validation was conducted internally using bootstrapping (optimism-corrected C statistic, 0.705) and externally (C statistic, 0.699). The 1-year incidence of HF hospitalization and/or HF death across quartile groups of the score was 1.1%, 4.5%, 6.9%, and 14.4%, respectively. LVS-HARMED also predicted incident stroke (C statistic, 0.753; 95% CI, 0.728-0.778).Conclusions: The LVS-HARMED score predicts new-onset HF after an ED visit for AF. Preventative strategies should be considered in patients with high LVS-HARMED HF risk.
|
|
| 9. |
- Johnson, Linda S B, et al.
(författare)
-
ST segment depression on 24-hour electrocardiography predicts incident atrial fibrillation in two population-based cohorts
- 2018
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 20:3, s. 429-434
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development.Methods and results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women.Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk.
|
|
| 10. |
- Krisai, Philipp, et al.
(författare)
-
Incidence and Predictors of Heart Failure in Patients With Atrial Fibrillation
- 2021
-
Ingår i: CJC Open. - : Elsevier BV. - 2589-790X. ; 3:12, s. 1482-1489
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is a frequent cause of hospitalization and death in patients with atrial fibrillation (AF). Identifying AF patients at risk of HF hospitalization could help select individuals for intensive follow-up and treatment. Methods: We pooled data from 3 randomized trials (ACTIVE-A, RE-LY, AVERROES) of AF patients, for derivation and internal validation of a risk score for first HF hospitalization. Secondary endpoints were cardiovascular death and a composite of HF hospitalizations and cardiovascular death. Results: In 23,503 patients, the mean age was 71.3 years, and 62% were male. Over a mean follow-up of 2.0 years, 875 patients (3.7%) experienced their first HF hospitalization, and 1037 patients (4.4%) died from cardiovascular causes. Incidence rates per 100 patient-years were 1.85 for HF hospitalizations, 2.15 for cardiovascular death, and 3.71 for the composite. Independent predictors for HF hospitalizations included the following: increased age, weight, heart rate and serum creatinine level, lower height and systolic blood pressure, diabetes, vascular disease, valvular disease, heart rhythm, left ventricular hypertrophy, and intraventricular conduction delay. The C-statistic (95% confidence intervals by bootstrap simulations) was 0.717 (0.705-0.732). At 2 years of follow-up, the incidence rate of the primary outcome increased across risk-score quintiles: 0.49, 0.87, 1.29, 2.44, and 4.51 per 100 patient-years, respectively. Patients in the highest quintile had an absolute risk of 6.8% for the primary endpoint at 2 years. Conclusions: In a large AF population, new-onset HF was common. A combination of characteristics can identify high-risk patients for whom strategies to prevent HF should be considered.
|
|
