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  • 151.
    Warensjö, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study2008In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 88, no 1, p. 203-209Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Desaturase indexes, as markers of endogenous fatty acid desaturation, and a characteristic serum fatty acid (FA) composition are related to cardiovascular and metabolic diseases, but the relation to mortality is poorly investigated. OBJECTIVE: The objective was to evaluate the relation between dietary fat biomarkers, desaturase indexes, and mortality. DESIGN: In this community-based prospective sample, 50-y-old men were followed for a maximum of 33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase indexes (stearoyl-CoA-desaturase and Delta(6)- and Delta(5)-desaturase) and the relation of individual serum esterified fatty acids (FAs) in relation to total and cardiovascular mortality in the total study sample (n = 2009) and in a healthy subsample (n = 1885). Desaturase indexes were estimated as product-to-precursor FA ratios. RESULTS: During follow-up, 1012 men in the total sample died and 931 men in the healthy subsample died. Desaturase indexes predicted both total and cardiovascular mortality. The relations were independent of smoking status, physical activity, BMI, total cholesterol, and hypertension. The adjusted and standardized (per SD) hazard ratios (HRs) and 95% CIs for cardiovascular mortality were 1.15 (1.04, 1.27) for stearoyl-CoA-desaturase, 1.12 (1.0, 1.24) for Delta(6)-desaturase, and 0.88 (0.80, 0.98) for Delta(5)-desaturase, respectively. The proportion of serum linoleic acid was inversely related, whereas serum FAs associated with saturated fat intake (palmitic, palmitoleic, and dihomo-gamma-linolenic acids) were directly related to total and cardiovascular mortality. CONCLUSIONS: Altered endogenous FA desaturation might contribute to mortality risk because we observed independent associations between desaturase activity indexes and mortality. The proportion of linoleic acid was inversely related, and FAs reflecting saturated fat intake were directly related to mortality.

  • 152. Wierup, Ia
    et al.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wandell, Per
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Borne, Yan
    Low anthropometric measures and mortality-results from the Malmo Diet and Cancer Study2015In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 47, no 4, p. 325-331Article in journal (Refereed)
    Abstract [en]

    Aim. To study the association between anthropometric measures: body mass index (BMI), percent body fat, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist-to-hip-to-height ratio (WHHR), and A Body Shape Index (ABSI); to see if individuals in the lowest 5 percentiles for these measures have an increased risk of mortality. Methods. A population-based prospective cohort study ( 10,304 men and 16,549 women), the Malmo Diet and Cancer study (MDC), aged 45-73 years. Results. During a mean follow-up of 14 +/- 3 years, 2,224 men and 1,983 women died. There was a significant increased mortality risk after adjustments for potential confounders in the group with the 5% lowest BMI ( referent 25%-75%); hazard ratios (HR) with 95% confidence intervals were 1.33 (1.10-1.61) for women and 1.27 (1.07-1.52) for men. A similar significant increased mortality risk was seen with the 5% lowest percent body fat, HR 1.31 (1.07-1.60) for women and 1.25 (1.04-1.50) for men. Women with an ABSI in the lowest 5 percentiles had a lower mortality risk HR 0.64 (0.48-0.85). Conclusion. These results imply that BMI or percent body fat could be used to identify lean individuals at increased mortality risk.

  • 153. Witasp, Anna
    et al.
    Carrero, Juan Jesús
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Adamsson, Viola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenvinkel, Peter
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Inflammatory biomarker pentraxin 3 (PTX3) in relation to obesity, body fat depots, and weight loss2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 5, p. 1373-1379Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The relation between inflammatory markers, adiposity and disease is under extensive study. Here we tested the hypothesis that the immunomodulatory protein pentraxin 3 (PTX3) is associated with adiposity in the general population.

    DESIGN AND METHODS: Serum PTX3 concentrations, body mass index (BMI), waist circumference (WC) and fat depots, as quantified by dual-energy X-ray absorptiometry and magnetic resonance imaging, were assessed in three community-based cohorts: ULSAM, n = 790, mean age 78 years; PIVUS, n = 1003, mean age 70 years, women 50%; and the NORDIET-trial, n = 86, mean age 53 years, women 63%. Participants were re-examined after 5 years (PIVUS, n = 804) or following a 6-week randomized controlled dietary intervention (NORDIET).

    RESULTS: PTX3 levels were inversely associated with BMI and WC as well as with total and visceral fat (P < 0.05 for all; adjusted for age, inflammatory biomarkers and cardiovascular risk factors). The association between PTX3 and BMI appeared even stronger in nonobese individuals. A decrease in BMI over 5 years as well as weight loss following the NORDIET intervention were associated with increased serum PTX3 concentrations (P < 0.001).

    CONCLUSIONS: These consistent data support an inverse association between circulating PTX3 and anthropometrical measures, calling for further mechanistic studies of the link between PTX3 and fat.

  • 154.
    Wu, Jason H. Y.
    et al.
    Univ New South Wales, George Inst Global Hlth, Fac Med, Sydney, NSW 2050, Australia..
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Imamura, Fumiaki
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England..
    Tintle, Nathan
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA..
    Korat, Andres V. Ardisson
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA..
    de Goede, Janette
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands..
    Zhou, Xia
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Yang, Wei-Sin
    Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Coll Publ Hlth, Taipei, Taiwan..
    Otto, Marcia C. de Oliveira
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA..
    Kroger, Janine
    German Inst Human Nutr, Potsdam, Germany..
    Qureshi, Waqas
    Wake Forest Univ, Winston Salem, NC 27109 USA..
    Virtanen, Jyrki K.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Bassett, Julie K.
    Canc Council Victoria, Melbourne, Vic, Australia..
    Frazier-Wood, Alexis C.
    ARS, USDA, Childrens Nutr Res Ctr, Houston, TX USA..
    Lankinen, Maria
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Murphy, Rachel A.
    Univ British Columbia, Vancouver, BC, Canada..
    Rajaobelina, Kalina
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, UMR 1219, Bordeaux, France..
    Del Gobbo, Liana C.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Forouhi, Nita G.
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England..
    Luben, Robert
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.;Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA..
    Wareham, Nick
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England..
    Kalsbeek, Anya
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.;Dordt Coll, Dept Biol, Sioux Ctr, IA USA..
    Veenstra, Jenna
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.;Dordt Coll, Dept Biol, Sioux Ctr, IA USA..
    Luo, Juhua
    Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA..
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA..
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Boeing, Heiner
    German Inst Human Nutr, Potsdam, Germany..
    Chen, Tzu-An
    ARS, USDA, Childrens Nutr Res Ctr, Houston, TX USA..
    Steffen, Brian
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA..
    Steffen, Lyn M.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Hodge, Allison
    Canc Council Victoria, Melbourne, Vic, Australia..
    Eriksdottir, Gudny
    Iceland Heart Inst, Kopavogur, Iceland..
    Smith, Albert V.
    Iceland Heart Inst, Kopavogur, Iceland..
    Gudnason, Vilmunder
    Iceland Heart Inst, Kopavogur, Iceland..
    Harris, Tamara B.
    NIA, Bethesda, MD 20892 USA..
    Brouwer, Ingeborg A.
    Vrije Univ Amsterdam, Hlth Sci, Amsterdam, Netherlands..
    Berr, Claudine
    Montpellier Univ, INSERM, U1061, Neuropsychiat Epidemiol & Clin Res, Montpellier, France.;Montpellier Univ, Montpellier Univ Hosp, Montpellier, France..
    Helmer, Catherine
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, UMR 1219, Bordeaux, France..
    Samieri, Cecilia
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, UMR 1219, Bordeaux, France..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Kuopio, Finland..
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA..
    Giles, Graham G.
    Canc Council Victoria, Melbourne, Vic, Australia..
    Nurmi, Tarja
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Wagenknecht, Lynne
    Wake Forest Univ, Winston Salem, NC 27109 USA..
    Schulze, Matthias B.
    German Inst Human Nutr, Potsdam, Germany..
    Lemaitre, Rozenn N.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA..
    Chien, Kuo-Liong
    Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Coll Publ Hlth, Taipei, Taiwan.;Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    Soedamah-Muthu, Sabita S.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands..
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands..
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA..
    Harris, William S.
    Univ South Dakota, Sanford Sch Med, Dept Internal Med, Sioux Falls, SD USA.;OmegaQuant Analyt, Sioux Falls, SD USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies2017In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, no 12, p. 965-974Article in journal (Refereed)
    Abstract [en]

    Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23.3-28.4 kg/m(2), who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0.65, 95% CI 0.60-0.72, p<0.0001; I-2=53.9%, p(heterogeneity) = 0.002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0.96, 95% CI 0.88-1.05; p=0.38; I-2 = 63.0%, p(heterogeneity) < 0.0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p(heterogeneity) >= 0-13). Interpretation Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.

  • 155. Xiong, Zibo
    et al.
    Xu, Hong
    Huang, Xiaoyan
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Qureshi, Abdul Rashid
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Nonesterified Fatty Acids and Cardiovascular Mortality in Elderly Men with CKD2015In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 10, no 4, p. 584-591Article in journal (Refereed)
    Abstract [en]

    Background and objectives Although nonesterified fatty acids (NEFAs) are essential as energy substrate for the myocardium, an excess of circulating NEFAs can be harmful. This study aimed to assess plausible relationships between serum NEFA and mortality due to cardiovascular disease (CVD) in individuals with CKD. Design, setting, participants, & measurements This was a prospective cohort study from the third examination cycle of the Uppsala LongitudinaL Study of Adult Men, a population-based survey of 1221 elderly men aged 70-71 years residing in Uppsala, Sweden. Data collection took place during 1991-1995. All participants had measures of kidney function; this study investigated 623 (51.7%) of these patients with manifest CKD (defined as either eGFR<60 ml/min per 1.73 m(2) or urine albumin excretion rate >= 20 mu g/min). Follow-up for mortality was done from examination date until death or December 31, 2007. After a median follow-up of 14 years (nterquartile range, 8-16.8), associations of NEFAs with mortality (related to all causes, CVD, ischemic heart disease [IHD], or acute myocardial infarction) were ascertained. Results The median serum NEFA was 14.1 mg/dl (interquartile range, 11.3-17.8). No association was found with measures of kidney function. Diabetes and serum triglycerides were the only multivariate correlates of NEFA. During follow-up, 453 participants died, of which 209 deaths were due to CVD, including 88 IHD deaths, with 41 attributed to acute myocardial infarction (AMI). In fully adjusted covariates, serum NEFA was an independent risk factor for all-cause mortality (hazard ratio [HR] per log(2) increase, 1.22; 95% confidence interval [95% CI], 1.00 to 1.48) and CVD-related death (HR, 1.51; 95% CI, 1.15 to 1.99), including both IHD (HR, 1.51; 95% CI, 1.00 to 2.32) and AMI mortality (HR, 2.08; 95% CI, 1.09 to 3.98). Conclusions Elevated serum NEFA associated with CVD mortality, and particularly with mortality due to AMI, in a homogeneous population of older men with moderate CKD.

  • 156.
    Xu, H.
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Rossi, M.
    Princess Alexandra Hosp, Ctr Kidney Dis Res, Brisbane, Qld 4102, Australia.;Kings Coll London, Div Diabet & Nutr Sci, London WC2R 2LS, England..
    Campbell, K. L.
    Princess Alexandra Hosp, Ctr Kidney Dis Res, Brisbane, Qld 4102, Australia.;Bond Univ, Fac Hlth Sci & Med, Robina, Australia..
    Sencion, G. L.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, B.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Carrero, J. J.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, SE-14186 Stockholm, Sweden..
    Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease2016In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, no 7, p. 597-602Article in journal (Refereed)
    Abstract [en]

    Background and aims: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.

  • 157.
    Xu, H.
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, B.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, J. J.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Lipophilic index, kidney function, and kidney function decline2016In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, no 12, p. 1096-1103Article in journal (Refereed)
    Abstract [en]

    Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.

  • 158. Xu, Hong
    et al.
    Huang, Xiaoyan
    Arnlov, Johan
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Stenvinkel, Peter
    Lindholm, Bengt
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Clinical Correlates of Insulin Sensitivity and Its Association with Mortality among Men with CKD Stages 3 and 42014In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 9, no 4, p. 690-697Article in journal (Refereed)
    Abstract [en]

    Background and objectivesInsulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined.Design, setting, participants, & measurementsThe prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70-71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m(2) (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m(2); range=20.2-59.5 ml/min per 1.73 m(2)).ResultsThe mean of glucose disposal rate was 5.41.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (-0.48; 95% confidence interval, -0.86 to -0.11), hyperlipidemia (-0.51; 95% confidence interval, -0.84 to -0.18), and body mass index (-0.32; 95% confidence interval, -0.37 to -0.27). During follow-up (median=10.0 years; interquartile range=8.7-11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.97) but not their counterparts.ConclusioneGFR, together with various components of the metabolic syndrome, contributed to explain the variance of insulin sensitivity in men with CKD stages 3 and 4. Insulin sensitivity was associated with a lower mortality risk in individuals who smoked and individuals who were physically inactive.

  • 159. Xu, Hong
    et al.
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesus
    Urinary Albumin Excretion, Blood Pressure Changes and Hypertension Incidence in the Community: Effect Modification by Kidney Function2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 79-79Article in journal (Other academic)
  • 160. Xu, Hong
    et al.
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Carrero, Juan Jesus
    Fiber Intake, Kidney Function, Inflammation, and Mortality in a Community-Based Cohort2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 49-49Article in journal (Other academic)
  • 161. Xu, Hong
    et al.
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Krishnamurthy, Vidya M.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlov, Johan
    Lindholm, Bengt
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk2014In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 9, no 12, p. 2104-2110Article in journal (Refereed)
    Abstract [en]

    Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR >= 60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction.

  • 162. Xu, Hong
    et al.
    Huang, Xiaoyan
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesus
    Urinary albumin excretion, blood pressure changes and hypertension incidence in the community: effect modification by kidney function2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 8, p. 1538-1545Article in journal (Refereed)
    Abstract [en]

    Both increased albuminuria and reduced kidney function may predict blood pressure (BP) progression in the community, while they exacerbate each other's effects. We investigated associations and interactions between these two risk factors, BP changes and hypertension incidence in community-dwelling elderly men. Observational study from the Uppsala Longitudinal Study of Adult Men, which included 1051 men (all aged 71 years) with assessments on urinary albumin excretion rate (UAER), 24-hour ambulatory BP monitoring (ABPM) and cystatin-C estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years, and ABPM measurements were again recorded to assess blood pressure changes and hypertension incidence. UAER was found to be associated with ABPM measurements both at baseline and longitudinally. In longitudinal analysis, there were significant interactions between UAER and kidney function in its association with the changes of systolic BP, mean arterial pressure and pulse pressure. After stratification for renal function state, UAER independently predicted BP changes only in those who had eGFR < 60 mL/min/1.73 m(2). At re-examination, 71 new cases of hypertension were recorded. In multivariable logistic models, similar interactions were observed on hypertension incidence: UAER was an independent predictor of incident hypertension only in those with reduced renal function. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER (< 20 A mu g/min). In community-dwelling elderly men, UAER associates with BP progression and hypertension incidence, even within the normal range. Concurrent reduction of renal function modifies and exacerbates these associations.

  • 163. Xu, Hong
    et al.
    Huang, Xiaoyan
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesús
    Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5, p. 560-566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.

    METHODS: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).

    RESULTS: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.

    CONCLUSIONS: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.

  • 164. Xu, Hong
    et al.
    Jia, Ting
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Carrero, Juan-Jesus
    Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 8, p. 1561-1568Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We tested the hypothesis that dietary acid load may increase the risk of type 2 diabetes, and studied the association between acid load and insulin sensitivity as a possible mechanism involved. Methods An observational survey with prospective follow-up including 911 non-diabetic Swedish men aged 70-71 years was carried out. The gold standard euglycaemic-hyperinsulinaemic clamp technique and the OGTT were used to determine insulin sensitivity and beta cell function, respectively. Diabetes incidence was assessed during 18 years of follow-up. Renal function was estimated from serum cystatin C concentrations. Dietary acid load was calculated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) algorithms from 7 day food records. Adequate dietary reporters were identified by Goldberg cut-offs. Results PRAL and NEAP were not associated with insulin sensitivity or beta cell function. Underlying kidney function or consideration of dietary adequate reporters did not modify these null findings. During follow-up, 115 new cases of diabetes were validated. Neither PRAL nor NEAP was associated with diabetes incidence. Conclusios/interpretation Our results do not support the hypothesis that dietary acid load influences insulin sensitivity, beta cell function or diabetes risk. Interventional studies modifying acid-base dietary intake are needed to further elucidate a possible role of acid load in the development of type 2 diabetes.

  • 165.
    Xu, Hong
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Banerjee, Tanushree
    Univ Calif, Div Gen Internal Med, Dept Med, Davis, CA USA..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Mediation Analysis of Pro-Inflammatory Diets and Kidney Function in Two Community-Based Cohorts of Elderly2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 166. Xu, Hong
    et al.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Banerjee, Tanushree
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan Jesus
    A Proinflammatory Diet Is Associated with Systemic Inflammation and Reduced Kidney Function in Elderly Adults2015In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 145, no 4, p. 729-735Article in journal (Refereed)
    Abstract [en]

    Background: Diet can affect kidney health through its effects on inflammation. Objective: We tested whether the Adapted Dietary Inflammatory Index (ADII) is associated with kidney function and whether effects of diet on chronic low-grade inflammation explain this association. Methods: This was an observational analysis in 1942 elderly community-dwelling participants aged 70-71 y from 2 independent cohorts: the Uppsala Longitudinal Study of Adult Men (n = 1097 men) and the Prospective Investigation of Vasculature in Uppsala Seniors (n = 845 men and women). The ADII was calculated from 7-d food records, combining putatively proinflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements. The ADII was validated against serum C-reactive protein (CRP) concentrations. The estimated glomerular filtration rate (eGFR) was assessed from serum cystatin C (cys) and creatinine (crea). Associations between the ADII and eGFR were investigated, and CRP was considered to be a mediator. Results: In adjusted analysis, a 1-SD higher ADII was associated with higher CRP (beta: 6%, 95% Cl: 1%, 10%; P= 0.01) and lower eGFR [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)(cys): -2.1%, 95% Cl: -3.2%, -1.1%; CKD-EPi(cys+crea): -1.8%; 95% Cl: -2.7%, -0.9%; both P < 0.001]. CRP was also inversely associated with eGFR. Mediation analyses showed that of the total effect of the ADII on kidney function, 15% and 17% (for CKD-EPIcys+crea and CKD-EPIcys equations, respectively) were explained/mediated by serum CRP. Findings were similar when each cohort was analyzed separately. Conclusions: A proinflammatory diet was associated with systemic inflammation as well as with reduced kidney function in a combined analysis of 2 community-based cohorts of elderly individuals. Our results also suggest systemic inflammation to be one potential pathway through which this dietary pattern is linked to kidney function.

  • 167.
    Xu, Hong
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Xiong, Zibo
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Huang, Xiaoyan
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Qureshi, Abdul Rashid
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Non-Esterified Fatty Acids and Cardiovascular Mortality in Elderly Men with Chronic Kidney Disease2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 168.
    Xu, Hong
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Xiong, Zibo
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Circulating Alpha-Tocopherol and Insulin Sensitivity Among Elderly Men with Chronic Kidney Disease2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30Article in journal (Other academic)
  • 169.
    Xu, Hong
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Xiong, Zibo
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Peking Univ, Shenzhen Hosp, Div Nephrol, Shenzhen, Guangdong, Peoples R China..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Qureshi, Abdul Rashid
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Circulating Alpha-Tocopherol and Insulin Sensitivity Among Older Men With Chronic Kidney Disease2016In: Journal of renal nutrition (Print), ISSN 1051-2276, E-ISSN 1532-8503, Vol. 26, no 3, p. 177-182Article in journal (Refereed)
    Abstract [en]

    Objective: Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD. Design: Observational study. Setting: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate, < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate >= 20 mg/minute from the third examination cycle of Uppsala Longitudinal Study of Adult Men. Subjects: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate, 60 mL/minute/1.73 m(2) or urinary albumin excretion rate >= 20 mu g/minute. Methods: Serum alpha-, beta-, and gamma-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as mmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records. Main Outcome Measure: Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols. Results: The mean serum concentration of alpha-, beta-, and gamma- was 37.4 +/- 6.58, 0.89 +/- 0.23, and 4.32 +/- 1.69 mu mol/mmol, respectively. Median dietary vitamin E intake was 6.14 (interquartile range, 5.48-6.82) mg/day. In crude and fully-adjusted multivariate regression analyses, serum alpha-tocopherol levels were directly and strongly associated with M/I (standard beta = 0.17, P = .003). No such association was observed for dietary vitamin E, serum beta-, and gamma-tocopherol concentrations. Conclusions: Serum a-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.

  • 170.
    Xu, Hong
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Lipophilic Index, Kidney Function, And Kidney Function Decline2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 177-177Article in journal (Other academic)
  • 171. Yubero-Serrano, Elena M
    et al.
    Delgado-Lista, Javier
    Tierney, Audrey C
    Perez-Martinez, Pablo
    Garcia-Rios, Antonio
    Alcala-Diaz, Juan F
    Castaño, Justo P
    Tinahones, Francisco J
    Drevon, Christian A
    Defoort, Catherine
    Blaak, Ellen E
    Dembinska-Kieć, Aldona
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lovegrove, Julie A
    Perez-Jimenez, Francisco
    Roche, Helen M
    Lopez-Miranda, Jose
    Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study2015In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, no 6, p. 1509-1517Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established.

    OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors.

    DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined.

    RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05).

    CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.

  • 172.
    Ärnlöv, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Myocardial performance index, a Doppler-derived index of global left ventricular function, predicts congestive heart failure in elderly men2004In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 25, no 24, p. 2220-2225Article in journal (Refereed)
    Abstract [en]

    AIMS: There is limited data on echocardiographic and Doppler indices of cardiac function as predictors for congestive heart failure (CHF) in the general population. Myocardial performance index (MPI, also denoted TEI-Doppler index) reflects both left ventricular (LV) systolic and diastolic function.

    METHODS AND RESULTS: We compared eight different echocardiographic and Doppler indices of cardiac function as predictors of CHF using a population-based cohort of 552 seventy-year-old men without CHF and significant valve disease at baseline (median follow-up time 8.2 years). In a stepwise multivariable Cox proportional-hazard analysis including the different indices of cardiac function, high MPI (above the 90th percentile of MPI [> or =0.91]), abnormal LV wall motion score index and a pseudo-normalized/restrictive E/A-ratio pattern independently predicted future CHF morbidity. After adding traditional CHF risk factors (age, previous myocardial infarction, hypertension, diabetes mellitus, hyperlipidaemia, smoking, LV hypertrophy and body mass index) to the above model, only a high MPI remained a significant predictor (hazard ratio 4.72, 95% CI 1.75-12.76, p=0.002).

    CONCLUSION: MPI provides important prognostic information for the risk of future CHF, beyond other measurements of cardiac function and traditional heart failure risk factors in elderly men. MPI seems to be a clinically relevant indicator of cardiac function and may prove to be a valuable tool in assessing the risk of future CHF.

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