A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

OBJECTIVES: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP). BACKGROUND: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored. METHODS: IHD subjects with a positive exercise test were studied. Groups I and II (12 subjects each) underwent 2 successive Naughton protocol exercise echocardiography tests (with 1 min instead of 2 min stages for Group II). Group D (10 subjects) had type II diabetes, were on > or =10 mg daily of the K+-ATP blocker, glibenclamide, and underwent the group I exercise protocol. The ischemic threshold or rate-pressure product at 1 mm ST segment depression, ST depression corresponding to the peak rate-pressure product of the first exercise (maximum ST depression equivalent), and left ventricular wall motion indexes before and immediately after each exercise were analyzed. RESULTS: Exercise-induced myocardial ischemia with re-exercise was similarly attenuated in groups I, II, and D. The ischemic threshold was raised by nearly 20% with re-exercise (p=0.001, p=0.02, and p=0.02, respectively) and the maximum ST depression equivalent was nearly halved on re-exercise (p=0.005, p=0.006, and p=0.001, respectively). Exercise-induced wall motion dysfunction was attenuated with re-exercise. In group I, wall motion returned to the initial baseline score prior to exercise 2, whereas in the more intense protocol of group II, wall motion dysfunction persisted prior to exercise 2. CONCLUSIONS: Thus, the attenuation of myocardial ischemia observed with re-exercise appears to be independent of the intensity of the exercise protocol and is not explained by down-regulation of myocardial contractility induced by the initial ischemic stimulus. Since results were similar in diabetic subjects on robust doses of glibenclamide, this phenomenon does not appear to be mediated by K+-ATP activation.

Effect of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates.

The effects of gender, time variables, menstrual cycle phases, plasma sex hormone concentrations and physiologic urinary pH on CYP2D6 phenotyping were studied using two widely employed CYP2D6 probe drugs, namely dextromethorphan and metoprolol. Phenotyping on a single occasion of 150 young, healthy, drug-free women and men revealed that the dextromethorphan: dextrorphan metabolic ratio (MR) was significantly lower (P < 0.0001) in 56 female extensive metabolizers (0.008+/-0.021) compared to 86 male extensive metabolizers (0.020 +/-0.040). Urinary pH was a significant predictor of dextromethorphan: dextrorphan MRs in men and women (P < 0.001). Once-a-month phenotyping with dextromethorphan of 12 healthy young men (eight extensive metabolizers and four poor metabolizers) over a 1-year period, as well as every-other-day phenotyping with dextromethorphan of healthy, pre-menopausal women (10 extensive metabolizers and 2 poor metabolizers) during a complete menstrual cycle, did not follow a particular pattern and showed similar intrasubject variability ranging from 24.1% to 74.5% (mean 50.9%) in men and from 20.5% to 96.2% (mean 52.0%) in women, independent of the CYP2D6 phenotype (P = 0.342). Using metoprolol as a probe drug, considerable intrasubject variability (38.6+/- 12.0%) but no correlation between metoprolol: alpha-hydroxymetoprolol MRs and pre-ovulatory, ovulatory and luteal phases (mean +/- SD metoprolol: a-hydroxymetoprolol MRs: 1.086+/- 1.137 pre-ovulatory; 1.159+/-1.158 ovulatory and 1.002+/-1.405 luteal phase; P> 0.9) or 17beta-oestradiol, progesterone or testosterone plasma concentrations was observed. There was a significant inverse relationship between physiologic urinary pH and sequential dextromethorphan: dextrorphan MRs as well as metoprolol: alpha-hydroxymetoprolol MRs in men and women, with metabolic ratios varying up to six-fold with metoprolol and up to 20-fold with dextromethorphan (ANCOVA P < 0.001). We conclude that apparent CYP2D6 activity is highly variable, independent of menstrual cycle phases, sex hormones, time variables or phenotype. Up to 80% of the observed variability can be explained by variations of urinary pH within the physiological range. An apparent phenotype shift as a result of variations in urinary pH may be observed in individuals who have metabolic ratios close to the population antimode.

Hypertension in women.

Hypertension in women has received little attention in comparison to men. There are only a handful of studies focusing on women with hypertension. Nevertheless, the data provide some information on the prevalence of hypertension in women, complications and the effectiveness of treatment. The Framingham Study showed that blood pressure (BP) increased with age in both men and women. The Hypertension Detection and Follow-up Program study demonstrated that hypertension was much more prevalent in men than women. However, in the postmenopausal group more than half were hypertensive. High BP is prevalent in older women. In absolute values, the complication rate is lower in women than in men but increases with age. At all levels of BP, the morbidity and mortality associated with BP is lower in women than men. Nevertheless, there is a five- to sixfold increase in risk in hypertensive compared with normotensive women. Furthermore, hypertensive women with a myocardial infarction have a worse prognosis than men. No study data using newer agents such as calcium channel blockers and angiotensin-converting enzyme inhibitors are available yet. Since antihypertensive treatment appears to be effective in smokers, cessation of smoking is a very important intervention. Studies such as the European Working Party on Hypertension in Elderly, Systolic Hypertension in Elderly, Swedish Trial of Old Patients with Hypertension, and Medical Research Council 1992 have recruited patients 60 years of age and older, mainly women. These trials have shown that in the elderly hypertensive all-cause mortality is reduced by 30%, stroke by 33%, congestive heart disease mortality by 20% and heart failure by 40% to 50% with treatment. However, even these newer trials have used the so-called "old medications'. Studies using "newer drugs' are in progress.

Impact of systolic and diastolic blood pressure on ischemic vascular diseases in French-Canadian men from 1974 to 1990.

The relationships of systolic and diastolic blood pressure (BP) to ischemic heart disease (IHD), intermittent claudication (IC) and stroke were evaluated in 4385 men (aged 35 to 64 years in 1973) clinically free from these vascular diseases at entry and followed for 16 years. The mean of two readings measured in 1973-74 was used as the baseline BP. The cut-of for quintile 5 was systolic BP greater than 152 mmHg and diastolic BP greater than 92 mmHg. Relative risks (RR) were adjusted for main risk factors and calculated separately for systolic and diastolic BP. From 1974-90, 1120 first ischemic vascular events were documented: 792 IHD, 216 IC and 112 strokes. The incidences of each ischemic vascular disease increased, starting at quintile 4, for either systolic or diastolic BP. For systolic BP, the adjusted RR of quintile 5 compared with quintile 1 were 1.8 for IHD (95% confidence interval 1.4 to 2.2), 2.7 for IC (1.8 to 4.2) and 3.8 for stroke (2.1 to 7.0); for diastolic BP, the RR were 1.8 for IHD (1.5 to 2.3), 1.5 for IC (1.0 to 2.1) and 3.5 for stroke (2.0 to 6.4). For IHD, the RR of BP were similar for angina and myocardial infarction, and more pronounced for coronary death. In this population, elevated BP constitutes an important risk factor not only for stroke, but also for the main manifestations of IHD and IC. The impact of systolic BP was at least as significant as that of diastolic BP on these ischemic vascular events.

Importance of outside hospital mortality as a first acute ischemic heart event: the Quebec Cardiovascular Study.

Among 4371 men aged 35 to 64 in 1973 who were randomly selected, living in Quebec City suburbs, without clinical evidence of ischemic heart disease (IHD) at entry and followed for 16 years, 426 had a first acute IHD event; of these, 296 had a nonfatal myocardial infarction (MI), 50 a fatal MI (death within four weeks of the acute event) and 80 an early death, ie, they died before the diagnosis of MI was made. Among these 80 early deaths attributed to IHD in the absence of any other apparent cause, 55 men died within 1 h from the onset of symptoms or were found dead in their bed (group A) while 25 died more than 1 h after the onset of symptoms (group B). In this population, a first acute IHD event carried a 31% (130 of 426) case fatality within the first four weeks. Groups A and B accounted for 42% (55 of 130) and 19% (25 of 130) of the total acute ischemic mortality, respectively. As expected, fatal events increased with age, but the proportion of early deaths over the total IHD mortality was as frequent in younger men as in older men. Smoking, increased systolic and diastolic blood pressure and serum cholesterol were associated with increased nonfatal events. A similar association, except for serum cholesterol, was observed for all fatal events. No significant risk factor profile differentiated early from late fatal events. In conclusion, in this population, nearly a third of men with a first IHD event died, most of them outside the hospital. None of the main established risk factors differentiated men with a fatal MI from those with an early death.

First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study.

The incidence of first coronary heart disease (CHD) events was evaluated prospectively in relation to the baseline measurements of systolic and diastolic blood pressure, serum cholesterol, smoking status and education in a cohort of 4576 Quebec men aged 35 to 64 and free from CHD at entry in 1974. From 1974 to 1986, 603 first CHD events were documented. The most frequent first manifestation was angina (6.7/1000 person-years) followed by nonfatal myocardial infarction (4.7/1000) and CHD death 2.2/1000). There was a positive relationship between the first CHD event and systolic (Z = 4.67) and diastolic (Z = 6.50) blood pressure. This relation was observed for angina, nonfatal myocardial infarction and CHD death. Serum cholesterol was also related to all events (Z = 4.99) but more specifically to angina and nonfatal myocardial infarction. Cigarette smoking was significantly related to first CHD manifestations. This relationship for specific CHD events was observed in men who smoked more than 20 cigarettes per day. Men who discontinued smoking one year before the study had a risk not different from those who never smoked. No relationship was observed between years of schooling and CHD events. Blood pressure, cholesterol and smoking constituted nearly two-thirds of the attributable risk of first CHD events.

Smoking, alcohol consumption, lipid and lipoprotein levels.

The lipid profiles of 1165 French Canadian men (aged 42 to 59 years) were studied and related to drinking and smoking habits. Alcohol consumption and smoking were closely related, smokers consuming twice as much alcohol as non-smokers. When relative body weight, total cholesterol, triglyceride and alcohol consumption were controlled in a covariate analysis, plasma levels of high density lipoprotein (HDL) cholesterol, HDL2 and HDL3 differed significantly between smokers, ex-smokers and nonsmokers. Ex-smokers had higher levels of HDL cholesterol than nonsmokers who had higher levels than smokers. The higher levels of HDL in ex-smokers could be explained by the confounding effects of alcohol intake. Alcohol users had significantly higher levels of HDL cholesterol, HDL2 and HDL3 than nondrinkers. Men who drank the equivalent of more than 3 ounces of absolute alcohol per week had significantly higher levels of HDL cholesterol and HDL3 than those who drank less than 3 ounces or did not drink at all. HDL2 levels were only significantly different between nondrinkers and those who consumed more than 3 ounces per week. These results show that smoking and alcohol have strong but opposing effects on HDL and its subfractions in middle-aged French Canadian men.

Total and coronary heart disease mortality in relation to major risk factors--Quebec cardiovascular study.

The relationships of blood pressure, smoking, serum cholesterol and education levels on total and coronary artery disease (CAD) mortality were evaluated in 4576 Quebec men aged 35 to 64 years, free from overt CAD at entry and followed for 12 years. From January 1974 to January 1986, there were 417 deaths, 131 due to CAD. A progressive increase in total and CAD mortality was observed from quintile 3 to 5 for both systolic and diastolic blood pressure. In comparison to quintile 1, the adjusted relative risks of quintiles 4 and 5 for systolic blood pressure were significantly elevated (2 P less than 0.01), being 1.5 and 2.0 for total mortality, and 2.6 and 3.5 for CAD mortality, respectively. The relative risks of quintiles 4 and 5 for diastolic blood pressure were also significantly elevated (2 P less than 0.04), being 1.5 and 1.6 for total mortality and 1.9 and 2.7 for CAD mortality, respectively. In comparison to those who never smoked, the relative risks of smoking one to 20, and 21 and more cigarettes per day, were 2.1 (2 P less than 0.003) and 3.1 (2 P less than 0.0001) for overall mortality, and 2.2 (2 P less than 0.08) and 3.5 (2 P less than 0.002) for CAD mortality. Men who had discontinued smoking at least one year before the study, had a relative risk not different from those who had never smoked. Serum cholesterol and education levels were not significantly associated with total or CAD mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

[Control of arterial hypertension: effectiveness of an intervention performed by family practitioners]. / Le contrôle de l'hypertension artérielle: effet d'une intervention réalisée auprès des médecins de famille.

OBJECTIVE: To evaluate the effectiveness of a program to improve hypertension control practices in primary care. DESIGN: Retrospective quasi-experimental study. SETTING: Three hospital-based family medicine centres (FMCs) PARTICIPANTS: Two study groups of 100 randomly-selected adult patients each, who visited the study FMC before implementation of the hypertension program (from April 1, 1983 to March 31, 1984) or afterward (from April 1, 1986 to March 31, 1987). These patients were compared to patients from control FMCs A and B seen during the same time frames (100 patients before and after at FMC A and 60 at FMC B). INTERVENTIONS: 1) Educational sessions for physicians to standardize knowledge of the recommendations of the Canadian Hypertension Society on hypertension treatment and 2) specific operational incentives to improve hypertension control, including a reference guide placed in each physician's office, a specific hypertension follow-up form placed with each patient's chart, a recall card file, and hypertension information handouts. MAIN OUTCOME MEASURE: Blood pressure measurements recorded in patient charts. Hypertension control is determined from the Canadian Hypertension Society recommendations. RESULTS: The hypertension control rate was 52% in the study group before program implementation and 34.3% afterward (p = 0.01); the corresponding rates in the two control groups moved from 47.4% to 59.8% (p > 0.05) in Group A and from 40.7% to 39.3% (p > 0.05) in Group B. Patients listed in the recall card file were not controlled more frequently (33.3%) than those not listed (35.3%). CONCLUSION: This intervention did not improve physician practice regarding hypertension control. Clinicians did not follow the protocol as recommended. Physicians must be convinced that a change in their practice is needed before any specific strategies are introduced to support the change. Different suggestions and alternatives related to hypertension management are discussed.

Intermittent claudication in Quebec men from 1974-1986: the Quebec Cardiovascular Study.

The incidence and risk factors of intermittent claudication (IC) and its association with coronary heart disease were evaluated in a cohort of 4570 men, aged 35 to 64 in 1973, free of cardiovascular diseases and followed for 12 years. During the follow-up, 188 developed IC, an annual incidence of 41/10,000. The risk of IC increased with age. In comparison to the rest of the cohort, men with IC were older and had a higher prevalence of smoking, elevated blood pressure, and diabetes. Cigarette smoking was the predominant factor, quadrupling the risk of IC compared to those who never smoked, while those who stopped smoking one year before the study had a risk similar to non-smokers. Quintile 5 of systolic blood pressure doubled the risk of IC. Diabetes requiring a pharmacological treatment at entry in the study was significantly more prevalent in men with than in men without IC (7.5% vs 1.5%). There was no significant relationship between IC and serum cholesterol, body weight, or number of years at school. During the follow-up, 84 of the 188 men with IC had a coronary heart disease event, angina being the most frequent manifestation. Furthermore, 11% of men with IC died and in nearly two-thirds of these, death was attributable to coronary heart disease; this was twice the rate observed in the other men. In these Quebec men, IC is a common health problem and is associated with a high rate of coronary heart disease. Since IC is related to modifiable risk factors, primary prevention of these factors appears warrant.

Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine.

Caffeine consumption is extensive in industrialized countries and its role in drug-drug interactions is often overlooked. CYP1A2, the major cytochrome P450 isoform involved in the metabolism of caffeine, has also been implicated in the formation of N-hydroxymexiletine, the major metabolite of mexiletine. Therefore, the objective of this study was to assess the effects of a clinically relevant dosage of caffeine on the stereoselective disposition of mexiletine. Fourteen healthy volunteers--10 extensive metabolizers (EMs) and 4 poor metabolizers (PMs) of CYP2D6--received a single 200 mg oral dose of racemic mexiletine hydrochloride on two occasions (1 week apart): once by itself and once during administration of caffeine (100 mg four times daily). Serial blood and urine samples were collected and pharmacokinetic parameters were estimated. Although the total clearance of mexiletine was not significantly altered by the coadministration of caffeine in EMs and PMs, a stereoselective decrease (16% in EMs and 14% in PMs) in the urinary recovery of N-hydroxymexiletine from the R-(-)-enantiomer was observed. Also, the partial metabolic clearance of R-(-)-mexiletine to N-hydroxymexiletine glucuronide was reduced from 126 +/- 48 mL/min to 106 +/- 32 mL/min and 152.6 (73.4-196.2) mL/min to 109 (77-127) mL/min by the coadministration of caffeine in EMs and PMs, respectively. Consequently, the R/S ratio for urinary recovery and the partial metabolic clearance of mexiletine to N-hydroxymexiletine were 28% lower during the coadministration of caffeine. In conclusion, data obtained in this study indicate that coadministration of caffeine does not lead to clinically significant changes in mexiletine plasma concentrations. However, results obtained suggest that CYP1A2 is involved in the formation of N-hydroxymexiletine.

[Incidence of arterial hypertension in the Quebec region]. / Incidence d'hypertension artérielle dans la région de Québec.

The objectives of this study were to determine the incidence of high blood pressure (HBP) in Quebec suburbs and evaluate age, baseline blood pressure level and overweight as determinants of future hypertension. From a cohort of 4828 men, aged 35-64, screened in 1974, 1090 normotensives (blood pressure less than 160/95 mmHg without medication) free of cardiovascular disease were re-evaluated in 1979-1980. Among these 1090 men, 183 have developed a blood pressure greater than or equal to 160/95 mmHg or less than 160/95 mmHg associated with antihypertensive medication. There was no significant variation of the incidence by age (10-year strata). In the group of subjects with a baseline systolic blood pressure (SBP) between 140 and 159 mmHg the incidence of systolic hypertension was 6.3 times higher than in the group with baseline SBP less than 140 mmHg. Similarly, in the group of subjects with a baseline diastolic blood pressure (DBP) between 90 and 94 mmHg the incidence of diastolic hypertension was 3 times higher than in the group with a baseline DBP less than 90 mmHg. The incidence of HBP was correlated with overweight. Furthermore overweight was a highly prevalent risk factor in the study population. In summary, the incidence of HBP is 169 per 1000 in 5 years. Baseline blood pressure and overweight are strong determinants of a future HBP and can be used to identify the high risk subgroup.

[Physical fitness improves after mitral valve replacement]. / L'entraînement physique après un remplacement valvulaire mitral.

To determine whether women with mitral valve prostheses can improve their physical fitness without suffering cardiac dysfunction or hemolysis, 10 women (mean age 47 years) who had undergone mitral valve replacement (an average of 3.7 years earlier) were enrolled in an 8-week program of exercise on a bicycle ergometer. They exercised three times a week, starting at 60% and increasing to 80% of their maximal heart rate achieved during stress testing. Nine other women with similar clinical characteristics (mean age 48 years) constituted a control group. Exercise produced significant cardiovascular improvement, as evidenced by a mean decrease of 12 beats/min in the heart rate at steady-state work load (p less than or equal to 0.01), a mean increase of 121 kpm in the maximal tolerated work load (p less than or equal to 0.01), and a mean increase of 4 ml/kg X min-1 in the peak oxygen consumption (p less than or equal to 0.01). There was a small increase in the mean plasma hemoglobin level (15 to 29 mg/dl) and the mean reticulocyte count (1.8% to 2.4%) after the program (p less than or equal to 0.05). There were no significant changes in any of the variables studied in the control group. There were no changes in the clinical, electrocardiographic or echocardiographic findings in the experimental group. Although slightly increased hemolysis may occur, women with mitral valve replacement can improve their cardiovascular condition by exercising.

[Rehabilitation after aorto-coronary bypass and return to work]. / Réadaptation post-pontage aorto-coronarien et retour au travail.

In Quebec, deceptively few patients who have successfully undergone coronary artery bypass have been returning to work. Those aged 55 to 64 years, blue collar workers or those who were off work for 13 weeks or more were likely not to return to work after surgery. From Jan. 1, 1983, all patients aged 64 years and younger, who successfully underwent coronary artery bypass grafting were invited to attend a 6-week rehabilitation program, starting 6 weeks after operation. The aim of the program was to improve the rate of return to work through a low-intensity physical activity course (60% to 70% maximal working capacity and calisthenics ). Up to Mar. 31, 1984, 68 patients had participated in the program. The proportion of patients returning to work was significantly (p less than 0.01) improved and the trend was observed in all age groups, and for all types of employment and length of time off work before operation.

Lipid profile of a French-Canadian population: 1. Association of plasma lipid and lipoprotein levels with age, relative body weight and education.

Plasma lipid and lipoprotein levels were determined in a randomly selected population of 1169 French-Canadian men in the Quebec City area. The mean levels of total plasma cholesterol and triglycerides were 224.0 and 166.5 mg/dL respectively. The mean level of low-density lipoprotein cholesterol was higher and the mean level of high-density lipoprotein (HDL) cholesterol lower than those reported in a recent study in English-Canadian men. The mean HDL2 and HDL3 levels were lower than those reported in American men. Stratification of plasma triglyceride levels for all age groups showed that mean HDL2 levels decreased rapidly with moderate rises in triglyceride levels. Less than 9% of the variation in lipid or lipoprotein levels was related to age or relative body weight. Education had no significant effect on the levels.

Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina.

BACKGROUND: Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear. METHODS AND RESULTS: Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms. There were no significant differences between the 2 groups for any of the variables studied, although fibrinogen and F 1+2 tended to be slightly higher in the angina group (P = .09 for each). These significant correlations were present: age with fibrinogen, homocyst(e)ine, and vWF; factor VII with apo B, homocyst(e)ine, and TPA; apo B with TPA and CRP; CRP with fibrinogen, TPA, PAI-1, and factor VII; fibrinogen with vWF. CONCLUSIONS: Examination of atherogenic, hemostatic, inflammation, and genetic variables in the clinically quiescent state permitted no distinction between subjects with a previous isolated myocardial infarction in contrast to those with long-standing uncomplicated stable angina, favoring the notion that acute coronary events occur at random on a varying background of atherosclerosis. The multiple correlations found among these variables also underscore their complex interaction in the atherosclerotic process.

Blood pressure profile in two adult male populations.

Causal blood pressure measurements were recorded in two groups of men aged 40 to 64 years; of the 7024 men in metropolitan Saint John, NB, and the 4044 men in seven suburbs of Quebec who were asked, 5840 (83.1%) and 3097 (76.6%) respectively agreed to participate. Of the Saint John group 9.0% were taking antihypertensive drugs, as compared with only 3.3% of the Quebec group (p less than 0.0001). Among the treated subjects 33% in Saint John and 53% in Quebec still had a diastolic pressure greater than 95 mm Hg (p less than 0.01). Among the participants not taking antihypertensive drugs the systolic blood pressure increased with age, but the diastolic blood pressure increased only slightly up to 55 years of age and then decreased. On average the subjects in Saint John who were not being treated had a systolic pressure 6.2 mm Hg lower and a diastolic blood pressure 3.6 mm Hg lower than their Quebec counterparts (p less than 0.0001). This difference was observed in all the age groups and was not the result of the treatment of a greater proportion of the Saint John cohort. Despite the higher blood pressures and the smaller number receiving adequate treatment in the Quebec group, the rate of death due to coronary artery disease was 10% lower than that in the Saint John group. A bias in the data from Quebec may have influenced the magnitude of the differences between the two samples, but if present it should have underestimated the blood pressures in the Quebec group and therefore not have changed the outcome.