Cognitive function and blood rheology: results from the Caerphilly cohort of older men

OBJECTIVES: Vascular lesions are important contributors to cerebral disease, yet relatively little work has been done on relationships between haematological factors and cognitive function. We have explored these relationships in the Caerphilly cohort of older men. DESIGN: The development of vascular disease and the decline in cognitive function are being studied in a cohort of older men in Caerphilly, South Wales, UK. We have recorded a range of life-style, dietary, lipid, haematological and rheological factors which are, or may be, predictive of vascular disease. We have examined the relationships between these and both incident myocardial infarction and stroke, and identified factors relevant to cognitive function. SETTING: A community-based study based upon a representative population sample of older men. We collected data for the study from around 90% of the survivors of the original cohort. SUBJECTS: 2154 men who were aged 55-69 years at the time blood was taken for the haematological tests and cognitive function was tested. MAIN OUTCOME MEASURES: We present data from the AH4 test of general cognitive performance and from choice reaction time, a test of vigilance. RESULTS: There is a U-shaped relationship between haematocrit and cognitive function, the best cognitive function scores occurring at a mean haematocrit of 0.46. The relationship is significant for the choice reaction time (P < 0.05). The relationship between haematocrit and the AH4 test score is also curvilinear, but it is not significant. Plasma viscosity showed strong and robust relationships, with significantly better cognitive performance and faster reaction times at lower levels of viscosity (both relationships P < 0.001). Plasma fibrinogen concentration did not show any significant relationships with cognitive function. All these relationships are present, but are much weaker, with rheological tests that had been carried out 5 years before the cognitive testing. CONCLUSIONS: Blood rheology, as estimated by both haematocrit and plasma viscosity, is a significant determinant of cognitive function in older men. On the other hand, the thrombotic potential of blood, as indicated by fibrinogen level, shows no significant relationships. The relationships with rheology seem to be direct, presumably through blood flow at the time of testing, rather than through underlying long-term disease processes.     

Prevalence of ischaemic heart disease: the Caerphilly and Speedwell surveys.

Mortality from ischaemic heart disease remains high in the United Kingdom, and the present report describes the prevalence of the various epidemiological manifestations of the disease in two recent community studies with a common core protocol, each containing samples of over 2000 men, carried out in South Wales (Caerphilly) and the West of England (Speedwell, Bristol). The prevalence of electrocardiographic evidence of ischaemia was similar in the two communities--8.7% of men aged 45-49 years rising to 18.6% in men aged 55-59 years in the samples from South Wales, and 8.0% and 17.2% respectively in the Bristol population. The overall prevalence of angina was 7.7% in Caerphilly and 7.8% in Speedwell in men aged 45-59 years, but symptoms of severe chest pain were more commonly reported in South Wales than in Speedwell (10.1% compared with 6.3%). The data, however, suggested that the overall prevalence of ischaemic heart disease was very similar in the two areas. The prevalence of ischaemic heart disease was compared with that found in other population studies carried out in the United Kingdom and was higher than that found when employed men only were studied. There were substantial differences in mortality between the two areas; possible reasons for this are differences in community or medical services, smoking habit, or unemployment rates.     

Vascular disease and cognitive function: evidence from the Whitehall II Study

OBJECTIVES: : To test the hypothesis of an inverse association between indicators of vascular disease and cognitive function in the general, stroke-free population. DESIGN: : A longitudinal, British civil service-based cohort study. Measures of vascular disease examined were prevalent at baseline or traced over a median of 11 years, between Phases 1 (1985-1988) and 5 (1997-1999) of data collection. Cognitive function was assessed at Phase 5 of data collection. SETTING: : Twenty London-based Civil Service departments. PARTICIPANTS: : Four thousand one hundred forty-one men and 1,681 women, aged 46 to 68 when tested for cognitive function. MEASUREMENTS: : A battery of cognitive tests consisting of: memory test, Alice Heim 4, Mill-Hill, phonemic, and semantic fluency. RESULTS: : The occurrence of angina pectoris (P<.001), myocardial infarction (P=.02), all coronary heart disease (P<.001), and intermittent claudication (P=.004) was associated with poor cognitive function. These effects were independent of age and socioeconomic status. The association between indicators of vascular disease and cognitive function applied to the entire range of cognitive function measures examined in the study. CONCLUSION: : The findings support the view that vascular disease is predictive of poor cognitive function in the general population. The fact that presence of vascular disease was associated with diminished cognitive function even in a relatively young cohort has implications for the management of vascular disease.     

The natural history of prevalent ischaemic heart disease in middle-aged men.

OBJECTIVE: To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. METHODS: 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. RESULTS: At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event. CONCLUSIONS: Differing manifestations of prevalent ischaemic heart disease are associated with widely differing outcome, and the majority of middle-aged men in the community who have evidence of ischaemic heart disease short of myocardial infarction survive for 15 years without heart attack or stroke. The excess risk associated with myocardial infarction appears more persistent than that associated with angina and other ischaemic heart disease, remaining high even after 10 years of event-free survival.     

A population survey of cardiovascular disease in elderly people: design, methods and prevalence results.

A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unsuspected vascular disease: A potential limitation to the use of the intra-aortic balloon

Since vascular tortuosity or stenosis may preclude placement of the Intra-aortic balloon, 63 consecutive patients (37 men) having routine Judkins' cardiac catheterization had an aortogram prior to withdrawal of the last catheter. No patient had a history of claudication, palpable aneurysms, pulse deficit, or bruit. No complications occurred. Significant peripheral vascular disease was found in ten patients: three had aortic, one had iliac, and six had femoral stenosis or tortuosity. All were men. The age of patients with peripheral vascular disease was 61.4 ± 7.7 years, while those without were 56.9 ± 9.3 years (P = NS). No difficulty was encountered entering the femoral artery in any patient; there was difficulty advancing the catheter in five of ten (50%) patients with peripheral vascular disease and in three of 54 (6%) patients without (P < 0.002). Fifteen patients without peripheral vascular disease had normal coronary arteries, while none with peripheral vascular disease was normal. In patients with coronary disease, the number of vessels involved was the same in both groups. Peripheral vascular disease that might preclude placement of the Intra-aortic balloon occurs in 14% of patients undergoing cardiac catheterization and 18% of patients with coronary artery disease. Aortography may be safely performed and should be considered during routine cardiac catheterization in patients who may require Intra-aortic balloon placement.     

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.     

Prevalence and vascular associations with migraine in older Australians

Background: Migraine is a common disorder with recently described vascular associations, yet there are few Australian population-based data describing migraine prevalence.
Aims: To assess the prevalence and vascular associations with lifetime past history of typical migraine headache in a representative sample of older Australians.
Methods: The Blue Mountains Eye Study examined 3654 permanent residents aged 49 or older living in two postcode areas, west of Sydney (82.4% participation) during 1992–4. A structured interview was administered, including questions about past or present history of typical migraine. The diagnosis was consistent with International Headache Society criteria.
Results: A lifetime past history of typical migraine was given by 17% of participants, including 22% of women and 10% of men, a female:male ratio of 2.3:1. A marked trend for declining lifetime migraine frequency with increasing age was found for both sexes. Modest statistically significant associations were found with vascular disease history, after multivariate adjustment, which included vascular risk factors. These associations were stronger in men than in women. Among men, typical migraine was significantly associated with history of angina, odds ratio (OR) 2.0, acute myocardial infarction (OR 1.9) and stroke (OR 2.2). Among women, statistically significant associations were present only with history of myocardial infarct (OR 1.8).
Conclusions: These data indicate similar prevalence rates for lifetime typical migraine history in a representative sample of older Australians, compared to recent US and Canadian populations. Modest, statistically significant associations between typical migraine and past history of vascular disease were found, with the strongest associations found in men.     

Effect of repetitive episodes of exercise induced myocardial ischaemia on left ventricular function in patients with chronic stable angina: evidence for cumulative stunning or ischaemic preconditioning?

BACKGROUND: Myocardial stunning is known to occur following a single episode of effort angina in patients with coronary artery disease. The effect on left ventricular (LV) function of repeated episodes of ischaemia is unknown. OBJECTIVES: To investigate the effects of repeated episodes of exercise induced ischaemia on LV function in patients with chronic stable angina. METHODS: Patients with significant coronary artery disease and normal LV function underwent two episodes of symptom limited treadmill exercise separated by three different time intervals: either 30 minutes (group A, n = 14); 60 minutes (group B, n = 14); or 240 minutes (group C, n = 14). Quantitative stress echocardiography was performed at repeated intervals between the two exercises and for 240 minutes following the second test. RESULTS: For all groups there was no difference between the degree of ischaemia judged by maximal ST depression during the two tests. All episodes of exercise induced ischaemia produced prolonged abnormalities of LV systolic and diastolic function despite rapid normalisation of haemodynamic and ECG changes. In group A (30 minutes) these abnormalities were less pronounced after the second test than after the first, while in group B (60 minutes) they were more severe and long lasting. In group C (240 minutes) the two tests produced similar abnormalities of LV function. CONCLUSIONS: Prolonged abnormalities of LV function occurred following exercise induced ischaemia with a time course consistent with myocardial stunning. The severity and degree of LV dysfunction caused by a further episode of ischaemia appear to be dependent on the time interval between ischaemic episodes.     

Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease

Coronary heart disease in insulin-dependent (IDDM) and in non-insulin-dependent diabetes (NIDDM) is associated with lipid and lipoprotein changes favouring atherosclerosis. Whether lipid and lipoprotein abnormalities are associated also with peripheral vascular disease in both types of diabetes is largely unknown. Therefore, we studied lipid and lipoprotein levels and their association with claudication in a representative sample of diabetic and non-diabetic subjects in East Finland. Altogether 87 subjects had IDDM (43 men, 44 women), 264 subjects NIDDM (126 men, 138 women) and 120 subjects were non-diabetic controls (63 men, 57 women). Patients with IDDM had an increased level of HDL and HDL2-cholesterol and patients with NIDDM a decreased level of HDL and HDL2-cholesterol and an increased level of total, LDL and VLDL triglycerides than did non-diabetic subjects. Analyses in both types of diabetes by claudication status revealed that total and LDL-cholesterol and total and VLDL triglycerides tended to be higher and HDL and HDL2-cholesterol lower in those having claudication as compared to those without a claudication symptom. Similarly, total cholesterol/HDL-cholesterol ratio and LDL-cholesterol/HDL-cholesterol ratio were also more atherogenic in patients with claudication than in those without claudication. In conclusion, our results indicate that in both types of diabetes peripheral vascular disease is associated with lipid and lipoprotein abnormalities favouring atherosclerosis.     

Exercise Testing in the Detection of Severe Coronary Artery Disease

Summary: The clinical value of exercise testing in the detection of severe coronary artery disease remains undefined. This question was examined in 289 men and 45 women. The diagnosis of coronary artery disease could be reliably made without exercise testing in patients with angina pectoris which markedly restricted walking or which was accompanied by pathological Q waves on the ECG. Such patients usually had coronary artery disease involving two or three major vessels.
Exercise testing was an aid to diagnosis in patients with a normal standard ECG and chest pain suspicious of myocardial ischaemia, either mild angina or atypical. When exercise testing resulted in both angina and ST segment depression in men, coronary artery disease was present in 38 of 41 (93%) of cases. On the other hand, three vessel disease was found in only six of 100 (6%) of men whose exercise test did not evoke angina and ST segment change. A normal exercise test in a woman with suspicious chest pain and a normal ECG was associated with normal coronary arteries in 14 of 15 (93%) of cases. It may be concluded that exercise testing is of most diagnostic value in the assessment of patients with a normal standard ECG and a differential diagnosis of mild angina pectoris and atypical chest pain.     

Cytomegalovirus seropositivity and incident ischaemic heart disease in the Caerphilly prospective heart disease study

OBJECTIVE: To assess the role of cytomegalovirus (CMV) infection in primary ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from men in Caerphilly, south Wales, were analysed for IgG antibodies to CMV by enzyme linked immunosorbent assay and latex tests. Incident ischaemic heart disease events were ascertained after five and 10 years from death certificates, hospital records, and ECG changes; 195 incident ischaemic heart disease cases were compared with 216 controls of a similar age drawn from the rest of the cohort. RESULTS: 164 cases (84%) and 180 controls (83%) were seropositive for CMV. Optical density, an indicator of CMV antibody titre, was similar for cases and controls. Among controls, seropositivity was not associated with age, socioeconomic status currently or in childhood, smoking, height, body mass index, blood pressure, total cholesterol, fibrinogen, plasma viscosity, or leucocyte count. The unadjusted odds ratio relating CMV seropositivity to incident ischaemic heart disease was 1.06 (95% confidence interval 0.63 to 1.79) and was little changed (1.11, 0.63 to 1.97) after adjustment for age, smoking, body mass index, systolic blood pressure, total cholesterol, and socioeconomic status currently and in childhood. CONCLUSIONS: CMV infection is unlikely to be a strong risk factor for development of myocardial infarction in middle aged men.     

Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study.

OBJECTIVE--To measure the prevalence and incidence of intermittent claudication, to describe the mortality associated wtih the condition, and to assess the relevance of risk factors for vascular disease. DESIGN--A standard questionnaire on calf pain when walking was given in the prospective Speedwell study, and a range of risk factors were measured. The men were re-examined at intervals of three years, and deaths over 11 years were identified. SETTING--The general population. PARTICIPANTS--All men aged 45 to 59 registered with 16 general practitioners. RESULTS--The prevalence of intermittent claudication increased from almost nil at ages 45-49 to 2.9% at ages 60-64. The annual incidence increased from 0.3% in the youngest men to 0.5% in those in their early 60s. Intermittent claudication was related to the existence of ischaemic heart disease, particularly angina, at the first examination. The relative odds of men with angina developing intermittent claudication was 6.7 (95% confidence interval (95% CI) 3.6 to 12.4). The risk of death in men with intermittent claudication was substantially raised. After standardisation for age and smoking the relative odds of death was 3.8 (95% CI 2.2 to 6.5). The excess was entirely from circulatory causes. Systolic blood pressure, fasting plasma glucose, triglycerides, and white cell count were all independently associated with the development of intermittent claudication, but the most striking association was with smoking. CONCLUSIONS--Intermittent claudication is an indicator for a very high risk of death. This is only partly explained by its strong association with ischaemic heart disease.     

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.     

Adverse Prognosis of ST Depression on the Resting Electrocardiogram in Stable Patients Following Acute Myocardial Infarction

Background: The aim of this study was to analyze the characteristics of stable patients with resting ST segment depression on the resting electrocardiogram (ECG) following an acute ischemic event (i.e., infarction or unstable angina) to better understand its association with subsequent cardiac death and nonfatal infarction. The recent Multicenter Study of Myocardial Ischemia (MSMI) demonstrated that the resting ST segment depression had an independent prognostic value. Methods: We studied clinical features, noninvasive test results and coronary arteriography findings in 99 patients with ST depression on the resting ECG and 837 patients without ST segment depression with respect to endpoints of cardiac death and hospitalization for acute myocardial infarction or unstable angina. Results: Our results showed that patients with resting ECG ST depression were significantly older with a higher incidence of hypertension, angina, claudication, and tobacco use. ST depression on the resting ECG correlated closely with ST segment depression on the 24-hour ambulatory ECG and the exercise ECG but not with redistribution on the thallium perfusion scan. Left ventricular diastolic pressure was higher and exercise duration less in patients with ST depression. Although not achieving statistical significance, patients with ST depression did show more extensive coronary disease and a lower ejection fraction. Conclusions: ECG ST depression was associated with cardiac death and nonfatal reinfarction over the follow-up period only in patients originally admitted with an acute infarction but not in patients hospitalized for unstable angina. The reason for this appears to be an association of ST depression with increased age, the presence of hypertension, the presence of more severe coronary disease, and more extensive myocardial damage.     

Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study

Intermittent claudication has been reported in previous studies to approximately double the risk of subsequent mortality. However, a history of claudication is often present in the absence of significant peripheral arterial disease (PAD) and absent in the presence of PAD. For this reason we evaluated the association between large-vessel and small-vessel PAD, measured by highly reliable and valid noninvasive tests, and mortality in 567 older subjects from a defined population followed-up for an average of 4 years. Large-vessel PAD was strongly and significantly predictive of all-cause mortality in both men and women with a relative risk of 4 to 5, and this finding was independent of other cardiovascular disease risk factors in multivariable analysis. In addition, this finding persisted after exclusion of subjects with extant cardiovascular disease at baseline. The associations of both claudication and abnormal peripheral pulses with mortality were weaker than the large-vessel PAD association. Isolated small-vessel PAD was unrelated to subsequent mortality. These findings suggest older subjects of both sexes at a high risk of impending mortality can be identified through noninvasive testing for large-vessel PAD.     

QT dispersion, QT maximum and risk of cardiac death in the Caerphilly Heart Study.

BACKGROUND: It has been postulated that increased inter-lead differences in QT interval (QT dispersion) and the maximum QT interval (QTmax), in the standard 12-lead electrocardiogram (ECG), may be associated with an increased risk of cardiac death. The aims of this study were to assess the relationship between QT dispersion and QTmax, corrected and uncorrected for heart rate, and the risk of cardiac death. DESIGN: Nested case-control study within the Caerphilly prospective cohort study. METHODS: We studied 2512 men who participated in phase 1 of the Caerphilly study between 1979 and 1983. After a mean follow up of 7.1 years, 218 men had died from coronary heart disease and these men were compared with 218 age-matched controls. RESULTS: Data are presented on 422 patients with ECG suitable for analysis, 207 cases and 215 controls. Four trained observers measured the QT intervals and the reliability of each observer was estimated using repeat measurements on a randomly chosen sub-sample of ECGs. Median corrected QT dispersion and corrected QTmax were significantly higher in cases than in controls (51.9 versus 47.7 ms [P=0.01] and 430 versus 421 ms [P<0.001] respectively). In univariate analyses by quartiles of corrected QT dispersion and corrected QTmax, increased risk was largely confined to the upper quartile of the distribution with these subjects having twice the risk of those in the lower quartile [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.2-3.7 and 2.56 (95% CI 1.5-4.5) respectively]. In logistic regression analysis, adjusted for age, smoking, body mass index, hypertension, history of myocardial infarction and ECG Minnesota code, we observed an increased risk in the upper quartile of the corrected QT dispersion relative to the other three quartiles combined [adjusted OR=1.74 (P=0.03)]. The magnitude of this association was increased in analyses based on the data from the most reliable observers. The association between corrected QTmax and cardiac death was attenuated in multivariate analysis. The findings in relation to both uncorrected QT dispersion and uncorrected QTmax were similar, i.e., consistent with a significant independent effect of QT dispersion but not QTmax for cardiac death in multivariate analysis. CONCLUSION: The data suggest that QT dispersion is an independent predictor of cardiac death provided it can be measured with sufficient reliability. The association is non-linear with increased risk largely confined to the upper quartile of the distribution. The QT maximum is not an independent predictor of cardiac death.     

Exercise Testing in the Detection of Severe Coronary Artery Disease

Summary: The clinical value of exercise testing in the detection of severe coronary artery disease remains undefined. This question was examined in 289 men and 45 women. The diagnosis of coronary artery disease could be reliably made without exercise testing in patients with angina pectoris which markedly restricted walking or which was accompanied by pathological Q waves on the ECG. Such patients usually had coronary artery disease involving two or three major vessels. Exercise testing was an aid to diagnosis in patients with a normal standard ECG and chest pain suspicious of myocardial ischaemia, either mild angina or atypical. When exercise testing resulted in both angina and ST segment depression in men, coronary artery disease was present in 38 of 41 (93%) of cases. On the other hand, three vessel disease was found in only six of 100 (6%) of men whose exercise test did not evoke angina and ST segment change. A normal exercise test in a woman with suspicious chest pain and a normal ECG was associated with normal coronary arteries in 14 of 15 (93%) of cases. It may be concluded that exercise testing is of most diagnostic value in the assessment of patients with a normal standard ECG and a differential diagnosis of mild angina pectoris and atypical chest pain.     

Clinico-epidemiological characteristics of ischemic heart disease in men of different age groups from the data of a single screening of a random population

A total of 742 men, aged 20-69 and representative of a random male population from a Leningrad district, were investigated. The incidence of coronary disease was 3.2% in subjects aged 20-29, and 33.3% in those aged 60-69. In 40-49-year-olds, coronary disease was mostly manifested in angina of effort (57.9%), whereas painless forms reflected in ECG at rest prevailed (55-58.5% in men above 50 years of age. The frequency of ischemic response to the treadmill test increases with advancing age (8.3% in subjects aged 40-49 and 28.2% at age 60-69). The results of the WHO Questionnaire on Angina of Effort demonstrate that ECG at rest and exercise tests are mutually complementary procedures for epidemiologic diagnosis of coronary disease, their combination ensuring the fullest possible identification of coronary disease in population screenings.     

Noninvasive detection of coronary artery disease in patients presenting with claudication

ECG chest wall mapping with bicycle ergometry which can detect not only myocardial ischaemia but also individual coronary artery territories involved has been used to screen 100 consecutive patients presenting with claudication. Fifty-three had a positive history and/or evidence of ischaemic heart disease on a resting ECG. The test was positive in 38, negative in 38 and inconclusive in 24, the latter because of inadequate heart rate response. In 11 out of 38 (29%) with a positive test there was no history or evidence of myocardial ischaemia on a conventional resting ECG. ECG changes suggestive of three vessel coronary disease were found in three, single vessel coronary disease in 16 and two vessel disease in 19. Of the latter, eight had changes in the LAD/circumflex distribution, indicating left main stem or equivalent disease. These together with the three with triple vessel coronary disease constituted a subset of 11 (11%) high risk patients who merited coronary angiography with a view to confirming the presence of severe coronary disease.