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1. Body mass index, smoking, and risk of death between 40 and 70 years of age in a Norwegian cohort of 32,727 women and 33,475 men.

Author

Hjellvik V, Selmer R, Gjessing HK, Tverdal A, and Vollset SE

Subjects
Adult, Age Factors, Aged, Anthropometry, Cause of Death, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Norway epidemiology, Regression Analysis, Residence Characteristics, Rural Population, Smoking adverse effects, Socioeconomic Factors, Surveys and Questionnaires, White People, Body Mass Index, Obesity mortality, Risk Assessment, Smoking mortality
Abstract

Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40-69 years) death risk-overall and by causes-in a Norwegian cohort of 32,727 women and 33,475 men who were 35-49 years old when baseline measurements and lifestyle information were collected in 1974-1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11% in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5-24.9 BMI group to 31% (adjusted 28%) in obese (BMI > 30 kg/m(2)) heavy smokers (≥20 cigarettes/day). The corresponding figures in men were 10% and 53% (adjusted 45%). Obese never smokers and light (1-9 cigarettes/day) smokers in the 22.5-24.9 BMI groups both experienced a twofold increase in middle age risks of death. For women, cancer (56%) was the most common cause of death followed by cardiovascular disease (22%). In men, cardiovascular disease was most common (41%) followed by cancer (34%). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths.

Published
2013
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2. Metabolic factors and blood cancers among 578,000 adults in the metabolic syndrome and cancer project (Me-Can).

Author

Nagel G, Stocks T, Späth D, Hjartåker A, Lindkvist B, Hallmans G, Jonsson H, Bjørge T, Manjer J, Häggström C, Engeland A, Ulmer H, Selmer R, Concin H, Stattin P, and Schlenk RF

Subjects
Adult, Cohort Studies, Female, Follow-Up Studies, Hematologic Neoplasms blood, Humans, Male, Metabolic Syndrome blood, Middle Aged, Blood Glucose metabolism, Body Mass Index, Hematologic Neoplasms epidemiology, Hematologic Neoplasms metabolism, Metabolic Syndrome epidemiology, Metabolic Syndrome metabolism
Abstract

We investigated associations between metabolic factors and blood cancer subtypes. Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol, and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean age = 44 years). Relative risks of blood cancers were calculated from Cox regression models. During mean follow-up of 12 years, 2,751 incident and 1,070 fatal cases of blood cancers occurred. Overall, higher BMI was associated with an increased blood cancer risk. In gender-specific subgroup analyses, BMI was positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p = 0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were inversely associated with myeloid neoplasms in women (p = 0.01), particularly acute myeloid leukemia (p = 0.003), and glucose was positively associated with chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively associated with risk of high-grade B-cell lymphoma and multiple myeloma, while cholesterol was inversely associated with low-grade B-cell lymphoma. The metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma among women. BMI showed up as the most consistent risk factor, particularly in women. A clear pattern was not found for other metabolic factors.

Published
2012
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3. Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults.

Author

Borena W, Strohmaier S, Lukanova A, Bjørge T, Lindkvist B, Hallmans G, Edlinger M, Stocks T, Nagel G, Manjer J, Engeland A, Selmer R, Häggström C, Tretli S, Concin H, Jonsson H, Stattin P, and Ulmer H

Subjects
Adult, Aged, Austria epidemiology, Blood Pressure, Cholesterol blood, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Metabolic Syndrome blood, Middle Aged, Norway epidemiology, Proportional Hazards Models, Prospective Studies, Risk Factors, Sweden epidemiology, Triglycerides blood, Blood Glucose, Body Mass Index, Lipids blood, Liver Neoplasms epidemiology, Liver Neoplasms metabolism, Metabolic Syndrome complications
Abstract

Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24-1.58), mid blood pressure 2.08 (0.95-4.73), blood glucose 2.13 (1.55-2.94) cholesterol 0.62 (0.51-0.76) and serum triglycerides 0.85 (0.65-1.10). The RR per one unit increment of the MetS z-score was 1.35 (1.12-1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer., (Copyright © 2011 UICC.)

Published
2012
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4. A prospective study of body mass index, weight change, and risk of cancer in the proximal and distal colon.

Author

Laake I, Thune I, Selmer R, Tretli S, Slattery ML, and Veierød MB

Subjects
Adult, Cohort Studies, Colonic Neoplasms etiology, Colonic Neoplasms pathology, Female, Humans, Male, Middle Aged, Norway epidemiology, Prospective Studies, Risk Factors, Weight Gain, Weight Loss, Young Adult, Body Mass Index, Colonic Neoplasms epidemiology
Abstract

Background: Body mass index (BMI) is an established risk factor for colon cancer, but risks may differ between genders and colon subsites. Moreover, whether weight change influences risk is not yet clarified. We investigated these issues in a large, Norwegian, population-based cohort study., Methods: Participants' weight was measured at examinations up to three times between 1974 and 1988. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox regression., Results: During follow-up of 38,822 men and 37,357 women, we identified 228 proximal and 174 distal colon cancer cases in men and 237 and 159 cases, respectively, in women. The association between BMI and colon cancer risk differed between subsites in men (P = 0.02) but not in women (P = 0.95). In men, HRs (95% CIs) per 5 kg/m(2) were 1.07 (0.86-1.33) and 1.49 (1.19-1.87) for proximal and distal colon, respectively. In women, corresponding HRs (95% CIs) were 1.15 (0.99-1.34) and 1.25 (1.05-1.49). Among overweight men (BMI > or = 25 kg/m(2)), weight gain > or = 10 kg gave higher colon cancer risk than weight maintenance (HR, 2.09; 95% CI, 1.21-3.63), whereas risks were similar among men with stable weight, weight loss, or gains <10 kg. Weight change was not associated with risk in women., Conclusions: The influence of BMI on colon cancer risk differed between subsites in men. Weight gains <10 kg did not influence risk., Impact: Our results support gender differences and the hypothesis of different etiologies for colon subsites. Whether weight loss in the overweight decreases risk of colon cancer warrants further study., (Copyright 2010 AACR.)

Published
2010
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5. Influence of physical, mental and intellectual development on disability in young Norwegian men.

Author

Gravseth HM, Bjerkedal T, Irgens LM, Aalen OO, Selmer R, and Kristensen P

Subjects
Adult, Educational Status, Family Characteristics, Humans, Male, Norway, Risk Factors, Body Height, Body Mass Index, Disabled Persons statistics & numerical data, Intelligence
Abstract

Background: Few studies have examined the effects of educational level, intellectual performance, mental function, body mass index and height as well as their interrelationship on the risk of disability pension (DP), taking other life course factors into account., Methods: We linked several national registers, comprising the Medical Birth Registry, the Central Population Register, the Education Register, the Norwegian Labour and Welfare Organisation and the Norwegian Armed Forces Personnel Data Base, providing personal data on biological and social variables from childhood to young adult age. Participants were all males live born during the period 1967-76, followed up through 2003. Men were excluded who died, emigrated or were granted a DP until age 23 years (when follow-up started) and persons who did not become gainfully employed during the study period. Thus, the study population comprised 302 330 men, and the study outcome was being granted a DP after age 23 years., Results: 3651 men (1.2%) were granted a DP. The DP rate was inversely associated with both educational level and intellectual performance. The adjusted population attributable risks (PAR) values for these two variables were 47% and 35%, respectively. The effect of the other variables was modest. Over- and underweight and short stature were associated with DP, but the effect was largely reduced after adjusting for intellectual performance. Impaired mental function seemed to have an independent effect., Conclusion: Receiving an early DP is dependent on several factors acting at different stages of life, above all educational level and intellectual performance. High education can modify some of the effects of low intellectual performance.

Published
2008
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6. Body mass index and cardiovascular mortality at different levels of blood pressure: a prospective study of Norwegian men and women.

Author

Selmer R and Tverdal A

Subjects
Adult, Aged, Cause of Death, Cerebrovascular Disorders epidemiology, Cohort Studies, Coronary Disease epidemiology, Female, Humans, Hypertension epidemiology, Hypertension mortality, Hypertension physiopathology, Male, Middle Aged, Norway epidemiology, Prospective Studies, Blood Pressure physiology, Body Mass Index, Cerebrovascular Disorders mortality, Coronary Disease mortality
Abstract

Study Objective: The study investigated the joint effect of body mass index and systolic blood pressure on cardiovascular and total mortality., Design: This was a prospective cohort study. The main outcome measures were age adjusted mortality and relative risks estimated from survival models., Setting: The population of the city of Bergen, Norway., Participants: Subjects were 21,145 men and 30,330 women aged 30-79 years at the time of examination in 1963., Main Results: Both cause specific and all cause mortality increased with systolic blood pressure within each category of body mass index. Stroke mortality was not significantly associated with body mass index when adjusted for systolic blood pressure in either age group of men or women. Coronary heart disease mortality increased on average 30% per 5 kg/m2 increase in body mass index in men and women aged 30-59 years at baseline. Adjusted for systolic blood pressure, the relative risks were reduced to 1.20 (95% confidence interval (CI) 1.12, 1.29) in men and 1.10 (95% CI 1.03, 1.18) in women. They were similar at each level of systolic blood pressure. For coronary heart disease mortality in men and women aged 60-79 years at measurement a negative interaction between body mass index and systolic blood pressure was suggested in the first five years. Excluding the first five years, adjusted relative risks per 5 kg/m2, were 1.05 (95% CI 0.96, 1.15) in men and 1.11 (95% CI 1.04, 1.17) in women in the older age group. There was an upturn in cardiovascular mortality at low levels of body mass index in both age groups of women, but not in men., Conclusions: Hypertension is an important risk factor for cardiovascular and all cause mortality even in the obese. Body mass index is generally a weak predictor of cardiovascular mortality in this population. It is a stronger risk factor of coronary death in men when measured at a younger age. Thin people with hypertension are not at particularly high risk of death from coronary heart disease compared with their obese counterparts, except possibly in the first few years after measurement in the elderly. Being underweight is associated with increased risk of death from all cardiovascular causes in women, but not in men.

Published
1995
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8. Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980793 adults from 68 prospective studies

Author

Gnatiuc, L, Herrington, WG, Halsey, J, Tuomilehto, J, Fang, X, Kim, HC, DeBacquer, D, Dobson, AJ, Criqui, MH, Jacobs, DR, Leon, DA, Peters, SAE, Ueshima, H, Sherliker, P, Peto, R, Collins, R, Huxley, RR, Emberson, JR, Woodward, M, Lewington, S, De Backer, G, De Bacquer, D, Kornitzer, M, Morris, R, Wannamethee, SG, Whincup, P, Law, M, Morris, J, Wald, N, Kromhout, D, Benetos, A, Guize, L, Jensen, G, Schnohr, P, Jousilahti, P, Puska, P, Vartiainen, E, Aromaa, A, Knekt, P, Reunanen, A, Johansen, NB, Thomsen, T, Bengtsson, C, Bjorkelund, C, Lissner, L, Goldbourt, U, Selmer, R, Tverdal, A, Meade, T, Haheim, L, Hjermann, I, Holme, I, Leren, P, Ducimetiere, P, Empana, J, Assmann, G, Schulte, H, Smith, GD, Hart, C, Hole, D, Tunstall-Pedoe, H, Sweetnam, P, Yarnell, J, Arnesen, E, Bonaa, K, Marmot, M, Shipley, M, Gillis, C, Chambless, L, Luszcz, M, Dhaliwal, SS, Welborn, TA, Bartholomew, H, Knuiman, MW, Kronmal, R, Nietert, PJ, Sutherland, SE, Bachman, DL, Gazes, P, Boyle, E, Jackson, R, MacMahon, S, Norton, R, Whitlock, G, D'Agostino, R, Levy, D, Silbershatz, H, Curb, JD, Sharp, D, Giles, GG, Hashimoto, S, Sakata, K, Blackburn, H, Jacobs, D, Luepker, R, Dobson, A, Cox, C, Broadhurst, R, Hobbs, M, Jamrozik, K, Garcia-Palmieri, M, Sorlie, P, Keller, J, Guasch-Ferre, M, Hu, F, Willett, W, Eliassen, H, Maegawa, H, Okayama, A, Aoki, N, Nakamura, M, Wu, ZL, Shifu, X, Tamakoshi, A, Sritara, P, Gu, DF, Jiang, CQ, Lam, TH, Ho, SC, Woo, J, Iso, H, Kitamura, A, Sato, S, Murayama, T, Nishimoto, Y, Tomita, M, Jee, SH, Kim, IS, Suh, I, Kita, Y, Niki, I, Naito, Y, Hozawa, A, Imai, Y, Ohkubo, T, Imai, K, Date, C, Nakayama, T, Yokoyama, T, Yoshiike, N, Tanaka, H, Nozaki, A, Horibe, H, Kagaya, M, Matsutani, Y, Hughes, K, Lee, J, Heng, D, Saitoh, S, Shimamoto, K, Pan, WH, Yao, SX, Baigent, C, Carstensen, J, Chen, Z, Clarke, R, Duffy, S, Neaton, J, Qizilbash, N, Rodgers, A, Tominaga, S, Tornberg, S, Bennett, D, Gu, D, Huxley, R, and Zhang, XH

Subjects
Male, Endocrinology, Diabetes and Metabolism, BLOOD-PRESSURE, Blood Pressure, 030204 cardiovascular system & hematology, Body Mass Index, MELLITUS, 0302 clinical medicine, Endocrinology, Medicine and Health Sciences, Prospective Studies, Prospective Studies Collaboration and Asia Pacific Cohort Studies Collaboration, Prospective cohort study, media_common, Aged, 80 and over, Mortality rate, Absolute risk reduction, WOMEN, MEN, ASSOCIATION, Middle Aged, 3. Good health, 1101 Medical Biochemistry and Metabolomics, Cardiovascular Diseases, Female, HEALTH, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, 1117 Public Health and Health Services, Diabetes Complications, 03 medical and health sciences, Endocrinology & Metabolism, Sex Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, media_common.cataloged_instance, Humans, COHORT, European union, Mortality, Aged, Science & Technology, business.industry, 1103 Clinical Sciences, medicine.disease, RANDOMIZED-TRIALS, Relative risk, RISK-FACTORS, business, Body mass index
Abstract

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p

Published
2018

9. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies

Author

Whitlock, Gary, Lewington, Sarah, Sherliker, Paul, Clarke, Robert, Emberson, Jonathan, Halsey, Jim, Qizilbash, Nawab, Collins, Rory, Peto, Richard, Lewington, S, MacMahon, S, Peto, R, Aromaa, A, Baigent, C, Carstensen, J, Chen, Z, Clarke, R, Collins, R, Duffy, S, Kromhout, D, Neaton, J, Qizilbash, N, Rodgers, A, Tominaga, S, Toernberg, S, Tunstall-Pedoe, H, Whitlock, G, Chambless, L, De Backer, G, De Bacquer, D, Kornitzer, M, Whincup, P, Wannamethee, SG, Morris, R, Wald, N, Morris, J, Law, M, Knuiman, M, Bartholomew, H, Smith, G Davey, Sweetnam, P, Elwood, P, Yarnell, J, Kronmal, R, Sutherland, S, Keil, J, Jensen, G, Schnohr, P, Hames, C, Tyroler, A, Knekt, P, Reunanen, A, Tuomilehto, J, Jousilahti, P, VArtiainen, E, Puska, P, Kuznetsova, Tatiana, Richart, Tom, Staessen, Jan A, Thijs, Lutgarde, Jorgensen, T, Thomsen, T, Sharp, D, Curb, JD, Iso, H, Sato, S, Kitamura, A, Naito, Y, Benetos, A, Guize, L, Goldbourt, U, Tomita, M, Nishimoto, Y, Murayama, T, Criqui, M, Davis, C, Hart, C, Hole, D, Gillis, C, Jacobs, D, Blackburn, H, Luepker, R, Eberly, L, Cox, C, Levy, D, D'Agostino, R, Silbershatz, H, Tverdal, A, Selmer, R, Meade, T, Garrow, K, Cooper, J, Speizer, F, Stampfer, M, Menotti, A, Spagnolo, A, Tsuji, I, Imai, Y, Ohkubo, T, Hisamichi, S, Haheim, L, Holme, I, Hjermann, I, Leren, P, Ducimetiere, P, Empana, J, Jamrozik, K, Broadhurst, R, Assmann, G, Schulte, H, Bengtsson, C, Bjoerkelund, C, Lissner, L, Sorlie, P, Garcia-Palmieri, M, Barrett-Conner, E, Langer, R, Nakachi, K, Imai, K, Fang, X, Buzina, R, Nissinen, A, Aravanis, C, Dontas, A, Kafatos, A, Adachi, H, Toshima, H, Imaizumi, T, Nedeljkovic, S, Ostojic, M, CHen, Z, Nakayama, T, Yoshiike, N, Yokoyama, T, Date, C, Tanaka, H, Keller, J, Bonaa, K, Arnesen, E, Rimm, E, Gaziano, M, Buring, JE, Hennekens, C, Tornberg, S, Shipley, M, Leon, D, Marmot, M, Emberson, J, Halsey, J, Palmer, A, Parish, S, and Sherliker, P

Subjects
Male, obesity, Nutrition and Disease, Respiratory Tract Diseases, Myocardial Ischemia, individual data, 030204 cardiovascular system & hematology, Overweight, Body Mass Index, 0302 clinical medicine, blood-pressure, Cause of Death, Voeding en Ziekte, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, risk, Cause of death, Aged, 80 and over, Hazard ratio, Articles, General Medicine, Middle Aged, 3. Good health, Stroke, Female, medicine.symptom, Adult, medicine.medical_specialty, Waist, abdominal adiposity, united-states, 03 medical and health sciences, vascular mortality, Internal medicine, Humans, korean men, Mortality, Aged, VLAG, business.industry, Anthropometry, medicine.disease, Obesity, Surgery, randomized-trials, coronary-heart-disease, business, Body mass index
Abstract

Summary Background The main associations of body-mass index (BMI) with overall and cause-specific mortality can best be assessed by long-term prospective follow-up of large numbers of people. The Prospective Studies Collaboration aimed to investigate these associations by sharing data from many studies. Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants, mostly in western Europe and North America (61% [n=541 452] male, mean recruitment age 46 [SD 11] years, median recruitment year 1979 [IQR 1975–85], mean BMI 25 [SD 4] kg/m2). The analyses were adjusted for age, sex, smoking status, and study. To limit reverse causality, the first 5 years of follow-up were excluded, leaving 66 552 deaths of known cause during a mean of 8 (SD 6) further years of follow-up (mean age at death 67 [SD 10] years): 30 416 vascular; 2070 diabetic, renal or hepatic; 22 592 neoplastic; 3770 respiratory; 7704 other. Findings In both sexes, mortality was lowest at about 22·5–25 kg/m2. Above this range, positive associations were recorded for several specific causes and inverse associations for none, the absolute excess risks for higher BMI and smoking were roughly additive, and each 5 kg/m2 higher BMI was on average associated with about 30% higher overall mortality (hazard ratio per 5 kg/m2 [HR] 1·29 [95% CI 1·27–1·32]): 40% for vascular mortality (HR 1·41 [1·37–1·45]); 60–120% for diabetic, renal, and hepatic mortality (HRs 2·16 [1·89–2·46], 1·59 [1·27–1·99], and 1·82 [1·59–2·09], respectively); 10% for neoplastic mortality (HR 1·10 [1·06–1·15]); and 20% for respiratory and for all other mortality (HRs 1·20 [1·07–1·34] and 1·20 [1·16–1·25], respectively). Below the range 22·5–25 kg/m2, BMI was associated inversely with overall mortality, mainly because of strong inverse associations with respiratory disease and lung cancer. These inverse associations were much stronger for smokers than for non-smokers, despite cigarette consumption per smoker varying little with BMI. Interpretation Although other anthropometric measures (eg, waist circumference, waist-to-hip ratio) could well add extra information to BMI, and BMI to them, BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2. The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal. At 30–35 kg/m2, median survival is reduced by 2–4 years; at 40–45 kg/m2, it is reduced by 8–10 years (which is comparable with the effects of smoking). The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases, and is not fully explained. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, EU BIOMED programme, US National Institute on Aging, and Clinical Trial Service Unit (Oxford, UK).

Published
2009
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10. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

Author

Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh JTipping RW, Ford CE, Pressel SL, Walldius G, Jungner I, Folsom AR, Chambless L, Ballantyne CM, Panagiotakos D, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman MW, Goldbourt U, Benderly M, Tanne D, Whincup P, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Mayr A, Schett G, Wald N, Ebrahim S, Lawlor D, Yarnell J, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, Cushman M, Psaty BM, Tracy R, Tybjaerg Hansen A, Nordestgaard BG, Zacho J, Frikke Schmidt R, Giampaoli S, Palmieri L, Vanuzzo D, Pilotto L, de la Cámara AG, Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee A, Taylor J, Guralnik JM, Phillips CL, Wallace RB, Blazer DG, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB, Wolf PA, Vasan RS, Benjamin EJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker J, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Nyyssönen K, Tuomainen TP, Laukkanen JA, Deeg DJ, Bremmer MA, Meade TW, Cooper JA, Hedblad B, Berglund G, Engström G, Verschuren WM, Blokstra A, Shea S, Döring A, Koenig W, Meisinger C, Bueno de Mesquita HB, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum RF, Mussolino M, Hankinson S, Manson JE, Knottenbelt C, Bauer KA, Davidson K, Kirkland S, Shaffer J, Korin MR, Naito Y, Holme I, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Luc G, Crespo CJ, Garcia Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrieres J, Schulte H, Assmann G, Packard CJ, Sattar N, Westendorp RG, Buckley BM, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett Connor E, Wingard DL, Bettencourt RR, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Breteler MM, Hofman A, Tunstall Pedoe H, Tavendale R, Howard BV, Zhang Y, Best L, Umans J, Ben Shlomo Y, Davey Smith G, Onat A, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Basu S, Cederholm T, Byberg L, Gaziano JM, Stampfer M, Ridker PM, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Wassertheil Smoller S, Marmot IM, Clarke R, Fletcher A, Brunner E, Shipley M, Buring J, Shepherd J, Cobbe S, Ford I, Robertson M, He Y, Ibañez AM, Feskens EJ, Walker M, Watson S, Erqou S, Lewington S, Pennells L, Perry PL, Ray KK, Sarwar N, Alexander M, Thompson A, White IR, Wood AM, Danesh J., PANICO, SALVATORE, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), RS: CARIM School for Cardiovascular Diseases, General practice, EMGO - Lifestyle, overweight and diabetes, Psychiatry, EMGO - Mental health, Emerging Risk Factors, Collaboration, Kaptoge, S, Di Angelantonio, E, Lowe, G, Pepys, Mb, Thompson, Sg, Collins, R, Danesh JTipping, Rw, Ford, Ce, Pressel, Sl, Walldius, G, Jungner, I, Folsom, Ar, Chambless, L, Ballantyne, Cm, Panagiotakos, D, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, Mw, Goldbourt, U, Benderly, M, Tanne, D, Whincup, P, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Mayr, A, Schett, G, Wald, N, Ebrahim, S, Lawlor, D, Yarnell, J, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, R, Tybjaerg Hansen, A, Nordestgaard, Bg, Zacho, J, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, de la Cámara, Ag, Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, A, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, Rb, Blazer, Dg, Khaw, Kt, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Benjamin, Ej, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, Te, Kiyohara, Y, Arima, H, Doi, Y, Ninomiya, T, Rodriguez, B, Dekker, J, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Laukkanen, Ja, Deeg, Dj, Bremmer, Ma, Meade, Tw, Cooper, Ja, Hedblad, B, Berglund, G, Engström, G, Verschuren, Wm, Blokstra, A, Shea, S, Döring, A, Koenig, W, Meisinger, C, Bueno de Mesquita, Hb, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, Rf, Mussolino, M, Hankinson, S, Manson, Je, Knottenbelt, C, Bauer, Ka, Davidson, K, Kirkland, S, Shaffer, J, Korin, Mr, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Luc, G, Crespo, Cj, Garcia Palmieri, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Packard, Cj, Sattar, N, Westendorp, Rg, Buckley, Bm, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, Dl, Bettencourt, Rr, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, Mm, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Howard, Bv, Zhang, Y, Best, L, Umans, J, Ben Shlomo, Y, Davey Smith, G, Onat, A, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Basu, S, Cederholm, T, Byberg, L, Gaziano, Jm, Stampfer, M, Ridker, Pm, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Wassertheil Smoller, S, Marmot, Im, Clarke, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Shepherd, J, Cobbe, S, Ford, I, Robertson, M, He, Y, Ibañez, Am, Feskens, Ej, Walker, M, Watson, S, Erqou, S, Lewington, S, Pennells, L, Perry, Pl, Ray, Kk, Sarwar, N, Alexander, M, Thompson, A, White, Ir, Wood, Am, and Danesh, J.

Subjects
Lung Diseases, Male, Databases, Factual, Plasma-fibrinogen, Blood Pressure, Coronary Disease, 030204 cardiovascular system & hematology, Associations, Body Mass Index, Low-density-lipoprotein, Leukocyte Count, 0302 clinical medicine, Risk Factors, Neoplasms, 030212 general & internal medicine, Stroke, Framingham Risk Score, biology, Smoking, 11 Medical And Health Sciences, General Medicine, Articles, Middle Aged, 3. Good health, C-Reactive Protein, Cholesterol, Regression Analysis, low-density lipoprotein cardiovascular-disease nonvascular mortality regression dilution plasma-fibrinogen mendelian randomization independent predictor prospective cohorts vascular-disease inflammation, Female, Risk assessment, medicine.medical_specialty, Alcohol Drinking, Regression dilution, Motor Activity, Risk Assessment, 03 medical and health sciences, Sex Factors, Cardiovascular-disease, General & Internal Medicine, Internal medicine, Diabetes Mellitus, medicine, Humans, Women, Risk factor, Serum Albumin, Triglycerides, Inflammation, Markers, Independent predictor, Interleukin-6, business.industry, Vascular disease, C-reactive protein, Fibrinogen, medicine.disease, Surgery, Relative risk, biology.protein, Nonvascular mortality, business, Biomarkers
Abstract

Udgivelsesdato: 2010-Jan-9 BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

Published
2010
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11. Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

Author

Nagel, G., Bjørge, T., Stocks, T., Manjer, J., Hallmans, G., Edlinger, M., Häggström, C., Engeland, A., Johansen, D., Kleiner, A., Selmer, R., Ulmer, H., Tretli, S., Jonsson, H., Concin, H., Stattin, P., and Lukanova, A.

Subjects
METABOLIC syndrome risk factors, DISEASE risk factors, SKIN cancer, MELANOMA, SQUAMOUS cell carcinoma, PROPORTIONAL hazards models, BODY mass index, BLOOD pressure
Abstract

Background Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Objectives To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). Methods During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. Results Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels ( P-trend 0·02) and there was a trend with triglyceride concentration ( P-trend 0·09). Conclusion These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Published
2012
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12. Metabolic syndrome and rare gynecological cancers in the Metabolic syndrome and Cancer project (Me-Can).

Author

Nagel, G., Concin, H., Bjørge, T., Rapp, K., Manjer, J., Hallmans, G., Diem, G., Häggström, C., Engeland, A., Almquist, M., Jonsson, H., Selmer, R., Stocks, T., Tretli, S., Ulmer, H., Stattin, P., and Lukanova, A.

Subjects
*METABOLIC syndrome, *CANCER in women, *FOLLOW-up studies (Medicine), *REGRESSION analysis, *BODY mass index, *EPIDEMIOLOGY, *RARE diseases, *GYNECOLOGIC cancer
Abstract

Background: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role.Materials and methods: The Metabolic syndrome and Cancer project cohort includes 288 834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors.Results: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30–2.41) and vaginal cancer (HR 1.87, 95% CI 1.07–3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23–1.66), vulvar (HR 1.36, 95% CI 1.11–1.69) and vaginal cancer (HR 1.79, 95% CI 1.30–2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10–3.58 and HR 2.09, 95% CI 1.39–3.15, respectively).Conclusion: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors. [ABSTRACT FROM AUTHOR]

Published
2011
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