Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study

BACKGROUND: The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population. OBJECTIVE: The objective was to examine the relation between baseline plasma vitamin C concentrations and risk of incident stroke in a British population. DESIGN: A population-based prospective study was conducted in 20,649 men and women aged 40-79 y without prevalent stroke at baseline and participating in the European Prospective Investigation into Cancer-Norfolk prospective population study. The participants completed a health questionnaire and attended a clinic during 1993-1997 and were followed up for incident strokes through March 2005. RESULTS: Over 196,713 total person-years (average follow-up: 9.5 y), 448 incident strokes occurred. In a Cox proportional hazards model, persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use. Similar results were obtained after exclusion of persons with illnesses, users of ascorbic acid-containing supplements, and persons with a history of early strokes during the initial 2 y of follow-up. CONCLUSIONS: Plasma vitamin C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke.     

More acidic dietary acid-base load is associated with reduced calcaneal broadband ultrasound attenuation in women but not in men: results from the EPIC-Norfolk cohort study

BACKGROUND: Dietary patterns that promote mild metabolic acidosis may have a negative effect on bone density. OBJECTIVE: We investigated the relation between a measure of dietary acid-base load, potential renal acid load (PRAL), and calcaneal broadband ultrasound attenuation (BUA) after adjustment for confounders and also compared the results with different estimates of acid-base load. DESIGN: A cross-sectional study was conducted in 14 563 men and women aged 42-82 y living in Norfolk, United Kingdom, in which measures of calcaneal BUA and dietary PRAL were estimated by using the European Prospective Investigation into Cancer and Nutrition Norfolk (EPIC-Norfolk) food-frequency questionnaire. RESULTS: A more acidic dietary intake (high PRAL) was significantly associated with lower calcaneal BUA in women but not in men; there was a difference of approximately 2% in BUA between the highest and lowest quintiles of PRAL, independent of age, body mass index, smoking habit, physical activity, diagnosed osteoporosis, and history of fracture, and (in women) hormone replacement therapy. No relation was observed between history of fracture or incident fracture and PRAL. Those with the greatest PRAL had higher intakes of meat, fish, eggs, and cereal and cereal products and lower intakes of fruit and vegetables, tea, and coffee. CONCLUSION: PRAL was inversely associated with bone ultrasound measures in women, but the magnitude of the association was relatively small compared with other known risk factors. Further longitudinal studies are required to establish whether, in the long term, these small effects are important in overall fracture risk in populations.     

Modifiable lifestyle behaviors and functional health in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study

OBJECTIVE: To examine the association between modifiable lifestyle behaviors and functional health. METHOD: Population-based cross-sectional study in 16,678 men and women aged 40-79 years at baseline in 1993-1997 participating in the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. RESULTS: Smoking and physical inactivity were associated with poorer physical functional health, equivalent to being 7 years and 10-13 years older, respectively, and poorer mental functional health compared to non-smoking or being physically active. After adjusting for age, body mass index, social class, education, prevalent illness, and other lifestyles; men and women who currently smoke were more likely to report poor physical functional health compared to non-smokers {Odds Ratio (OR)=1.85 (95% confidence interval (CI): 1.49, 2.30) and 1.56 (1.30, 1.87)} and poor mental functional health {1.38 (1.12, 1.70); 1.77 (1.51, 2.07)}, respectively. The OR for good physical function in those who were physically active compared to inactive was 1.67 (1.41, 1.97) in men and 1.63 (1.39, 1.91) in women. Moderate alcohol consumption was positively associated with good physical and mental functional health. CONCLUSION: Modifiable behavioral factors are associated with substantial differences in the observed age-related decline in physical functional health and the prevalence of those in good and poor functional health in the community.     

Smoking status and differential white cell count in men and women in the EPIC-Norfolk population

The total white blood cell (WBC) count is reported to be an independent predictor of mortality in several prospective studies. We investigated the association between total and differential WBC counts and cigarette smoking habit in a cross-sectional population-based study of 6902 men and 8405 women 39-79 years of age participating between July 1994 and 1997 in the European Prospective Investigation of Cancer (EPIC-Norfolk) study. Main outcome measures included WBC, granulocyte, lymphocyte and monocyte counts measured at a baseline health check and self-reported cigarette smoking habit. The age- and body mass index-adjusted mean total WBC counts were 7.8, 6.4, and 6.2x10(3) per ul (P<0.0001) among male current, former and never smokers, respectively, and 7.4, 6.3 and 6.2x10(3) per ul (P<0.0001), respectively, in women. The greatest absolute and percentage differences between smoking groups were observed for the granulocyte count. Current smoking habit had a stronger effect on mean total WBC counts than cumulative exposure as measured by pack years. Among former smokers mean age- and body mass index-adjusted WBC, granulocyte and lymphocyte counts were inversely related to duration of smoking cessation (P< or =0.02). Smokers who had given up less than 12 months previously had WBC counts substantially lower (6.7 and 6.9x10(3) per ul, respectively, in men and women) than current smokers. In conclusion, the total WBC count and its components (particularly the granulocyte count) are strongly associated with cigarette smoking habit. Smoking cessation may have an almost immediate impact at least on pathophysiologic processes such as inflammation that may be indicated by the WBC count. The apparent almost immediate reversibility of effects of smoking on inflammation, as indicated by the WBC count, may help motivate efforts to stop smoking.     

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKCα subversion induces up-regulation of PKCβII expression in B lymphocytes

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKCα leads to an up-regulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis.     

Positive effect of a targeted intervention to improve access and availability of fruit and vegetables in an area of deprivation

Increasing fruit and vegetable intake has the potential to prevent chronic disease risk but substantial inequalities in intake exist between advantaged and disadvantaged communities. Access and availability of fruit and vegetables have been shown to be important determinants of intake. The current study aimed to evaluate the effectiveness of a Mobile Food Store intervention to improve access to fruit and vegetables by making cost-price produce available to targeted communities. Postcode mapping identified communities with low fruit and vegetable intake and high chronic disease risk. The Mobile Food Store travelled to these communities each week. Evaluation of self-reported fruit and vegetable intake was collected by validated questionnaire for 255 users (62% response rate). Store use resulted in a significant increase in intake (1.2 portions per day, 95%CI 0.83-1.48; p<0.001) which was greater than all but one previous intervention in the UK. The targeted model of improving access to fruit and vegetables was effective in increasing intake; however future controlled trials are required to objectively examine potential effects on fruit and vegetable intake and health outcomes.