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BackgroundDespite the accumulation of research papers on aspirin and cancer, there is doubt as to whether or not aspirin is an acceptable and effective adjunct treatment of cancer. The results of several randomised trials are awaited, and these should give clear evidence on three common cancers: colon, breast and prostate. The biological effects of aspirin appear likely however to be of relevance to cancer generally, and to metastatic spread, rather than just to one or a few cancers, and there is already a lot of evidence, mainly from observational studies, on the association between aspirin and survival in a wide range of cancers.AimsIn order to test the hypothesis that aspirin taking is associated with an increase in the survival of patients with cancer, we conducted a series of systematic literature searches to identify clinical studies of patients with cancer, some of whom took aspirin after having received a diagnosis of cancer.ResultsThree literature searches identified 118 published observational studies in patients with 18 different cancers. Eighty-one studies report on aspirin and cancer mortality and 63 studies report on all-cause mortality. Within a total of about a quarter of a million patients with cancer who reported taking aspirin, representing 20%-25% of the total cohort, we found aspirin to be associated with a reduction of about 20% in cancer deaths (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84 in 70 reports and a pooled odds ratio (OR): 0.67; 0.45, 1.00 in 11 reports) with similar reductions in all-cause mortality (HR: 0.80; 0.74, 0.86 in 56 studies and OR: 0.57; 0.36, 0.89 in seven studies). The relative safety of aspirin taking was examined in the studies and the corresponding author of every paper was written to asking for additional information on bleeding. As expected, the frequency of bleeding increased in the patients taking aspirin, but fatal bleeding was rare and no author reported a significant excess in fatal bleeds associated with aspirin. No author mentioned cerebral bleeding in the patients they had followed.ConclusionsThere is a considerable body of evidence suggestive of about a 20% reduction in mortality in patients with cancer who take aspirin, and the benefit appears not to be restricted to one or a few cancers. Aspirin, therefore, appears to deserve serious consideration as an adjuvant treatment of cancer, and patients with cancer, and their carers, have a right to be informed of the available evidence.

Objective:\ud To examine the long-term effects of amateur boxing in a representative population sample of men.\ud Design:\ud The sample was examined every 5 years for 35 years. Cognition was assessed repeatedly from the third examination. Previous boxing experience and dementia were assessed at the fifth examination, and dementia assessed subsequently through medical records.\ud Setting and Assessment of Rick Factors:\ud The Caerphilly Prospective Study investigates risk factors for a range of chronic diseases of diseases. These include life style and behavior, together with biological factors relevant to vascular disease.\ud Participants:\ud 1123 adult men aged 45 to 59 years at baseline, followed for 35 years.\ud Main Outcome Measures:\ud Cognitive impairment.\ud Results:\ud A report by a subject of having boxed “seriously” when younger was associated with a 2-fold increase in cognitive impairment [odds ratio (OR) = 2.27; 95% confidence intervals = 1.18-4.38]. For amnestic (Alzheimer-like) impairment, this rises to OR = 2.78 (95% confidence limits 1.37–5.65). Having boxed is associated with an “advancement” in the onset of the dementia (4.8 years; 95% confidence limits 0.9-8.8 years).\ud Conclusions:\ud Amateur boxing is associated with an increased risk and an earlier onset of cognitive impairment and dementia.

Behaviors which are associated with the preservation of health include nonsmoking, regular exercise, a low body weight, a healthy diet, and a low alcohol intake. Together, as a healthy lifestyle, these have been shown to be associated with marked protection against a wide range of diseases: diabetes, vascular disease, cancer, and dementia. On the other hand, the protection associated with statins and aspirin, the two most commonly used preventive drugs, is limited to vascular disease and, probably for aspirin, cancer.\ud \ud These are not alternative prophylactics and any two, or all three—a healthy lifestyle, a statin, and aspirin—can reasonably be taken together.\ud \ud Only a small proportion of the members of the community follow a healthy lifestyle. Yet a small increase in the uptake of the healthy behaviors throughout the community can be shown to have relatively large effects on the incidence of disease.\ud \ud There is therefore an urgent need for health promotion activities across the whole community to be greatly increased and for new challenging and encouraging strategies to be devised and tested.

Purpose The association between egg consumption and cardiovascular disease (CVD) or type 2 diabetes (T2D) remains controversial. We investigated the association between egg consumption and risk of CVD (primary outcome), T2D and mortality in the Caerphilly prospective cohort study (CAPS) and National Diet and Nutritional Survey (NDNS). Methods CAPS included 2512 men aged 45–59 years (1979–1983). Dietary intake, disease incidence and mortality were updated at 5-year intervals. NDNS included 754 adults aged 19–64 years from 2008 to 2012. Results Men free of CVD (n = 1781) were followed up for a mean of 22.8 years, egg consumption was not associated with new incidence of CVD (n = 715), mortality (n = 1028) or T2D (n = 120). When stroke (n = 248), MI (n = 477), heart failure (n = 201) were investigated separately, no associations between egg consumption and stroke and MI were identified, however, increased risk of stroke in subjects with T2D and/or impaired glucose tolerance (IGT, fasting plasma glucose ≥ 6.1 mmol/L), adjusted hazard ratios (95% CI) were 1.0 (reference), 1.09 (0.41, 2.88), 0.96 (0.37, 2.50), 1.39 (0.54, 3.56) and 2.87 (1.13, 7.27) for egg intake (n) of 0 ≤ n ≤ 1, 1

Context UK Biobank is a prospective study of half a million subjects, almost all aged 40–69 years, identified in 22 centres across the UK during 2006–2010. Objective A healthy lifestyle has been described as ‘better than any pill, and no side effects [5]. We therefore examined the relationships between healthy behaviours: low alcohol intake, non-smoking, healthy BMI, physical activity and a healthy diet, and the risk of all cancers, colon, breast and prostate cancers in a large dataset. Method Data on lifestyle behaviours were provided by 343,150 subjects, and height and weight were measured at recruitment. 14,285 subjects were diagnosed with cancer during a median of 5.1 years of follow-up. Results Compared with subjects who followed none or a single healthy behaviour, a healthy lifestyle based on all five behaviours was associated with a reduction of about one-third in incident cancer (hazard ratio [HR] 0.68; 95% confidence intervals [CI] 0.63–0.74). Colorectal cancer was reduced in subjects following the five behaviours by about one-quarter (HR 0.75; 95% CI 0.58–0.97), and breast cancer by about one-third (HR 0.65; 95% CI 0.52–0.83). The association between a healthy lifestyle and prostate cancer suggested a significant increase in risk, but this can be attributed to bias consequent on inequalities in the uptake of the prostate specific antigen screening test. Conclusions Taken together with reported reductions in diabetes, vascular disease and dementia, it is clearly important that every effort is taken to promote healthy lifestyles throughout the population, and it is pointed out that cancer and other screening clinics afford ‘teachable moments’ for the promotion of a healthy lifestyle.

Background Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. Methods Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. Results Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall metaanalyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72(95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). Conclusion Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?

ObjectiveProspective data on the associations between vitamin D intake and risk of CVD and all-cause mortality are limited and inconclusive. The aim of the present study was to investigate the associations between vitamin D intake and CVD risk and all-cause mortality in the Caerphilly Prospective Cohort Study.DesignThe associations of vitamin D intake with CVD risk markers were examined cross-sectionally at baseline and longitudinally at 5-year, 10-year and >20-year follow-ups. In addition, the predictive value of vitamin D intake for CVD events and all-cause mortality after >20 years of follow-up was examined. Logistic regression and general linear regression were used for data analysis.SettingParticipants in the UK.SubjectsMen (n452) who were free from CVD and type 2 diabetes at recruitment.ResultsHigher vitamin D intake was associated with increased HDL cholesterol (P=0·003) and pulse pressure (P=0·04) and decreased total cholesterol:HDL cholesterol (P=0·008) cross-sectionally at baseline, but the associations were lost during follow-up. Furthermore, higher vitamin D intake was associated with decreased concentration of plasma TAG at baseline (P=0·01) and at the 5-year (P=0·01), but not the 10-year examination. After >20 years of follow-up, vitamin D was not associated with stroke (n72), myocardial infarctions (n142), heart failure (n43) or all-cause mortality (n281), but was positively associated with increased diastolic blood pressure (P=0·03).ConclusionsThe study supports associations of higher vitamin D intake with lower fasting plasma TAG and higher diastolic blood pressure.

Implications Overall, milk consumption provides health benefits to all age groups. Effects of cheese, butter, and fat-reduced and saturated fat-reduced milk and dairy products are less clear and require more research. Public health nutrition policy related to milk consumption should be based on the evidence presented and not solely on the believed negative effects of dietary fat. Milk is not a white elixir since no study has reported eternal youth from drinking it, but there is certainly no evidence that milk is a white poison!

BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.

Arterial stiffness is an independent predictor of cardiovascular disease (CVD) events and all-cause mortality and may be differentially affected by dietary fatty acid (FA) intake. The aim of this study was to investigate the relationship between FA consumption and arterial stiffness and blood pressure in a community-based population.The Caerphilly Prospective Study recruited 2398 men, aged 45-59 years, who were followed up at 5-year intervals for a mean of 17.8-years (n 787). A semi-quantitative food frequency questionnaire estimated intakes of total, saturated, mono- and poly-unsaturated fatty acids (SFA, MUFA, PUFA). Multiple regression models investigated associations between intakes of FA at baseline with aortic pulse wave velocity (aPWV), augmentation index (AIx), systolic and diastolic blood pressure (SBP, DBP) and pulse pressure after a 17.8-year follow-up--as well as cross-sectional relationships with metabolic markers. After adjustment, higher SFA consumption at baseline was associated with higher SBP (P = 0.043) and DBP (P = 0.002) and after a 17.8-year follow-up was associated with a 0.51 m/s higher aPWV (P = 0.006). After adjustment, higher PUFA consumption at baseline was associated with lower SBP (P = 0.022) and DBP (P = 0.036) and after a 17.8-year follow-up was associated with a 0.63 m/s lower aPWV (P = 0.007).This study suggests that consumption of SFA and PUFA have opposing effects on arterial stiffness and blood pressure. Importantly, this study suggests that consumption of FA is an important risk factor for arterial stiffness and CVD.

To examine the hypothesis that caloric intake in mid-life is associated with later dementia or cognitive impairment not dementia (CIND). A prospective cohort study was conducted in Caerphilly, South Wales, United Kingdom. Men aged 45-59 years were identified from the electoral roll and general practice. 2,512 men were examined between July 1979 until September 1983. Four follow-up examinations were conducted every 4-5 years until 2004. Participants were categorized on the basis of their average daily caloric intake over each of the first three phases. Outcomes were CIND and dementia ascertained at phase five (2004). 192 men (15% of 1,248 participants at phase five) had CIND and 100 (8%) dementia. Age adjusted odds ratios demonstrated strongest associations between average energy consumption and vascular CIND or dementia (OR 1.62 95% CI 1.25-2.10). Adjustment for nutritional factors, vascular disease, diabetes, smoking, BP and BMI if anything increased the association (OR 1.64, 95% CI 1.03-2.60). After adjusting for social class, associations were attenuated and consistent with chance (OR 1.48, 95% CI 0.92-2.38). When adjusted for social class, the previously observed association between caloric intake and cognitive outcomes is modest, consistent with chance, and may be due to residual confounding.

BackgroundBenzodiazepine use is widespread in older people, although its benefit is uncertain.AimTo investigate the long-term effect of benzodiazepine use upon dementia risk.MethodsA prospective cohort of men seen on five occasions over 22 years with full medication histories, repeat measures of cognitive function and a clinical diagnosis of dementia.ResultsOf 1134 men with complete data, 103 (9.1%) had been taking benzodiazepines regularly at one or more phases. These men showed a marked increased incidence of dementia (OR=3.50, 95% CI 1.57 to 7.79, p=0.002), which persisted despite adjustment for psychological distress and other covariates. Men exposed in earlier phases showed a greater association than more recent exposure, counter to what one would expect if this was due to reverse causation, though we failed to demonstrate a dose–response effect with drug duration.ConclusionThe taking of benzodiazepines is associated with an increased risk of dementia.

The health effects of milk and dairy food consumption would best be determined in randomised controlled trials. No adequately powered trial has been reported and none is likely because of the numbers required. The best evidence comes, therefore, from prospective cohort studies with disease events and death as outcomes. Medline was searched for prospective studies of dairy food consumption and incident vascular disease and Type 2 diabetes, based on representative population samples. Reports in which evaluation was in incident disease or death were selected. Meta-analyses of the adjusted estimates of relative risk for disease outcomes in these reports were conducted. Relevant case-control retrospective studies were also identified and the results are summarised in this article. Meta-analyses suggest a reduction in risk in the subjects with the highest dairy consumption relative to those with the lowest intake: 0.87 (0.77, 0.98) for all-cause deaths, 0.92 (0.80, 0.99) for ischaemic heart disease, 0.79 (0.68, 0.91) for stroke and 0.85 (0.75, 0.96) for incident diabetes. The number of cohort studies which give evidence on individual dairy food items is very small, but, again, there is no convincing evidence of harm from consumption of the separate food items. In conclusion, there appears to be an enormous mis-match between the evidence from long-term prospective studies and perceptions of harm from the consumption of dairy food items.

Objective— Hemostasis and inflammation have been implicated in dementia. This study investigates the role of specific hemostatic and inflammatory pathways with incident vascular and nonvascular dementia. Methods and Results— This was a prospective study of a population sample of men aged 65 to 84 years, with baseline assessment of hemostatic and inflammatory factors and cognition measured 17 years later. The sample included 865 men (59 had dementia and 112 had cognitive impairment, not dementia), free of vascular disease at baseline and for whom hemostatic and inflammatory marker data were available and cognitive status was known. A total of 15 hemostatic and 6 inflammatory markers were assessed. Factor analysis was used to identify hemostatic subsystems. The National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurologie criteria were used to identify vascular dementia. By using standardized ( z ) scores for hemostatic and inflammatory markers, and after adjustment for age and risk factors, vascular dementia was associated with fibrinogen (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.02–2.76), factor VIII (HR, 1.79; 95% CI, 1.09–3.00), and plasminogen activator inhibitor 1 (HR, 3.13; 95% CI, 1.73–5.70). For vascular dementia, the HR risk from high levels of all three hemostatic variables (fibrinogen, factor VIII, and plasminogen activator inhibitor 1) was 2.97 ( P Conclusion— The associations of these hemostatic markers with vascular dementia may implicate clot formation as the primary mechanism and are consistent with a microinfarct model of vascular dementia.

Objectives: To report a negative association between milk or dairy consumption and the metabolic syndrome and to examine associations within the Caerphilly cohort. Setting: A representative sample of men aged 45–59 years in Caerphilly, UK. Participants and data: Data on fasting blood glucose and plasma insulin, fasting plasma triglycerides and high-density lipoprotein cholesterol, body mass index, and blood pressure were used to define the metabolic syndrome in terms of levels of two or more variates within the top 10%. The clinical importance of the syndrome was assessed from 20-year incidence of diabetes, vascular events and deaths. The relationships between the syndrome and the consumption of milk and dairy products was examined using data from both a semiquantitative food frequence questionnaire, and from a 7-day weighed intake record which had been kept by a 1:3 subsample of the men. Main results: There were 2375 men without diabetes in the cohort. The prevalence of the metabolic syndrome was 15%. Men with the syndrome had significantly increased risks of a subsequent ischaemic heart disease event, death or diabetes. Negative relationships were shown between both the consumption of milk and dairy produce, and the syndrome. Adjusted odds ratio in men who regularly drank a pint of milk or more daily was 0.38 (0.18 to 0.78) and that for dairy food consumption was 0.44 (0.21 to 0.91). Milk intake showed no significant trend with incident diabetes. Conclusions: The consumption of milk and dairy products is associated with a markedly reduced prevalence of the metabolic syndrome, and these items therefore fit well into a healthy eating pattern.

Study objective: There is evidence suggesting that artificial feeding is associated with a reduction in cognitive function in infants and children, in contrast with breast feeding, but the available evidence suffers from confounding by social and educational factors. An opportunity arose in the Caerphilly cohort study to examine relations between cognitive function in older men and their feeding as infants, when breast feeding was usual. Design: A prospective cohort study. Setting: Caerphilly, South Wales, UK, was a deprived coal mining community when the men had been born in 1920–35. Most had been breast fed as infants. Participants: 779 men aged 60–74 years when tested. The men had earlier been asked to obtain from their mothers their birth weight, and how they had been fed as infants. Results: Complete data were obtained for 779 men. In those whose birth weight had been at or above the median, the adjusted mean cognitive function was only slightly and non-significantly lower in those who had been artificially fed. In the men whose birth weight had been below the median, having been artificially fed was associated with significantly lower results in both a test of reasoning (the AH4) and word power (the national adult reading test (NART)). Two standard deviations below the median birth weight, artificial feeding was associated with a reduction of six points (70% of a SD) on word power (the NART). Conclusions: In men whose birth weight had been low, having been artificially fed is associated with poorer cognitive function in late adult life.

Milk consumption is considered a risk factor for vascular disease on the basis of relevant biological mechanisms and data from ecological studies. The aim was to identify published prospective studies of milk drinking and vascular disease, and conduct an overview.The literature was searched for cohort studies, in which an estimate of the consumption of milk, or the intake of calcium from dairy sources, has been related to incident vascular disease.Ischaemic heart disease and ischaemic stroke.In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk. A pooled estimate of relative odds in these subjects, relative to the risk in subjects with the lowest consumption, is 0.87 (95% CI 0.74-1.03) for ischaemic heart disease and 0.83 (0.77-0.90) for ischaemic stroke. The odds ratio for any vascular event is 0.84 (0.78-0.90).Cohort studies provide no convincing evidence that milk is harmful. While there still could be residual confounding from unidentified factors, the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk.The University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

SummaryFibrinogen, plasma viscocity, and the white blood cell count predict ischaemic heart disease, but there is less certainty for their predictive power for ischaemic stroke. Studying stroke and ischaemic heart disease in the same cohort prospectively allows comparison of predictive strengths. The Caerphilly and Speedwell cohorts consist of a population sample of 4,860 men aged 45-59 years at recruitment who had baseline measurements of fibrinogen, plasma viscosity, and white blood cell counts. After 15-19 years of follow-up, men in the two cohorts experienced 312 ischaemic strokes and 557 ischaemic heart disease events. Mean fibrinogen, plasma viscosity and white blood cell counts differed significantly after adjustment for confounding factors between men with and without ischaemic heart disease, 0.25 g/l (95% CIs 0.18-0.32); 0.036 cp (95% CIs 0.027-0.044); 0.67 X 109/l (95% CIs 0.50-0.84) respectively. The same measurements showed no significant differences after adjustment for the same confounding factors for men with and without ischaemic stroke, 0.05 g/l (95% CIs -0.04-0.14); 0.008 cp (95% CIs -0.003-0.019); 0.16 X 109/l (95% CIs -0.06-0.38) respectively.

OBJECTIVES: Stroke can impair cognitive function, but the associations between other manifestations of vascular disease and cognitive function have not been adequately studied in representative population samples of subjects. We report the associations between cardiac and peripheral vascular disease and cognitive function for a large representative sample of men in Caerphilly, South Wales, UK. DESIGN: The Caerphilly cohort is the basis of on-going studies of vascular disease, of cognitive function and of predictors of these. We have made intensive attempts to identify all cases of vascular disease: myocardial infarction, angina, ECG ischaemia, peripheral vascular disease (intermittent claudication) and stroke. Here we present data on associations between vascular disease and cognitive function. SETTING: The study is based upon a representative population sample of over 1,500 men in South Wales, aged 55-69 years when cognitive function was measured. The men, and hospital and GP notes relating to them, had been repeatedly examined for evidence of vascular disease during the previous ten years. MAIN OUTCOME MEASURES: Standard tests of cognitive function: the AH4, CAMCOG, MMSE and choice reaction time. RESULTS: After the omission of men who had had a stroke, we detected significant associations between cognitive function and the presence of angina, ECG ischaemia, past myocardial infarction and intermittent claudication. The strength of the associations between cognitive function and the various manifestations of vascular disease were similar, and the various cognitive function tests showed effects of similar size. Overall, cardiac and peripheral vascular disease is associated with a significant reduction in cognitive function equivalent to about one sixth of the standard deviation of a number of tests of cognitive function. The size of this effect is roughly equivalent to the decline in cognitive performance over five years of ageing. CONCLUSIONS: Subjects with evidence of cardiac or peripheral vascular disease have on average a significant reduction in cognitive function equivalent to about four or five years of additional age. The effect of long-term, low-dose aspirin on cognitive decline should now be tested.

A platelet test that is predictive of myocardial infarction (MI) and/or stroke would enable the targeting of anti-platelet drugs towards high-risk patients. The predictive power of several platelet tests for MI and for stroke was examined in 2000 older men in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The tests were: aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP); aggregation to ADP in whole blood measured using an impedance method and a test of platelet aggregation induced in whole blood by high-shear flow. Around 200 MIs and 100 ischaemic strokes occurred during a 10-year follow-up. Neither primary nor secondary aggregation in PRP was predictive of MI. However, the fifth of men in whom the primary response to ADP was least, showed the highest risk of a subsequent stroke [relative odds (RO) 1·64; 95% confidence interval (CI) 1·12–2·43]. Aggregation in whole blood was not predictive of MI but, again, the fifth of men with the least platelet response showed the highest stroke incidence (RO 1·79; 95% CI 1·06–3·00). Retention of platelets in the high-shear test was not predictive of either event.

Arterial stiffness is an independent predictor of cardiovascular disease events and mortality, and like blood pressure, may be influenced by dairy food intake. Few studies have investigated the effects of consumption of these foods on prospective measures of arterial stiffness. The present analysis aimed to investigate the prospective relationship between milk, cheese, cream, and butter consumption and aortic pulse wave velocity, augmentation index, systolic and diastolic blood pressure, as well as cross-sectional relationships between these foods and systolic and diastolic blood pressure and metabolic markers using data from the Caerphilly Prospective Study. Included in this cohort were 2512 men, aged 45 to 59 years, who were followed up at 5-year intervals for a mean of 22.8 years (number follow-up 787). Augmentation index was 1.8% lower in subjects in the highest quartiles of dairy product intake compared with the lowest ( P trend=0.021), whereas in the highest group of milk consumption systolic blood pressure was 10.4 mm Hg lower ( P trend=0.033) than in nonmilk consumers after a 22.8-year follow-up. Cross-sectional analyses indicated that across increasing quartiles of butter intake, insulin ( P trend=0.011), triacylglycerol ( P trend=0.023), total cholesterol ( P trend=0.002), and diastolic blood pressure ( P trend=0.027) were higher. Across increasing groups of milk intake and quartiles of dairy product intake, glucose ( P trend=0.032) and triglyceride concentrations ( P trend=0.031) were lower, respectively. The present results confirm that consumption of milk predicts prospective blood pressure, whereas dairy product consumption, excluding butter, is not detrimental to arterial stiffness and metabolic markers. Further research is needed to better understand the mechanisms that underpin these relationships.

The stressed bleeding time is a simple 'global' test of haemostasis, dependent upon platelet function, rheology, thrombosis and intimal function. It could be of considerable value in clinical practice if it were shown to be predictive of vascular disease events. A stressed bleeding time test was done on 1319 men aged 55-69 years in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The men were followed-up and during the following 7-10 years 155 men had a myocardial infarction (MI) and 72 an ischaemic stroke. The mean bleeding time was 323 (SD 113)s. This was shorter in men who smoked by an average of 45 s, and lengthened in men who took aspirin daily by 40s. After making statistical adjustments for numerous possible confounding factors, the relative odds (ROs) of an MI within the third of men with the longest bleeding times, compared to the third with the shortest times, was 0.90 (0.40-2.03). For ischaemic stroke, the ROs in the third of men with the longest times were 1.42 (0.39-5.21). The stressed bleeding time does not predict either MI or ischaemic stroke. It has no place in health screening.

In order to determine the taking of regular aspirin within a representative community sample of adults residing in the south Wales county of Caerphilly, we conducted a survey of a sample 9,551 adults resident in the county aged ≥18 years. Questionnaires were returned by 4,558 individuals aged between 25 and 82 years. Nearly 12% of the respondents reported a previous vascular event. Of these, 68% of the men and 55% of the women stated that they took aspirin regularly. Among those with no previous vascular event, 22% of the men and 13% of the women stated that they took aspirin regularly. For those over 50 years of age, the respective figures were 28% of men and 19% of women. Of those taking aspirin, 47% stated that they took 300 mg tablets. There was a small inverse relationship found between aspirin taking and social class, namely 67% and 56% in the manual and non-manual classes respectively. The prevalence of prophylactic aspirin taking by persons who have had a vascular event should be increased, particularly in women. Knowledge of the benefits and the risks of aspirin prophylaxis could be promoted through the community and there should be ongoing monitoring of aspirin taking.

OBJECTIVE--To examine the associations between physical activity and a wide range of risk factors for ischaemic heart disease including fibrinogen concentration and viscosity. DESIGN--Cross sectional evidence from the 2398 men aged 50-64 years in the Caerphilly Prospective Heart Disease Study. METHODS--Validated questionnaires were used to quantify energy expenditure on leisure activities and to grade activities related to occupation. Risk factors for heart disease examined included blood pressure, lipids, fibrinogen, and plasma viscosity. Possible confounding variables included smoking, employment, and prevalent heart disease (angina, previous myocardial infarction, and electrocardiographic evidence of ischaemia). RESULTS--Fibrinogen concentration was lower by 0.24 g/l and viscosity by 0.026 cP in the third of men who were most active in leisure activities (about 0.25 x 1 SD). A weak positive relation was found with high density lipoprotein cholesterol, but none with total cholesterol or fasting glucose concentrations or blood pressure. Triglyceride concentrations seem to be substantially lower in the most active men, although the evidence for this is not consistent. Work related activity showed relation with the lipid concentration but not with the haemostatic tests. CONCLUSIONS--Leisure activities of all levels seem to affect haemostatic and lipid factors beneficially. These effects correspond to a difference in the risk of heart disease for an active man and a sedentary man of at least 7% or 8%. Fasting triglyceride concentrations have already been shown to be strongly predictive of heart disease in this cohort of men, and the effect of exercise on this factor is also likely to confer benefit.

Honey is a broad spectrum antimicrobial agent which can enhance wound healing. A beneficial effect in cancer has been shown in cell cultures and in animal studies and a number of further nutritional and physiological effects of relevance to health and function have been shown for honey. A representative sub-sample of 665 men within the Caerphilly Cohort kept a weighed dietary record for seven days. Risk factors for vascular and other diseases in 41 men who recorded eating honey suggest that these men were on the whole healthier than the 624 men who had not recorded honey consumption. All-cause mortality during 25 years of follow-up was considerably lower in the men who had consumed honey, the hazard ratio, adjusted for a number of possible confounding factors, being 0.44 (95% confidence limits 0.23, 0.86; P < 0.017). Because of the small number of subjects and of deaths in this study, further data from other large cohorts will be required before any effect upon mortality and other health effects of honey consumption can be adequately evaluated.

Objective: To examine the association of anxiety with incident dementia and cognitive impairment not dementia (CIND). Methods: We conducted a prospective study of men aged 48 to 67 years at baseline anxiety assessment; we measured cognition 17 years later. We studied 1481 men who were either eligible for examination or were known to have dementia. Trait Anxiety was assessed using the Spielberger State Trait Anxiety Inventory. Psychological distress was assessed using the 30-item general health questionnaire. Cognitive screening was followed by a clinical examination. Medical notes and death certificates of those not seen were also examined. Outcomes were CIND and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) dementia. Results: Of 1160 men who were cognitively screened, 174 cases of CIND and 69 cases of dementia were identified. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function associations with higher anxiety (31st–95th centile) were for CIND odds ratio (OR) 2.31 (95% Confidence Interval (CI) = 1.20–4.44) and for dementia OR 2.37 (95% CI = 0.98–5.71). These associations were slightly stronger for nonvascular (OR = 2.45; 95% CI = 1.28–4.68) than for vascular impairment (OR = 1.94; 95% CI = 0.77–4.89). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examination of the Elderly subscales found some evidence for decline in learning memory with higher anxiety score (bage adj = −0.291 (−0.551, −0.032), but not for any other subscale. Conclusions: Anxiety is a risk factor for CIND and dementia. The extent to which the association is independent of depression and whether or not it is causal requires further study.

Objectives: To conduct a detailed evaluation, with meta-analyses, of the published evidence on milk and dairy consumption and the incidence of vascular diseases and diabetes. Also to summarise the evidence on milk and dairy consumption and cancer reported by the World Cancer Research Fund and then to consider the relevance of milk and dairy consumption to survival in the UK, a typical Western community. Finally, published evidence on relationships with whole milk and fat-reduced milks was examined. Methods: Prospective cohort studies of vascular disease and diabetes with baseline data on milk or dairy consumption and a relevant disease outcome were identified by searching MEDLINE, and reference lists in the relevant published reports. Meta-analyses of relationships in these reports were conducted. The likely effect of milk and dairy consumption on survival was then considered, taking into account the results of published overviews of relationships of these foods with cancer. Results: From meta-analysis of 15 studies the relative risk of stroke and/or heart disease in subjects with high milk or dairy consumption was 0.84 (95% CI 0.76, 0.93) and 0.79 (0.75, 0.82) respectively, relative to the risk in those with low consumption. Four studies reported incident diabetes as an outcome, and the relative risk in the subjects with the highest intake of milk or diary foods was 0.92 (0.86, 0.97). Conclusions: Set against the proportion of total deaths attributable to the life-threatening diseases in the UK, vascular disease, diabetes and cancer, the results of meta-analyses provide evidence of an overall survival advantage from the consumption of milk and dairy foods.

Background/Aims: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65–84 years). Methods: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG 9) being neurologically examined. Results: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. Conclusion: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority.

Objective: To test the hypothesis that sleep disorders are relevant to the risk of ischaemic stroke and ischaemic heart disease events in older men. Design: A cohort study. Setting: The Caerphilly cohort, a representative population sample of older men in South Wales, UK. Participants: 1986 men aged 55–69 years completed a questionnaire on sleep patterns with help from their partners. This asked about symptoms of disturbed sleep: insomnia, snoring, restless legs, obstructive sleep apnoea, and about daytime sleepiness. During the following 10 years 107 men experienced an ischaemic stroke and 213 had an ischaemic heart disease event. Main results: Up to one third of the men reported at least one symptom suggestive of sleep disturbance, and one third reported daytime sleepiness. Compared with men who reported no such symptoms, the adjusted relative odds of an ischaemic stroke were significantly increased in men with any sleep disturbance, the strongest association being with sleep apnoea (relative odds 1.97; 1.26 to 3.09). The association with daytime sleepiness was not significant for stroke. Relations with ischaemic heart disease events were all raised in men with symptoms of sleep disturbance, but none was significant, other than daytime sleepiness (relative odds: 1.41; 1.04 to 1.92). There were no significant relations with blood pressure. Conclusion: The risk of an ischaemic stroke is increased in men whose sleep is frequently disturbed, and daytime sleepiness is associated with a significant increase in ischaemic heart disease events.

Objective: To compare vascular and glucose related mechanisms of type 2 diabetes on cognitive performance. Research design and methods: A cross-sectional observational study of type 2 diabetes defined by non insulin dependant self-report diabetes or fasting blood glucose ≤ 7.0 mmol/l of 2205 men eligible for the third phase of the Caerphilly Collaborative Heart Disease Study. Men were aged 55–69 years at time of testing. Tests of cognitive function included NART (crystallised IQ), AH4 (fluid IQ), verbal fluency (executive function) Cambridge Cognitive Examination (CAMCOG) and Mini Mental State Examination (MMSE) (global function), four choice serial reaction time (psychomotor function) and memory. Men with prior stroke were omitted from the analysis. Results: Men with diabetes showed cognitive deficits for verbal fluency, National Adult Reacting Test (NART) and AH4. Adjusting for vascular risk factors had minimal effect. Including blood glucose removed the deficit for verbal fluency and NART but the effect on AH4 score (−2.58; 95% CI: −5.0, −0.1, p = 0.039) was retained. More detailed analyses of AH4 score on men with diabetes showed a curvilinear relationship indicating that men with both low and high glucose levels had worse performance (AH4 = −66 + 80 loge glucose – 18 loge glucose2; 95% CI: −29, −6; p=0.002). Conclusions: These data identify a direct effect of glucose regulation on cognitive performance associated with diabetes in a population sample. These data suggest that an effect of glucose regulation on cognitive performance in diabetes is distinct from any effect of macro-vascular disease.

Objective: To examine associations between milk consumption and incident heart disease and stroke. Design: A representative population sample of men was asked to weigh and record their food intake for seven days. The total consumption of milk was obtained from these records. Details of all deaths and vascular events were collected during the following 20 years. Incident ischaemic strokes and heart disease events were diagnosed by standard criteria. Setting: The Caerphilly cohort, a representative population sample of men in South Wales, aged 45–59 when first seen in 1979–83. Participants: A representative 3:10 subsample of the men in the cohort. Main results: 665 men (87% of those approached) returned satisfactory seven day diet diaries. After adjustment, the relative odds of an event in the men whose milk consumption was the median or higher, relative to those with lower intakes of milk, were 0.52 (0.27 to 0.99) for an ischaemic stroke and 0.88 (0.56 to 1.40) for an ischaemic heart disease event. Deaths from all causes were similar in the two milk consumption groups (relative odds 1.08; 0.74 to 1.58). Conclusions: These results give no convincing evidence of an increased risk of vascular disease from milk drinking. Rather, the subjects who drank more than the median amount of milk had a reduced risk of an ischaemic stroke, and possibly a reduced risk of an ischaemic heart disease event. These conclusions are in agreement with the results of a previously reported overview of 10 large, long term cohort studies based on food frequency intake records.

To test the hypothesis that milk drinking increases the risk of ischaemic heart disease (IHD) and ischaemic stroke in a prospective study.In the Caerphilly Cohort Study dietary data, including milk consumption, were collected by a semiquantitative food frequency questionnaire in 1979-1983. The cohort has been followed for 20-24 y and incident IHD and stroke events identified.A representative population sample in South Wales, of 2512 men, aged 45-59 y at recruitment.In total, 493 men had an IHD event and 185 an ischaemic stroke during follow-up.After adjustment, the hazard ratio in men with a milk consumption of one pint (0.57 l) or more per day, relative to men who stated that they consumed no milk, is 0.71 (0.40-1.26) for IHD and 0.66 (0.24-1.81) for ischaemic stroke. At baseline, 606 men had had clinical or ECG evidence of vascular disease, and in these the vascular risk was even lower (0.37; 0.15-0.90). The hazard ratio for IHD and ischaemic stroke combined is 0.64 (0.39-1.06) in all men and 0.37 (0.15-0.90) in those who had had a prior vascular event.The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk. Evidence from an overview of all published cohort studies on this topic should be informative.: The Medical Research Council, the University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

Objectives: vascular lesions are important contributors to cerebral disease, yet relatively little work has been done on relationships between haematological factors and cognitive function. We have explored these relationships in the Caerphilly cohort of older men. Design: the development of vascular disease and the decline in cognitive function are being studied in a cohort of older men in Caerphilly, South Wales, UK. We have recorded a range of life‐style, dietary, lipid, haematological and rheological factors which are, or may be, predictive of vascular disease. We have examined the relationships between these and both incident myocardial infarction and stroke, and identified factors relevant to cognitive function. Setting: a community‐based study based upon a representative population sample of older men. We collected data for the study from around 90% of the survivors of the original cohort. Subjects: 2154 men who were aged 55–69 years at the time blood was taken for the haematological tests and cognitive function was tested. Main outcome measures: we present data from the AH4 test of general cognitive performance and from choice reaction time, a test of vigilance. Results: there is a U‐shaped relationship between haematocrit and cognitive function, the best cognitive function scores occurring at a mean haematocrit of 0.46. The relationship is significant for the choice reaction time (P

Background: Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.\ud Methods: In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.\ud Findings: Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours

STUDY OBJECTIVES: To examine the cognitive function in a large, ongoing cohort study of older men, and to identify associations with social and lifestyle factors. DESIGN: A cross sectional study of cognitive function was conducted within the Caerphilly Prospective Study of Heart Disease and stroke. SETTING: The Caerphilly Study was originally set up in 1979-83 when the men were 45-59 years of age. Extensive data are available on a wide range of lifestyle and other factors of possible relevance to cognitive decline. Associations between some of these and cognitive function are reported. PARTICIPANTS: A representative sample of 1870 men aged 55-69 years. MAIN RESULTS: Age, social class, medication, and mood were found to be powerful determinants of performance. Self report data on the involvement of the men in leisure pursuits were examined by factor analysis. This indicated that the more intellectual leisure pursuits are the most strongly linked with performance. A measure of social contact showed a weak positive association with the test scores. Current cigarette smokers gave lower test cognitive function scores than either men who had never smoked, or ex-smokers. There was however no evidence of any gradient in function with the total lifetime consumption of tobacco. The disparity between these two data sets suggests that there had been prior selection of men who had originally started to smoke, but more particularly selection of those who later quit smoking. There was no significant association between alcohol consumption and cognitive function, though ex-drinkers had markedly lower test scores than either current drinkers or men who had never drunk alcohol. This seemed probably to be a consequence of an high prevalence of illness among the ex-drinkers. CONCLUSIONS: Age and social class show strong associations with cognitive function. Leisure persuits and social contact are also both positively associated. Neither tobacco smoking nor the drinking of alcohol seem to be associated with cognitive function, though there is evidence suggestive of self selection of both men who had never smoked and ex-smokers.

Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50-64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 micromol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 micromol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 micromol/l (95% CI = -0.13 to 1.11 micromol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 micromol/l (95% CI= -0.17 to 1.88 micromol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P0.05).

Current population screening for vascular disease is neither efficient nor effective. Peter Elwood and colleagues believe we should have a public information strategy highlighting the benefits (and risks) of aspirin for older people, but Colin Baigent argues that the evidence of benefit is not yet strong enough It is 30 years since the first randomised trial was published showing a link between aspirin and myocardial infarction.1 We believe that the evidence now supports more widespread use of aspirin prophylaxis, and there needs to be a strategy to inform the public and enable older people to make their own decision. The evidence focuses on a crucial question—namely, at what age does the balance between benefit and risk justify low dose aspirin prophylaxis? Of further relevance is a possible reduction of cancer and dementia by aspirin. Although several groups have recommended aspirin prophylaxis based on age alone, including a recommendation of daily aspirin for everyone over 50,2 3 cardioprotection is usually given only to people at vascular risk. Many formulas are available to assess risk, and one of these4 is the basis of the recommendation that prophylactic aspirin be considered if the five year risk of a vascular event is 3% or more.5 Application of the Framingham risk formula4 to the …

EDITOR—The case for the wider use of aspirin in vascular prophylaxis arises from the belief that subjects should be empowered to make their own decision about protecting their own health. This will be achieved only if information on the risks and benefits of preventive measures, including low dose aspirin, is widely available. Granted, the numerical risk-harm balance of aspirin in trials based …