Mary A. Sheehan

AN ANALYSIS OF THE LOWEST EFFECTIVE INTENSITY OF PROPHYLACTIC ANTICOAGULATION FOR PATIENTS WITH NONRHEUMATIC ATRIAL FIBRILLATION

BACKGROUND To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case-control study. METHODS We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin. For each patient with stroke, three controls with nonrheumatic atrial fibrillation who were treated as outpatients were randomly selected from the 1994 registry of the anticoagulant-therapy unit (222 controls). We used the international normalized ratio (INR) to measure the intensity of anticoagulation. For the patients with stroke, we used INR at admission; for the controls, we selected the INR that was measured closest to the month and day of the matched case patients hospital admission. RESULTS The risk of stroke rose steeply at INRs below 2.0. At an INR of 1.7, the adjusted odds ratio for stroke, as compared with the risk at an INR of 2.0, was 2.0 (95 percent confidence interval, 1.6 to 2.4); at an INR of 1.5, it was 3.3 (95 percent confidence interval, 2.4 to 4.6); and at an INR of 1.3, it was 6.0 (95 percent confidence interval, 3.6 to 9.8). Other independent risk factors were previous stroke (odds ratio, 10.4; 95 percent confidence interval, 4.4 to 24.5), diabetes mellitus (odds ratio, 2.95; 95 percent confidence interval, 1.3 to 6.5), hypertension (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 5.7), and current smoking (odds ratio, 5.7; 95 percent confidence interval, 1.4 to 24.0). CONCLUSIONS Among patients with atrial fibrillation, anticoagulant prophylaxis is effective at INRs of 2.0 or greater. Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0, tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower, less effective levels of anticoagulation.

Effects of Diet and Exercise in Men and Postmenopausal Women with Low Levels of HDL Cholesterol and High Levels of LDL Cholesterol

BACKGROUND Guidelines established by the National Cholesterol Education Program (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein levels. Little is known, however, about the effects of exercise or the NCEP diet, which is moderately low in fat and cholesterol, in persons with lipoprotein levels that place them at high risk for coronary heart disease. METHODS We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or =44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus exercise, or to a control group, which received no intervention. RESULTS Dietary intake of fat and cholesterol decreased during the one-year study (P<0.001), as did body weight, in women and men in either the diet group or the diet-plus-exercise group, as compared with the controls (P<0.001) and the exercise group (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups, for subjects of either sex. The serum level of LDL cholesterol was significantly reduced among women (a decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg per deciliter) in the diet-plus-exercise group, as compared with the control group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group (3.6+/-18.8 mg per deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the controls. CONCLUSIONS The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.

Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.

BACKGROUND AND PURPOSE The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. METHODS To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group). RESULTS The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1). CONCLUSIONS We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.

Stage of Motivational Readiness: Predictive Ability for Exercise Behavior.

OBJECTIVE To determine if stage of motivational readiness for exercise predicted adherence to a 9-month exercise intervention. METHODS Three hundred forty-two individuals were randomized into a diet and physical activity trial. The exercise goal was to complete or add at least 10 miles of weekly brisk walking or jogging. Adherence was determined from logs. RESULTS Sixty-four percent of men and 34% of women reported an increase of at least 10 miles per week. Adherence did not differ by baseline exercise motivational readiness stage. CONCLUSIONS Future work should determine in what contexts stage-targeted interventions are most successful for adoption and maintenance of physical activity.