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  • 1.
    Andersen, Kasper
    et al.
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala University, Uppsala, Sweden.
    Byberg, Liisa
    Uppsala University, Uppsala, Sweden.
    Michaëlsson, Karl
    Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Uppsala University, Uppsala, Sweden.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN: Population-based cohort study.

    METHODS: We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS: During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS: Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 2. Carlsson, A. C.
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Sundström, J.
    Michaëlsson, K.
    Byberg, L.
    Lind, L.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    Method and results: At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m2, n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m2, n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m2, n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    Conclusions: Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up. 

  • 3. Carlsson, Axel C
    et al.
    Sundström, Johan
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Stenemo, Markus
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala University.
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria.2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 4, p. 340-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 4. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala university.
    Larsson, Anders
    Cystatin C-based glomerular filtration rate associates more closely with mortality than creatinine-based or combined glomerular filtration rate equations in unselected patients2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 15, p. 1649-1657Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Decreased glomerular filtration rate (GFR) is an important cardiovascular risk factor, but estimated GFR (eGFR) may differ depending on whether it is based on creatinine or cystatin C. A combined creatinine/cystatin C equation has recently been shown to best estimate GFR; however, the benefits of using the combined equation for risk prediction in routine clinical care have been less studied. This study compares mortality risk prediction by eGFR using the combined creatinine/cystatin C equation (CKD-EPI), a sole creatinine equation (CKD-EPI) and a sole cystatin C equation (CAPA), respectively, using assays that are traceable to international calibrators.

    METHODS AND RESULTS: All patients analysed for both creatinine and cystatin C from the same blood sample tube (n = 13,054) during 2005-2007 in Uppsala University Hospital Laboratory were divided into eGFR risk categories>60, 30-60 and <30 mL/min/1.73 m(2) by each eGFR equation. During follow-up (median 4.6 years), 4398 participants died, of which 1396 deaths were due to cardiovascular causes. Reduced eGFR was significantly associated with death as assessed by all eGFR equations. The net reclassification improvement (NRI) for the combination equation compared with the sole creatinine equation was 0.10 (p < 0.001) for all-cause mortality and 0.08 (p < 0.001) for cardiovascular mortality, indicating improved reclassification. In contrast, NRI for the combination equation, compared with the sole cystatin C equation, was -0.06 (p < 0.001) for all-cause mortality and -0.02 (p = 0.032) for cardiovascular mortality, indicating a worsened reclassification.

    CONCLUSIONS: In routine clinical care, cystatin C-based eGFR was more closely associated with mortality compared with both creatinine-based eGFR and creatinine/cystatin C-based eGFR.

  • 5. Holzmann, Martin J
    et al.
    Carlsson, Axel C
    Hammar, Niklas
    Ivert, Torbjörn
    Walldius, Göran
    Jungner, Ingmar
    Wändell, Per
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala university.
    Chronic kidney disease and 10-year risk of cardiovascular death2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 11, p. 1187-1194Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent clinical guidelines, individuals with chronic kidney disease are considered to have a similar 10-year absolute risk of cardiovascular death as individuals with diabetes or established cardiovascular disease. There is limited evidence to support this claim.

    METHODS: We investigated the 10-year risk for cardiovascular death in individuals with moderate or severe chronic kidney disease (glomerular filtration rate of 30-60 or <30 mL/min/1.73 m(2), respectively) in a cohort of primary care health check-ups in Stockholm, Sweden (n = 295,191, 46% women, 4290 cardiovascular deaths during 10 years follow-up). We also assessed the risk associated with diabetes or cardiovascular disease. The inclusion criteria, exposure, study outcome and follow-up period adhered strictly to the definitions of the European Society of Cardiology guidelines.

    RESULTS: The absolute 10-year risk of cardiovascular death was 3.9% and 14.0% in individuals with moderate and severe chronic kidney disease, respectively, but was substantially lower in women and in younger individuals. The risk in individuals with prevalent diabetes and cardiovascular disease was approximately two and three times higher compared to the risk estimate for moderate chronic kidney disease (hazard ratio (HR) 4.1, 95% confidence interval (CI) 3.8-4.5 and HR 6.2, 95% CI 5.7-6.7 vs. HR 2.3 95% CI 2.0-2.6, respectively) while the risk for individuals with severe chronic kidney disease appeared more congruent to that of diabetes and cardiovascular disease (HR 5.5, 95% CI 3.3-8.9).

    CONCLUSIONS: Although moderate chronic kidney disease is an independent predictor for an increased 10-year risk of cardiovascular death, only those with severe chronic kidney disease had similar risk to those with diabetes or cardiovascular disease.

  • 6. Hållmarker, Ulf
    et al.
    Michaëlsson, Karl
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Hellberg, Dan
    Lagerqvist, Bo
    Lindbäck, Johan
    James, Stefan
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

    Aims: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    Methods and Results: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    Conclusions: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death. 

  • 7. Torell, Matilda F
    et al.
    Strömsöe, Anneli
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Zagerholm, Ellen
    Herlitz, Johan
    Claesson, Andreas
    Svensson, Leif
    Börjesson, Mats
    Higher survival rates in exercise-related out-of-hospital cardiac arrests, compared to non-exercise-related - a study from the Swedish Register of Cardiopulmonary Resuscitation2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 15, p. 1673-1679Article in journal (Refereed)
    Abstract [en]

    Background: Despite the positive effects of physical activity, the risk of sudden cardiac arrest is transiently increased during and immediately after exercise. The purpose of this study was to assess the incidence of exercise-related out-of-hospital cardiac arrest in the general population and to compare characteristics and prognosis of these cardiac arrests with non-exercise-related out-of-hospital cardiac arrests.

    Methods: Data from all cases of treated out-of-hospital cardiac arrest outside of home reported to the Swedish Register of Cardiopulmonary Resuscitation from 2011-2015 in three counties of Sweden were investigated (population 2.1 m). This registry captures almost 100% of all out-of-hospital cardiac arrests in Sweden. Results Of 1825 out-of hospital cardiac arrests, 137 (7.5%) were exercise-related, resulting in an incidence of 1.2 per 100,000 person-years. The 30-day survival rate was significantly higher among exercise-related out-of hospital cardiac arrests compared to non-exercise-related out-of-hospital cardiac arrests (54.3 % vs 19.4%, p < 0.0001). Patients suffering an exercise-related out-of-hospital cardiac arrest were on average 10 years younger than those who had a non-exercise-related out-of-hospital cardiac arrest, 56.4 years compared to 67.2 years. Exercise-related out-of-hospital cardiac arrests were more often witnessed (89.4% vs 78.6%, p = 0.002), had higher rates of bystander cardiopulmonary resuscitation (80.3% vs 61.0%, p < 0.0001) and were more frequently connected to an automated external defibrillator (20.4% vs 4.6%, p < 0.0001).

    Conclusions: Cardiac arrests that occur in relation to exercise have a significantly better prognosis and outcome than non-exercise-related cardiac arrests. This may be explained by favourable circumstances but may also reflect that these persons experience a sudden cardiac arrest at a lower degree of coronary artery disease, due to their younger age and to exercise being a trigger.

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