| 1. |
- Pereira Filho, Antonio J. G., et al.
(författare)
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Impact of Ankle Brachial Index Calculations on Peripheral Arterial Disease Prevalence and as a Predictor of Cardiovascular Risk
- 2022
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier. - 1078-5884 .- 1532-2165. ; 64:2-3, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to estimate the prevalence and predictive accuracy for cardiovascular (CV) morbidity by using different ankle brachial index (ABI) calculation methods in the general population.Methods: ABI measurements and questionnaire data were collected from 5 080 randomly selected citizens aged 60 - 90 years. A 10 year follow up with data from Swedish national health registries was carried out. ABI was calculated using as numerator the highest (ABI-HI) or the lowest (ABI-LO) ankle BP obtained in each leg. Subjects were defined as references or having peripheral arterial disease (PAD) based on ABI-LO (Group 1) or ABI-HI (Group 2). Prevalence, mortality, CV events and risk were then analysed for these three groups, and their predictive power by using the area under the curve (AUC).Results: A total of 4 909 inhabitants were included in the cohort (References: 83.8%, Group 1: 6.7% and Group 2: 9.6%). The prevalence of PAD was 16% using ABI-LO, and 9.6% using ABI-HI. The 10 year all cause mortality for references and Groups 1 and 2 was 27.6%, 48.8%, and 67.2%, respectively. The overall age adjusted hazard ratio (95% confidence interval) for the composite outcome of CV mortality and a non-fatal CV event was 1.25 (1.06 - 1.49) for Group 1 and 2.11 (1.85 - 2.39) for Group 2. The prediction accuracy for ABI < 0.9 in predicting CV event measured with AUC was 0.60 for ABI-HI and 0.62 for ABI-LO.Conclusion: An ABI < 0.9 should be considered a strong risk marker for future CV morbidity. Applying the traditional ABI calculation method of using the highest measured ankle BP, a group of subjects with high CV risk may be overlooked for intervention, and this why the lowest ankle BP should be the preferred for risk stratification. However, as a single predictive tool an ABI < 0.9 cannot adequately discriminate which individual will have a future CV event regardless of calculation method used.
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| 2. |
- Sartipy, Fredrik, et al.
(författare)
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Cardiovascular long-term outcome and prophylactic treatment patterns in peripheral arterial disease in a population-based cohort
- 2019
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : OXFORD UNIV PRESS. - 2058-5225 .- 2058-1742. ; 5:4, s. 310-320
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study evaluates 10-year follow-up data on associated comorbidity, mortality, and pharmacological treatment patterns for men and women with different stages of peripheral arterial disease (PAD) in a population-based setting.Methods and results: This was a prospective observational population-based cohort study, based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ankle-brachial index levels and reported symptoms; asymptomatic PAD (APAD), intermittent claudication (IC), severe limb ischaemia (SLI), or references (Ref). Cox proportional hazards regression models were used for analysis with adjustments for sex and baseline age and comorbidity. The cohort consisted of 5080 subjects (45% males). At baseline, APAD, IC, and SLI were prevalent in 559 (11%), 320 (6.3%), and 78 (1.5%) subjects, respectively. A significant increased risk for cardiovascular (CV) death, even when adjusted for age and baseline morbidity, were noted in all PAD stages as compared with reference group with a small difference between APAD and IC, an adjusted hazard ratio 1.80 (confidence interval 1.45-2.22) and 1.95 (1.50-2.53), respectively. Only about 60% of PAD subjects received medical prophylactic treatment as recommended in guidelines.Conclusion: Peripheral arterial disease subjects had significantly increased CV morbidity and mortality risks, especially males. Asymptomatic PAD subjects confer similar risk for CV events as symptomatic patients. Our findings motivate enhanced preventive efforts of all PAD stages, including in asymptomatic disease.
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| 3. |
- Sartipy, Fredrik, et al.
(författare)
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Presence of asymptomatic Peripheral Arterial Disease in combination with common risk factors elevates the cardiovascular risk Substantially
- 2022
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Ingår i: INTERNATIONAL JOURNAL OF CARDIOLOGY CARDIOVASCULAR RISK AND PREVENTION. - Philadelphia, PA, United States : Elsevier. - 2772-4875. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: This study evaluates the risks for adverse cardiovascular (CV) events in Asymptomatic Peripheral Arterial Disease (APAD) combined with different traditional CV risk factors. Methods: A population-based observational study of 8000 subjects, identified 559 subjects as having APAD through ankle-brachial index (ABI) measurements and questionnaires regarding limb symptoms. This cohort and subgroups classified by presence of different traditional CV risk factors at baseline were assessed for 10 years on CV outcome. The recorded endpoints were all-cause mortality, CV mortality and non-fatal CV events. Results: Before subdividing the APAD subjects, the CV mortality incidence was 28.5 deaths per 1000 person-years as compared to 8.7 deaths for references without APAD. For subjects with hypertension at baseline the CV mortality incidence was 35.4 when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p < 0.001]. Conclusions: ABI measurements should be considered an important indication for aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor. In hypertension, diabetes mellitus and a smoking history, coexisting APAD contributes significantly to the increased age-adjusted CV risk.
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| 4. |
- Sartipy, Fredrik, et al.
(författare)
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Ten Year Mortality in Different Peripheral Arterial Disease Stages : A Population Based Observational Study on Outcome
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 55:4, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease (PAD) stages in a population based setting. Methods: A randomly selected population sample of 5080 subjects was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages and reference subjects. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was then compared with PAD stage determined at baseline in 2005. Results: The 10 year all cause mortality was 27% for reference cases, 56% for asymptomatic PAD (APAD), 63% for intermittent claudication (IC), and 75% for severe limb ischaemia (SLI). Among all PAD subjects, cardiovascular (CV) causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 (95% CI 1.5-2.3) for APAD, 2.6 (95% CI 2.1-3.4) for IC, and 3.5 (95% CI 2.3-5.2) for SLI. Conclusion: PAD subjects, including the APAD subjects, are still at high risk of CV death. The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. Awareness and improved risk reduction management of PAD are still warranted.
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| 5. |
- Andersson, Henrik, et al.
(författare)
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Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
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Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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| 6. |
- Christoffersson, Jonas, 1986-
(författare)
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Organs-on-chips for the pharmaceutical development process : design perspectives and implementations
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organs-on-chips are dynamic cell culture devices created with the intention to mimic organ function in vitro. Their purpose is to assess the toxicity and efficacy of drugs and, as early as possible in the pharmaceutical development process, predict the outcome of clinical trials. The aim of this thesis is to explain and discuss these cell culture devices from a design perspective and to experimentally exemplify some of the specific functions that characterize organs-on-chips.The cells in our body reside in complex environments with chemical and mechanical cues that affect their function and purpose. Such a complex environment is difficult to recreate in the laboratory and has therefore been overlooked in favor of more simple models, i.e. static twodimensional (2D) cell cultures. Numerous recent reports have shown cell culture systems that can resemble the cell’s natural habitat and enhance cell functionality and thereby potentially provide results that better reflects animal and human trials. The way these organs-on-chips improve in vitro cell culture assays is to include e.g. a three-dimensional cell architecture (3D), mechanical stimuli, gradients of oxygen or nutrients, or by combining several relevant cell types that affect each other in close proximity.The research conducted for this thesis shows how cells in 3D spheroids or in 3D hydrogels can be cultured in perfused microbioreactors. Furthermore, a pump based on electroosmosis, and a method for an objective conceptual design process, is introduced to the field of organs-on-chips.
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| 7. |
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| 8. |
- Kallonen, Janica, et al.
(författare)
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Quality of life and functional status after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension : A Swedish single-center study
- 2023
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Ingår i: Pulmonary Circulation. - : Wiley. - 2045-8932 .- 2045-8940. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about long-term quality of life (QOL) and functional status after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). We investigated QOL and functional status late after PEA. All patients who underwent PEA for CTEPH 1993–2020 at one Swedish center were included. Baseline characteristics and data from right heart catheterization, 6-min walk test, and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) were obtained from patient charts and national registers. The RAND 36-Item Health Survey was sent by post, and Karnofsky Performance Status (KPS) was evaluated by telephone. A total of 110 patients were included. The survey was completed by 49/66 (74%) patients who were alive in 2020. In all domains except for bodily pain, QOL was slightly lower than that of an age-matched reference population. The KPS score was obtained from 42/49 (86%) patients; of these, 31 patients (74%) had a KPS score of ≥80% (able to carry on normal activity). All 42 patients were able to live at home and care for personal needs. The median postoperative CAMPHOR scores were: 4 for symptoms, 4 for activity, and 2.5 for QOL. We observed that QOL after PEA approached the expected QOL in a reference population and that CAMPHOR scores were comparable to those of a large UK cohort after PEA. Functional status improved when assessed late after PEA. Three-quarters of the study population were able to conduct normal activities at late follow-up. Our findings suggest that many patients enjoy satisfactory QOL and high functional status late after PEA.
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| 9. |
- Mandenius, Carl-Fredrik, et al.
(författare)
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Cardiotoxicity testing using pluripotent stem cell-derived human cardiomyocytes and state-of-the-art bioanalytics: a review
- 2011
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Ingår i: JOURNAL OF APPLIED TOXICOLOGY. - : John Wiley and Sons, Ltd. - 0260-437X .- 1099-1263. ; 31:3, s. 191-205
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Forskningsöversikt (refereegranskat)abstract
- In this article, recent progress in cardiotoxicity testing based on the use of immortalized cell lines or human embryonic stem cell (hESC) derived cardiomyocytes in combination with state-of-the-art bioanalytical methods and sensors is reviewed. The focus is on hESC-derived cells and their refinement into competent testing cells, but the access and utility of other relevant cell types are also discussed. Recent developments in sensor techniques and bioanalytical approaches for measuring critical cardiotoxicity parameters are highlighted, together with aspects of data evaluation and validation. Finally, recommendations for further research are given.
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| 10. |
- Sartipy, Fredrik
(författare)
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Cardiovascular risk assessments in peripheral arterial disease : results of a ten-year follow-up of a Swedish population-based cohort
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: An updated knowledge on natural history in Peripheral Arterial Disease (PAD) is lacking, in particular for the asymptomatic stage (APAD). The disease has strong associations with other atherosclerotic manifestations such as myocardial infarction or stroke, which could be prevented with prophylactic measures. PAD is easily detected through simple ankle and brachial blood pressure measurements, why screening for this condition has been suggested but is yet not proven cost-effective. Identification of PAD could be useful in cardiovascular (CV) risk assessments. To improve health in society and to reduce costs for care, improved prophylactic strategies is needed in CV management. Before that, improved knowledge of the natural history of PAD is essential. This project describes mortality, CV outcome and treatment patterns in symptomatic and asymptomatic PAD men and women. Methods and Results: Study I. A population sample of 5080 subjects, selected through randomization, was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was compared with the PAD stage determined at baseline in 2005. The age-adjusted hazard ratios for a main cause of death by a CV event were 1.9 [95% CI 1.5-2.3] in Asymptomatic PAD, 2.6 [95% CI 2.1-3.4] in Intermittent Claudication, and 3.5 [95% CI 2.3-5.2] in Severe Limb Ischemia stage groups. Study II. This was a prospective observational population-based cohort study based on physical examinations and questionnaires at baseline supplemented with national register data between 2005 and 2015. Subjects were placed in subgroups defined by ABI levels and reported symptoms as in study I. After adjustments for age, comorbidity, and sex, the risk was almost doubled for CV death in Intermittent Claudication and APAD subjects (HR 1.95 and 1.80) as compared to a reference population. The risk for other comorbidity as diabetes, non-fatal myocardial infarction and stoke and renal failure was doubled in PAD. Some 60% of symptomatic PAD subjects received the pharmacological prophylactic treatment as recommended in guidelines. Study III. This study evaluated the risks for adverse CV events in subjects with APAD in combination with different known traditional CV risk factors over a ten-year observation period. For subjects with hypertension at baseline the CV mortality incidence was 35.4 deaths per 1000 person-years when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p<0.001]. Study IV. This prospective study assessed the differences in CV outcome if using the highest (ABI-HI) or lowest (ABI-LO) ankle blood pressure for ABI calculation for PAD diagnosis in a population-based cohort. The prevalence of PAD, defined by an ABI<0.9, by using ABI-LO and ABI-HI was 16.3% (n=799) and 9.6 % (n=469), respectively. For the subgroups defined by ABI-LO and ABI-HI, the age-adjusted HR [95% CI] for the composite outcome CV mortality and non-fatal CV events, was 1.25 [1.06-1.49] and 2.11 [1.85-2.39] respectively. The predictive value of an ABI<0.9 to foresee a future event was low for both calculation methods. Conclusions: The mortality is more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. The prognosis for this group has not changed over the last decades in contrary to other CV manifestations. Among all PAD subjects, CV causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. APAD subjects confer almost similar risk for CV events as symptomatic patients. PAD is more common in women, but men face a higher risk for death and CV events. Some 60% of symptomatic PAD subjects received prophylactic drugs according to guidelines by 2015. Subjects with APAD and any other CV risk factor have significantly higher risks for CV events and could therefore constitute suitable populations for further studies of screening with ABI measurements and subsequent intensified CV prophylactic treatment. When using the ABI-LO method more subjects at risk were identified, but their average risk was lower when comparing to the ABI-HI method which identified less subjects at risk. These differences are important to be aware of in further studies of screening. ABI measurements should be considered an important indication in aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor.
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