1. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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2. |
- Hayes, A., et al.
(författare)
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A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts
- 2020
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 92:8, s. 1065-1074
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Tidskriftsartikel (refereegranskat)abstract
- Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
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3. |
- Morin, D. P., et al.
(författare)
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QRS duration predicts sudden cardiac death in hypertensive patients undergoing intensive medical therapy: the LIFE study
- 2009
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Ingår i: European Heart Journal. - 1522-9645. ; 30:23, s. 2908-14
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To determine whether QRS duration predicts sudden cardiac death (SCD) in patients with left ventricular hypertrophy and treated hypertension. METHODS AND RESULTS: Over 4.8 +/- 0.9 years follow-up of 9193 hypertensive patients with electrocardiographic evidence of LVH who were treated with atenolol- or losartan-based regimens, 178 patients (1.9%) suffered SCD. In multivariable analysis including randomized treatment, changing blood pressure over time, and baseline differences between patients with and without SCD, QRS duration was independently predictive of SCD (HR per 10 ms increase = 1.22, P < 0.001). Baseline QRS duration remained a significant predictor of SCD even after controlling for the presence or absence of left bundle branch block (HR = 1.17, P = 0.001) and for changes in ECG LVH severity over the course of the study (HR = 1.16, P = 0.017). CONCLUSION: In the setting of aggressive antihypertensive therapy, prolonged QRS duration identifies hypertensive patients at higher risk for SCD, even after controlling for left bundle branch block, other known risk factors for SCD, and changes in blood pressure and severity of left ventricular hypertrophy.
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4. |
- Oikarinen, L., et al.
(författare)
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QRS duration and QT interval predict mortality in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention for Endpoint Reduction in Hypertension Study
- 2004
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Ingår i: Hypertension. - 1524-4563. ; 43:5, s. 1029-34
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular hypertrophy is a risk factor for cardiovascular mortality, including sudden cardiac death. Experimentally, left ventricular hypertrophy delays ventricular conduction and prolongs action potential duration. Electrocardiographic QRS duration and QT interval measures reflect these changes, but whether these measures can further stratify risk in patients with electrocardiographic left ventricular hypertrophy is unknown. We measured the QRS duration and QT intervals from the baseline 12-lead electrocardiograms in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, which included hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy randomized to either losartan-based or atenolol-based treatment to lower blood pressure. In the present study, we related study baseline electrocardiographic measures to cardiovascular and all-cause mortality. There were 5429 patients (male 45.8%; mean age 66+/-7 years) included in the present analyses. After a mean follow-up of 4.9+/-0.8 years, there were 417 deaths from all causes, including 214 cardiovascular deaths. In separate univariate Cox regression analyses, QRS duration and several QT measures were significant predictors of cardiovascular mortality and all-cause mortality. However, in multivariate Cox analyses including all electrocardiographic measures and adjusting for other risk factors as well as treatment strategy, only QRS duration and maximum rate-adjusted QT(apex) interval remained as significant independent predictors of cardiovascular (P=0.022 and P=0.037, respectively) and all-cause mortality (P=0.038 and P=0.002, respectively). In conclusion, in a hypertensive risk population identified by electrocardiographic left ventricular hypertrophy, increased QRS duration and maximum QT(apex) interval can further stratify mortality risk even in the setting of effective blood pressure-lowering treatment.
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5. |
- Okin, P. M., et al.
(författare)
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Electrocardiographic strain pattern and prediction of cardiovascular morbidity and mortality in hypertensive patients
- 2004
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Ingår i: Hypertension. - 1524-4563. ; 44:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.
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6. |
- Okin, P. M., et al.
(författare)
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Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study
- 2006
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Ingår i: Circulation. - 1524-4539. ; 113:1, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear. METHODS AND RESULTS: The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7+/-1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio [HR], 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences between patients with and without new-onset CHF, in-treatment differences in systolic and diastolic pressures, Sokolow-Lyon voltage, and Cornell product, and the impact of treatment with losartan versus atenolol on outcomes, ECG strain remained a significant predictor of incident CHF (HR, 1.80; 95% CI, 1.30 to 2.48) and CHF-related death (HR, 2.78; 95% CI, 1.02 to 7.63). CONCLUSIONS: ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering.
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8. |
- Albrektsson, Tomas, 1945, et al.
(författare)
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Histologic investigations on 33 retrieved Nobelpharma implants.
- 1993
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Ingår i: Clinical materials. - 0267-6605. ; 12:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Thirty Nobelpharma implants were retrieved from 17 patients despite a remaining clinical stability, after between 1 and 16 years of clinical function. The reasons for implant removal were bone resorption in combination with soft tissue disorders, psychological causes, implant fracture and post mortem cases. When measured at the cortical passage, there was an average of 84.9% direct bone-to-implant contact and 81.8% average surface bone area in individual threads as evaluated in a computerized morphometric system at the light microscopic level.
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9. |
- Gerdts, E., et al.
(författare)
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Left atrial size and risk of major cardiovascular events during antihypertensive treatment: losartan intervention for endpoint reduction in hypertension trial
- 2007
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Ingår i: Hypertension. - 1524-4563. ; 49:2, s. 311-6
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Tidskriftsartikel (refereegranskat)abstract
- The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=-0.13+/-0.03 cm/m; P<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients.
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11. |
- Hildebrandt, P., et al.
(författare)
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Impairment of cardiac function in hypertensive patients with Type 2 diabetes: a LIFE study
- 2005
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Ingår i: Diabet Med. - 0742-3071. ; 22:8, s. 1005-11
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Type 2 diabetic patients with hypertension have an increased left ventricular (LV) mass and impaired cardiac function compared to hypertensive patients without diabetes. However, it is unknown if the impaired cardiac function can be explained solely by LV hypertrophy, or is independently related to diabetes. The aim of the present study was to compare LV function between diabetic and non-diabetic hypertensive patients with electrocardiographic LV hypertrophy. METHODS: In 937 patients participating in the LIFE echocardiographic substudy, all echocardiograms were centrally evaluated by a core reading centre measuring LV mass, systolic and diastolic LV function. Known diabetes was present in 105 patients. RESULTS: Left ventricular mass was similar in diabetic and non-diabetic patients. Endocardial systolic LV function, estimated by LV ejection fraction, was reduced and indices of midwall systolic LV function were impaired in the diabetic patients. Diastolic LV filling pattern was impaired and arterial stiffness, measured by pulse pressure/stroke index, was increased in diabetic patients. CONCLUSIONS: Systolic and diastolic LV function in hypertensive patients with electrocardiographic LV hypertrophy and diabetes are impaired independent of LV mass, most likely reflecting the adverse effects of diabetes per se.
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13. |
- Okin, P. M., et al.
(författare)
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Regression of electrocardiographic left ventricular hypertrophy predicts regression of echocardiographic left ventricular mass: the LIFE study
- 2004
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Ingår i: J Hum Hypertens. - 0950-9240. ; 18:6, s. 403-9
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiogram (ECG) is widely used for detection of left ventricular hypertrophy (LVH). However, whether changes in ECG LVH during antihypertensive therapy predict changes in LV mass remains unclear. Baseline and year-1 ECGs and echocardiograms were assessed in 584 hypertensive patients with ECG LVH by Sokolow-Lyon or Cornell voltage-duration product criteria at entry into the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. A >/=25% decrease in Cornell product defined regression of ECG LVH; a <25% decrease defined no significant regression; and an increase defined progression of ECG LVH. Regression of echocardiographic LVH was defined by a >/=20% reduction in LV mass. After 1 year of therapy, 155 patients (27%) had regression of ECG LVH, 286 (49%) had no significant change, and 143 (25%) had progression of ECG LVH. Compared with patients with progression of ECG LVH, patients with no significant decrease and patients with regression of ECG LVH had stepwise greater absolute decreases in LV mass (-16+/-33 vs -29+/-37 vs -32+/-41 g, P<0.001), greater percent reductions in LV mass (-5.7+/-14.6 vs -11.3+/-13.6 vs -12.3+/-15.6%, P<0.001), and were more likely to decrease LV mass by >/=20% (11.2 vs 24.8 vs 36.1%, P<0.001), even after adjusting for possible effects of baseline and change in systolic and diastolic pressures. Compared with progression of ECG LVH, regression of the Cornell product ECG LVH is associated with greater reduction in LV mass and a greater likelihood of regression of anatomic LVH.
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14. |
- Olsen, M. H., et al.
(författare)
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Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study
- 2006
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Ingår i: J Hypertens. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 24:4, s. 775-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, reduced urine albumin/creatinine ratio (UACR) as well as regression of left ventricular hypertrophy have been associated with lower incidence of cardiovascular events. We wanted to investigate whether these prognostic improvements were independent. METHODS: In 6679 hypertensive patients included in the LIFE study, we measured UACR, left ventricular hypertrophy by electrocardiography, serum cholesterol, plasma glucose and blood pressure after 2 weeks of placebo treatment and again after 1 year of anti-hypertensive treatment with either an atenolol- or a losartan-based regimen. During this first year of treatment, 77 patients encountered a non-fatal stroke or myocardial infarction and were excluded to avoid bias. During the next 3-4 years, 610 composite endpoints [cardiovascular death (n = 228), fatal or non-fatal myocardial infarction or stroke] were recorded. RESULTS: In Cox regression analyses, the composite endpoint was after adjustment for treatment allocation predicted by baseline logUACR [hazard ratio (HR) = 1.16 per 10-fold increase, P < 0.05], 1-year logUACR (HR = 1.29 per 10-fold increase), baseline Sokolow-Lyon voltage (HR = 1.01 per mm, both P < 0.001) and 1-year Cornell product (HR = 1.01 per 100 mm x ms, P < 0.01). Cardiovascular death was predicted by 1-year logUACR (HR = 1.59, P < 0.001), baseline Sokolow-Lyon voltage (HR = 1.01, P = 0.06) and 1-year Cornell product (HR = 1.02, P < 0.001). Both were predicted independent of age, Framingham risk score, current smoking, history of cardiovascular disease and diabetes. Gender, serum cholesterol, plasma glucose and blood pressure did not enter the models. CONCLUSIONS: Baseline UACR and Sokolow-Lyon voltage, as well as in-treatment UACR and Cornell product, added to the risk prediction independent of traditional risk factors, indicating that albuminuria and left ventricular hypertrophy reflect different aspects of cardiovascular damage and are modifiable cardiovascular risk factors.
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15. |
- Palmieri, V., et al.
(författare)
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Electrocardiographic strain pattern and left ventricular diastolic function in hypertensive patients with left ventricular hypertrophy: the LIFE study
- 2006
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Ingår i: J Hypertens. - 0263-6352. ; 24:10, s. 2079-84
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether the typical electrocardiographic (ECG) strain pattern (Strain, in leads V5 and/or V6), which is associated with left ventricular hypertrophy (LVH) and LV systolic dysfunction, is independently associated with LV diastolic dysfunction is unknown. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study enrolled hypertensive patients with ECG-LVH, of whom 10% underwent Doppler echocardiography. LV diastolic function measures included peak mitral E and A wave velocities and their ratio (E/A); E wave deceleration time (EDT); atrial filling fraction (AFF); and isovolumic relaxation time (IVRT). Normal filling pattern was defined by E/A < 1 with EDT >or= 150 and or=60 ms; abnormal relaxation by E/A < 1 with EDT > 250 ms or IVRT > 100 ms; pseudonormal filling pattern by E/A >or= 1 associated with IVRT > 100 ms or EDT > 250 ms; restrictive pattern by E/A >or= 1 with IVRT < 100 ms and EDT < 250 ms. A combined index of LV systolic-diastolic function was also computed (isovolumic time/ejection time, modified myocardial performance index). Of LIFE echo substudy participants with all needed ECG and Doppler data (n = 791), 110 (14%) had Strain. RESULTS: Strain was associated with male gender, African-American race, diabetes, history of coronary heart disease (CHD), higher systolic blood pressure (BP), LV mass and relative wall thickness, and higher prevalences of echo-LV hypertrophy and wall motion abnormalities, and with slower heart rate (all P < 0.05). Age, diastolic BP and LV ejection fraction were similar in patients with or without Strain. Diastolic parameters, and prevalences of different LV filling patterns, did not differ significantly between patients with versus those without Strain (all P > 0.1), but modified myocardial performance index was higher with Strain (P < 0.05). Findings were consistent in multivariate analyses. The association of Strain with higher modified myocardial performance index was no longer statistically significant after accounting for LV systolic function and wall motion abnormalities. CONCLUSIONS: In hypertensive patients with ECG-LVH, the ECG Strain pattern did not identify independently those with more severe LV diastolic abnormalities.
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16. |
- Stefan, Ioana, et al.
(författare)
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The dark side of open innovation : Individual affective responses as hidden tolls of the paradox of openness
- 2022
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Ingår i: Journal of Business Research. - : Elsevier Inc.. - 0148-2963 .- 1873-7978. ; 138, s. 360-373
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Tidskriftsartikel (refereegranskat)abstract
- While creating value in open innovation (OI) requires knowledge sharing, appropriating value in OI entails some closedness and protectiveness. Hence, tensions between generating and appropriating value, known as the paradox of openness, may emerge in OI collaborations. Such tensions have been scarcely explored at the micro-level, even though it is a crucial piece to fully grasping the paradox of openness. Our study bridges this gap by examining individuals’ affective responses to tensions and their outcomes in OI, thereby capturing the microfoundations of the paradox of openness. The study adopts an inductive qualitative approach and delineates various micro-level coping mechanisms that build on figurative language and humor. Accordingly, our study reveals hidden tolls of the paradox of openness, highlighted by the dominance of destructive rather than constructive affective responses. These hidden tolls illuminate a “dark side” of OI, which taps into the potential failures and high costs of opening up.
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