Pre-existing Ischaemic Heart Disease Research Articles

Environmental tobacco smoke and ischaemic heart disease: a case study in applying causal criteria.

Whether ischaemic heart disease (IHD) is caused by exposure to environmental tobacco smoke (ETS), commonly known as "passive smoking", has been debated from both epidemiological and biological perspectives. In this paper we use Bradford Hill criteria to synthesize results from the biological and epidemiological literature in a formal assessment of the strength of support for such a relationship. Although we find that these criteria, designed for clinical trials, do not give an ideal framework for assessment of epidemiological and biological studies, nevertheless they do provide systematic guidance for this assessment. For the general population, of the nine tests proposed by Hill we find that one (biological plausibility) seems to be supported, though not unarguably; three (strength, consistency. specificity) appear to fail by accepted standards; and the remaining five have insufficient data for a clear evaluation (biological gradient, experimental evidence, temporality, coherence, analogy). Overall, this provides at best weak support for a causal association between ETS and IHD across the general community. Conversely, there appears to be more support, especially in the biology studies, for an association between ETS and IHD for those with preexisting disease, although epidemiological studies are limited in this area. One of the outcomes of this review is the identification of areas of focus for future epidemiological and biological research. First, we find that stronger associations may be found in the particular subpopulation with pre-existing IHD. In this case, more convincing biological plausibility and experimental evidence indicate a need for relevant epidemiological studies, although individual responses are very variable. Second, we identify the need for further, more detailed evaluations of the nature of vessel wall thickenings occurring in experimental models of ETS exposure. Third, we propose long-term animal studies of initiation of IHD, including direct assessment of effects on the accumulation of lipid in vessel walls, at appropriate ETS exposure levels.

Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error

Objective: To assess the influence of differential precision in the measurement of the correlated variables total cholesterol and high density lipoprotein (HDL) cholesterol on the estimates of the risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels. Design, setting and participants: The Caerphilly Heart Disease Study (CHDS), a prospective cohort study of 2512 middle-aged men living in the town of Caerphilly, south Wales, UK. The results from two sub-studies were used to estimate the degree of measurement imprecision (laboratory error and within-person variation) in triglycerides, total cholesterol and HDL cholesterol. Main outcome measures: Multivariable risk estimates for major IHD calculated from logistic regression analysis, adjusted and not adjusted for measurement imprecision. Major IHD events were defined as death from IHD, clinical non-fatal myocardial infarction or electrocardiographic myocardial infarction. Results: There were 261 men with major IHD events during follow-up. In age-adjusted analyses, taking measurement imprecision into account strengthened associations with IHD for all lipid factors. The odds ratio (OR) for one S.D. increase in triglycerides, ignoring measurement imprecision, was 1.36 (95% confidence interval [95% CI] 1.20–1.55) but 1.57 (95% CI 1.30–1.89) when taking imprecision into account. The standardised odds ratio for triglycerides adjusted for measurement imprecision and the two other lipid factors was 1.35 (95% CI 1.09–1.69). In this model, the triglyceride level showed a stronger association than total cholesterol (OR 1.28; 95% CI 1.05–1.56) and HDL cholesterol (OR for one S.D. decrease 1.20; 95% CI 0.97–1.49). When adding fasting blood glucose and diastolic blood pressure, however, the effect of triglycerides was reduced and ceased to be statistically significant (OR 1.19; 95% CI 0.95–1.49). This was further attenuated upon inclusion of body mass index, smoking status and history of pre-existing IHD. Total cholesterol remained a statistically significant ( P<0.05) risk factor in all models. Conclusions: In contrast to other cohort studies, triglyceride concentration in the CHDS shows an association with the risk of IHD which is independent of total and HDL cholesterol. This effect was pronounced after adjustment for measurement imprecision. It was reduced, however, when adjusted for other factors. While hypertriglyceridaemia may exert an influence independent of other lipid factors, insulin resistance is probably the underlying metabolic disturbance.

Abstracts of Literature

Abstracts of Literature

Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study.

Plasma fibrinogen is a consistent predictor of ischemic heart disease (IHD) in prospective studies, but there are fewer data relating other hemostatic variables to IHD and also to stroke. We therefore studied the relationships of plasma fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (TPA) antigen, factor VII, and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease. In the Edinburgh Artery study, 1592 men and women aged 55 to 74 years, randomly sampled from the general population, were followed prospectively over 5 years to detect fatal and nonfatal IHD and stroke events. During the 5 years, 268 new vascular events were identified. Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking, LDL-cholesterol, systolic blood pressure, and preexisting IHD (relative risk [RR] 1.52, 95% confidence interval [CI] 1.17, 1.98). TPA antigen, and fibrin D-dimer were also independently associated with risk of stroke (RR 1.69,95% CI 1.22,2.35 and RR 1.96, 95% CI 1.12,3.41, respectively). Significant relationships were found between TPA antigen and myocardial infarction (P < or = .05). In older men and women, increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events (both IHD and stroke).

Hematocrit and Risk of NIDDM

There is limited evidence that raised hematocrit levels may be associated with insulin resistance, which links cardiovascular disease with NIDDM. The association between hematocrit level at screening and the subsequent development of physician-diagnosed NIDDM during 12.8 years of follow-up was examined in a prospective study of 7,735 middle-aged men drawn at random from general practice in 24 British towns. With the exclusion of men with missing hematocrit data and men with diabetes at screening, data were available for 7,193 men, in whom there were 187 new cases of NIDDM during follow-up. The risk of NIDDM increased significantly with increasing hematocrit levels. There was more than a fourfold increase in relative risk (RR) of diabetes among men with a hematocrit of > or = 48% relative to those with a hematocrit <42%, adjusted for age and BMI (RR 4.5; 95% CI 2.5-6.3). On further adjustment for predictors of NIDDM with which hematocrit is correlated, there remained a strong linear association with the risk of diabetes. There was a nearly fourfold increased risk of NIDDM in the highest relative to the lowest hematocrit group in the fully adjusted proportional hazard model (RR 3.6; 95% CI 1.7-7.6). The strong positive association between hematocrit level and risk of diabetes was seen even after exclusion of men with preexisting ischemic heart disease. The findings suggest that a raised hematocrit level, which is a major determinant of whole blood viscosity, should be added to the cluster of risk factors that link NIDDM with atheromatous, vascular disease.

Blood pressure and cancer in middle-aged British men.

This paper examines the relationship between blood pressure and cancer mortality. A prospective study of 7735 middle-aged men drawn at random from one general practice in each of 24 British towns. During a mean follow-up period of 12.75 years there were 351 deaths from cancers. The relationship between blood pressure and cancer differed with respect to follow-up period. In the first 5 years of follow-up, a significant inverse relationship was seen between systolic (SBP) and diastolic blood pressure (DBP) and cancer mortality even after adjustment for age, smoking, social class, physical activity, alcohol intake, body mass index, diabetes, pre-existing ischaemic heart disease, use of antihypertensive drugs, cholesterol, heart rate and serum albumin. In the subsequent follow-up period (5.1-12.75 years) a significant positive association was seen between SBP (but not DBP) and risk of cancer mortality, even after adjustment for the other risk factors. Men in the top fifth of SBP ( > or = 161 mmHg) showed over a 50% increase in risk of cancer mortality compared to men in the bottom quintile (RR = 1.56 95% CI 95% CI: 1.04-2.38). This positive relationship between SBP and cancer was seen only in current cigarette smokers. Use of antihypertensive drugs was not associated with cancer mortality. The association of elevated SBP with increased risk of cancer mortality seen only in current smokers warrants the search for factors which affect SBP, interact with smoking and are potentially carcinogenic.

Respiratory Function and Risk of Stroke

This report examines the relationship between lung function and risk of major stroke events (fatal and nonfatal). We completed a prospective study of 7735 men aged 40 to 59 years at screening selected at random from one general practice in each of 24 British towns. During the mean follow-up period of 14.8 years, there were 277 major stroke events in the 7650 men with data on forced expiratory volume in 1 second (FEV1). After exclusion of 499 men with definite myocardial infarction, stroke, or atrial fibrillation at screening, 7151 men experienced 239 major stroke events. Lower levels of FEV1 were associated with a significant increase in risk of stroke even after adjustment for age, smoking, social class, physical activity, alcohol intake, systolic blood pressure, antihypertensive treatment, diabetes, and preexisting ischemic heart disease. Relative risk in the low third (< 3.10 L) versus high third (> 3.65 L) was 1.4 (95% confidence interval, 1.0 to 2.0). The inverse association between FEV1 and stroke was only apparent in older men, current nonsmokers, hypertensive men, and men with preexisting ischemic heart disease. Lower FEV1 was associated with higher rates of stroke in hypertensive men irrespective of smoking status. Inclusion of FEV1 in a risk score for stroke provided only a small increase in the absolute risk or the yield of cases in the top fifth of the score distribution during the follow-up period. Lower levels of FEV1 are associated with an increased risk of stroke in those already at high risk, eg, those with ischemic heart disease or hypertension. However, the association is not strong enough to warrant the use of FEV1 in making clinical decisions regarding the treatment of hypertension as it relates to the prevention of stroke.

Gamma-glutamyltransferase: Determinants and Association with Mortality from Ischemic Heart Disease and All Causes

The association of serum levels of gamma-glutamyltransferase (GGT) with cardiovascular disease risk factors, and with mortality from all causes, cardiovascular disease, and non-cardiovascular diseases, has been examined in a prospective study of 7,613 middle-aged British men followed for 11.5 years. GGT levels were strongly associated with all-cause mortality, largely due to a significant increase in deaths from ischemic heart disease and other non-cardiovascular disease causes, i.e., non-cancer deaths, in the top quintile of the GGT distribution. No association was seen with cancer mortality. However, GGT was significantly (positively) associated with alcohol intake, body mass index, smoking, preexisting ischemic heart disease, diabetes mellitus, antihypertensive medication, systolic and diastolic blood pressure, total and high density lipoprotein cholesterol, heart rate, and blood glucose, and negatively associated with physical activity and lung function (forced expiratory volume in 1 second (FEV1)). After adjustment for these personal characteristics and biologic variables, elevated GGT (highest quintile > or = 24 unit/liter vs. the rest) was still associated with a significant increase in mortality from all causes (relative risk (RR) = 1.22, 95% confidence interval (CI) 1.01-1.42; n = 818 deaths) and from ischemic heart disease (RR = 1.42, 95% CI 1.12-1.80; n = 332 deaths). The increase in other non-cardiovascular disease causes was of marginal significance (RR = 1.45, 95% CI 0.95-2.20; n = 127 deaths). When examined separately by the presence or absence of preexisting ischemic heart disease, the increased risk of ischemic heart disease mortality was more marked in those with evidence of ischemic heart disease at screening, particularly in those with previous myocardial infarction (RR = 1.67, 95% CI 1.03-2.69; n = 84 deaths). The increased risk of other non-cardiovascular disease deaths was only seen in men without preexisting ischemic heart disease, largely due to an excess of hepatic cirrhosis. In summary, many factors other than alcohol intake are associated with increased levels of GGT, in particular body mass index, diabetes mellitus, and serum total cholesterol. The finding of increased risk of ischemic heart disease mortality seen in men with preexisting ischemic heart disease is related to the severity of the underlying myocardial damage. The biologic significance of raised GGT in men with preexisting ischemic heart disease merits further study.

Risk factors for sudden cardiac death in middle-aged British men.

Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (> or = 90 beats per minute), physical activity (all, P < .05), and, to a lesser extent, smoking (P = .06), HDL cholesterol (P < .07), and elevated hematocrit (> or = 46%, P < .09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non-sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD.

Serum sodium concentration and risk of stroke in middle-aged males

Clinical disturbances of the circulating sodium concentration are both a cause and a consequence of cerebrovascular disease. We examined the relationship between serum sodium level and risk of stroke and major ischaemic heart disease in a prospective study of 7690 middle-aged males drawn from general practices in 24 British towns followed over a 9.5-year period. The mean serum sodium level was 141.5 mmol/l and 375 males on antihypertensive treatment were excluded from the analyses. A significant inverse trend was seen between serum sodium and risk of stroke up to 144 mmol/l; above this the risk of stroke was increased. Those with levels of 143-144 mmol/l showed over a 70% reduction in risk of stroke compared with those with levels of < or = 140 mmol/l. The inverse relationship between sodium and stroke up to 144 mmol/l was seen in males with and without pre-existing ischaemic heart disease or stroke, in normotensives and untreated hypertensives, and in non-smokers and current smokers. A weak but significant inverse association was seen between serum sodium and diastolic but not systolic blood pressure. The association between serum sodium level and stroke remained significant after adjustment for diastolic blood pressure and other factors associated with stroke: age, smoking, social class, body mass index, physical activity, heavy drinking, presence of diabetes, blood glucose and pre-existing ischaemic heart disease. No association was seen between serum sodium level and risk of ischaemic heart disease after adjustment for other risk factors. All-cause and non-cardiovascular mortality were significantly increased at serum sodium levels of < or = 138 mmol/l, probably due to an association between lung cancer and hyponatraemia. These findings suggest that sodium concentration may be related to risk of stroke even at levels of sodium usually regarded as normal.

Does non-diabetic hyperglycemia predict future ihd? Evidence from the caerphilly and speedwell studies

We have examined the risk of subsequent ischemic heart disease (IHD) in men according to their initial fasting plasma glucose level in a prospective cohort study (Caerphilly Collaborative Study) of 4860 middle aged men from South Wales and Bristol, U.K. Ninety-four men reported themselves to be diabetic at initial screening and fasting venous plasma glucose levels were determined in these men and in a further 4519 non-diabetic men. At follow-up new IHD events occurred twice as commonly in diabetics compared to non-diabetics and overall mortality was increased 4-fold. Among non-diabetics however, increased IHD events only occurred in men with fasting values at the upper end of the distribution of baseline plasma glucose values [at 6.8 mmol/l (122 mg/dl) or more]. This association was reduced, but remained statistically significant, after adjusting for factors associated with plasma glucose levels; body mass index, plasma triglyceride, smoking habit and pre-existing IHD. In conclusion there is no evidence of a consistent, graded increase in risk of IHD by initial fasting plasma glucose level although the risk is significantly increased in men with baseline plasma values at 6.8 mmol/l (122 mg/dl) or more, and also in diabetics. This study suggests that such levels probably represent a pre-diabetic state in many individuals. Appropriate non-pharmacological intervention may be useful in halting the progression to the diabetic state, although this should be tested in experimental studies.

Haematocrit, hypertension and risk of stroke.

To assess the relationship between haematocrit and risk of stroke. Prospective study of a cohort of men followed up for 9.5 years. General practices in 24 towns in England, Scotland and Wales (British Regional Heart Study). A total of 7735 men aged 40-59 years at screening, selected at random from one general practice in each of 24 towns. Fatal and non-fatal strokes. During a follow-up period of 9.5 years for all men there were 123 stroke events (33 fatal) in the 7346 men in whom the haematocrit level had been determined. In the cohort as a whole, risk of stroke was significantly raised at haematocrit levels > or = 51% (relative risk [RR] = 2.5; 95% confidence intervals [CI] 1.2-5.0) after adjustment for age, social class, smoking, body mass index, physical activity, presence of diabetes and pre-existing ischaemic heart disease. Further adjustment for systolic blood pressure did not attenuate this association (RR = 2.4; 95% CI 1.2-4.9). A raised haematocrit was associated with an increase of stroke only in men with hypertension (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 90 mmHg or on regular antihypertensive treatment). No increased risk of stroke was seen at the higher haematocrit level (> or = 51%) in normotensive men. At haematocrit levels below 51%, hypertension was associated with a three-fold increase in risk of stroke compared with normotension (RR = 3.4, 95% CI 2.3, 5.1). At haematocrit levels > or = 51%, hypertension was associated with a nine-fold increase in risk of stroke compared with normotension (RR = 9.3; 95% CI 4.2, 21.0). Exclusion of men receiving regular antihypertensive therapy did not alter the strong associations seen. The data suggest that an elevated haematocrit is an independent risk factor for stroke and that it interacts synergistically with elevated blood pressure.

Heart rate, ischaemic heart disease, and sudden cardiac death in middle-aged British men.

To examine the relation between resting heart rate and new major ischaemic heart disease events in middle aged men with and without pre-existing ischaemic heart disease. Prospective study of a cohort of men with eight years follow up for cardiovascular morbidity and mortality for all men. General practices in 24 British towns (the British Regional Heart study). 7735 men aged 40-59 years drawn at random from the age-sex registers of one general practice in each town. Major ischaemic heart disease events such as sudden cardiac death, other deaths attributed to ischaemic heart disease, and non-fatal myocardial infarction. During the follow up period of eight years, 488 men had a major ischaemic heart disease event (217 fatal and 271 non-fatal). Of these, 117 were classified as sudden cardiac death (death within one hour of the start of symptoms). The relation between heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease deaths, and sudden cardiac death was examined separately in men with and without pre-existing ischaemic heart disease. In men with no evidence of ischaemic heart disease, there was a strong positive association between resting heart rate and age adjusted rates of all major ischaemic heart disease events (fatal and non-fatal), ischaemic heart disease deaths, and sudden cardiac death. This association remained significant even after adjustment for age, systolic blood pressure, blood cholesterol, smoking, social class, heavy drinking, and physical activity, with particularly high risk in those with heart rate > or = 90 beats/min. The increased risk seen in those with increased heart rate was largely due to a significantly increased risk of sudden cardiac death, which was five times higher than in those with heart rate < 60 beats/min. The effect of heart rate on sudden cardiac death was present irrespective of blood pressure or smoking state. In men with pre-existing ischaemic heart disease a positive association was seen between raised heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease death, and sudden cardiac death, but the effect was less noticeable than in men without pre-existing ischaemic heart disease. In this study of middle aged British men increased heart rate > or = 90 beats/min) is a risk factor for fatal ischaemic heart disease events but particularly for sudden cardiac death. The effect is not dependent on the presence of other established coronary risk factors and is most clearly seen in men free of pre-existing ischaemic heart disease at initial examination.

Alcohol and sudden cardiac death.

To assess the relation between alcohol intake and sudden cardiac death--ie, death within one hour of the onset of symptoms. Prospective study of a cohort of men followed up for eight years. General practices in 24 towns in England, Wales, and Scotland. 7735 men aged 40-59 at screening who were selected at random from one general practice in each of 24 towns. All deaths from ischaemic heart disease with particular reference to those that were sudden (death within one hour of the onset of symptoms). During the follow up period of eight years there were 217 deaths from ischaemic heart disease of which 117 (54%) were classified as sudden. Although heavy drinkers (more than six drinks daily) did not show a high incidence rate of fatal heart attack, they showed the highest incidence rate of sudden cardiac death. This was seen in both manual and non-manual workers and was most clearly seen in older (50-59) men. Death from ischaemic heart disease was more likely to be sudden in heavy drinkers than in other drinking groups; this phenomenon was seen irrespective of the presence or degree of pre-existing ischaemic heart disease. The positive association between heavy drinking and the incidence of sudden death was most apparent in men without pre-existing ischaemic heart disease, with heavy drinkers showing an increase of > 60% compared with occasional or light drinkers. After adjustment for age, social class, and smoking, heavy drinkers free of pre-existing ischaemic heart disease had a marginally significantly higher incidence rates of sudden death than other drinkers combined (relative risk 2.00, 95% confidence interval 0.98 to 4.8). Additional adjustment for systolic blood pressure reduced the risk to 1.7. This study suggests that heavy drinking is associated with an increased risk of sudden death. Studies that do not take pre-existing ischaemic heart disease into account are likely to underestimate the adverse effects of heavy drinking on the incidence of sudden death because the effects are not as evident in men with pre-existing ischaemic heart disease.

Physical activity and stroke in British middle aged men.

To assess the relation between physical activity and stroke and to determine the overall benefit of physical activity for all major cardiovascular events. Prospective study of a cohort of men followed up for 9.5 years. General practices in 24 towns in England, Wales, and Scotland (British regional heart study). 7735 men aged 40-59 at screening, selected at random from one general practice in each of 24 towns. Fatal and non-fatal strokes and heart attacks. 128 major strokes (fatal and non-fatal) occurred. Physical activity was inversely associated with risk of stroke independent of coronary risk factors, heavy drinking, and pre-existing ischaemic heart disease or stroke (relative risk 1.0 for inactivity, 0.6 moderate activity, and 0.3 vigorous activity; test for trend p = 0.008). The association remained after excluding men reporting regular sporting (vigorous) activity. However, vigorous physical activity was associated with a marginally significant increased risk of heart attack compared with moderate or moderately vigorous activity in men with no pre-existing ischaemic heart disease or stroke (relative risk 1.6%; 95% confidence interval 0.96 to 2.8). In men with symptomatic ischaemic heart disease or stroke those doing moderately vigorous or vigorous activity had a risk of heart attack slightly higher than that in inactive men (relative risk = 1.6; 0.8 to 3.3). Moderate physical activity significantly reduces the risk of stroke and heart attacks in men both with and without pre-existing ischaemic heart disease. More vigorous activity did not confer any further protection. Moderate activity, such as frequent walking and recreational activity or weekly sporting activity, should be encouraged without restriction.

Physical activity and ischaemic heart disease in middle-aged British men.

To assess the relation between reported physical activity and the risk of heart attacks in middle aged British men. Prospective study of middle-aged men followed for a period of eight years (The British Regional Heart Study). One general practice in each of 24 British towns. 7735 men aged 40-59 years at initial examination. Heart attacks (non-fatal and fatal). During the follow up period of eight years 488 men suffered at least one major heart attack. A physical activity score used was developed and validated against heart rate and lung function (FEV1) in men without evidence of ischaemic heart disease. Risk of heart attack decreased significantly with increasing physical activity; the groups reporting moderate and moderately vigorous activity experienced less than half the rate seen in inactive men. The benefits of physical activity were seen most consistently in men without preexisting ischaemic heart disease and up to levels of moderately vigorous activity. Vigorously active men had higher rates of heart attack than men with moderate or moderately vigorous activity. The relation between physical activity and the risk of heart attack seemed to be independent of other cardiovascular risk factors. Men with symptomatic ischaemic heart disease showed a reduction in the rate of heart attack at light or moderate levels of physical activity, beyond which the risk of heart attack increased. Men with asymptomatic ischaemic heart disease showed an increasing risk of heart attack with increasing levels of physical activity, but with a progressive decrease in case fatality. Overall, men who engaged in vigorous (sporting) activity of any frequency had significantly lower rates of heart attack than men who reported no sporting activity. However, when all men reporting regular sporting activity at least once a month were excluded from analysis, there remained a strong inverse relation between physical activity and the risk of heart attack in men without pre-existing ischaemic heart disease. This study suggests that the overall level of physical activity is an important independent protective factor in ischaemic heart disease and that vigorous (sporting) exercise, although beneficial in its own right, is not essential in order to obtain such an effect.

Risk factors for stroke in middle aged British men.

To determine the risk factors for stroke in a cohort representative of middle aged British men. Prospective study of a cohort of men followed up for eight years. General practices in 24 towns in England, Wales, and Scotland (the British regional heart study). 7735 men aged 40-59 at screening, selected at random from one general practice in each town. Fatal and non-fatal strokes. 110 of the men had at least one stroke; there were four times as many non-fatal as fatal strokes. The relative risk of stroke was 12.1 in men who had high blood pressure (systolic blood pressure greater than or equal to 160 mm Hg) and were current smokers compared with normotensive, non-smoking men. Diastolic blood pressure yielded no additional information, and former cigarette smokers had the same risk as men who had never smoked. Heavy alcohol intake was associated with a relative risk of stroke of 3.8 in men without previously diagnosed cardiovascular disease. Men with pre-existing ischaemic heart disease had an increased risk of stroke, but only when left ventricular hypertrophy on electrocardiography was also present. Systolic blood pressure, cigarette smoking, and left ventricular hypertrophy on electrocardiography in men with pre-existing ischaemic heart disease were found to be the major risk factors for stroke in middle aged British men. Heavy alcohol intake seemed to increase the risk of stroke in men without previously diagnosed cardiovascular disease. A large proportion of strokes should be preventable by controlling blood pressure and stopping smoking.

The J-shaped relationship between coronary heart disease and achieved blood pressure level in treated hypertension: further analyses of 12 years of follow-up of treated hypertensives in the Primary Prevention Trial in Gothenburg, Sweden

The relationship between the blood pressure level achieved through antihypertensive treatment and the incidence of coronary heart disease (CHD) was studied in 686 middle-aged hypertensive men. The patients studied came from a random population sample and were followed-up for 12 years, yielding a total of 6563 patient-years for the study. Eighty-seven patients suffered a non-fatal myocardial infarction or died from CHD. The incidence of CHD showed a J-shaped distribution in relation to achieved treated systolic and diastolic blood pressure levels. The incidence of CHD, adjusted for entry characteristics, age, serum cholesterol, blood pressure and smoking habits, decreased with reductions in blood pressure achieved through treatment, to a level of about 150/85 mmHg, below which the incidence rate again increased. This J-shaped pattern was also observed when data from patients with pre-existing signs or symptoms of ischemic heart disease at entry were excluded. Using a quadratic term as the best fit to the observed relationship between achieved treated diastolic blood pressure level and the incidence of CHD, a Cox regression analysis showed that the nadir of the J-shaped incidence curve was at a diastolic blood pressure value of 81 mmHg. There did not seem to be any association between the absolute size of the blood pressure reduction during treatment and the incidence of CHD. Although we cannot exclude the possibility that the increased incidence of CHD in patients with a low treated blood pressure is due primarily to pre-existing but subclinical ischemic heart disease, our findings indicate that an excessive lowering of blood pressure in hypertensive patients may be harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of risk factors in heart attacks occurring in men with pre-existing ischaemic heart disease.

The importance of three risk factors--serum total cholesterol, systolic blood pressure, and cigarette smoking--on the risk of new major ischaemic heart disease events in men who already have evidence of ischaemic heart disease was assessed. Data from the initial examination in a large prospective study of cardiovascular disease in middle aged men (the British Regional Heart Study) were used to separate 7710 men into three groups on the basis of a resting electrocardiogram, a standardised chest pain questionnaire, and recall of a doctor's diagnosis of angina or of a previous heart attack: (group 1) no evidence of ischaemic heart disease (75%), (group 2) evidence of ischaemic heart disease short of a definite myocardial infarction (20%), (group 3) definite myocardial infarction (6%). In the average follow up period of 7.5 years, 443 men suffered a new major event caused by ischaemic heart disease (fatal or non-fatal myocardial infarction or sudden cardiac death). Age standardised event rates were determined for each of the three groups for varying levels of the established risk factors. Cigarette smoking is strongly associated with the event rate in group 1 but in men with existing heart disease, especially group 3, differences in risk between the smoking categories were smaller. The strong relation between systolic blood pressure and event rate persisted in groups 1 and 2 but not in group 3. The positive association between serum concentration of total cholesterol and the event rate was strongest in group 1 and weaker in groups 2 and 3, though it remained highly significant. These observations, taken together with the results of previous prospective studies and intervention trials, suggest that the important association between serum total cholesterol and the risk of heart attack persists in men with pre-existing ischaemic heart disease, including myocardial infarction. Therefore, in these men the reduction of serum total cholesterol concentration may be at least as important as it is in men without evidence of ischaemic heart disease.

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.