| 8701. |
- Kraen, Morten, et al.
(författare)
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Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both myocardial perfusion single-photon emission computed tomography (MPS) and exercise ECG (Ex-ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex-ECG improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of chronic coronary syndrome, but Ex-ECG could still be of incremental prognostic importance. METHODS AND RESULTS: This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex-ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS−/Ex-ECG+, n=126 and MPS+/Ex-ECG−, n=76). During follow-up, 95 events occurred. Annualized event rates significantly increased across groups (MPS−/Ex-ECG− =1.3%, MPS−/Ex-ECG+ =3.0%, MPS+/Ex-ECG− =5.1% and MPS+/Ex-ECG+ =8.0%). In multivariable analy-ses MPS was the strongest predictor regardless of Ex-ECG findings (MPS+/Ex-ECG−, hazard ratio [HR], 3.0, P=0.001 or MPS+/Ex-ECG+, HR,4.0, P<0.001). However, an abnormal Ex-ECG almost doubled the risk in subjects with normal MPS (MPS−/Ex-ECG+, HR, 1.9, P=0.04). CONCLUSIONS: In patients with chronic coronary syndrome, combining the results from MPS and Ex-ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex-ECG to MPS, especially in patients with normal MPS.
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| 8702. |
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| 8703. |
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| 8704. |
- Krawczyk, Katarzyna, et al.
(författare)
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Myocardin Family Members Drive Formation of Caveolae.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae are membrane organelles that play roles in glucose and lipid metabolism and in vascular function. Formation of caveolae requires caveolins and cavins. The make-up of caveolae and their density is considered to reflect cell-specific transcriptional control mechanisms for caveolins and cavins, but knowledge regarding regulation of caveolae genes is incomplete. Myocardin (MYOCD) and its relative MRTF-A (MKL1) are transcriptional coactivators that control genes which promote smooth muscle differentiation. MRTF-A communicates changes in actin polymerization to nuclear gene transcription. Here we tested if myocardin family proteins control biogenesis of caveolae via activation of caveolin and cavin transcription. Using human coronary artery smooth muscle cells we found that jasplakinolide and latrunculin B (LatB), substances that promote and inhibit actin polymerization, increased and decreased protein levels of caveolins and cavins, respectively. The effect of LatB was associated with reduced mRNA levels for these genes and this was replicated by the MRTF inhibitor CCG-1423 which was non-additive with LatB. Overexpression of myocardin and MRTF-A caused 5-10-fold induction of caveolins whereas cavin-1 and cavin-2 were induced 2-3-fold. PACSIN2 also increased, establishing positive regulation of caveolae genes from three families. Full regulation of CAV1 was retained in its proximal promoter. Knock down of the serum response factor (SRF), which mediates many of the effects of myocardin, decreased cavin-1 but increased caveolin-1 and -2 mRNAs. Viral transduction of myocardin increased the density of caveolae 5-fold in vitro. A decrease of CAV1 was observed concomitant with a decrease of the smooth muscle marker calponin in aortic aneurysms from mice (C57Bl/6) infused with angiotensin II. Human expression data disclosed correlations of MYOCD with CAV1 in a majority of human tissues and in the heart, correlation with MKL2 (MRTF-B) was observed. The myocardin family of transcriptional coactivators therefore drives formation of caveolae and this effect is largely independent of SRF.
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| 8705. |
- Krawczyk, Katarzyna
(författare)
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Transcriptional control in the vascular wall. Actin-responsive coactivators and smooth muscle transcripts.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease (CVD) is the leading cause of death globally. In the European Union (EU) alone, CVD accounts for 1.8 million deaths each year. CVD is a group of disorders involving the heart and the blood vessels. The main risk factors of CVD include unhealthy lifestyles, tobacco smoking, and obesity. It has been demonstrated that chronic high blood pressure (medically termed hypertension) leads to serious clinical complications like myocardial infarction and stroke. Medical costs related to health care of CVD patients are estimated to €111 billion in the EU. It is well established that vascular smooth muscle cells (VSMCs) surrounding the blood vessels contribute to the development and progression of cardiovascular disease states. VSMCs are responsible for maintaining the vascular tone and for the regulation of blood flow and blood pressure. VSMCs are characterized by a high plasticity, which enables them to modulate their phenotype in response to intracellular and extracellular stimuli, like shear stress, high blood pressure, and hormones. VSMCs can adopt a de-differentiated, synthetic phenotype, which is associated with altered expression of many smooth muscle proteins involved in the contraction-relaxation process. The ability of VSMCs to modulate their phenotype is also termed phenotypic switching. The synthetic, proliferative VSMCs are essential during the development of vessels and in wound healing processes, whereas in adult blood vessels, most VSMCs exhibit a differentiated, quiescent phenotype. Many studies have demonstrated the contribution of dedifferentiated SMCs to maladaptive arterial remodelling. Hence, understanding the molecular mechanisms involved in phenotypic modulation of VSMCs is crucial to improve global health. The main aim of this thesis was to unravel new molecular mechanisms underlying phenotypic modulation of VSMCs. Here, I demonstrate what is likely to be a major regulatory mechanism for biogenesis of caveolae, which are small membrane organelles typical of contractile and quiescent VSMCs. I find that the expression of caveolin and cavin genes is regulated by two members of the myocardin-related transcription factors: MYOCD and MRTF-A. In the second study, we show that Notch signalling impairment decreases the expression of soluble guanylyl cyclase in VSMCs in hypertension. In my third study, I show that the expression of endothelin type B receptors is controlled by MRTF-B, ELK1, and actin cytoskeletal dynamics. In my last study, finally, synemin is identified as a new target of myocardin-related transcription factors in VSMCs. Taken together, the findings in this thesis expand the knowledge of transcriptional control mechanisms and physiology of vascular smooth muscle. Such understanding is likely to be essential for the development of new effective strategies for the prevention and treatment of cardiovascular disease.
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| 8706. |
- Kreiner, Marcelo, et al.
(författare)
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Orofacial Pain and Toothache as the Sole Symptom of an Acute Myocardial Infarction Entails a Major Risk of Misdiagnosis and Death
- 2020
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Ingår i: Journal of Oral & Facial Pain and Headache. - : QUINTESSENCE PUBLISHING. - 2333-0384 .- 2333-0376. ; 34:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To provide an update of knowledge regarding the clinical presentation and neurophysiologic aspects of orofacial pain of cardiac origin in the form of a literature review. Methods: The peer-reviewed databases Scopus/Embase, NCBI (PubMed), and Science Direct were searched up to December 2018. Results: Patients with myocardial infarction presenting without chest pain run a higher risk of death due to missed diagnosis and subsequently a significantly greater delay between the onset of symptoms and arrival at the hospital. During myocardial ischemia, orofacial pain is reported by 4 in 10 patients and described as oppressive and/or burning. Up to 4% of myocardial infarction patients experience pain solely in the orofacial structures, women more often than men. Orofacial pain during myocardial ischemia is associated with ischemia within the inferior wall of the heart, suggesting the involvement of the vagal system. Conclusion: The clinician’s awareness of the full spectrum of clinical characteristics of a myocardial infarction constitutes a key factor in accurate diagnosis. Health care professionals and the general public should be aware of the possibility of myocardial infarction presenting with orofacial pain, toothache, or ear/temporomandibular joint pain as the only symptom.
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| 8707. |
- Kremer, Christine, et al.
(författare)
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Sex differences in Outcome after Carotid Revascularization in Symptomatic and Asymptomatic Carotid Artery Stenosis
- 2023
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Ingår i: Journal of Vascular Surgery. - 1097-6809. ; 78:3, s. 10-827
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveSex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials leading to limited conclusions regarding the safety and efficacy of acute stroke treatments.MethodsA systematic review and meta-analysis was performed by literature search including 4 databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed.ResultsRegarding carotid endarterectomy (CEA) in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (p=0.16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565; 7.2% vs 5.0%; OR 1.49, 95% CI 1.04-2.12; I2=0%; p=0.03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs. 6.7%; OR 2.81,95% CI 1.66-4.75; p=0.0001). For carotid stenting (CAS) in symptomatic artery stenosis data showed a non-significant tendency toward higher peri-procedural stroke in women. Whereas, for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women compared to men after CEA had similar rates of stroke, stroke or death and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared to men (1 study, 372 patients; 10.8% vs 3.2%; OR 3.71, 95% CI 1.49-9.2; p=0.005).Furthermore, carotid stenting in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs. 0.6%, OR 2.01, 95%CI 1.23-3.28, I2=0%, p=0.005).ConclusionsA few sex-differences in short term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in RCTs, to better understand if sex differences exist and to tailor carotid revascularization accordingly.
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| 8708. |
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| 8709. |
- Kreutz, Reinhold, et al.
(författare)
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Beta-blocker bashing and downgrading in hypertension management : A fashionable trend representing a matter of concern
- 2024
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 42:6, s. 966-967
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Tidskriftsartikel (refereegranskat)abstract
- In their commentary, Shantsila et al.[1] while discussing some relevant issues of the 2023 Guidelines for the Management of Hypertension of the European Society of Hypertension (ESH) [2], for example, the length of the text and the involvement of only a few primary care physicians, they largely focus on the discussion on beta-blockers. The authors conclude that ‘the 2023 ESH Guidelines still argue in favour of beta-blockers that their clinical inferiority was simply to lesser blood pressure (BP) reduction rather than class effect’. However, this is an oversimplification that does not reflect the numerous arguments and facts that support the overall rationale of the 2023 ESH Guidelines for the recommended use of beta-blockers in the management of hypertension [2]. Taken together with other similar comments [3], it appears that it has become fashionable to down-grade beta-blockers and to dismiss the points already put forward in the 2023 ESH guidelines [2] and in previous publications revisiting beta-blocker benefits in detail [4,5]. Against this background, we use this opportunity to emphasize on key aspects of the beta-blocker discussion in brief. For a more comprehensive review of the literature, we refer to a very recent publication by us regarding the role of beta-blocker in hypertension [6].
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| 8710. |
- Kreutz, Reinhold, et al.
(författare)
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Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? : A critical review
- 2022
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 40:5, s. 839-846
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Forskningsöversikt (refereegranskat)abstract
- Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.
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