| 1. |
- Sahlén, Anders, et al.
(författare)
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Cardiac fatigue in long-distance runners is associated with ventricular repolarization abnormalities.
- 2009
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Ingår i: Heart rhythm : the official journal of the Heart Rhythm Society. - : Elsevier BV. - 1556-3871 .- 1547-5271. ; 6:4, s. 512-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown. OBJECTIVE: The objective of this study was to examine changes in ventricular repolarization after a 30-km cross-country race in runners aged >or=55 years. METHODS: Fifteen healthy participants (62 +/- 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace. RESULTS: During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 microg/L (0.015-0.05). Global strain (19.1% +/- 2.2%) decreased on day 1 (17.2% +/- 1.8%) and day 6 (17.9% +/- 1.5%; P <.01). QT(c) increased from 431 +/- 15 ms prerace to 445 +/- 22 ms postrace and 445 +/- 15 ms on day 1 (P <.05), mainly because of an increased T(peak-end) interval (prerace 108 +/- 13 ms, postrace 127 +/- 43 ms, day 1 127 +/- 43 ms; P <.05). Postrace, T(area) (baseline 75 +/- 26 microVs) peaked on day 1 (105 +/- 42 microVs) and remained high on day 6 (89 +/- 37 microVs; P <.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho = -0.68 to -0.54; P <.05) and a larger increase in T(area) (rho = 0.73; P <.01). CONCLUSION: Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.
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| 2. |
- Almroth, Henrik, et al.
(författare)
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Atorvastatin and persistent atrial fibrillation following cardioversion : a randomized placebo-controlled multicentre study
- 2009
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Ingår i: European Heart Journal. - Philadelphia : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 30:7, s. 827-833
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION: Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.
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| 3. |
- Held, Claes, et al.
(författare)
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Effects of revascularization within 14 days of hospital admission due to acute coronary syndrome on 1-year mortality in patients with previous coronary artery bypass graft surgery
- 2007
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:3, s. 316-325
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Tidskriftsartikel (refereegranskat)abstract
- Aims To determine whether revascularization within 14 days reduces 1 -year mortality in patients with a previous CABG admitted for non-ST-elevation ACS. Current guidelines for patients with acute coronary syndrome (ACS) include early revascularization. The evidence is derived from studies, in which patients with previous coronary artery by-pass graft (CABG) surgery often were excluded and thus insufficient to support a similar strategy in these high-risk patients in whom coronary interventions are associated with lower success and higher complication rates. Methods and results A cohort of 10469 patients <80 years old from a national registry, admitted to coronary care units in Sweden, was studied. We obtained 1-year mortality data from the Swedish National Cause of Death Registry. Relative risk (RR) in patients undergoing revascularization within 14 days (n = 4269) of admission compared to those who did not (n = 6200) was calculated by using multivariable logistic regression analyses and propensity scores for the likelihood of early revascularization. At 1-year, unadjusted mortality was 5.4% in the revascularized group and 13.1% in the conservatively treated group. In multiple regression analyses, revascularization was associated with a reduction of 1-year mortality (RR 0.67; 95% Cl, 0.56-0.81; P< 0.001). Conclusion In patients with a previous CABG admitted for ACS, revascularization within 14 days of hospital admission was associated with a marked reduction in 1-year mortality, supporting an early invasive approach also in this subset of patients.
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| 4. |
- Israelsson, Elisabeth, et al.
(författare)
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Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa
- 2009
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:136
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Tidskriftsartikel (refereegranskat)abstract
- Background C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group. Methods The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes. Results The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T. Conclusion This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.
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| 5. |
- Kovacs, Alexander, et al.
(författare)
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Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:34, s. 13768-13773
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Tidskriftsartikel (refereegranskat)abstract
- Increased baseline values of the acute-phase reactant C-reactive protein (CRP) are significantly associated with future cardiovascular disease, and some in vitro studies have claimed that human CRP (hCRP) has proatherogenic effects. In vivo studies in apolipoprotein E-deficient mouse models, however, have given conflicting results. We bred atherosclerosis-prone mice (Apob 100/100Ldlr-/-), which have human-like hypercholesterolemia, with hCRP transgenic mice (hCRP+/0) and studied lesion development at 15, 30, 40, and 50 weeks of age. Atherosclerotic lesions were smaller in hCRP+/0 Apob100/100Ldlr-/- mice than in hCRP0/0Apob100/100Ldlr-/- controls, as judged from the lesion surface areas of pinned-out aortas from mice at 40 and 50 weeks of age. In lesions from 40-week-old mice, mRNA expression levels of several genes in the proteasome degradation pathway were higher in hCRP +/0Apob100/100Ldlr-/- mice than in littermate controls, as shown by global gene expression profiles. These results were confirmed by real-time PCR, which also indicated that the activities of those genes were the same at 30 and 40 weeks in hCRP+/0Apob 100/100Ldlr-/- mice but were significantly lower at 40 weeks than at 30 weeks in controls. Our results show that hCRP is not proatherogenic but instead slows atherogenesis, possibly through proteasome-mediated protein degradation. © 2007 by The National Academy of Sciences of the USA.
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| 6. |
- Lundman, Pia, et al.
(författare)
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A high-fat meal is accompanied by increased plasma interleukin-6 concentrations
- 2007
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 17:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Enhanced and prolonged postprandial lipaemia is associated with coronary heart disease (CHD). However, the mechanisms linking postprandial lipaemia to the increased risk of atherosclerosis and CHD remain to be determined. The aim of the present study was to examine the effects of a high-fat meal on plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and cellular adhesion molecules in CHD patients and control subjects. METHODS AND RESULTS: Forty-one middle-aged men with premature CHD and 26 healthy male controls were investigated. The plasma triglyceride response to the high-fat meal was significantly greater among cases than controls. The oral fat load induced a twofold increase in plasma concentrations of IL-6, an increase that was similar in CHD patients and control subjects. No changes could be detected in plasma concentrations of cellular adhesion molecules in response to postprandial lipaemia in either CHD patients or control subjects. CONCLUSION: The results of the present study suggest that a high-fat meal affects mechanisms that induce increased inflammatory activity, which is recognised as a key modulator in the development of atherosclerosis and CHD. However, the increased levels of plasma IL-6 appear not to be determined by the magnitude of the postprandial triglyceridaemia.
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| 7. |
- Nijm, Johnny, 1969-
(författare)
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Inflammation and cortisol response in coronary artery disease
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is characterized by a chronic inflammation, involving autoimmune components, in the arterial wall. An increase in proinflammatory activity relative to anti-inflammatory activity is considered to cause a progression of the disease towards plaque instability and risk of atherothrombotic events, such as acute coronary syndrome (ACS). Cortisol, the end product of the hypothalamus-pituitary-adrenal (HPA) axis, is a powerful endogenous anti-inflammatory mediator. Disturbances in the HPA axis have been reported in chronic inflammatory/autoimmune diseases, like rheumatoid arthritis. The aim of this thesis was to study various markers of systemic inflammation in patients with acute and stable conditions of coronary artery disease (CAD) and relate these findings to the cortisol response.Both patients with ACS and patients with stable CAD had high levels of C-reactive protein (CRP), interleukin (IL)-6 and IL-1 receptor antagonist, compared with healthy controls. In addition, patients with stable CAD had significantly more neutrophil-platelet aggregates than controls, as a possible indicator of neutrophil activation.The cortisol response was determined in two different cohorts of CAD patients; one consisting of patients with a first-time myocardial infarction and one consisting of patients with long-term stable CAD. From the acute phase to 3 months, the patients with a myocardial infarction showed a higher 24-h cortisol secretion and a flattened diurnal slope caused by higher cortisol levels in the evening, as compared with healthy controls. The patients with long-term stable CAD showed similarly high levels of cortisol in the evening. The levels of evening cortisol were strongly correlated with CRP and IL-6. When exposed to acute physical or acute psychological stress at 3 months, the ACS patients showed a markedly blunted cortisol response compared with healthy controls. Following the stress tests, a significant increase in CRP was observed in the patients but not in the controls, indicating a failure of the HPA axis to compensate for stress-induced inflammation in CAD.In the ACS patients, the time course of matrix metalloproteinases (MMPs) and their tissue inhibitor TIMP-1 was determined during the 3 months follow-up. A major finding was that the MMP-9 and TIMP-1 levels remained significantly higher in the patients at all time points compared to the controls. MMP-9 and TIMP-1, but not MMP-2, MMP-3 or MMP-7, were related to inflammatory activity, as assessed by CRP and IL-6. MMP-9 and TIMP-1 showed significant correlation with evening cortisol, even after adjustment for CRP and IL-6, lending further support for a link between ´high´ flat cortisol rhythm and systemic inflammatory activity.The activation status of neutrophils in stable CAD was further examined by measuring the expression, affinity state and signalling capacity of b2-integrins and the innate production of reactive oxygen species (ROS). However, the neutrophils in patients were not more activated in vivo than were cells in healthy controls, neither were they more prone to activation ex vivo. The data rather indicated an impaired function of neutrophils in stable CAD.The neutrophils in CAD patients showed a significantly lower number of total glucocorticoid receptors (GRs) and a lower GRa:GRb ratio compared to healthy controls, indicating a chronic over activation of the HPA axis and, possibly, a state of glucocorticoid resistance. Moreover, the evening cortisol levels in patients were associated with an overexpression of annexin-1, the ´second messenger´ of glucocorticoid action. In contrast to neutrophils in controls, the neutrophils in patients also showed a hyper responsiveness to exogenous annexin-1 resulting in impaired neutrophil function.To conclude, clinically stable CAD was associated with a systemic inflammatory activity, involving a high MMP-9:TIMP-1 ratio and an increased inflammatory response to acute stress but not any activation of neutrophils. This inflammatory activity was associated with a dysregulated cortisol secretion, defined by a flat diurnal rhythm and a blunted cortisol response to stress. Although the clinical relevance remains to be verified, an intriguing hypothesis is that a hyporesponsive HPA axis favours the development towards plaque instability.
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| 8. |
- Nilsson, Tage, et al.
(författare)
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Coronary angiography of patients with a previous coronary artery by-pass operation is associated with a three times increased risk for neurological complications : A report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2009
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 43:6, s. 374-379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study aimed to determine the incidence of complications of diagnostic coronary angiography that was not followed by percutaneous coronary interventions and to compare differences in complication rates between patients with or without previous coronary artery by-pass surgery. DESIGN: We evaluated major complications due to diagnostic coronary angiography by merging the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), the Swedish Hospital Discharge Registry and the National Population Registry. RESULTS: A total of 1 115 complications were recorded (2.2%). There was a higher incidence of any complications in patients with a previous coronary by-pass surgery in uni-variable analysis (2.7% vs. 2.1%, p=0.003) but not in multi-variable analysis after adjustment for differences in background and procedural factors. Neurological complications were not common (0.20%) but after adjustment for differences in background and procedural factors, the risk of neurological complications was nearly three times higher in patients with a previous CABG compared to patients without previous CABG, odds ratio 2.89 (95% CI 1.68-4.97). CONCLUSION: Neurological complications are significantly more common in patients with previous by-pass surgery. Considering the risk for neurological complications the risk-benefit ratio may be higher when compared with patients without previous by-pass surgery.
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