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Carlsson, Axel C
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Publications (10 of 82) Show all publications
Feldreich, T., Nowak, C., Fall, T., Carlsson, A. C., Carrero, J.-J., Ripsweden, J., . . . Arnlov, J. (2019). Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease. JN. Journal of Nephrology (Milano. 1992), 32(1), 111-119
Open this publication in new window or tab >>Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
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2019 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, no 1, p. 111-119Article in journal (Refereed) Published
Abstract [en]

Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).

Results

In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.

Conclusions

Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

Keywords
CVD, ESRD, Proteomics
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-378193 (URN)10.1007/s40620-018-0556-5 (DOI)000458699800013 ()30499038 (PubMedID)
Funder
Swedish Research CouncilEU, Horizon 2020, 722609EU, Horizon 2020, 634869Swedish Heart Lung FoundationSwedish Society for Medical Research (SSMF)
Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-03-04Bibliographically approved
Carlsson, A. C., Ruge, T., Kjøller, E., Hilden, J., Kolmos, H. J., Sajadieh, A., . . . Ärnlöv, J. (2018). 10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(9), Article ID e008299.
Open this publication in new window or tab >>10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

Keywords
cohort study, coronary atherosclerosis, tumor necrosis factor‐α
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-349365 (URN)10.1161/JAHA.117.008299 (DOI)000432332800014 ()29686027 (PubMedID)
Funder
Swedish Research CouncilMarianne and Marcus Wallenberg FoundationSwedish Heart Lung Foundation
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-07-27Bibliographically approved
Wändell, P., Carlsson, A. C., Sundquist, J. & Sundquist, K. (2018). Antihypertensive drugs and relevant cardiovascular pharmacotherapies and the risk of incident dementia in patients with atrial fibrillation. International Journal of Cardiology, 272, 149-154
Open this publication in new window or tab >>Antihypertensive drugs and relevant cardiovascular pharmacotherapies and the risk of incident dementia in patients with atrial fibrillation
2018 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 272, p. 149-154Article in journal (Refereed) Published
Abstract [en]

Background: Atrial fibrillation (AF) and dementia arc predominant among the elderly; patients with AF have an increased dementia risk. We aimed to study if prescribed antihypertensive drugs and cardiovascular pharmacotherapies are associated with a lower relative risk of dementia.

Methods: All included patients were >= 45 years and diagnosed with AF in primary care; 12,096 (6580 men and 5516 women) in Sweden. We excluded patients with a dementia diagnosis before onset of AF. Cox regression was used (hazard ratios, HRs, and 95% confidence interval, CI) with adjustments for sex, age, socioeconomic factors and co-morbidities.

Results: Incident dementia occurred in 750 patients (6.2%) during an average of 5.6 years of follow-up (a total of 69,214 person-years). Patients prescribed thiazides HR 0.81 (95% CI 0.66-0.99) and warfarin HR 0.78 (95% CI 0.66-0.92) had a lower risk of dementia than patients without these drugs. The use of 1-4 of the different antihypertensive drug classes ( thiazides, beta blocker, vessel active calcium channel blockers or renin angiotensin aldosterone (RAAS) blockers) were associated with a reduction of incident dementia; HR 0.80 (95% CI 0.64-1.00) for one to two drugs, and HR 0.63 (95% CI 0.46-0.84) for three or four drugs, versus having no prescribed anlihy-pertensive drugs. The combination of a RAAS-blocker and a thiazide was significant, HR 0.70 (95% CI 0.53-0.92), versus not having that particular combination prescribed, while RAAS-blockers or thiazides separately were not significant.

Conclusion: Prescribed antihypertensive drugs, including thiazide/RAAS-blocker combination therapy and use of warfarin, were associated with a decreased incidence of dementia.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2018
Keywords
Atrial fibrillation, Dementia, Anti hypertensive drugs, Hypertension
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-367013 (URN)10.1016/j.ijcard.2018.07.106 (DOI)000446025200030 ()30072151 (PubMedID)
Funder
Swedish Research Council, 2014-02517Swedish Research Council, 2014-10134Swedish Research Council, 2016-01176
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2018-11-28Bibliographically approved
Wändell, P., Carlsson, A. C., Holzmann, M. J., Ärnlöv, J., Sundquist, J. & Sundquist, K. (2018). Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care. Journal of Hypertension, 36(9), 1929-1935
Open this publication in new window or tab >>Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care
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2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 9, p. 1929-1935Article in journal (Refereed) Published
Abstract [en]

Objective: To study association between relevant cardiovascular pharmacotherapy and incident congestive heart failure (CHF) in patients with atrial fibrillation treated in primary health care.

Methods: Study population included all adults (n=7975) aged 45 years and older diagnosed with atrial fibrillation at 75 primary care centers in Sweden between 2001 and 2007. Outcome was defined as a first diagnosis of CHF post-atrial fibrillation diagnosis. Association between CHF and treatment with relevant cardiovascular pharmacotherapies (beta blockers, calcium blockers, digitalis, diuretics, RAS blockers, and statins) was explored using Cox regression analysis with hazard ratios and 95% CIs. Adjustments were made for age, sociodemographic variables, and comorbid conditions (with or without cardiovascular disorders).

Results: During a mean of 5.7 years (SD 2.3) of follow-up, totally 1552 patients (19.5%; 803 women and 749 men) had a recorded CHF diagnosis. Thiazides (hazard ratio 0.74, 95% CI 0.65-0.84), vessel-active calcium channel blockers (hazard ratio 0.76, 95% CI 0.67-0.86), and nonselective beta blockers (hazard ratio 0.84, 95% CI 0.72-0.98), with specifically sotalol representing 80% of nonselective beta blockers (hazard ratio 0.81, 95% CI 0.69-0.97), were associated with lower CHF risk in fully adjusted models. Loop diuretics (hazard ratio 1.41, 95% CI 1.25-1.57) were associated with a higher risk. Findings for thiazides and vessel-active channel blockers were consistent in the tested subgroups.

Conclusion: In this clinical setting, we found that thiazides, vessel-active calcium channel blockers, and nonselective beta blockers (specifically sotalol) were associated with a lower risk of incident CHF among patients with atrial fibrillation. The findings of the present study need to be confirmed in other settings.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
atrial fibrillation, congestive heart failure, drug treatment, sex
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-362473 (URN)10.1097/HJH.0000000000001813 (DOI)000442250500023 ()29870433 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Waendell, P. E., de Waard, A.-K. M., Holzmann, M. J., Gornitzki, C., Lionis, C., de Wit, N., . . . Carlsson, A. C. (2018). Barriers and facilitators among health professionals in primary care to prevention of cardiometabolic diseases: A systematic review. Family Practice, 35(4), 383-398
Open this publication in new window or tab >>Barriers and facilitators among health professionals in primary care to prevention of cardiometabolic diseases: A systematic review
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2018 (English)In: Family Practice, ISSN 0263-2136, E-ISSN 1460-2229, Vol. 35, no 4, p. 383-398Article, review/survey (Refereed) Published
Abstract [en]

The aim of this study is to identify potential facilitators and barriers for health care professionals to undertake selective prevention of cardiometabolic diseases (CMD) in primary health care. We developed a search string for Medline, Embase, Cinahl and PubMed. We also screened reference lists of relevant articles to retain barriers and facilitators for prevention of CMD. We found 19 qualitative studies, 7 quantitative studies and 2 mixed qualitative and quantitative studies. In terms of five overarching categories, the most frequently reported barriers and facilitators were as follows: Structural (barriers: time restraints, ineffective counselling and interventions, insufficient reimbursement and problems with guidelines; facilitators: feasible and effective counselling and interventions, sufficient assistance and support, adequate referral, and identification of obstacles), Organizational (barriers: general organizational problems, role of practice, insufficient IT support, communication problems within health teams and lack of support services, role of staff, lack of suitable appointment times; facilitators: structured practice, IT support, flexibility of counselling, sufficient logistic/practical support and cooperation with allied health staff/community resources, responsibility to offer and importance of prevention), Professional (barriers: insufficient counselling skills, lack of knowledge and of experience; facilitators: sufficient training, effective in motivating patients), Patient-related factors (barriers: low adherence, causes problems for patients; facilitators: strong GP-patient relationship, appreciation from patients), and Attitudinal (barriers: negative attitudes to prevention; facilitators: positive attitudes of importance of prevention). We identified several frequently reported barriers and facilitators for prevention of CMD, which may be used in designing future implementation and intervention studies.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
Coronary heart disease, diabetes, general practitioner, health check, myocardial infarction, selective prevention, stroke
National Category
Health Care Service and Management, Health Policy and Services and Health Economy Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-366457 (URN)10.1093/fampra/cmx137 (DOI)000439794800006 ()29385438 (PubMedID)
Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22Bibliographically approved
de Waard, A.-K. M., Wändell, P. E., Holzmann, M. J., Korevaar, J. C., Hollander, M., Gornitzki, C., . . . Carlsson, A. C. (2018). Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care: A systematic review. European Journal of Preventive Cardiology, 25(12), 1326-1340
Open this publication in new window or tab >>Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care: A systematic review
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2018 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 12, p. 1326-1340Article, review/survey (Refereed) Published
Abstract [en]

Background: Health checks for cardiometabolic diseases could play a role in the identification of persons at high risk for disease. To improve the uptake of these health checks in primary care, we need to know what barriers and facilitators determine participation.

Methods: We used an iterative search strategy consisting of three steps: (a) identification of key-articles; (b) systematic literature search in PubMed, Medline and Embase based on keywords; (c) screening of titles and abstracts and subsequently full-text screening. We summarised the results into four categories: characteristics, attitudes, practical reasons and healthcare provider-related factors.

Results: Thirty-nine studies were included. Attitudes such as wanting to know of cardiometabolic disease risk, feeling responsible for, and concerns about one's own health were facilitators for participation. Younger age, smoking, low education and attitudes such as not wanting to be, or being, worried about the outcome, low perceived severity or susceptibility, and negative attitude towards health checks or prevention in general were barriers. Furthermore, practical issues such as information and the ease of access to appointments could influence participation.

Conclusion: Barriers and facilitators to participation in health checks for cardiometabolic diseases were heterogeneous. Hence, it is not possible to develop a one size fits all' approach to maximise the uptake. For optimal implementation we suggest a multifactorial approach adapted to the national context with special attention to people who might be more difficult to reach. Increasing the uptake of health checks could contribute to identifying the people at risk to be able to start preventive interventions.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2018
Keywords
Health check, cardiometabolic disease, cardiovascular disease, diabetes, prevention, primary care, general practitioner, attendance, participation
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-365169 (URN)10.1177/2047487318780751 (DOI)000441767300017 ()29916723 (PubMedID)
Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2018-11-09Bibliographically approved
Hagström, H., Andreasson, A., Carlsson, A. C., Jerkeman, M. & Carlsten, M. (2018). Body composition measurements and risk of hematological malignancies: A population-based cohort study during 20 years of follow-up. PLoS ONE, 13(8), Article ID e0202651.
Open this publication in new window or tab >>Body composition measurements and risk of hematological malignancies: A population-based cohort study during 20 years of follow-up
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 8, article id e0202651Article in journal (Refereed) Published
Abstract [en]

High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365823 (URN)10.1371/journal.pone.0202651 (DOI)000442800100102 ()30138405 (PubMedID)
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Ivert, T., Malmström, H., Hammar, N., Carlsson, A. C., Wändell, P. E., Holzmann, M. J., . . . Walldius, G. (2018). Cardiovascular events in patients under age fifty with early findings of elevated lipid and glucose levels - The AMORIS study. PLoS ONE, 13(8), Article ID e0201972.
Open this publication in new window or tab >>Cardiovascular events in patients under age fifty with early findings of elevated lipid and glucose levels - The AMORIS study
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 8, article id e0201972Article in journal (Refereed) Published
Abstract [en]

Background: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age.

Methods and findings: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985-1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6-3.7) for TC >= 5 mmol/L and TG >= 1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels.

Conclusions: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-365824 (URN)10.1371/journal.pone.0201972 (DOI)000442800100031 ()30138379 (PubMedID)
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Wuopio, J., Hilden, J., Bring, C., Kastrup, J., Sajadieh, A., Jensen, G. B., . . . Ärnlöv, J. (2018). Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study.. Atherosclerosis, 278, 97-102
Open this publication in new window or tab >>Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study.
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2018 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 278, p. 97-102Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease.

METHODS: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs.

RESULTS: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05-1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07-1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events.

CONCLUSIONS: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.

Keywords
Cardiovascular biomarker, Cardiovascular risk, Cathepsin, Coronary heart disease, Ischemic heart disease, Mortality
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363384 (URN)10.1016/j.atherosclerosis.2018.09.006 (DOI)000451056500013 ()30261474 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationThuréus stiftelse för främjande av geriatrisk forskningMarianne and Marcus Wallenberg Foundation
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2019-01-24Bibliographically approved
Ruge, T., Carlsson, A. C., Ingelsson, E., Risérus, U., Sundström, J., Larsson, A., . . . Ärnlöv, J. (2018). Circulating endostatin and the incidence of heart failure.. Scandinavian Cardiovascular Journal, 1-6
Open this publication in new window or tab >>Circulating endostatin and the incidence of heart failure.
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2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, p. 1-6Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

DESIGN: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

RESULTS: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

Keywords
Heart failure, angiogenesis, anti-angiogenesis, epidemiology, left ventricular systolic function, population based studies, remodelling of extracellular matrix
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363655 (URN)10.1080/14017431.2018.1483080 (DOI)29893146 (PubMedID)
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2019-01-23Bibliographically approved
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