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Biomedical subjects

M A Mittleman

Publications and source records attributed to M A Mittleman.

At least 19 recordsLinked to original sources
PubMed2000

Association of blood pressure with fibrinolytic potential in the Framingham offspring population.

BACKGROUND: Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. METHODS AND RESULTS: We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP (P<0.001). Plasma viscosity was positively related to SBP (P=0.008) and DBP (P=0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. CONCLUSIONS: These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.

Adult↗
PubMed2000

Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study.

CONTEXT: Increased risk for cardiovascular disease in persons with glucose intolerance (impaired glucose tolerance and type 2 diabetes mellitus) is not fully explained by concomitant elevations in traditional atherosclerosis risk factors. Hyperinsulinemia associated with glucose intolerance may increase risk directly, or its effect could be mediated through impaired hemostatic function. OBJECTIVE: To evaluate associations between fasting insulin levels and hemostatic factors in subjects with normal and impaired glucose homeostasis. DESIGN: Cross-sectional analysis conducted between January 1991 and June 1995. SETTING: The population-based Framingham Offspring Study. SUBJECTS: A total of 1331 men and 1631 women aged 26 to 82 years, without diagnosed diabetes or cardiovascular disease and classified as having normal glucose tolerance (80.2%) or glucose intolerance (impaired glucose tolerance and impaired fasting glucose combined, 15.2%; previously undiagnosed diabetes, 4.7%) using an oral glucose tolerance test. MAIN OUTCOME MEASURES: Trends across quintiles of fasting insulin in levels of plasminogen activator inhibitor 1 (PAI-1) antigen, tissue-type plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, factor VII antigen, fibrinogen, and plasma viscosity. We stratified analyses by sex and glucose tolerance status and adjusted hemostatic factor levels for obesity, lipid levels, and traditional cardiovascular disease risk factors. RESULTS: Mean levels of all hemostatic factors (except for fibrinogen in men) increased across fasting insulin quintiles among subjects with normal glucose tolerance (P<.001 for trend). Levels of PAI-1 and tPA antigens, but not other hemostatic factors, were higher comparing subjects with glucose intolerance with those with normal glucose tolerance (P<.001). Among subjects with glucose intolerance, levels of PAI-1 and tPA antigen in men and women (P<.01 for trend) and vWF antigen in men (P<.05 for trend) increased significantly across insulin quintiles, but levels of factor VII antigen, fibrinogen, and plasma viscosity did not increase. CONCLUSIONS: Elevated levels of fasting insulin are associated with impaired fibrinolysis and hypercoagulability in subjects with normal glucose tolerance. Hyperinsulinemia is associated primarily with impaired fibrinolysis in subjects with glucose intolerance. Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis.

Adult↗
PubMed2000

Job stress and the occupational gradient in coronary heart disease risk in women. The Stockholm Female Coronary Risk Study.

Recent studies of men have shown that job stress is important in understanding the occupational gradient in coronary heart disease (CHD), but these relationships have rarely been studied in women. With increasing numbers of women in the workforce it is important to have a more complete understanding of how CHD risk may be mediated by job stress as well as other biological and behavioural risk factors. The objective of this study was to examine the occupational gradient in CHD risk in relation to job stress and other traditional risk factors in currently employed women. We used data from the Stockholm Female Coronary Risk Study, a population based case-control study, comprising 292 women with CHD aged 65 years or younger and 292 age-matched healthy women (controls). An inversely graded association was observed between occupational class and CHD risk. Compared with the highest (executive/professional), women in the lowest occupational class (semi/unskilled) had a four-fold (95% CI 1.75-8.83) increased age-adjusted risk for CHD. Simultaneous adjustment for traditional risk factors and job stress attenuated this risk to 2.45 (95% CI 1.01-6.14). Neither job control nor the Karasek demand-control model of job stress substantially explained the increased CHD risk of women in the lowest occupational classes. It is likely that lower occupational class working women face multiple and sometimes interacting sources of work and non-work stress that are mediated by behavioural and biological factors that increase their CHD risk.

Case-Control Studies↗
PubMed2000

Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study.

AIMS: Several studies have reported that women with coronary heart disease have a poorer prognosis than men. Psychosocial factors, including social isolation and depressive symptoms have been suggested as a possible cause. However, little is known about these factors and their independent predictive value in women. Therefore, we investigated the prognostic impact of depression, lack of social integration and their interaction in the Stockholm Female Coronary Risk Study. METHODS AND RESULTS: Two hundred and ninety-two women patients aged 30 to 65 years and admitted for an acute coronary event between 1991 and 1994, were followed for 5 years from baseline assessments, which were performed between 3 and 6 months after admission. Lack of social integration and depressive symptoms, assessed at baseline by standardized questionnaires, were associated with recurrent events, including cardiovascular mortality, acute myocardial infarction and revascularization procedures (percutaneous transluminal coronary angioplasty and coronary artery bypass grafting). Adjusting for age, diagnosis at index event, symptoms of heart failure, diabetes mellitus, high density lipoprotein (HDL) cholesterol, history of hypertension, systolic blood pressure, smoking, sedentary lifestyle, body mass index, and severity of angina pectoris symptoms, the hazard ratio associated with low (lowest quartile) as compared to high social integration (upper quartile) was 2.3 (95% CI 1.2-4.5) and the hazard ratio associated with two or more (upper three quartiles) as compared to one or no depressive symptoms was 1.9 (95% CI 1.02-3.6). CONCLUSIONS: The presence of two or more depressive symptoms and lack of social integration independently predicted recurrent cardiac events in women with coronary heart disease. Women who were free of both these risk factors, had the best prognosis.

Acute Disease↗
PubMed2000

Increased risk of congestive heart failure among infarctions with nighttime onset.

BACKGROUND: The onset of acute myocardial infarction varies by time of day, with a peak in the morning and a trough at night. Whether infarct-related complications differ by the timing of the infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 3625 patients with acute myocardial infarction. We assessed the time of onset of symptoms, the presence of ventricular tachycardia or congestive heart failure, and peak creatine kinase levels (in 1043 patients). We found significant circadian variation in the risk of congestive heart failure (P =.001). The risk dropped from 17% for infarctions that began between 6 PM and midnight to 10% for infarctions that began between 6 AM and noon. Adjustment for differences in the time from symptom onset to presentation for care and use of thrombolytic agents did not change the results. We found no circadian variation in the risk of ventricular tachycardia or in peak creatine kinase levels. CONCLUSIONS: The risk of congestive heart failure is highest among infarctions that begin at night. Further research may clarify whether this reflects differences in the pathophysiologic characteristics of infarction or the quality of medical care provided for daytime and nighttime infarctions.

Adult↗
PubMed2000

Should we use a case-crossover design?

The first decade of experience with case-crossover studies has shown that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects on risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared with exposure frequencies during control times rather than in control persons. One or more control times are supplied by each of the cases themselves, to control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published case-crossover studies is designed to help the reader prepare a better research proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and hazard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.

Acute Disease↗
PubMed1999

Triggering of myocardial infarction by cocaine.

BACKGROUND: Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

Adult↗
PubMed1999

Long-term prognostic value of preoperative dipyridamole thallium imaging and clinical indexes in patients with diabetes mellitus undergoing peripheral vascular surgery.

The objective of this study is to assess the prognostic impact of preoperative dipyridamole thallium imaging and clinical variables on the long-term outcome of diabetic patients undergoing peripheral vascular surgery. Complete follow-up was obtained in 101 consecutive patients with diabetes mellitus undergoing routine dipyridamole thallium scintigraphy before vascular surgery (mean 4.2 +/- 3.2 years, range 1 month to 11 years). Low risk was defined by diabetes alone with a normal resting electrocardiogram. High risk was defined as a history of angina, myocardial infarction, congestive heart failure, or resting electrocardiogram abnormalities. There were 71 deaths in 98 patients discharged alive from the hospital (median survival 4.4 years). Age, the presence of resting electrocardiogram abnormalities, and an abnormal thallium scan were independent predictors of late death. After adjusting for age >70 years and thallium abnormalities, high-risk patients had a death rate 4.8 times (95% confidence interval 1.7 to 13.4, p <0.002) greater than low-risk patients. The presence of >2 reversible thallium defects was useful in further risk stratification of both low- and high-risk patients. Low-risk patients with >2 reversible defects had a median survival of 4.0 years compared with 9.4 years in those with < or =2 reversible defects (p <0.001). Similarly, high-risk patients with < or =2 reversible defects had an intermediate median survival rate of 4.7 years compared with 1.8 years in the group with >2 reversible defects (p <0.001). Therefore, advanced age and the presence of resting electrocardiographic or thallium abnormalities identifies a subset of diabetic patients with a poor long-term outcome after vascular surgery. Combined clinical and thallium variables may identify a population in whom intensive medical or surgical interventions may be warranted to reduce both perioperative and late cardiac events.

Aged↗
PubMed1999

Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction.

To determine the ability to detect thrombus by angiography, angioscopy was performed before angiography in patients undergoing interventional procedures and the data collected in a blinded fashion. These data demonstrated that the sensitivity of angiography to detect white thrombus was 50% and the specificity was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%, respectively; the positive and negative predictive value of detecting thrombus in general was 89% and 83%, respectively.

Aged↗
PubMed1999

Lack of effect of recent alcohol consumption on the course of acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Alcohol has marked effects on hemodynamic and hemostatic variables that might alter the presentation of acute myocardial infarction that follows its use. We sought to determine whether recent alcohol consumption alters the course or complications of acute myocardial infarction. METHODS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 2161 patients who did not receive thrombolytic therapy. We assessed alcohol use before infarction, peak creatine kinase levels (1043 patients), electrocardiographic interpretations (1408 patients), and the presence of ventricular arrhythmias or congestive heart failure (all patients). RESULTS: Among the 2161 patients, 399 (18.5%) drank alcohol within 24 hours before myocardial infarction. We found no significant difference in mean peak creatine kinase level between those who had recently used alcohol and those who had not in an adjusted comparison (-6.1% difference; 95% confidence interval [CI] -20.3%-10.7%; P =.46). We also found no differences in adjusted risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmias (odds ratios 1.03 [95% CI, 0.73-1.45; P =.88], 1.01 [95% CI, 0.67-1.54; P =.95], and 1.04 [95% CI, 0.66-1.65; P =.86]). Categorization of the duration since last alcohol use into 6-hour intervals revealed no trends between time since last use of alcohol and any of these outcomes. CONCLUSIONS: Recent alcohol use is not associated with changes in infarct size or risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmia among this population.

Aged↗
PubMed1999

Recent aspirin use is associated with smaller myocardial infarct size and lower likelihood of Q-wave infarction.

BACKGROUND: Controversy exists about the effect of recent aspirin use on infarct size and the likelihood of Q-wave infarction in patients who sustain myocardial infarction. METHODS: We performed face-to-face interviews and chart reviews on 3665 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. For the 2206 patients who did not receive thrombolytic therapy, we assessed aspirin use, peak creatine kinase levels (in 1043 patients), and electrocardiographic interpretations (in 1447 patients). RESULTS: Of the initial 1043 patients, 317 (30. 3%) subjects reported aspirin use in the 4 days before their infarction. The mean +/- SD peak creatine kinase level for aspirin users was 701 +/- 570 IU/mL versus 851 +/- 727 IU/mL for nonusers, an 18% difference (95% confidence interval [CI], 8% to 26%; P <.001). After adjustment for confounding factors, the difference was 12% (95% CI, 2% to 21%; P =.03). Similarly, 38.9% of the aspirin users and 48.7% of the nonusers sustained a Q-wave infarction, an odds ratio of 0.67 (95% CI, 0.54 to 0.83, P <.001). The adjusted odds ratio was 0.77 (95% CI, 0.61 to 0.97, P =.03). CONCLUSIONS: Recent aspirin use was associated with smaller infarct size and fewer Q-wave infarctions among this population of early survivors of acute myocardial infarction who did not receive thrombolytic therapy.

Aged↗
PubMed1999

Short stature and prognosis of coronary heart disease in women.

OBJECTIVES: To investigate the effect of short stature on prognosis following an acute event of coronary heart disease (CHD) in women. SETTING: All women who were hospitalized for an acute event of CHD in any of the 10 cardiology clinics in greater Stockholm were investigated for the first time in the Stockholm Female Coronary Risk Study between 1991 and 1994, and were followed until August 1997 for recurrent coronary events. DESIGN: A follow-up study of women with either acute myocardial infarction (AMI) or unstable angina pectoris. Median follow-up period was 4.8 years. SUBJECTS: A total of 292 Swedish women. aged 65 years or younger. MAIN OUTCOME MEASURES: Recurrent AMI, death from CHD or revascularization procedure (percutaneous transluminal coronary angioplasty and coronary artery bypass grafting). RESULTS: Independent of the confounding effects of other risk factors of clinical importance for CHD (age, socioeconomic status, menopausal status, index event, congestive heart failure, angina severity, diabetes, hypertension, smoking, triglycerides and HDL cholesterol), the shortest 25% of women (< 160 cm) had a 2.1-fold (95% CI = 1.0-4.4) increased rate of developing adverse cardiac events (cardiovascular death, recurrent AMI or revascularization procedure) compared with the tallest 25% (> 165 cm). In addition, an increased rate was observed for each 10 cm difference in height (hazard ratio = 1.7, 95% CI = 1.4-2.7). Similar results were observed when analysing each outcome separately. CONCLUSIONS: These data indicate that short stature is a strong predictor of poor prognosis after an acute coronary event in women, independent of socioeconomic status and other risk factors for CHD.

Angina, Unstable↗
PubMed1999

Relationship between plasma fibrinogen and coronary heart disease in women.

Plasma fibrinogen is an independent risk factor for coronary heart disease (CHD) in men; however, its role in women is less clear. We examined the ability of plasma fibrinogen to predict CHD in a community-based, case-control study of women aged 65 years or younger living in the greater Stockholm area. Cases were all patients hospitalized for an acute coronary event between February 1991 and February 1994. Controls were randomly selected from the city census and were matched to cases by age and catchment area. Plasma fibrinogen was measured 3 to 6 months after hospitalization by using a fibrinogen assay based on fibrinogen polymerization time measurement. Of the 292 consecutive cases, 110 (37%) were hospitalized for an acute myocardial infarction and 182 (63%) for angina pectoris. The mean age+/-SD in both patients and controls was 56+/-7 years. Mean levels of plasma fibrinogen in patients and controls were 3.66+/-0.81 and 3.25+/-0.64 g/L (P<0.0001), respectively. The age-adjusted odds ratio (OR) for CHD in the highest versus the lowest quartile of plasma fibrinogen was 6.0 (95% confidence interval [CI], 3.5 to 10.4). After adjustment for age, cigarette smoking, body mass index, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, and educational level, the OR was 3.0 (95% CI, 1.6 to 5.5). Further adjustment for C-reactive protein yielded the same result. In both premenopausal and postmenopausal women, the multivariate-adjusted ORs were 7.0 (95% CI, 1.8 to 28.3) and 2.1 (95% CI, 1.0 to 4.4), respectively. These results provide evidence that plasma fibrinogen is associated with an excess risk of CHD in women.

Adult↗
PubMed1999

Social relations and the metabolic syndrome in middle-aged Swedish women.

BACKGROUND: Both social isolation and the metabolic syndrome are independently associated with greater than normal cardiovascular risk. DESIGN: A population-based cross-sectional study of middle-aged Swedish women. METHODS: The study group consisted of 300 healthy women (aged 31-65 years) who were representative of women living in the greater Stockholm area. Social isolation was measured by using a condensed version of the Interpersonal Support Evaluation List. Health behaviours were assessed and a full serum-lipid-level and haemostatic profile was obtained by standardized methods. The metabolic syndrome was defined as the presence of two or more of these components: fasting serum level of glucose > or = 7.0 mmol/l, arterial blood pressure > or = 160/90 mmHg, fasting serum level of triglycerides > or = 1.7 mmol/l or high-density lipoprotein < 1.0 mmol/l, or both, and central obesity (waist:hip ratio > 0.85 or body mass index > 30 kg/m2, or both). RESULTS: After adjustment for age, menopausal status, educational level, smoking, exercise habits and consumption of alcohol, the risk ratio for the metabolic syndrome for women in the lower compared with women in the upper social-support quartile was 3.5 (95% confidence interval 1.1-11.4), whereas that of women in the two middle quartiles was 2.2 (95% confidence interval 0.67-7.2; P for trend 0.02). CONCLUSIONS: Social isolation was associated with the metabolic syndrome for these middle-aged women. The findings suggest that the metabolic syndrome and its components may be mediators of the reported association between social isolation and cardiovascular disease.

Adult↗
PubMed1999

Potential explanations for the educational gradient in coronary heart disease: a population-based case-control study of Swedish women.

OBJECTIVES: This study examined the association between educational attainment and coronary heart disease (CHD) and the factors that may explain this association. METHODS: This population-based case-control study included 292 women with CHD who were 65 years or younger and 292 age-matched controls. RESULTS: Compared with the adjusted odds ratio for CHD associated with college education, the age-adjusted odds ratio associated with mandatory education (< or = 9 years) was 1.87 (95% confidence interval [CI] = 1.23, 2.84) and the odds ratio for high school education was 1.35 (95% CI = 0.81, 2.25) (P for trend < .01). The odds ratio for mandatory education was reduced by 82%, to 1.16 (95% CI = 0.69, 2.09), after adjustment for psychosocial stress, unhealthy lifestyle patterns, hemostatic factors, hypertension, and lipids. CONCLUSIONS: Much of the increased risk of CHD in women with low education appears to be linked to psychosocial stress and lifestyle factors. Hemostatic factors, lipids, and hypertension also contribute to a lesser extent. These factors may be considered in strategies geared to reducing socioeconomic inequalities in cardiovascular health.

Adult↗
PubMed1999

Education and the metabolic syndrome in women.

OBJECTIVE: The main objective was to examine the association between the metabolic syndrome and socioeconomic position (as indicated by education) among women. RESEARCH DESIGN AND METHODS: The study sample comprised healthy women (aged 30-65 years) in Sweden who were representative of the general population in a metropolitan area. Socioeconomic position was measured by educational level (mandatory [< or = 9 years], high school, or college/university). The metabolic syndrome was defined as the presence of two or more of the following components: 1) fasting plasma glucose level > or = 7.0 mmol/l; 2) arterial blood pressure > or = 160/90 mmHg; 3) fasting plasma triglycerides > or = 1.7 mmol/l and/or HDL cholesterol < 1.0 mmol/l; and 4) central obesity (waist-to-hip ratio > 0.85 and/or BMI > 30 kg/m2). RESULTS: After adjustment for age, the risk ratio for the presence of the metabolic syndrome comparing the lowest (< or = 9 years) with the highest (college/university) education was 2.7 (95% CI 1.1-6.8). This association persisted after controlling for menopausal status, family history of diabetes, and behavioral risk factors. CONCLUSIONS: Low education is associated with increased risk for metabolic syndrome in middle-aged women. These findings show that not only are women with low socioeconomic position at increased risk for individual risk factors that are associated with cardiovascular disease and type 2 diabetes, they are also at increased risk for the metabolic clustering of risk factors.

Adult↗