A.P. Haines

Haemostatic function and ischaemic heart disease: principal results of the Northwick Park heart study

The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol.

HÆMOSTATIC FUNCTION AND CARDIOVASCULAR DEATH: EARLY RESULTS OF A PROSPECTIVE STUDY

Abstract Components of the haemostatic system which may be involved in the pathogenesis of ischaemic heart disease (IHD) were measured in the Northwick Park Heart Study. Of 1510 white men aged 40-64 at recruitment, 49 have since died. 27 died from cardiovascular disease (IHD in all but 3), 18 from cancer, and 4 from other causes. The mean recruitment levels of factor VIIc, factor VIIIc, and fibrinogen were significantly higher in those who died of cardiovascular disease than in those who survived. The independent associations of factor VIIc and fibrinogen with cardiovascular death were at least as strong as the association of blood cholesterol with cardiovascular death. A clustering of two or three high clotting-factor values (factor VIIc, factor VIIIc, and fibrinogen) was present at recruitment in 63% of those who died of cardiovascular disease, compared with 23% of those who survived. The clotting-factor results appeared to be specific for cardio- vascular disease: there was no evidence that high levels of factor VIIc, factor VIIIc, and fibrinogen were associated with death from cancer. The general epidemiology of fac- tor VIIc, factor VIIIc, and fibrinogen is consistent with their having a role in the pathogenesis of IHD.

Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.

Epidemiological characteristics of platelet aggregability.

The epidemiological characteristics of platelet aggregability were established in 958 participants in the Northwick Park Heart Study. The main analyses were based on the dose of adenosine diphosphate at which primary aggregation occurred at half its maximum velocity. Aggregability increased with age in both sexes, was greater in whites than blacks (particularly among men), and tended to decrease with the level of habitual alcohol consumption. Aggregability was, however, greater in women than men and in nonsmokers than smokers. There was no relation between aggregability on the one hand and obesity, current or past oral contraceptive use, menopausal state, or blood cholesterol and triglyceride concentrations on the other. Aggregability was somewhat, though not significantly, higher in men with a history of ischaemic heart disease and in those with electrocardiographic evidence of ischaemia than in those without. There was a strong association between the plasma fibrinogen concentration and aggregability. The widely held concept of platelet aggregability and its implications is probably an oversimplification. In the prevention of thrombosis it may be as useful to consider modifying external influences on platelet behaviour, such as plasma fibrinogen concentration or thrombin production, as it is to rely solely on platelet active agents.

The Lancet CommissionsSafeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation–Lancet Commission on planetary health

Earths natural systems represent a growing threat to human health. And yet, global health has mainly improved as these changes have gathered pace. What is the explanation? As a Commission, we are deeply concerned that the explanation is straightforward and sobering: we have been mortgaging the health of future generations to realise economic and development gains in the present. By unsustainably exploiting natures resources, human civilisation has fl ourished but now risks substantial health eff ects from the degradation of natures life support systems in the future. Health eff ects from changes to the environment including climatic change, ocean acidifi cation, land degradation, water scarcity, overexploitation of fi sheries, and biodiversity loss pose serious challenges to the global health gains of the past several decades and are likely to become increasingly dominant during the second half of this century and beyond. These striking trends are driven by highly inequitable, ineffi cient, and unsustainable patterns of resource consumption and technological development, together with population growth. We identify three categories of challenges that have to be addressed to maintain and enhance human health in the face of increasingly harmful environmental trends. Firstly, conceptual and empathy failures (imagination challenges), such as an over-reliance on gross domestic product as a measure of human progress, the failure to account for future health and environmental harms over present day gains, and the disproportionate eff ect of those harms on the poor and those in developing nations. Secondly, knowledge failures (research and information challenges), such as failure to address social and environmental drivers of ill health, a historical scarcity of transdisciplinary research and funding, together with an unwillingness or inability to deal with uncertainty within decision making frameworks. Thirdly, implementation failures (governance challenges), such as how governments and institutions delay recognition and responses to threats, especially when faced with uncertainties, pooled common resources, and time lags between action and eff ect. Although better evidence is needed to underpin appropriate policies than is available at present, this should not be used as an excuse for inaction. Substantial potential exists to link action to reduce environmental damage with improved health outcomes for nations at all levels of economic development. This Commission identifi es opportunities for action by six key constituencies: health professionals, research funders and the academic community, the UN and Bretton Woods bodies, governments, investors and corporate reporting bodies, and civil society organisations. Depreciation of natural capital and natures subsidy should be accounted for so that economy and nature are not falsely separated. Policies should balance social progress, environmental sustainability, and the economy. To support a world population of 9-10 billion people or more, resilient food and agricultural systems are needed to address both undernutrition and overnutrition, reduce waste, diversify diets, and minimise environmental damage. Meeting the need for modern family planning can improve health in the short termeg, from reduced maternal mortality and reduced pressures on the environment and on infrastructure. Planetary health off ers an unprecedented opportunity for advocacy of global and national reforms of taxes and subsidies for many sectors of the economy, including energy, agriculture, water, fi sheries, and health. Regional trade treaties should act to further incorporate the protection of health in the near and long term. Several essential steps need to be taken to transform the economy to support planetary health. These steps include a reduction of waste through the creation of products that are more durable and require less energy and materials to manufacture than those often produced at present; the incentivisation of recycling, reuse, and repair; and the substitution of hazardous materials with safer alternatives. Despite present limitations, the Sustainable Development Goals provide a great opportunity to integrate health and sustainability through the judicious selection of relevant indicators relevant to human wellbeing, the enabling infrastructure for development, and the supporting natural systems, together with the need for strong governance. The landscape, ecosystems, and the biodiversity they contain can be managed to protect natural systems, and indirectly, reduce human disease risk. Intact and restored ecosystems can contribute to resilience (see panel 1 for glossary of terms used in this report), for example, through improved coastal protection (eg, through wave attenuation) and the ability of fl oodplains and greening of river catchments to protect from river fl ooding events by diverting and holding excess water. The growth in urban populations emphasises the importance of policies to improve health and the urban environment, such as through reduced air pollution, increased physical activity, provision of green space, and urban planning to prevent sprawl and decrease the magnitude of urban heat islands. Transdisciplinary research activities and capacity need substantial and urgent expansion. Present research limitations should not delay action. In situations where technology and knowledge can deliver win-win solutions and co-benefi ts, rapid scale-up can be achieved if researchers move ahead and assess the implementation of potential solutions. Recent scientifi c investments towards understanding non-linear state shifts in ecosystems are very important, but in the absence of improved understanding and predictability of such changes, eff orts to improve resilience for human health and adaptation strategies remain a priority. The creation of integrated surveillance systems that collect rigorous health, socioeconomic, and environmental data for defi ned populations over long time periods can provide early detection of emerging disease outbreaks or changes in nutrition and non-communicable disease burden. The improvement of risk communication to policy makers and the public and the support of policy makers to make evidence-informed decisions can be helped by an increased capacity to do systematic reviews and the provision of rigorous policy briefs. Health professionals have an essential role in the achievement of planetary health: working across sectors to integrate policies that advance health and environmental sustainability, tackling health inequities, reducing the environmental impacts of health systems, and increasing the resilience of health systems and populations to environmental change. Humanity can be stewarded successfully through the 21st century by addressing the unacceptable inequities in health and wealth within the environmental limits of the Earth, but this will require the generation of new knowledge, implementation of wise policies, decisive action, and inspirational leadership.

Effects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics

A randomised trial of the effects of 15 gm per day of a fish oil supplement (MaxEPA) on blood lipids, haemostatic variables (including platelet function) and albuminuria was undertaken in 41 insulin dependent diabetics. Compared with the control group there was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement. The extent of platelet aggregation was not altered but the lag phase before aggregation was prolonged. There were also statistically significant increases in plasma LDL cholesterol, fibrinogen and clotting factor X in the group who took the fish oil supplement. No other significant differences were noted.

HÆMOSTATIC, LIPID, AND BLOOD-PRESSURE PROFILES OF WOMEN ON ORAL CONTRACEPTIVES CONTAINING 50 µg OR 30 µg ŒSTROGEN

Abstract In 15 women on oral contraceptives containing 30 μg œstrogen, mean values for factors II, VII, and x, fibrinogen, fibrinolytic activity, antithrombin III, cholesterol, and fasting triglycerides were intermediate between values for 63 women on preparations containing 50 μg œstrogen and those for 243 premenopausal women not on oral contraceptives. Mean blood-pressure levels, however, were higher in women on 30 μg than in those on 50 μg preparations. In 28 women on 50 μg preparations containing 3 mg or 4 mg norethisterone, mean values of factor VII, fibrinogen, fibrinolytic activity, cholesterol, fasting triglycerides, and systolic blood-pressure were higher than in 15 women whose preparations contained only 1 mg of norethisterone. A less consistent picture was found in women on 30 μg œstrogen preparations containing either 250 μg (10 women) or 150 μg (5 women) d -norgestrel. It is concluded that 30 μg œstrogen preparations probably result in smaller haemostatic and lipid changes than 50 μg preparations but that they may have a blood-pressure-raising effect attributable to the particular progestagen, d -norgestrel, used in 30 μg preparations. The safety of these 30 μg œstrogen preparations may thus depend partly on the balance between these two sets of effects. It is also concluded that norethisterone may have effects similar to those attributed to œstrogens.

Breath-methane in patients with cancer of the large bowel.

In 30 patients with cancer of the large bowel, 24 (80%) had detectable levels of methane in their breath, compared with 25 (39%) of 64 patients with non-malignant large-bowel disease and 83 (40%) of 208 subjects without large-bowel disease. These findings suggest that there may be a difference in anaerobic intestinal flora between patients with cancer of the large bowel and those without the disease. This difference may antedate the development of the tumour or, alternatively, result from the tumour.

A comparative study of zinc, copper, cadmium, and lead levels in fertile and infertile men

Eighty infertile men and 38 men of known fertility were studied for investigation of both the importance of zinc, copper, cadmium, and lead to fertility and the possible interrelationships between these trace elements. The infertile men had higher mean concentrations of plasma copper than those of proven fertility. The difference was statistically significant (P less than 0.01) but was of small magnitude (approximately 1.5 mumol mean difference). The concentrations of plasma zinc, erythrocyte zinc, whole blood lead and cadmium, and seminal plasma zinc and copper did not differ significantly between infertile and fertile men. There was a significant positive relationship between sperm density and seminal plasma zinc concentration in the fertile, but not in the infertile, men. The infertile men with antisperm antibodies or counts greater than 20 million/ml had significantly higher mean levels of seminal plasma zinc than infertile men with oligospermia. The higher semen zinc in these two groups may reflect an abnormal fragility of the spermatozoa, resulting in the release of zinc, but the absence of significant overall differences between fertile and infertile men suggests that measurement of the concentration of zinc in plasma or zinc and copper in seminal plasma has little value in the routine investigation of infertility.

Haemostatic variables in vegetarians and non-vegetarians

Abstract Factors V, VII, VIII, fibrinogen, fibrinolytic activity and antithrombin III (immunological and biological), as well as blood lipids and blood pressure have been measured in 50 vegetarians, and compared with 282 participants in a prospective study of ischaemic heart disease. Mean levels of factor VII, cholesterol and diastolic blood pressure were lower in vegetarians of both sexes than in the comparison group. Factors II and X were measured in 25 of the male vegetarians and 25 age matched participants; the mean level of factor II was lower in the male vegetarians. These observations are consistent with the hypothesis that lower levels of certain coagulation factors are associated with a reduced incidence of IHD. However, fibrinolytic activity and antithrombin III (immunological) levels were also lower in male vegetarians. One explanation for these apparently paradoxical findings may be that those at low risk of IHD have a correspondingly low requirement for protective, antithrombotic mechanisms.