Milk drinking, ischaemic heart disease and ischaemic stroke I. Evidence from the Caerphilly cohort.

OBJECTIVE: To test the hypothesis that milk drinking increases the risk of ischaemic heart disease (IHD) and ischaemic stroke in a prospective study. DESIGN: 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. SUBJECTS: A representative population sample in South Wales, of 2512 men, aged 45-59 y at recruitment. MAIN OUTCOME MEASURES: In total, 493 men had an IHD event and 185 an ischaemic stroke during follow-up. RESULTS: 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. CONCLUSION: 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. SPONSORSHIP: : The Medical Research Council, the University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies.

OBJECTIVE: 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. DESIGN: 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. MAIN OUTCOME MEASURES: Ischaemic heart disease and ischaemic stroke. RESULTS: 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). CONCLUSIONS: 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. SPONSORSHIP: The University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

Lack of benefit of dietary advice to men with angina: results of a controlled trial.

OBJECTIVE: To see whether mortality among men with angina can be reduced by dietary advice. DESIGN: A randomized controlled factorial trial. SETTING: Male patients of general practitioners in south Wales. SUBJECTS: A total of 3114 men under 70 y of age with angina. INTERVENTIONS: Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y. RESULTS: Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication. CONCLUSIONS: Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.

Frequency of fruit and vegetable consumption and blood antioxidants in the Caerphilly cohort of older men.

OBJECTIVE: To assess the number of portions of fruit and vegetables consumed daily by a large representative sample of older men, and to determine how blood antioxidant (vitamins E, A and carotenoids) concentrations vary with fruit and vegetable consumption. DESIGN: Cross-sectional study of free-living men. SUBJECTS: Men aged 55-69 y (dietary data, n=1957; blood data, n=1874) participating in Phase III (1989-1993) of the Caerphilly and Speedwell Collaborative Heart Disease Studies. METHODS: Dietary data were obtained by semi-quantitative food-frequency questionnaire and blood samples were analysed for antioxidant vitamins. Men were subdivided into groups on the basis of portions per day of fruit and vegetables. Within these sub-groups, mean and 95% ranges of intakes and of blood antioxidant levels were obtained. Log transformations were performed where appropriate. RESULTS: Only 4.3% of the men met the recommended target of five portions, while 33.3% of the men consumed one or fewer portions of fruit and vegetables per day. Those men who consumed the poorest diets with respect to fruit and vegetable intakes were more likely to be from lower socio-economic classes, drink more alcohol and be current smokers. Fruit and vegetable intake reflected plasma concentrations of antioxidants, which showed a dose-response relationship to frequency of consumption. CONCLUSIONS: Older men in the UK consume much less fruit and vegetables than current recommendations. Major difficulties are likely to be encountered in trying to meet a dietary target that is clearly much higher than the fruit and vegetable consumption of large sections of the older population in the UK. SPONSORSHIP: This work was supported by the Medical Research Council.

Diet, lung function, and lung function decline in a cohort of 2512 middle aged men.

BACKGROUND: A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS: At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV(1)) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS: Good lung function, indicated by high maximum FEV(1) given age and height, was associated with high intakes of vitamin C, vitamin E, beta-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58 to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS: A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.

Antioxidant enzymes, inflammatory indices and lifestyle factors in older men: a cohort analysis.

We examined the relationship between blood antioxidant enzyme activities, indices of inflammatory status and a number of lifestyle factors in the Caerphilly prospective cohort study of ischaemic heart disease. The study began in 1979 and is based on a representative male population sample. Initially 2512 men were seen in phase I, and followed-up every 5 years in phases II and III; they have recently been seen in phase IV. Data on social class, smoking habit, alcohol consumption were obtained by questionnaire, and body mass index was measured. Antioxidant enzyme activities and indices of inflammatory status were estimated by standard techniques. Significant associations were observed for: age with alpha-1-antichymotrypsin (p < 0.0001) and with caeruloplasmin, both protein and oxidase (p < 0.0001); smoking habit with alpha-1-antichymotrypsin (p < 0.0001), with caeruloplasmin, both protein and oxidase (p < 0.0001) and with glutathione peroxidose (GPX) (p < 0.0001); social class with alpha-1-antichymotrypsin (p < 0.0001), with caeruloplasmin both protein (p < 0.001) and oxidase (p < 0.01) and with GPX (p < 0.0001); body mass index with alpha-1-antichymotrypsin (p < 0.0001) and with caeruloplasmin protein (p < 0.001). There was no significant association between alcohol consumption and any of the blood enzymes measured. Factor analysis produced a three-factor model (explaining 65.9% of the variation in the data set) which appeared to indicate close inter-relationships among antioxidants.

Homocysteine and ischaemic heart disease in the Caerphilly cohort.

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 (P > 0.05).

Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study.

Antioxidant flavonols and their major food source, black tea, have been associated with a lower risk of ischemic heart disease (IHD) and stroke in Dutch men. We investigated whether flavonol intake predicted a lower rate of IHD in 1900 Welsh men aged 45-59 y, who were followed up for 14 y. Flavonol intake, mainly from tea to which milk is customarily added, was not related to IHD incidence [relative risk (RR), highest compared with lowest quartile: 1.0; 95% CI: 0.6, 1.6; P for trend = 0.996; n = 186] but was weakly positively related to IHD mortality (RR: 1.6; 95% CI: 0.9, 2.9; P = 0.119; n = 131) and cancer mortality (RR: 1.3; 95% CI: 0.7, 2.3; P = 0.150; n = 104) and strongly related to total mortality (RR: 1.4; 95% CI: 1.0, 2.0; P = 0.014; n = 334). Men with the highest consumption of tea (> 1.2 L, or > 8 cups/d) had an RR of 2.4 (95% CI: 1.5, 3.9) of dying in the follow-up period compared with men consuming < 300 mL/d (< 2 cups/d). We conclude that intake of antioxidant flavonols is not inversely associated with IHD risk in the United Kingdom. Possibly, flavonols from tea to which milk is added are not absorbed; experimental evidence suggests that adding milk to tea abolishes the plasma antioxidant-raising capacity of tea. The apparent association between tea consumption and increased mortality in this population merits further investigation.

Dietary magnesium does not predict ischaemic heart disease in the Caerphilly cohort.

OBJECTIVES: To examine the association between dietary magnesium intake and the risk of an ischaemic heart disease (IHD) event. DESIGN: Estimates were made of dietary magnesium intake from food frequency records, supplemented by seven-day weighted intake records. The subsequent incidence of ischaemic heart disease events was recorded. The relative odds of an IHD event was related to base-line magnesium intake. SETTING: Data on dietary magnesium intakes are available for 2172 men aged 45-59 y in the Caerphilly cohort. These have now been followed for ten years since base-line dietary data were collected, and during this time a total of 269 IHD events occurred. Of these, 96 were acute deaths (ICD 410) and 136 were non-fatal myocardial infarctions. RESULTS: The overall mean dietary intake of magnesium was estimated to be 279 (s.d. 83) mg/day. The daily intake of those men who later experienced any IHD event was 266 (s.d. 84) mg/day and this differs from that in men who experienced no IHD event during this time (281 mg, P < 0.05). Men who suffered an acute IHD death had even lower intakes (mean 253 (s.d. 79); P < 0.005). Age, smoking habit, energy intake and alcohol consumption are all significantly associated with both Mg intake and IHD risk and are therefore possible confounding factors. Standardisation for these factors reduces the difference for all IHD events to 2.9 (s.e.m. 3.6) mg Mg/day, P > 0.05, and to 0.9 (s.e.m. 5.8) mg for acute IHD death. Similarly, when the men are ranked into fifths by their daily Mg intake, 70 of the 434 men with the lowest intakes went on to experience an IHD event, compared with only 41 of the 434 men with the highest Mg intakes. The relative odds (RO) for the fifth of men with the lowest intakes, compared with the fifth with the highest intakes, is 1.86 (P < 0.005), but standardisation for the confounding factors leads again to a loss of significance (RO 1.52, P > 0.05). CONCLUSION: Although trends in the data are suggestive, data from the Caerphilly cohort give no certain evidence that dietary magnesium intake is independently predictive of ischaemic heart disease in the population studied.

Fruit and vegetable consumption and cancer mortality in the Caerphilly Study.

We investigated whether the consumption of fruit and vegetables lowered cancer mortality in a cohort of 2112 Welsh men ages 45-69 years (The Caerphilly Study), which was followed-up for 13.8 years. At baseline (between 1979 and 1983), participants completed a 56-item food frequency questionnaire from which the consumption of fruit and vegetables was calculated. Relative risks (RR) were estimated with Cox proportional hazard analysis, with death from various types of cancer as a dependent variable, and fruit, vegetables, vitamin C, beta-carotene, dietary fiber, and potential confounders as independent variables. Mean consumption of vegetables and fruit at baseline was 118 g/day and 83 g/day, respectively. During follow-up 114 men died from cancer, including 51 men who died from respiratory tract cancer and 45 men who died from digestive tract cancer. Fruit consumption and the intake of dietary fiber were inversely related to respiratory tract cancer, but after adjustment for potential confounders including age, smoking, and social class, the association with fruit consumption became nonsignificant. Vegetable and fruit consumption was, independently from other risk factors, inversely related to mortality from cancer of the digestive tract (P for trend = 0.021), mainly due to an inverse association with fruit consumption (RR for the highest quartile versus the lowest was 0.3; 95% CI, 0.1-0.8). Vitamin C, beta-carotene, and dietary fiber were not significantly associated with cancers of the digestive tract. Vegetable and fruit consumption was also inversely related to all-cause cancer mortality, and the strongest association was observed for fruit consumption (RR in the highest versus lowest quartile was 0.5; 95% CI, 0.3-1.0). Consumption of vegetables and particularly the consumption of fruit could considerably lower the risk of dying from cancer in middle-aged men.

Dietary indices of atherogenicity and thrombogenicity and ischaemic heart disease risk: the Caerphilly Prospective Study.

The aim of the study was to investigate whether proposed dietary scores of atherogenicity and thrombogenicity predict ischaemic heart disease (IHD) risk in a community sample of men aged 45-59 years. Dietary scores were calculated from consumption of various fatty acids, estimated from 7 d weighed intake data obtained from 665 men. Investigation of associations with blood lipids, lipoproteins and haemostatic factors revealed positive associations with low-density-lipoprotein cholesterol (P < 0.05) and white cell count (P < 0.05), and a negative association with antithrombin III (P = 0.05), after taking into account the effects of age, body mass index and smoking. During a 5-year follow-up period, there were twenty-one new IHD events among the 512 men in whom there was no evidence of IHD at baseline. Men with higher atherogenicity or thrombogenicity scores at baseline tended to have a higher risk of subsequent IHD. The trend was consistent but not statistically significant. A similar trend was observed for total saturates, and an inverse trend for total polyunsaturates, expressed as a percentage of total fatty acids. It is, therefore, concluded that proposed dietary indices of atherogenicity and thrombogenicity may be weak predictors of IHD risk, but that these scores are unlikely to be substantially better predictors than more simple approaches such as intakes of total saturates. To enhance the predictive ability, more complex formulas which take into account other dietary factors as well as fatty acid intakes would probably be required.

Diet and incident ischaemic heart disease: the Caerphilly Study.

The Caerphilly Prospective Ischaemic Heart Disease (IHD) Study is based on a sample of 2512 men aged 45-59 years when first seen. Nutrient intakes, estimated using a self-administered semi-quantitative food frequency questionnaire, are available for 2423 men (96%). Amongst these, 148 major IHD events occurred during the first 5 years of follow-up. Associations were examined between these events and baseline diet. Incident IHD (new events) was negatively associated with total energy intake: men who went on to experience an IHD event had consumed 560 kJ (134 kcal)/d (6%) less at baseline than men who experienced no event (P = 0.01). The relative odds of an IHD event was 1.5 among men in the lowest fifth of energy intake, compared with 1.3, 1.2, 0.9 and 1.0 respectively for the other four fifths (P < 0.05). The difference in energy intake was reflected in lower intakes of every nutrient examined. When expressed as a percentage of total energy, mean intakes of men who experienced an IHD event were virtually identical to those of men who did not. There was some evidence suggesting a positive association between total fat intake and IHD risk, but the trend was not consistent and not statistically significant. There was no association for animal fat. Alcohol consumption was negatively associated with subsequent IHD, but only in men who already had evidence of IHD at baseline (P < 0.05). Dietary fibre, particularly from fruit and vegetables, was 7% lower in men who had an incident IHD event (P < 0.05), but the difference was not independent of total energy. There was a trend of increasing IHD risk with decreasing vitamin C intake, the relative odds of an IHD event being 1.6 among men in the lowest one-fifth of the vitamin C distribution, but this was not statistically significant.

Exercise, fibrinogen, and other risk factors for ischaemic heart disease. Caerphilly Prospective Heart Disease Study.

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.

Factors affecting bone density in young adults.

A 14-y follow-up of 581 children who took part in a randomized controlled trial of the effect of a milk supplement on growth of children was conducted to investigate the supplement's effect on adult bone mineral content (BMC) and density (BMD). BMC and BMD of the nondominant forearm were measured by single-photon absorptiometry in 371 subjects (64%) aged 20-23 y, at a proximal site (shaft of radius and ulna) and at a distal site near the wrist. BMCs and BMDs tended to be higher in the intervention group (NS). Cross-sectionally, BMD was positively associated with body weight (P less than 0.01) in both sexes; inversely associated with alcohol consumption (P less than 0.05), and positively with manual occupation (NS) in men; positively associated with current intakes of calcium (P less than 0.05), vitamin D (P less than 0.01), and sports activity during adolescence (P less than 0.01), and inversely with parity (NS) in women. In multiple linear-regression analysis body weight and sports activity during adolescence were stronger determinants of female BMD than was diet.

Alcohol and platelet aggregation: the Caerphilly Prospective Heart Disease Study.

Intakes of alcohol and saturated fatty acids were determined through a dietary questionnaire from 1600 men (aged 49-66 y) in the Caerphilly Prospective Heart Disease Study. Platelet aggregation induced by thrombin adenosine disphosphate (ADP), and collagen was studied in subjects who had fasted and had not recently taken drugs affecting platelets. In subjects who drank alcohol, the odds ratio of a high response to aggregation was significantly reduced (primary ADP, P less than 0.05; secondary ADP, P less than 0.001; collagen, P less than 0.02). The significance was enhanced by adjusting for smoking and by including only the subjects with a high intake of saturated fatty acids or a low intake of polyunsaturated fatty acids. By contrast, the responsiveness to thrombin was slightly increased at all levels of alcohol consumption. We therefore suggest that part of the effects of alcohol on coronary heart disease may be mediated by a dose-dependent effect on certain platelet functions, modulated by the intake of dietary fat.