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1.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
2.  Plasma Phospholipid Fatty Acid Concentration and Incident Coronary Heart Disease in Men and Women: The EPIC-Norfolk Prospective Study 
PLoS Medicine  2012;9(7):e1001255.
Kay-Tee Khaw and colleagues analyze data from a prospective cohort study and show associations between plasma concentrations of saturated phospholipid fatty acids and risk of coronary heart disease, and an inverse association between omega-6 polyunsaturated phospholipid fatty acids and risk of coronary heart disease.
Background
The lack of association found in several cohort studies between dietary saturated fat and coronary heart disease (CHD) risk has renewed debate over the link between dietary fats and CHD.
Methods and Findings
We assessed the relationship between plasma phospholipid fatty acid (PFA) concentration and incident CHD using a nested case control design within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40–79 years examined in 1993–1997 and followed up to 2009. Plasma PFA concentrations were measured by gas chromatography in baseline samples retrieved from frozen storage. In 2,424 men and women with incident CHD compared with 4,930 controls alive and free of cardiovascular disease, mean follow-up 13 years, saturated PFA (14:0, 16:0,18:0) plasma concentrations were significantly associated with increased CHD risk (odds ratio [OR] 1.75, 95% CI 1.27–2.41, p<0.0001), in top compared to bottom quartiles (Q), and omega-6 polyunsaturated PFA concentrations were inversely related (OR 0.77, 0.60–0.99, p<0.05) after adjusting for age, sex, body mass index, blood pressure, smoking, alcohol intake, plasma vitamin C, social class, education, and other PFAs. Monounsaturated PFA, omega-3 PFA, and trans PFA concentrations were not significantly associated with CHD. Odd chain PFA (15:0, 17:0) concentrations were significantly inversely associated with CHD (OR 0.73, 0.59–0.91, p<0.001, Q4 versus Q1). Within families of saturated PFA or polyunsaturated PFA, significantly heterogeneous relationships with CHD were observed for individual fatty acids.
Conclusions
In this study, plasma concentrations of even chain saturated PFA were found to be positively and omega-6 polyunsaturated PFA inversely related to subsequent coronary heart disease risk. These findings are consistent with accumulating evidence suggesting a protective role of omega-6 fats substituting for saturated fats for CHD prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Coronary heart disease (CHD) is a condition caused by a build-up of fatty deposits on the inner walls of the blood vessels that supply the heart, causing the affected person to experience pain, usually on exertion (angina). A complete occlusion of the vessel by deposits causes a heart attack (myocardial infarction). Lifestyle factors, such as diet (particularly one high in fat), contribute to causing CHD. There are different types of fat, some of which are thought to increase risk of CHD, such as saturated fat, typically found in meat and dairy foods. However, others, such as unsaturated fats (polyunsaturated and monounsaturated fats) found in foods such as vegetable oils, fish, and nuts, may actually help prevent this condition.
Why Was This Study Done?
Although there have been many studies investigating the role of different types of dietary fat in coronary heart disease, it is still not clear whether coronary heart disease can be prevented by changing the type of dietary fat consumed from saturated to unsaturated fats or by lowering all types of dietary fat. Furthermore, many of these studies have relied on participants recalling their dietary intake in questionnaires, which is an unreliable method for different fats. So in this study, the researchers used an established UK cohort to measure the levels of different types of fatty acids in blood to investigate whether a diet high in saturated fatty acids and low in unsaturated fatty acids increases CHD risk.
What Did the Researchers Do and Find?
The researchers used a selection of 10,000 participants (all men and women aged 40–79 years) from the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Blood samples from the selected participants taken at the start of the study in 1993–1997 were analyzed to determine levels of specific fatty acids. Participants were followed up till 2011. The researchers identified 2,424 participants who were subsequently diagnosed with CHD using death certificates and hospital discharge data and matched these with 4,930 controls who were still alive and free of known coronary disease. The researchers grouped the type of blood fatty acids identified in the blood samples into six families (even chain saturated fatty acid, odd chain saturated fatty acid, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid, monounsaturated fatty acid, and trans-fatty acid), which represented saturated and unsaturated fatty acids. Using statistical methods, the researchers then compared the risks of developing CHD between cases and controls by the concentration of fatty acid families after adjusting for age and sex and other factors, such as body mass index, physical activity, and smoking. Using these methods, the researchers found that there was no overall significant relationship between total blood fatty acid concentration and CHD but there was a positive association with increasing blood saturated fatty acid concentration after adjusting for other fatty acid concentrations, with an odds ratio of 1.83 comparing higher versus lower concentrations. This risk was attenuated after adjusting for cholesterol levels, indicating that much of the association between saturated fatty acid and CHD is likely to be mediated through blood cholesterol levels. In contrast, blood omega-6 poly-unsaturated fatty acid concentrations were associated with lower CHD risk. Blood monounsaturated fatty acids, omega-3 poly-unsaturated fatty acids, and trans-fatty acids were not consistently associated with CHD risk. The authors also noted that within families of fatty acids, individual fatty acids related differently to CHD risk.
What Do These Findings Mean?
These findings suggest that plasma concentrations of saturated fatty acids are associated with increased risk of CHD and that concentrations of omega-6 poly-unsaturated fatty acids are associated with decreased risk of CHD. These findings are consistent with other studies and with current dietary advice for preventing CHD, which encourages substituting foods high in saturated fat with n-6 polyunsaturated fats. The results also suggest that different fatty acids may relate differently to CHD risk and that the overall balance between different fatty acids is important. However, there are limitations to this study, such as that factors other than diet (genetic differences in metabolism, for example) may cause changes to blood fatty acid levels so a major question is to identify what factors influence blood fatty acid concentrations. Nevertheless, these findings suggest that individual fatty acids play a role in increasing or decreasing risks of CHD.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001255.
Information about the EPIC-Norfolk study is available
The American Heart Foundation provides patient-friendly information about different dietary fats as does Medline
The British Heart Foundation also provides patient-friendly information on heart conditions
doi:10.1371/journal.pmed.1001255
PMCID: PMC3389034  PMID: 22802735
3.  Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study 
PLoS Medicine  2008;5(1):e12.
Background
There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community.
Methods and Findings
We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age.
Conclusions
Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.
From a large prospective population study, Kay-Tee Khaw and colleagues estimate the combined impact of four behaviors--not smoking, not being physically inactive, moderate alcohol intake, and at least five vegetable servings a day--amounts to 14 additional years of life.
Editors' Summary
Background.
Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations.
Why Was This Study Done?
There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake.
What Did the Researchers Do and Find?
Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died.
What Do These Findings Mean?
These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.
The MedlinePlus encyclopedia contains a page on healthy living (in English and Spanish)
The MedlinePlus page on seniors' health contains links to many sites dealing with healthy lifestyles and longevity (in English and Spanish)
The European Prospective Investigation into Cancer and Nutrition (EPIC) study is investigating the relationship between nutrition and lifestyle and the development of cancer and other chronic diseases; information about the EPIC-Norfolk study is also available
The US Centers for Disease Control and Prevention provides information on healthy aging for older adults, including information on health-related behaviors (in English and Spanish)
The UK charity Age Concerns provides a fact sheet about staying healthy in later life
The London Health Observatory, which provides information for policy makers and practitioners about improving health and health care, has a section on how lifestyle and behavior affect health
doi:10.1371/journal.pmed.0050012
PMCID: PMC2174962  PMID: 18184033
4.  Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent Head and Neck Cancer 
Journal of Clinical Oncology  2013;31(21):2708-2715.
Purpose
Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.
Methods
We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.
Results
HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.
Conclusion
HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.
doi:10.1200/JCO.2012.47.2738
PMCID: PMC3709056  PMID: 23775966
5.  Self-Rated Health and Cardiovascular Disease Incidence: Results from a Longitudinal Population-Based Cohort in Norfolk, UK 
PLoS ONE  2013;8(6):e65290.
Introduction
Self-rated health (SRH) predicts chronic disease morbidity including cardiovascular disease (CVD). In a population-based cohort, we examined the association between SRH and incident CVD and whether this association was independent of socio-demographic, clinical and behavioural participant characteristics.
Methods
Population-based prospective cohort study (European Prospective Investigation of Cancer-Norfolk). 20,941 men and women aged 39–74 years without prevalent CVD attended a baseline health examination (1993–1998) and were followed for CVD events/death until March 2007 (mean 11 years). We used a Cox proportional hazards model to quantify the association between baseline SRH (reported on a four point scale – excellent, good, fair, poor) and risk of developing CVD at follow-up after adjusting for socio-demographic, clinical and behavioural risk factors.
Results
Baseline SRH was reported as excellent by 17.8% participants, good by 65.1%, fair by 16.0% and poor by 1.2%. During 225,508 person-years of follow-up, there were 55 (21.2%) CVD events in the poor SRH group and 259 (7.0%) in the excellent SRH group (HR 3.7, 95% CI 2.8–4.9). The HR remained significant after adjustment for behavioural risk factors (HR 2.6, 95% CI 1.9–3.5) and after adjustment for all socio-demographic, clinical and behavioural risk factors (HR 3.3, 95% CI 2.4–4.4). Associations were strong for both fatal and non-fatal events and remained strong over time.
Conclusions
SRH is a strong predictor of incident fatal and non-fatal CVD events in this healthy, middle-aged population. Some of the association is explained by lifestyle behaviours, but SRH remains a strong predictor after adjustment for socio-demographic, clinical and behavioural risk factors and after a decade of follow-up. This easily accessible patient-centred measure of health status may be a useful indicator of individual and population health for those working in primary care and public health.
doi:10.1371/journal.pone.0065290
PMCID: PMC3670935  PMID: 23755212
6.  Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study 
Background
The aetiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods
After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (CI).
Results
No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR = 1.62, 95% CI = 1.04-2.54) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR = 3.61, 95% CI = 1.75-7.46).
Conclusion
Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, appears to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation.
Impact
Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements.
doi:10.1158/1055-9965.EPI-10-0447
PMCID: PMC2990203  PMID: 20802020
Brain tumors; glioma; meningioma; reproductive factors; exogenous hormone use; oral contraceptive use; hormone replacement therapy; cohort studies
7.  Healthy lifestyle choices: could sense of coherence aid health promotion? 
Background
A research framework based on the personal characteristic defined by a sense of coherence (SOC) focuses on the effective use of resources to maintain good health.
Objectives
To test the hypothesis that individual differences in SOC are associated with healthier lifestyle choices independently of social class and education.
Design and setting
Cross sectional. Population based cohort study recruited through 35 general practice registers. Reported dietary intakes of alcohol, fruit and vegetables, fibre, saturated fat, non‐discretionary salt (sodium), and total sugars were assessed by food frequency questionnaire. Current cigarette smoking, physical inactivity, and SOC were assessed through questionnaires.
Participants
7863 men and 10 424 women. Residents of Norfolk (UK).
Results
Compared with participants with the weakest SOC, those with the strongest were 28% less likely to be current smokers (odds ratio 0.72 (95% confidence interval (CI), 0.58 to 0.89)), 36% less likely to be physically inactive (0.64 (0.55 to 0.75)), and reportedly consumed on average 63 g/day more fruit and vegetables (95% CI, 46 to 80), and 1.2 g/day more fibre (0.8 to 1.6). These associations were independent of age, sex, social class, and education. For physical inactivity and consumption of fruit, vegetables, and fibre, these differences exceeded those observed between the extremes of social class and education.
Conclusions
Individual differences in SOC are associated with healthy lifestyle choices independently of social class and education, and may therefore aid the design of future health promotion interventions.
doi:10.1136/jech.2006.056275
PMCID: PMC2652963  PMID: 17873222
sense of coherence; smoking; physical activity; alcohol; diet
8.  Clinical statistics 
Postgraduate Medical Journal  1996;72(853):702-703.
PMCID: PMC2398642
9.  Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: A GWAS data analysis 
Background
Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level.
Methods
Using GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by employing the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA).
Results
After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10−6) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10−4) in modifying the risk of pancreatic cancer was observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1 and GNAS. None of the individual genes or SNPs except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10−7) at a false discovery rate of 6%.
Conclusions
Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets.
Impact
Gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer.
doi:10.1158/1055-9965.EPI-13-0437-T
PMCID: PMC3947145  PMID: 24136929
GWAS; obesity; diabetes; interaction; pancreatic cancer; genetic susceptibility
10.  Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer 
Wang, Yufei | McKay, James D. | Rafnar, Thorunn | Wang, Zhaoming | Timofeeva, Maria | Broderick, Peter | Zong, Xuchen | Laplana, Marina | Wei, Yongyue | Han, Younghun | Lloyd, Amy | Delahaye-Sourdeix, Manon | Chubb, Daniel | Gaborieau, Valerie | Wheeler, William | Chatterjee, Nilanjan | Thorleifsson, Gudmar | Sulem, Patrick | Liu, Geoffrey | Kaaks, Rudolf | Henrion, Marc | Kinnersley, Ben | Vallée, Maxime | LeCalvez-Kelm, Florence | Stevens, Victoria L. | Gapstur, Susan M. | Chen, Wei V. | Zaridze, David | Szeszenia-Dabrowska, Neonilia | Lissowska, Jolanta | Rudnai, Peter | Fabianova, Eleonora | Mates, Dana | Bencko, Vladimir | Foretova, Lenka | Janout, Vladimir | Krokan, Hans E. | Gabrielsen, Maiken Elvestad | Skorpen, Frank | Vatten, Lars | Njølstad, Inger | Chen, Chu | Goodman, Gary | Benhamou, Simone | Vooder, Tonu | Valk, Kristjan | Nelis, Mari | Metspalu, Andres | Lener, Marcin | Lubiński, Jan | Johansson, Mattias | Vineis, Paolo | Agudo, Antonio | Clavel-Chapelon, Francoise | Bueno-de-Mesquita, H.Bas | Trichopoulos, Dimitrios | Khaw, Kay-Tee | Johansson, Mikael | Weiderpass, Elisabete | Tjønneland, Anne | Riboli, Elio | Lathrop, Mark | Scelo, Ghislaine | Albanes, Demetrius | Caporaso, Neil E. | Ye, Yuanqing | Gu, Jian | Wu, Xifeng | Spitz, Margaret R. | Dienemann, Hendrik | Rosenberger, Albert | Su, Li | Matakidou, Athena | Eisen, Timothy | Stefansson, Kari | Risch, Angela | Chanock, Stephen J. | Christiani, David C. | Hung, Rayjean J. | Brennan, Paul | Landi, Maria Teresa | Houlston, Richard S. | Amos, Christopher I.
Nature genetics  2014;46(7):736-741.
We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants of BRCA2-K3326X (rs11571833; odds ratio [OR]=2.47, P=4.74×10−20) and of CHEK2-I157T (rs17879961; OR=0.38 P=1.27×10−13). We also showed an association between common variation at 3q28 (TP63; rs13314271; OR=1.13, P=7.22×10−10) and lung adenocarcinoma previously only reported in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants having substantive effects on cancer risk from pre-existing GWAS data.
doi:10.1038/ng.3002
PMCID: PMC4074058  PMID: 24880342
13.  Blood pressure and contraceptive use 
In a survey of 461 women routinely attending family planning clinics those taking oral contraceptives had significantly higher mean systolic and diastolic blood pressures than those using non-hormonal contraception. There appeared to be a dose-response relation of blood pressure to the progestogen component of two oral contraceptives with an identical 30 μg ethinyloestradiol component. This supports the idea that the progestogen as well as the oestrogen component has an aetiological role in the rise in blood pressure. There was a significant correlation of blood pressure with duration of current use of oral contraceptive but not with total duration of use. There was also a significant negative correlation of blood pressure with time since oral contraceptives were last taken, and women who had stopped using oral contraceptives over a month previously had similar blood pressures to those who had never taken them. In women taking oral contraceptives those who had either a history of hypertension in pregnancy or a family history of hypertension had significantly higher mean blood pressures than those who did not. Both systolic and diastolic blood pressures correlated independently with weight and body mass index, but controlling for the effect of this and age did not affect the above relations. No significant differences in mean blood pressures were found between different ethnic groups, and there was no relation of blood pressure to reported marital state, social class, parity, smoking, or alcohol use.
Any oral contraceptive that has a less adverse effect on blood pressure has implications for general prescribing policy; thus even small differences in the progestogen contents of low-dose oestrogen pills may be important.
PMCID: PMC1499207  PMID: 6809102
14.  Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study 
Gut  2012;62(12):10.1136/gutjnl-2012-303006.
Objective
Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.
Design
We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study (EPIC). Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.
Results
Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a 2-fold higher risk of pancreatic cancer than individuals lower levels of these antibodies (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.05–4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified 2 groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR, 0.55; 95% CI, 0.36–0.83).
Conclusion
Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.
doi:10.1136/gutjnl-2012-303006
PMCID: PMC3815505  PMID: 22990306
infection; oral bacteria; pancreatic cancer; periodontal disease
15.  The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations 
Diabetes Care  2013;36(12):3961-3970.
OBJECTIVE
To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.
RESEARCH DESIGN AND METHODS
The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.
RESULTS
In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77–1.04]; P valuetrend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72–1.07]; P valuetrend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69–0.95]; P valuetrend = 0.020) and flavanols (HR 0.82 [95% CI 0.68–0.99]; P valuetrend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57–0.93]; P valuetrend = 0.029), were associated with a significantly reduced hazard of diabetes.
CONCLUSIONS
Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
doi:10.2337/dc13-0877
PMCID: PMC3836159  PMID: 24130345
16.  The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study 
Background There is limited evidence for an association between the pattern of lifetime alcohol use and cause-specific risk of death.
Methods Multivariable hazard ratios were estimated for different causes of death according to patterns of lifetime alcohol consumption using a competing risks approach: 111 953 men and 268 442 women from eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. Self-reported alcohol consumption at ages 20, 30, 40 or 50 years and at enrolment were used for the analysis; 26 411 deaths were observed during an average of 12.6 years of follow-up.
Results The association between lifetime alcohol use and death from cardiovascular diseases was different from the association seen for alcohol-related cancers, digestive, respiratory, external and other causes. Heavy users (>5 drinks/day for men and >2.5 drinks/day for women), regardless of time of cessation, had a 2- to 5-times higher risk of dying due to alcohol-related cancers, compared with subjects with lifetime light use (≤1 and ≤0.5 drink/week for men and women, respectively). Compared with lifetime light users, men who used <5 drinks/day throughout their lifetime had a 24% lower cardiovascular disease mortality (95% confidence interval 2-41). The risk of death from coronary heart disease was also found to be 34–46% lower among women who were moderate to occasionally heavy alcohol users compared with light users. However, this relationship was only evident among men and women who had no chronic disease at enrolment.
Conclusions Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes. However, the potential health benefits of alcohol use are difficult to establish due to the possibility of selection bias and competing risks related to diseases occurring later in life.
doi:10.1093/ije/dyt154
PMCID: PMC3887563  PMID: 24415611
Prospective study; lifetime alcohol use; cause-specific mortality; EPIC
17.  Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition 
Background
Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties.
Methods
This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression.
Results
There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 – 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis.
Conclusion
These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma.
Impact
This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association.
doi:10.1158/1055-9965.EPI-13-1210-T
PMCID: PMC4046912  PMID: 24646451
Insulin-like growth factor-I; differentiated thyroid carcinoma; nested case-control study
18.  The association between circulating lipoprotein(a) and type 2 diabetes: is it causal? 
Diabetes  2013;63(1):332-342.
Epidemiological evidence supports a direct and causal association between lipoprotein(a) [Lp(a)] levels and coronary risk, but the nature of the association between Lp(a) levels and risk of type 2 diabetes (T2D) is unclear. In this study, we assessed the association of Lp(a) levels with risk of incident T2D, and tested whether Lp(a) levels are causally linked to T2D. We analysed data on 18,490 participants from the EPIC-Norfolk cohort that included adults aged 40-79 years at baseline 1993-1997. During average 10 years of follow-up, 593 participants developed incident T2D. Cox regression models were used to estimate the association between Lp(a) levels and T2D. In Mendelian randomisation analyses, based on EPIC-Norfolk combined with DIAGRAM data involving a total of 10,088 diabetes cases and 68,346 controls, we used a genetic variant (rs10455872) as an instrument to test whether the association between Lp(a) levels and T2D is causal. In adjusted analyses there was an inverse association between Lp(a) levels and T2D: hazard ratio (HR) was 0.63 (95% confidence interval 0.49-0.81; p-trend=0.003) comparing the top versus bottom quintile of Lp(a). In EPIC-Norfolk, a 1-SD increase in logLp(a) was associated with a lower risk of T2D (OR=0.88, 95%CI: 0.80-0.95). However, in Mendelian randomisation analyses, a 1-SD increase in logLp(a) due to rs10455872, which explained 26.8% of the variability in Lp(a) levels, was not associated with risk of T2D (OR=1.03, 95%CI: 0.96-1.10, p = 0.41). These prospective findings demonstrate a strong inverse association of Lp(a) levels with risk of T2D. However, a genetic variant that elevated Lp(a) levels was not associated with risk of T2D, suggesting that elevated Lp(a) levels are not causally associated with a lower risk of T2D.
doi:10.2337/db13-1144
PMCID: PMC4246060  PMID: 24089516
lipoprotein(a); type 2 diabetes; causal association; coronary heart disease; hazard ratio; Mendelian randomisation; prospective study
19.  Association of self-rated health with multimorbidity, chronic disease and psychosocial factors in a large middle-aged and older cohort from general practice: a cross-sectional study 
BMC Family Practice  2014;15(1):185.
Background
The prevalence of coexisting chronic conditions (multimorbidity) is rising. Disease labels, however, give little information about impact on subjective health and personal illness experience. We aim to examine the strength of association of single and multimorbid physical chronic diseases with self-rated health in a middle-aged and older population in England, and to determine whether any association is mediated by depression and other psychosocial factors.
Methods
25 268 individuals aged 39 to 79 years recruited from general practice registers in the European Prospective Investigation of Cancer (EPIC-Norfolk) study, completed a survey including self-rated health, psychosocial function and presence of common physical chronic conditions (cancer, stroke, heart attack, diabetes, asthma/bronchitis and arthritis). Logistic regression models determined odds of “moderate/poor” compared to “good/excellent” health by condition and number of conditions adjusting for psychosocial measures.
Results
One-third (8252) reported one, around 7.5% (1899) two, and around 1% (194) three or more conditions. Odds of “moderate/poor” self-rated health worsened with increasing number of conditions (one (OR = 1.3(1.2–1.4)) versus three or more (OR = 3.4(2.3–5.1)), and were highest where there was comorbidity with stroke (OR = 8.7(4.6–16.7)) or heart attack (OR = 8.5(5.3–13.6)). Psychosocial measures did not explain the association between chronic diseases and multimorbidity with self-rated health.The relationship of multimorbidity with self-rated health was particularly strong in men compared to women (three or more conditions: men (OR = 5.2(3.0–8.9)), women OR = 2.1(1.1–3.9)).
Conclusions
Self-rated health provides a simple, integrative patient-centred assessment for evaluation of illness in the context of multiple chronic disease diagnoses. Those registering in general practice in particular men with three or more diseases or those with cardiovascular comorbidities and with poorer self-rated health may warrant further assessment and intervention to improve their physical and subjective health.
doi:10.1186/s12875-014-0185-6
PMCID: PMC4245775  PMID: 25421440
General practice/family medicine; General integrated subjective health multimorbidity comorbidity
20.  Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition – the EPIC-InterAct study 
Background
Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including 8 countries with large geographical variation.
Methods
Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. 24-h diet recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires.
Results
Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95 % CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22), (ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect [HR (95% CI)] using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 μg/day dietary vitamin D.
Conclusion
This observational study does not support an association between higher dietary vitamin D intake and type-2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.
doi:10.1038/ejcn.2013.235
PMCID: PMC4234029  PMID: 24253760
vitamin D; type-2 diabetes; dietary intake; observational study; EPIC
21.  Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer 
Hepatology (Baltimore, Md.)  2014;60(3):858-871.
Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02-1.46; P = 0.03; 1.90; 95% CI = 1.30-2.77; P = 0.001; 2.25; 95% CI = 1.43-3.54; P = 0.0005; and 2.09; 95% CI = 1.19-3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05-1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25-2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20-50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors. (Hepatology 2014;60:858–871)
doi:10.1002/hep.27016
PMCID: PMC4231978  PMID: 24443059
22.  Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study 
BMJ Open  2014;4(11):e006071.
Objectives
To explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population.
Design
Cross-sectional study.
Setting
European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study.
Participants
A total of 5018 men and women aged 48–92 years reported their sleep habits and had serum CRP levels measured.
Outcome and measures
CRP was measured (mg/L) during 2006–2011 in fresh blood samples using high-sensitivity methods. Participants reported napping habits during 2002–2004, and reported sleep quantity during 2006–2007. Multivariable linear regression models were used to examine the association between napping and log-transformed CRP, and geometric mean CRP levels were calculated.
Results
After adjustment for age and sex, those who reported napping had 10% higher CRP levels compared with those not napping. The association was attenuated but remained borderline significant (β=0.05 (95% CI 0.00 to 0.10)) after further adjustment for social class, education, marital status, body mass index, physical activity, smoking, alcohol intake, self-reported health, pre-existing diseases, systolic blood pressure, hypnotic drug use, depression and in women-only hormone replacement therapy use. The geometric means (95% CI) of CRP levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who reported napping and no napping, respectively. A U-shaped association was observed between time spent in bed at night and CRP levels, and nighttime sleep duration was not associated with serum CRP levels. The association between napping and CRP was stronger for older participants, and among extremes of time spent in bed at night.
Conclusions
Daytime napping was associated with increased CRP levels in an older aged British population. Further studies are needed to determine whether daytime napping is a cause for systemic inflammation, or if it is a symptom or consequence of underlying health problems.
doi:10.1136/bmjopen-2014-006071
PMCID: PMC4244397  PMID: 25387759
Sleep; Napping; C-reactive protein; Inflammation; Population
23.  Lifestyle, dietary factors and antibody levels to oral bacteria in cancer-free participants of a European cohort study 
Cancer causes & control : CCC  2013;24(11):10.1007/s10552-013-0265-2.
Background
Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria.
Methods
Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured.
Results
IgG antibody levels were substantially lower among current and former smokers (1697 and 1677 ng/mL, respectively) than never smokers (1960 ng/mL; p-trend = 0.01), but did not vary by other factors, including BMI, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country and smoking status. The highest levels of total IgG were found among individuals with low education (2419 ng/mL).
Conclusions
Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria.
doi:10.1007/s10552-013-0265-2
PMCID: PMC3823529  PMID: 23901020
24.  Age at Menarche and Type 2 Diabetes Risk 
Diabetes Care  2013;36(11):3526-3534.
OBJECTIVE
Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.
RESEARCH DESIGN AND METHODS
The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.
RESULTS
Mean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m2 lower adult BMI. Women in the earliest menarche quintile (8–11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49–1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18–1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.
CONCLUSIONS
Women with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
doi:10.2337/dc13-0446
PMCID: PMC3816901  PMID: 24159179
25.  A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease 
Atherosclerosis  2014;237(1):5-12.
Background
Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).
Methods and results
We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.
In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.
Conclusions
In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.
Highlights
•We examined evidence for an interaction between APOE genotype, smoking and risk of coronary heart disease.•This was conducted in the largest meta-analysis of published and unpublished data sets to date (>130,000 individuals).•Our analysis did not identify evidence of interaction.•These findings bring into question presence of a clinically meaningful interaction between APOE genotype and smoking.
doi:10.1016/j.atherosclerosis.2014.07.038
PMCID: PMC4232362  PMID: 25173947
APOE genotype; Smoking; Coronary heart disease; Gene–environment interaction

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