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  • 1.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hypertension, the Swedish Patient Register, and Selection Bias2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 6, p. 862-863Article in journal (Refereed)
  • 2.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis2018In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 1, p. 28-36Article in journal (Refereed)
    Abstract [en]

    Importance: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.

    Objective: To assess the association between BP lowering treatment and death and CVD at different BP levels.

    Data sources: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.

    Study selection: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.

    Data extraction and synthesis: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.

    Main outcomes and measures: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.

    Results: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).

    Conclusions and relevance: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

  • 3.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Questionable Conclusions Regarding Blood Pressure End Points Reply2018In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 4, p. 575-576Article in journal (Refereed)
  • 4. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Yakoob, Mohammad Y.
    Chiuve, Stephanie E.
    dela Cruz, Luicito
    Frazier-Wood, Alexis C.
    Fretts, Amanda M.
    Guallar, Eliseo
    Matsumoto, Chisa
    Prem, Kiesha
    Tanaka, Tosh
    Wu, Jason H. Y.
    Zhou, Xia
    Helmer, Catherine
    Ingelsson, Erik
    Yuan, Jian-Min
    Barberger-Gateau, Pascale
    Campos, Hannia
    Chaves, Paulo H. M.
    Djousse, Luc
    Giles, Graham G.
    Gomez-Aracena, Jose
    Hodge, Allison M.
    Hu, Frank B.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Lemaitre, Rozenn N.
    Lind, Lars
    Luben, Robert N.
    Rimm, Eric B.
    Riserus, Ulf
    Samieri, Cecilia
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Siscovick, David S.
    Stampfer, Meir
    Steffen, Lyn M.
    Steffen, Brian T.
    Tsai, Michael Y.
    van Dam, Rob M.
    Voutilainen, Sari
    Willett, Walter C.
    Woodward, Mark
    Mozaffarian, Dariush
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 8, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 5.
    Marklund, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Oral Appliance Therapy in Patients With Daytime Sleepiness and Snoring or Mild to Moderate Sleep Apnea: A Randomized Clinical Trial2015In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 175, no 8, p. 1278-1285Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Oral appliances that move the mandible forward during sleep are suggested as treatment for mild to moderate obstructive sleep apnea.

    OBJECTIVE: To test whether an adjustable, custom-made oral appliance improves daytime sleepiness and quality of life in patients with daytime sleepiness and snoring or mild to moderate obstructive sleep apnea.

    DESIGN, SETTING, AND PARTICIPANTS: Ninety-six patients with daytime sleepiness and an apnea-hypopnea index (AHI) lower than 30 were included in a randomized, placebo-controlled, parallel trial in Umeå, Sweden, from May 2007 through August 2011.

    INTERVENTIONS: Four months' intervention with an oral appliance or a placebo device.

    MAIN OUTCOMES AND MEASURES: Daytime sleepiness was measured with the Epworth Sleepiness Scale, the Karolinska Sleepiness Scale, and the Oxford Sleep Resistance (OSLER) test. Quality of life was assessed with the Short-Form 36-Item Health Survey (SF-36) and the Functional Outcomes of Sleep Questionnaire (FOSQ). Secondary outcomes included the apnea-hypopnea index, headaches, symptoms of restless legs, and insomnia.

    RESULTS: Oral appliance therapy was not associated with improvements in daytime sleepiness from baseline to 4-month follow-up when compared with the placebo device; Epworth score >10: 53% at baseline to 24% at follow-up for the oral appliance group vs 54% at baseline to 40% at follow-up for the placebo device group, P = .11; median (IQR) for Karolinska score ≥7/wk: 10 (8 to 14) at baseline to 7 (4 to 9) at follow-up for the oral appliance group vs 12 (6 to 15) at baseline to 8 (5 to 12) at follow-up for the placebo device group, P = .11; mean between-group difference in OSLER test, -2.4 min (95% CI, -6.3 to 1.4). The mean between-group difference for the total FOSQ score was insignificant (-1.2 [95% CI, -2.5 to 0.1]). No domain of the SF-36 differed significantly between the groups. The AHI was below 5 in 49% of patients using the active appliance and in 11% using placebo, with an odds ratio of 7.8 (95% CI, 2.6-23.5) and a number needed to treat of 3. Snoring (P < .001) and symptoms of restless legs (P = .02) were less frequent when using the oral appliance vs placebo, but this did not apply to headache or insomnia.

    CONCLUSIONS AND RELEVANCE: A custom-made, adjustable oral appliance reduces obstructive sleep apnea, snoring, and possibly restless legs without effects on daytime sleepiness and quality of life among patients with daytime sleepiness and snoring or mild to moderate sleep apnea.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00477009.

  • 6. Moore, Steven C.
    et al.
    Lee, I-Min
    Weiderpass, Elisabete
    Campbell, Peter T.
    Sampson, Joshua N.
    Kitahara, Cari M.
    Keadle, Sarah K.
    Arem, Hannah
    de Gonzalez, Amy Berrington
    Hartge, Patricia
    Adami, Hans-Olov
    Blair, Cindy K.
    Borch, Kristin B.
    Boyd, Eric
    Check, David P.
    Fournier, Agness
    Freedman, Neal D.
    Gunter, Marc
    Johannson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
    Khaw, Kay-Tee
    Linet, Martha S.
    Orsini, Nicola
    Park, Yikyung
    Riboli, Elio
    Robien, Kim
    Schairer, Catherine
    Sesso, Howard
    Spriggs, Michael
    Van Dusen, Roy
    Wolk, Alicja
    Matthews, Charles E.
    Patel, Alpa V.
    Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 6, p. 816-825Article in journal (Refereed)
    Abstract [en]

    Importance: Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood.

    Objective: To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking.

    Design, Setting, and Participants: We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015.

    Exposures: Leisure-time physical activity of a moderate to vigorous intensity.

    Main Outcomes and Measures: Incident cancer during follow-up.

    Results: A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers.

    Conclusions and Relevance: Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

  • 7. Mullee, Amy
    et al.
    Romaguera, Dora
    Pearson-Stuttard, Jonathan
    Viallon, Vivian
    Stepien, Magdalena
    Freisling, Heinz
    Fagherazzi, Guy
    Mancini, Francesca Romana
    Boutron-Ruault, Marie-Christine
    Kühn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Tjønneland, Anne
    Halkjær, Jytte
    Overvad, Kim
    Weiderpass, Elisabete
    Skeie, Guri
    Parr, Christine L
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Cirera, Lluís
    Ardanaz, Eva
    Khaw, Kay-Tee
    Tong, Tammy Y N
    Schmidt, Julie A
    Trichopoulou, Antonia
    Martimianaki, Georgia
    Karakatsani, Anna
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Verschuren, W M Monique
    Boer, Jolanda M A
    Vermeulen, Roel
    Ramne, Stina
    Sonestedt, Emily
    van Guelpen, Bethany
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Tsilidis, Konstantinos K
    Heath, Alicia K
    Muller, David
    Riboli, Elio
    Gunter, Marc J
    Murphy, Neil
    Association Between Soft Drink Consumption and Mortality in 10 European Countries.2019In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114Article in journal (Refereed)
    Abstract [en]

    Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.

    Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.

    Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018.

    Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks.

    Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors.

    Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001).

    Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

  • 8.
    Nordström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Pedersen, Nancy L
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Michaëlsson, Karl
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Risks of Myocardial Infarction, Death, and Diabetes in Identical Twin Pairs With Different Body Mass Indexes2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 10, p. 1522-1529Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Observational studies have shown that obesity is a major risk factor for cardiovascular disease and death. The extent of genetic confounding in these associations is unclear. OBJECTIVE To compare the risk of myocardial infarction (MI), type 2 diabetes, and death in monozygotic (MZ) twin pairs discordant for body mass index (BMI). DESIGN, SETTING, AND PARTICIPANTS A cohort of 4046 MZ twin pairs with discordant BMIs (difference >0.01) was identified using the nationwide Swedish twin registry. The study was conducted from March 17, 1998, to January 16, 2003, with follow-up regarding incident outcomes until December 31, 2013. MAIN OUTCOMES AND MEASURES The combined primary end point of death or MI and the secondary end point of incident diabetes were evaluated in heavier compared with leaner twins in a co-twin control analysis using multivariable conditional logistic regression. RESULTS Mean (SD) baseline age for both cohorts was 57.6 (9.5) years (range, 41.9-91.8 years). During a mean follow-up period of 12.4 (2.5) years, 203 MIs (5.0%) and 550 deaths (13.6%) occurred among heavier twins (mean [SD] BMI, 25.9 [3.6] [calculated as weight in kilograms divided by height in meters squared]) compared with 209 MIs (5.2%) and 633 deaths (15.6%) among leaner twins (mean [SD] BMI, 23.9 [3.1]; combined multivariable adjusted odds ratio [OR], 0.75; 95% CI, 0.63-0.91). Even in twin pairs with BMI discordance of 7.0 or more (mean [SE], 9.3 [0.7]), where the heavier twin had a BMI of 30.0 or more (n = 65 pairs), the risk of MI or death was not greater in heavier twins (OR, 0.42; 95% CI, 0.15-1.18). In contrast, in the total cohort of twins, the risk of incident diabetes was greater in heavier twins (OR, 2.14; 95% CI, 1.61-2.84). Finally, increases in BMI since 30 years before baseline were not associated with the later risk of MI or death (OR, 0.97; 95% CI, 0.89-1.05) but were associated with the risk of incident diabetes (OR, 1.13; 95% CI, 1.01-1.26). CONCLUSIONS AND RELEVANCE In MZ twin pairs, higher BMI was not associated with an increased risk of MI or death but was associated with the onset of diabetes. These results may suggest that lifestyle interventions to reduce obesity are more effective in decreasing the risk of diabetes than the risk of cardiovascular disease or death.

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