S J Pocock

British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns.

The British Regional Heart Study seeks to define risk factors for cardiovascular disease, to examine their interrelationships, and to explain the geographic variations in cardiovascular disease in Britain. A clinical survey of men aged 40-59 in 24 British towns was carried out and preliminary data from the survey analysed. On a town basis cardiovascular mortality was associated with mean systolic blood pressure and the prevalence of heavy cigarette smoking and heavy alcohol consumption. No such association was seen for body mass index or mean serum total cholesterol or high-density-lipoprotein cholesterol concentration. Cigarette smoking and alcohol intake and, to a less degree, systolic blood pressure were related to the social class (percentage of manual workers) of a town, and these factors may determine to some extent the increased risk of cardiovascular disease in manual workers. Blood pressure in individual subjects was affected predominantly by age, body mass index, and alcohol intake. Body mass index appeared to affect blood pressure to a greater extent than alcohol intake and did so with a consistent and positive linear trend. Nevertheless, the differences between towns in mean blood pressure readings appeared to be more closely associated with variations in the prevalence of heavy drinking than with variations in body mass index. Alcohol intake and body mass index explained only a part of the striking differences between towns in mean blood pressure readings, and some important townfactors remained unexplained.

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study.

Risk factors for major ischaemic heart disease (acute myocardial infarction or sudden death) have been investigated in a prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns. After a mean follow-up of 4.2 years, there have been 202 cases of major ischaemic heart disease. Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol, HDL-cholesterol and triglyceride concentrations, systolic and diastolic blood pressures, cigarette smoking, and body mass index are all associated with increased risk of ischaemic heart disease. Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease. All these factors were then considered simultaneously using multiple logistic models. Definite myocardial infarction on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease, after allowance for all other risk factors. Serum total cholesterol, blood pressure, and cigarette smoking each remained as highly significant independent risk factors whereas overweight, above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors. Men with and without pre-existing ischaemic heart disease were examined separately in the same way (using multiple logistic models). The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease, only age and serum total cholesterol remaining highly significant. Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease. Modification of these risk factors in the general population constitutes an important national priority.

British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality—namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0·25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1·7 mmol/l (170 mg/l), while any further increase in hardness beyond 1·7 mmol/l did not additionally lower cardiovascular mortality. Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.

Giving up smoking and the risk of heart attacks. A report from The British Regional Heart Study

In a prospective study of 7735 middle-aged men, both current and ex-cigarette-smokers had a risk of a major IHD event, within an average 6.2 years of screening, more than twice that in men who had never smoked cigarettes; men who had given up smoking more than 20 years ago still had an increased risk. This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure, serum total cholesterol, and body-mass index. An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk. In both current and former cigarette smokers, the number of years a man had smoked cigarettes (smoking-years) was the clearest indicator of IHD risk due to cigarettes. The major benefit of giving up smoking may lie in halting the accumulation of smoking years.

Effects of alcohol and smoking on blood lead in middle-aged British men.

A survey of middle-aged men in 24 British towns showed a strong association between blood lead concentrations, alcohol consumption, and cigarette smoking. The association with alcohol persisted after age, social class, body mass index, cigarette smoking, water lead concentrations, and the town of residence had been taken into account. There was an independent but less pronounced association between cigarette smoking and blood lead concentrations after adjustment for the other factors. The possible mechanisms include a decreased excretion of lead due to alcohol-induced hepatic dysfunction and an increased lead intake from cigarette smoking. These findings have implications for widespread measurement of blood lead concentrations in adults in the community and for all studies attempting to relate blood lead concentrations to environmental exposure.

Biochemical and Haematological Response to Alcohol Intake

In a clinical survey of 7735 middle-aged men, alcohol consumption has been related to 25 biochemical and haematological measurements obtained from a single blood sample. Most measurements showed some association with alcohol consumption, gamma-glutamyl transferase (GGT) being the most strongly associated. Lead, mean corpuscular haemoglobin (MCH), mean corpuscular volume, high-density lipoprotein-cholesterol (HDL-C), urate and aspartate transaminase also showed substantial associations with alcohol intake. Using a discriminant analysis technique, a simple score based on five variables (GGT, HDL-C, urate, MCH and lead) provided the best discrimination between heavy drinkers (e.g. more than three pints of beer daily) and occasional drinkers, but still failed to identify more than half of the heavy drinkers. This combined score may prove a useful measure of an individuals biochemical/haematological response to alcohol consumption for use in epidemiological and clinical studies of alcohol-related disorders. The use of such indices should complement but not replace measures of alcohol intake derived from questionnaires.

Blood lead concentration, blood pressure, and renal function.

Blood lead concentrations were related to blood pressure and indicators of renal function in a clinical survey of 7735 middle aged men from 24 British towns. There was no overall evidence that blood lead concentrations were associated with systolic or diastolic blood pressure (r = +0.03 and +0.01, respectively). In the 74 men with a blood lead concentration of 1.8 mumol/l (37.3 micrograms/100 ml) or more there was some suggestion of increased hypertension, but this did not reach significance. Blood lead concentration did not have any relation with serum creatinine concentration. Moderate increases in blood lead concentration were associated with small increases in mean serum urate concentration and small decreases in mean serum urea concentration; these associations were both reduced when alcohol consumption was taken into account. There is no indication that exposure to lead at concentrations commonly encountered in British men is responsible for impaired renal function or increased blood pressure.

Effects of tap water lead, water hardness, alcohol, and cigarettes on blood lead concentrations.

A survey of middle-aged men in 24 British towns has found pronounced geographical variation in blood lead concentrations. Towns with the highest mean blood lead concentrations have soft water supplies and have the highest water lead concentrations. Individual blood lead can be considerably increased by raised household tap water lead concentrations. Mean blood lead is estimated to be 43% higher for men when the concentration of lead in first-draw domestic tap water is 100 micrograms/l compared with a zero concentration. Individual blood lead is also affected by alcohol consumption and cigarette smoking, such that on average these two life-style habits together contribute an estimated 17% to the blood concentration of lead in middle-aged men. Lead in water should be given greater priority in any national campaign to reduce lead exposure.

Blood lead and blood pressure.

quinine, severe hypoglycaemia was not detected (p 1169) (Hall and Bhattacharya, unpublished). Quinidine has long been recognised to be at least as good a blood schizonticide as quinine. Recent studies in Thailand have shown both that this drug (the D-enantiomer ofquinine) is severalfold more active than quinine against P falciparum in vitro and that it may replace it for the treatment of uncomplicated infections (P Suntharasamai, S Vanijanond, T Harinasuta, et al, paper presented at 11th international congress of tropical medicine and malaria, Calgary, Canada, 1984). 0 The theoretical objection to quinidine is that it causes a greater prolongation of the Q-T interval than quinine, but it may be used to treat severe falciparum malaria.2 13 Again in Thailand, White and his team recommended a loading dose of quinidine of 15 mg base/kg followed by 7 5 mg base/kg every eight hours.3 They have not, however, done a controlled study ofintravenous quinine and intravenous quinidine. Quinine in the non-toxic doses used should normally be given for severe falciparum infections from areas other than Thailand (p 1169)2 (Hall and Bhattacharya, unpublished). Quinidine in equivalent doses should be used if quinine is not available in the hospital pharmacy. Preliminary reports suggest that an even more rapid schizonticidal response may follow the infusion of artesunate, a soluble derivative of the Chinese compound artemisinin. 14 There were 960 patients with falciparum malaria from Africa treated in Britain between 1983 and 1984 but only one patient from Thailand (Malaria Reference Laboratory reports). Supportive management of the life threatening complications of severe falciparum malaria include the reduction of hyperpyrexia, control of convulsions if present, exchange blood transfusion mentioned above, haemodialysis for anuric renal failure, and endotracheal intubation with intermittent positive pressure respiration for acute pulmonary oedema or severe coma (A P Hall, unpublished). Corticosteroids are now agreed to be contraindicated in the management of falciparum malaria.5 The careful maintenance of fluid balance is of vital importance, since fluid overload may precipitate acute pulmonary oedema with its serious prognosis.2 Malaria caused by some strains ofPfalciparum acquired in areas where chloroquine resistance is prevalent, and especially in South East Asia,3 may recrudesce after initial response to quinine or, less often, to quinidine. This problem may be avoided by concluding treatment with either a single dose of the pyrimethamine-sulfadoxine combination Fansidar in countries where this remains effective5 (Hall and Bhattacharya, unpublished) or a five to seven day course of tetracycline if resistance to this combination is present. 16