Self-reported long-standing psychiatric illness as a predictor of premature all-cause mortality and violent death: a 14-year follow-up study of native Swedes and foreign-born migrants

The present study focuses on the associations between self-rated long-standing psychiatric illness, ethnicity, all-cause mortality and violent death (accidents and suicide), in a sample of 39,155 Swedish-born and foreign-born individuals. The study was designed as a longitudinal follow-up study, covering the period between 1 January 1979 and 31 December 1996. The data were analysed by a proportional hazard model and the results are given as hazard ratios (HR) with 95% confidence intervals (CI). Self-reported long-standing psychiatric illness was a strong risk factor for total mortality: women had an HR of 2.13 (CI = 1.78-2.54) and men an HR of 1.84 (CI = 1.53-2.21), when adjusted for background factors such as country of birth, civil status and socio-economic factors. Finnish men had an increased risk of all-cause mortality compared to Swedes in the final model, when adjusted for socio-economic factors. Long-standing psychiatric illness was also a strong risk factor for violent death, with an HR of 3.51 (CI = 2.32-5.32). The risk of violent death was 2.4 times higher for men than for women. The conclusions of the present study are that self-reported long-standing psychiatric illness is a strong predictor of an increased all-cause mortality and increased mortality from violent death. The increased age-adjusted mortality risk for foreign-born men could be explained by disadvantaged social and economic conditions. Only Finnish men demonstrated an independent increased all-cause mortality risk.     

Chronotropic response to exercise. Improved performance of ST-segment depression criteria after adjustment for heart rate reserve

BACKGROUND: Heart rate (HR) response to exercise plays an important role in the diagnosis of coronary artery disease (CAD). Adjustment of ST-segment depression for the change in HR with exercise increases the accuracy of the exercise ECG in the detection of CAD. In addition, an attenuated HR response to exercise, a manifestation of chronotropic incompetence, may have independent diagnostic value for CAD. METHODS AND RESULTS: The diagnostic value of adjusting the magnitude of ST-segment depression, the ST-segment (ST)/HR index, and the ST/HR slope for chronotropic response to exercise was assessed in 283 control subjects and 337 patients with CAD by dividing each ST measurement by the fraction of HR reserve achieved. At a matched specificity of 96%, ST-segment depression of > 160 microV identified CAD with a sensitivity of 52%, an ST/HR index of > 1.69 microV/bpm identified CAD with a sensitivity of 90%, and an ST/HR slope of > 2.96 microV/bpm identified CAD with a sensitivity of 88%. Adjustment for HR reserve improved the sensitivity of each method: adjusted ST-segment depression of > 176 had a sensitivity of 87% (P < .0001), an adjusted ST/HR index of > 2.14 had a sensitivity of 94% (P = .005), and an adjusted ST/HR slope of > 3.47 had a sensitivity of 93% (P = .0001). In addition, the 94% and 93% sensitivities of the adjusted ST/HR index and ST/HR slope were significantly greater than the 87% sensitivity of adjusted ST-segment depression (P < .0001). CONCLUSIONS: Correction for an attenuated HR response to exercise improves performance of the simple and HR-adjusted ST-segment depression criteria for the identification of CAD. These findings support assessment of the degree of chronotropic reserve in routine evaluation of the exercise ECG.     

Relation of exercise-induced myocardial ischemia to cardiac and carotid structure

There is a strong relation of carotid atherosclerosis to coronary artery disease and left ventricular hypertrophy. In addition, abnormalities of carotid structure are strongly associated with abnormal left ventricular geometry and structure. However, little is known regarding the relation of exercise-induced ST depression to carotid atherosclerosis, carotid, or left ventricular structure in the absence of apparent coronary disease. The relationship of exercise ECG myocardial ischemia to the presence of carotid atherosclerosis and to carotid and left ventricular structure was assessed in 204 asymptomatic subjects free of clinical evidence of cardiovascular disease. Myocardial ischemia on the exercise ECG, defined by a chronotropically adjusted ST/HR slope of >3.47 microV/bpm, was associated with a nearly threefold greater likelihood of discrete carotid atherosclerosis (50% [6 of 12] versus 17% [29 of 192], P=.007) and with older age, male sex, higher systolic and diastolic blood pressures, greater left ventricular mass and mass index, and greater common carotid artery intimal-medial thickness and cross-sectional area index. Stepwise logistic regression analyses, including standard risk factors, revealed that only carotid artery cross-sectional area index (P=.0007) and systolic blood pressure (P=.005) independently predicted an abnormal chronotropically adjusted ST/heart rate slope. Moreover, among 132 subjects with > or = 10 microV of ST-segment depression, only left ventricular mass index and carotid artery cross-sectional area index were significant predictors of the chronotropically adjusted ST/heart rate slope response. Subendocardial ischemia on the exercise ECG is strongly associated with the presence of carotid atherosclerosis and is related to systolic blood pressure, carotid artery cross-sectional area index, and left ventricular mass index, independent of age, sex, and other cardiac risk factors. These findings provide additional insights into the relation between coronary and carotid atherosclerosis and suggest that an association among ischemia and left ventricular and carotid structural abnormalities may contribute to the pathogenesis of coronary events.     

Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death

OBJECTIVES: This study examined the relations of echocardiographically determined left ventricular (LV) mass and hypertrophy to the risk of sudden death. BACKGROUND: Echocardiographic LV hypertrophy is associated with increased risk for all-cause mortality and cardiovascular disease morbidity and mortality. However, little is known about the association of echocardiographic LV hypertrophy with sudden death. METHODS: We examined the relations of LV mass and hypertrophy to the incidence of sudden death in 3,661 subjects enrolled in the Framingham Heart Study who were > or =40 years of age. The baseline examination was performed from 1979 to 1983 and LV hypertrophy was defined as LV mass (adjusted for height) > 143 g/m in men and > 102 g/m in women. During up to 14 years of follow-up there were 60 sudden deaths. Cox models examined the relations of LV mass and LV hypertrophy to sudden death risk after adjusting for known risk factors. RESULTS: The prevalence of LV hypertrophy was 21.5%. The risk factor-adjusted hazard ratio (HR) for sudden death was 1.45 (95% confidence interval [CI] 1.10 to 1.92, p=0.008) for each 50-g/m increment in LV mass. For LV hypertrophy, the risk factor-adjusted HR for sudden death was 2.16 (95% CI 1.22 to 3.81, p=0.008). After excluding the first 4 years of follow-up, both increased LV mass and LV hypertrophy conferred long-term risk of sudden death (HR 1.53, 95% CI 1.01 to 2.28, p=0.047 and HR 3.28, 95% CI 1.58 to 6.83, p=0.002, respectively). CONCLUSIONS: Increased LV mass and hypertrophy are associated with increased risk for sudden death after accounting for known risk factors.     

Cardiac outcome in patients with subarachnoid hemorrhage and electrocardiographic abnormalities

OBJECTIVE: Approximately 25% of patients with subarachnoid hemorrhage (SAH) have electrocardiographic (ECG) abnormalities consistent with myocardial ischemia or myocardial infarction (MI), and their cardiac prognosis remains unclear. The objective of this study was to determine the cardiac and all-cause mortality rate of a series of patients with SAH with ECG changes consistent with ischemia or MI. METHODS: Using an existing database of patients with SAH and predetermined ECG criteria for ischemia or MI, a study group of patients with abnormal ECG results within 3 days of presentation and before aneurysm surgery was identified. Database patients without abnormal ECG results served as a control group. Cardiac mortality, defined as death resulting from arrhythmia, congestive heart failure, or cardiogenic shock, was assessed by chart review. RESULTS: Of 439 patients with SAH in the database, 58 met the criteria for the study group. Forty-one of these patients were treated neurosurgically. No deaths resulting from cardiac causes occurred, and 20 patients died as a result of noncardiac causes. In a multivariable analysis, age older than 65 years and Hunt and Hess grade of at least 3 were predictive of all-cause mortality. ECG abnormalities, however, were not a statistically significant predictor. CONCLUSION: In patients with SAH and ECG readings consistent with ischemia or MI, the risk of death resulting from cardiac causes is low, with or without aneurysm surgery. The ECG abnormalities are associated with more severe neurological injury but are not independently predictive of all-cause mortality.     

Mortality from major causes of death and its risk factors in the elderly--26-year follow-up study in Hisayama

The authors studied mortality from major causes of death and risk factors in the elderly in a long-term prospective survey conducted in a Japanese suburban community, Hisayama. In the baseline survey in 1961, we scrutinized 1658 residents of the town aged 40 years or older accounting for 92% of the total population in this age range. Of those, 591 residents (245 men and 346 women) aged 60 years or older, who were free from major cardiovascular disease, were selected for the present study. They were followed-up for 26 years from 1961 to 1987. The average age was 67 years for men and 70 years for women, being significantly higher for women than for men. During the follow-up period, 529 subjects (89.5%) died, and 448 were autopsied (autopsy rate 84.7%). The all-cause mortality (per 1,000 person-years) after adjustment for age was 89.9 for men and 56.7 for women, the former being significantly higher than the latter (p < 0.01). The age-adjusted mortality from cerebrovascular disease was estimated to be 21.4 for men and 9.9 for women, i.e. 8.9 and 8.8 from heart disease, and 19.9 and 10.6 from neoplasm, and 18.1 and 12.2 from-pneumonia, respectively. There was significant sex difference in mortality from cerebrovascular disease, neoplasm and pneumonia (p < 0.01) but not from heart disease (p > 0.1). Multiple Cox's proportional hazards regression analysis showed systolic blood pressure and male sex to be significant risk factors for death by cerebrovascular disease. Systolic blood pressure was also a predictor for death by heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of ventricular arrhythmia in hypertensive patients

OBJECTIVE: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. However, no clinical study demonstrated a significant relation between ventricular arrhythmias and mortality in systemic hypertension. DESIGN AND METHODS: To evaluate the prognostic value of arrhythmogenic markers in systemic hypertension, we included between 1987 and 1993. 214 hypertensive patients, 59.1 +/- 12.8 years old, without symptomatic coronary disease, myocardial infarction, systolic dysfunction, electrolyte disturbances or antiarrhythmic therapy. At inclusion, an ECG, a 24 h Holter ECG (204 patients) with Lown classification of ventricular arrhythmias, an echocardiography (reliable in 187 patients) with left ventricular mass index and ejection fraction calculation, a SAECG (125 patients, enrolled after 1988) with ventricular late potentials (LP) were recorded. QT interval dispersion (QTd) was calculated on 12 leads standard ECG and LVH was appreciated. RESULTS: At baseline echocardiographic LVH was recorded in 63 patients (33.7%) with normal ejection fraction (75 +/- 7.4%). Non-sustained ventricular tachycardia (Lown IVb) was found in 33 pts (16.2%) and LP in 27 patients (21.6%). After a mean follow up of 42.4 +/- 26.8 months, all-cause mortality was 11.2% (24 patients); 17 patients died of cardiac causes (7.9%); of these 9 patients (4.2%) died suddenly. In univariate analysis, age, strain pattern of LVH, advanced Lown classes and abnormal QT dispersion (> 80 ms) were significantly related to global, cardiac and sudden death (p < or = 0.01). Left ventricular mass index was closely related to cardiac mortality (p = 0.002). LP failed to predict mortality. In multivariate analysis, only Lown class IVb was an independent predictor of global and cardiac mortality, increasing the risk of global death 2.6 fold [1.2-6.0] (CI 95%) and the risk of cardiac death 3.5 fold [1.2-9.7] (CI 95%). CONCLUSIONS: In hypertensive patients the presence of non-sustained ventricular tachycardia on 24 h Holter has a prognostic value.     

Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal chromosome 11q

-The aim of the present study was to assess the effects of high heart rate on mortality in different subgroups in a French population according to age, gender, and blood pressure levels. We studied 19 386 subjects (12 123 men, 7263 women), aged 40 to 69 years, who had a routine health examination at the Centre d'Investigations Préventives et Cliniques (IPC) between 1974 and 1977. Heart rate (HR) measured by ECG was classified into 4 groups: HR1, <60; HR2, 60 to 80; HR3, 81 to 100; and HR4, >100 bpm. Mortality data were recorded for the period of 1974 through 1994. In both sexes, HR was a significant predictor of noncardiovascular mortality. In men, the relative risk (95% confidence interval) for cardiovascular death after adjustment for age and other risk factors in the HR2, HR3, and HR4 groups was 1.35 (1.01 to 1.80), 1.44 (1.04 to 2.00), and 2.18 (1.37 to 3.47), respectively, when compared with HR1. In women, HR did not influence cardiovascular mortality. The association of HR with cardiovascular mortality in men was (1) related to a strong association with coronary but not cerebrovascular mortality, (2) independent of age and hypertension, and (3) influenced by the level of pulse pressure; in patients with high pulse pressure (>65 mm Hg), accelerated HR was not associated with increased cardiovascular mortality. In conclusion, in a large French population, accelerated resting HR represents an independent predictor of noncardiovascular mortality in both genders, and of cardiovascular mortality in men, independent of age and the presence of hypertension. Further investigations are needed to explain the complex interactions between HR, pulse pressure, and cardiovascular complications.     

Association between depressive symptoms and mortality in older women. Study of Osteoporotic Fractures Research Group

BACKGROUND: Major depression is associated with increased mortality, but it is not known whether patients who report depressive symptoms have greater mortality. SUBJECTS AND METHODS: We performed a prospective cohort study of 7518 white women 67 years of age or older who were recruited from population-based listings in Baltimore, Md, Minneapolis, Minn, Portland, Ore, and the Monongahela Valley, Pa. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. Women were followed up for an average of 6 years. If a participant died, we obtained a copy of the official death certificate and hospital records, if available, and used International Classification of Diseases, Ninth Revision, codes to classify death attributable to cardiovascular, cancer, or noncancer, noncardiovascular cause. RESULTS: Mortality during 7-year follow-up varied from 7% in women with no depressive symptoms to 17% in those with 3 to 5 symptoms to 24% in those with 6 or more symptoms of depression (P<.001). Of 473 women (6.3%) with 6 or more depressive symptoms at baseline, 24% died (111 deaths in 2610 woman-years of follow-up) compared with 11% of women who reported 5 or fewer symptoms of depression (760 deaths in 41 460 woman-years of follow-up) (P<.001). Women with 6 or more depressive symptoms had a 2-fold increased risk of death (age-adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.75-2.61; P<.001) compared with those who had 5 or fewer depressive symptoms. This association remained strong after adjusting for potential confounding variables, including history of myocardial infarction, stroke, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, smoking, perceived health, and cognitive function (HR, 1.47; 95% CI, 1.14-1.88; P=.003). Depressive symptoms were associated with an increased adjusted risk of death from cardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.5; P= .003), and non-cancer, noncardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.7; P = .01), but were not associated with deaths from cancer (HR, 1.0; 95% CI, 0.6-1.7; P=.93). CONCLUSIONS: Depressive symptoms are a significant risk factor for cardiovascular and noncancer, noncardiovascular mortality but not cancer mortality in older women. Whether depressive symptoms are a marker for, or a cause of, life-threatening conditions remains to be determined.     

The main causes of death in Spain, 1992; comment

BACKGROUND: To study the mortality from the leading causes of death in Spain in 1992 and trends since 1980. POPULATION AND METHOD: The number of deaths was obtained from mortality statistics. We included the 12 causes with the highest mortality rates in 1992 and calculated for each cause of death the age adjusted mortality rates for each year in the study period, the percent change from 1990 to 1992 and from 1980 to 1992, and the adjusted ratio of rates between men and women in 1992. RESULTS: The leading causes of death in 1992 were malignant neoplasms, with 24.3% of deaths and a mortality rate of 205.6 per 100,000 population; diseases of the heart, with 22.6% and a rate of 191.8 per 100,000; and cerebrovascular disease, with 12.7% and a rate of 107.6 per 100,000 population. Between 1980 and 1992 the adjusted mortality rate increased for four causes of death: malignant neoplasms; chronic obstructive pulmonary disease and similar diseases; nephritis, nephrotic syndrome and nephrosis; and suicide. From 1990 to 1992, the adjusted mortality rate declined for all other causes of death. From 1990 to 1992, the adjusted mortality rate declined for all causes of death except for malignant neoplasms and human immunodeficiency virus (HIV) infection, which rose 0.4% and 69%, respectively. The adjusted mortality rate was higher in men than in women for all causes of death except for diabetes mellitus and atherosclerosis. CONCLUSIONS: Except for malignant neoplasms and HIV infection, mortality from all other leading causes of death declined in 1992 with respect to 1990, independently of the trend experienced by each cause of death in the eighties.     

Brain alcohol detectability increase with repeated administration in humans: a proton spectroscopy study

BACKGROUND AND PURPOSE: There is evidence that an allelic variation in the angiotensin-converting enzyme (ACE) gene may confer an increased risk of vascular disease. The roles of the ACE insertion/deletion polymorphism and circulating ACE levels are unknown in cerebrovascular disease. METHODS: We studied an insertion/deletion polymorphism within intron 16 of the ACE gene by polymerase chain reaction and plasma ACE activity in 467 cases of stroke, the pathological type of which was established by cranial CT, and 231 control subjects. ACE genotype and activity were related to stroke type and mortality at 4 weeks and 3 months. RESULTS: No difference in genotype frequency was observed between all subjects with stroke and control subjects or between control subjects and subjects with cerebral infarction or cerebral hemorrhage. Plasma ACE activity was significantly lower in stroke patients at presentation (64.1 IU/L) than in control subjects (79.6 IU/L; P<.0001). Twenty-one patients (4.5%) with cerebral infarction died within 4 weeks and 56 patients (12%) within 3 months. These patients had significantly lower plasma ACE activity than patients who survived. There was some evidence that risk of death within 4 weeks increased with the number of D alleles (P=.02). Among survivors, plasma ACE activity showed a mean increase of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels at presentation and at 3 months (73.6 IU/L), the latter being similar to ACE activity in control subjects. CONCLUSIONS: Low ACE activity at sroke presentation and possession of the D allele may be associated with increased risk of early death from acute cerebral infarction.     

Rarity of colorectal adenomas in the African black population

CONTEXT: Early risk stratification of patients with myocardial infarction is critical to determine optimum treatment strategies and enhance outcomes, but knowledge of the prognostic importance of the initial electrocardiogram (ECG) is limited. OBJECTIVE: To assess the independent value of the initial ECG for short-term risk stratification after acute myocardial infarction. DESIGN: Retrospective analysis of the Global Utilization of Streptokinase and t-PA (alteplase) for Occluded Coronary Arteries (GUSTO-I) clinical trial database. SETTING: A total of 1081 hospitals in 15 countries. PATIENTS: From the 41 021 patients enrolled in the overall study, we selected those who presented within 6 hours of chest pain onset with ST-segment elevation and no confounding factors (paced rhythms, ventricular rhythms, or left bundle-branch block) on the ECG performed before thrombolysis was administered (n=34 166). MAIN OUTCOME MEASURE: Ability of initial ECG to predict all-cause mortality at 30 days. RESULTS: Most ECG variables were associated with 30-day mortality in a univariable analysis. In a multivariable analysis combining the initial ECG variables and clinical predictors of mortality, the sum of the absolute ST-segment deviation (both ST elevation and ST depression: odds ratio [OR], 1.53; 95% confidence interval [CI], 1.38-1.69), ECG, heart rate (OR, 1.49; 95% CI, 1.41-1.59), QRS duration (for anterior infarct: OR, 1.55; 95% CI, 1.43-1.68), and ECG evidence of prior infarction (for new inferior infarct: OR, 2.47; 95% CI, 2.02-3.00) were the strongest ECG predictors of mortality. A nomogram based on the multivariable model produced excellent discrimination of 30-day mortality (C-index, 0.830). CONCLUSIONS: In patients presenting with myocardial infarction accompanied by ST-segment elevation, components of the initial ECG help predict 30-day mortality. This information should be valuable in early risk stratification, when the opportunity to reduce mortality is greatest, and may help in assessing outcomes adjusted for patient risk.     

Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke

BACKGROUND AND PURPOSE: Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men. METHODS: We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up. RESULTS: The median serum creatinine concentration was 98 micromol/L (95% range, 76 to 129 micromol/L). Stroke risk was significantly increased at levels above 116 micromol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; > 116 micromol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 micromol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; > or = 130 micromol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (> or = 116 micromol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality. CONCLUSIONS: A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.     

Survival and incidence of myocardial infarction in men with ambulatory ECG-detected frequent and complex ventricular arrhythmias. 10 year follow-up of the 'Men born 1914' study in Malm?, Sweden

AIM: To assess to what extent do frequent or complex ventricular arrhythmias, detected during 24 h ambulatory electrocardiographic recording (ECG), influence prognosis with regard to survival and incidence of ischaemic heart disease. METHODS AND RESULTS: The study subjects were the 456 randomly selected men born in 1914, the population-based cohort study of 1982-83, in Malm?, Sweden. The main outcome measures were total mortality and incidence of cardiac event (myocardial infarction and death from ischaemic heart disease). Frequent or complex ventricular arrhythmias (Lown classes 2-5) were detected in 49% of the men with (n = 77), and in 35% of those without, a history of myocardial infarction or angina pectoris at baseline, P = 0.019. Independent of clinically evident coronary artery disease at baseline, and after adjustment for traditional atherosclerotic risk factors and use of digitalis or beta-blocker therapy, frequent or complex ventricular arrhythmias were associated with an increased mortality from ischaemic heart disease (relative risk (RR), 2.1; 95% confidence interval (CI), 1.2-3.9) and an increased cardiac event rate (RR, 1.6; 95% CI, 1.0-2.5)). Men free from both ischaemic-type ST depression and frequent or complex ventricular arrhythmias (used as the control group) had the lowest ischaemic heart disease death rate, 5.9 per 1000 person-years. The combination of ST depression and frequent or complex ventricular arrhythmias was associated with an ischaemic heart disease death rate of 20.9 per 1000 person-years. The cardiac event rate in these two groups was 15.6 and 76.1 per 1000 person-years, respectively (adjusted RR, 2.3; CI, 1.1-4.6). CONCLUSIONS: In elderly men without a history of myocardial infarction and angina pectoris, frequent or complex ventricular arrhythmias during ambulatory ECG recording is associated with an increased incidence of myocardial infarction and mortality. Men who, during ambulatory ECG recording, also demonstrate ST-segment depression have an even less favourable prognosis.     

Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study

BACKGROUND: Several recent studies have suggested that calcium antagonist drugs, which are widely used for the treatment of hypertension, are associated with increased risk of cardiovascular disease. These studies have cast doubts on the long-term safety of calcium antagonists. OBJECTIVE: To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study. SUBJECTS AND METHODS: We stratified 3539 subjects (mean+/-SD age, 64+/-13 years) from the Framingham Heart Study who had hypertension at routine clinic examinations, according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination. At each follow-up examination (every 2-4 years), subjects were reclassified with regard to the use of calcium antagonists. The end point of the study was all-cause mortality. Hazard ratios and 95% confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models. RESULTS: There were 970 deaths during follow-up. Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 (95% confidence interval, 0.72-1.21; P=.59) for subjects with hypertension without coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P=.58) for those with coronary heart disease at baseline. All models were adjusted for age, sex, current smoking, systolic and diastolic blood pressure, use of beta-blockers, and use of other antihypertensive medications. CONCLUSIONS: In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not. Results were similar among subjects with hypertension with and without coronary heart disease. The results of ongoing long-term, randomized clinical trials will provide more definitive data on the safety of calcium antagonists.     

Temporal variability of asymptomatic embolization in carotid artery stenosis and optimal recording protocols

BACKGROUND AND PURPOSE: Although asymptomatic embolization can be detected in patients with carotid artery stenosis, its temporal variability is unclear. An understanding of this is important in designing optimal recording protocols for future prospective studies of the predictive value of embolic signals (ES). We determined the effect of repeating and extending recording times in patients with symptomatic and asymptomatic carotid stenosis. METHODS: In 20 asymptomatic and 20 symptomatic subjects with > 60% carotid stenosis, we used transcranial Doppler ultrasound to record for ES in the ipsilateral middle cerebral artery. Three 1-hour recordings were performed on three separate days, and on one occasion (not necessarily the first) the recording was extended to 2 hours. The recordings were saved onto digital tape for subsequent blinded analysis. RESULTS: Marked temporal variability was seen in symptomatic patients in whom the cumulative proportion of subjects with ES increased from 10 (50%) after a single hour of recording to 12 (60%) and 15 (75%) after two and three recordings, respectively. Extending the recording to 2 hours increased the yield of ES-positive patients from 6 (30%) to 8 (40%). In symptomatic patients there was excellent agreement between whether patients were positive for ES during each of two consecutive 1-hour recordings (kappa = 0.78, P = 0.0003) but poor agreement between the results of two single-hour recordings performed on different days (kappa = 0.22, P = 0.27). In asymptomatic patients, 4 (20%) were ES positive during the first hour; this increased to 5 (25%) after the recording was repeated once, with no further increase after the third recording. Extending the recording to 2 hours increased the yield from 3 (15%) to 7 (35%). In contrast to symptomatic stenoses, in patients with asymptomatic stenoses there was fair agreement between whether patients were ES positive on two consecutive 1-hour recordings (kappa = 0.49, P = 0.01) or two single-hour recordings performed on different days (kappa = 0.48, P = 0.02). Symptomatic subjects were more likely to have ES (when all 1-hour recordings were considered, 24/60 versus 10/60; P = 0.0046). ES in symptomatic subjects had a higher relative intensity increase than in asymptomatic subjects (P = 0.01). CONCLUSIONS: The temporal variability of ES needs to be taken into account in the design of optimal recording protocols and comparisons of results from different studies. Extending the duration of recording beyond an hour in symptomatic stenoses is of less value, but repeating the recording on a different day will often identify additional subjects with ES. In intervention studies in symptomatic patients, the time since last symptoms must be considered. In asymptomatic stenosis, extending the duration of recording beyond an hour will increase the proportion of patients positive for ES.     

Mortality after the treatment of hyperthyroidism with radioactive iodine

BACKGROUND: Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS: We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS: During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS: Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.     

Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study

OBJECTIVE: To describe the long term effects of the use of oral contraceptives on mortality. DESIGN: Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was "flagged" on the NHS central registers. SETTING: 1400 general practices throughout Britain. SUBJECTS: 46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years. MAIN OUTCOME MEASURES: Relative risks of death adjusted for age, parity, social class, and smoking. RESULTS: Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use >/= 10 years previously there were no significant excesses or deficits either overall or for any specific cause of death. CONCLUSION: Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.     

Arrhythmias documented by 24-hour continuous ambulatory electrocardiographic monitoring in young women without apparent heart disease

Results are reported of 24-hour ambulatory ECG recordings in 50 young women without apparent heart disease. During waking periods, maximum (sinus) rates ranged from 122 to 189 beats/min (bpm) (153 +/- 14 mean +/- SD) and minimum rates from 40 to 73 bpm (56 +/- 7). During sleeping periods, maximum and minimum rates ranged from 71 to 128 bpm (105 +/- 13) and from 37 to 59 bpm (48 +/- 6), respectively. Thirty-two subjects (64%) had atrial premature beats, with only one subject (2%) having greater than 100 beats/24 hrs. Twenty-seven subjects (54%) had ventricular premature beats, with only three subjects (6%) having greater than 50 beats/24 hrs. One subject (2%) had one three-beat episode of ventricular tachycardia. Two subjects (4%) had transient type I second-degree atrioventricular block.     

Adverse prognostic value of a blunted circadian rhythm of heart rate in essential hypertension

BACKGROUND: Previous studies revealed a direct association between resting heart rate and risk of mortality in essential hypertension. However, resting heart rate is a highly variable measure since it is affected by the alerting reaction to the visit. OBJECTIVE: To investigate whether the heart rate values recorded during the 24 h of ambulatory blood pressure monitoring are independent predictors of survival of uncomplicated subjects with essential hypertension. METHODS: We followed up 1942 initially untreated and uncomplicated subjects with essential hypertension (mean age 51.7 years, 52% men) for an average of 3.6 years (range 0-10 years). All subjects underwent baseline procedures including 24 h non-invasive blood pressure monitoring with simultaneous assessment of heart rate, one reading every 15 min for 24 h. MAIN OUTCOME MEASURES: All-cause mortality and cardiovascular morbidity. RESULTS: During follow-up there were 74 deaths from all causes (1.06 per 100 person-years) and 182 total (fatal plus non-fatal) cardiovascular morbid events (2.66 per 100 person-years). Clinic, average 24 h, daytime and night-time heart rates exhibited no association with total mortality. However, the subjects who subsequently died had had a blunted reduction of heart rate on going from day to night during the baseline examination. After adjustment for age (P < 0.001), diabetes (P < 0.001) and average 24 h systolic blood pressure (SBP, P= 0.002) in a Cox model, for each 10% less reduction in the heart rate from day to night the relative risk of mortality was 1.30 (95% confidence interval 1.02-1.65, P = 0.04). Rates of death were 0.38, 0.71, 0.94 and 2.0 per 100 person-years among subjects in the four quartiles of the distribution of the percentage reduction in heart rate from day to night The baseline day-night changes in the heart rate exhibited an inverse correlation to age and to clinic and ambulatory SBP and a direct association with the day-night changes in blood pressure. The degree of reduction of heart rate from day to night also had an independent inverse association with total cardiovascular morbidity after adjustment for age, diabetes and left ventricular hypertrophy, but this association did not remain significant when average 24 h SBP and the degree of day-night reduction in SBP were entered into the equation. CONCLUSIONS: A flattened diurnal rhythm of heart rate in uncomplicated subjects with essential hypertension is a marker of risk for subsequent all-cause mortality and this association persists after adjustment for several risk factors. For assessing these subjects, a limited and uniformly distributed period of ambulatory heart rate recording during the 24 h is clinically valuable.