BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate ...goal of therapy should be lowering LDL-C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/-0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.
The hypothesis that increased blood pressure reactivity to stress is an early risk marker of hypertension was tested in a 1994 follow-up of the 1974 to 1978 Air Traffic Controller Health Change Study ...sample.
Assessments in 1974 to 1978 included physical examinations and recordings (every 20 minutes for 5 hours) of both workload (planes within controller airspace) and blood pressure reactivity. Individual differences in reactivity were used to predict 1994 self-report of ever having been told by a physician to take antihypertensive medication, assessed in a telephone survey of 218 respondents who were normotensive or stage 1 hypertensive in 1974 to 1978.
Each SD increase in baseline systolic reactivity was associated with a 1.7 (p <.019) increase in the relative-odds of 1994 hypertension, after controlling for age, body mass index, and clinic systolic and diastolic blood pressure at clinical examination, with effects comparable for baseline normotensives and stage 1 hypertensives.
A 20-year follow-up of originally normotensive and stage I hypertensive workers suggests that increased systolic blood pressure reactivity to work stress is associated with long-term risk of hypertension.
Women undergoing coronary artery bypass graft (CABG) surgery have a worse medical condition and fewer social and financial resources than men. Some studies have found that women recover less well ...than men after CABG, whereas others have found women's outcomes comparable to those of men. Past studies of health-related quality of life after CABG have too few women for adequate comparison with men and have not included patients whose data are not available at baseline (eg, emergency CABG), limiting generalizability.
A longitudinal study of symptoms and health-related quality of life was conducted among patients from four clinical centers enrolling both men (n = 405) and women (n = 269) in the Post CABG Biobehavioral Study in the United States and Canada.
After 6 weeks from CABG (average 81 days), both men and women had less anxiety and symptoms related to depression than before surgery (
P < .001). After 6 months (average 294 days), both men and women improved in physical and social functioning (
P < .001). Although changes in scale scores were similar for men and women at each time point, women scored lower than men on these domains (
P < .001, adjusted for baseline medical and sociodemographic differences) and had more symptoms related to depression through 1 year after CABG (
P = .003).
Both male and female patients improve in physical, social, and emotional functioning after CABG, and recovery over time is similar in men and women. However, women's health-related quality-of-life scale scores remained less favorable than men's through 1 year after surgery.
Objective: We have previously shown that women with preeclampsia demonstrate cerebral hyperperfusion and abnormal cerebrovascular autoregulation. In the current study, we tested the hypothesis that ...abnormal cerebrovascular function can be detected before the clinical onset of preeclampsia. Study Design: Transcranial Doppler ultrasonography was performed for 166 women in the second trimester of pregnancy to measure peak, end-diastolic, and mean velocities in the middle cerebral arteries. Preeclampsia developed in 10 patients who were initially normotensive. In a nested case-controlled design, each patient with preeclampsia who was initially normotensive was matched for gestational age at the time of initial examination, maternal age, and parity with two pregnant women who remained normotensive and who were delivered at term. All measurements were performed with the subject in the left lateral position at baseline, during 5% carbon dioxide inhalation, and during a 2-minute isometric handgrip test. Blood pressure, heart rate, oxygen saturation, and end-tidal PCO2 were recorded with each Doppler measurement. The mean pulsatility index, resistance index, and cerebral perfusion pressure at each time were calculated and compared. Statistical significance was set at a probability value of <.05. Results: The studies were performed at 19 to 28 weeks of gestation. Preeclampsia developed an average of 13.6 ± 1.0 weeks after the study. Baseline mean blood pressure and heart rate were similar, but middle cerebral arteries pulsatility and resistance indices were lower in the women with preeclampsia who were initially normotensive compared with the pregnant women who were normotensive (0.83 and 0.54 vs 0.73 and 0.50, respectively; P <.05). Both maneuvers caused a significant reduction in the pulsatility and resistance indices. With the use of baseline values as covariates, no significant differences were noted in the response to either carbon dioxide inhalation or handgrip between the group of women who remained normotensive and the group of women with preeclampsia who were initially normotensive. Conclusion: Normotensive pregnant women who later have preeclampsia demonstrate lower baseline pulsatility and resistance indices but normal vasodilatory responses to challenge tests. These findings suggest that women who are destined to have preeclampsia experience cerebral hemodynamic changes that predate the development of overt preeclampsia symptoms. (Am J Obstet Gynecol 2002;187:1667-72.)
The Heart and Estrogen/Progestin Replacement Study (HERS) found no overall effect of estrogen plus progestin (compared with placebo) on coronary event rates in 2763 postmenopausal women with ...established coronary disease (mean 4.1 years of follow-up). In addition to the events trial, a carotid ultrasound substudy was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process.
Within the larger HERS, a subset of 362 participants underwent carotid B-mode ultrasound examinations at baseline and the end of follow-up. Progression of carotid atherosclerosis was measured as the temporal change in intimal-medial thickness (IMT).
IMT progressed in the hormone treatment and placebo groups, although there was no statistical difference between the rates: IMT progressed 26 microm/y (95% CI 18 to 34 microm/y) in the hormone group and 31 microm/y (95% CI 21 to 40 microm/y) in the placebo group (P=0.44). There were also no significant treatment effects when the results were examined by carotid segment or were adjusted for covariates. These data support the American Heart Association recommendation that women with established coronary disease should not initiate hormone therapy with an expectation of atherosclerotic benefit.
J. A. Herd
Department of Medicine, Baylor College of Medicine, Houston, Texas.
The behavioral characteristics of psychological stressors have been
operationally defined. A psychological stressor is ...one that causes a stress
response in a predictable percentage of index subjects. However, it may not
always produce a stress response, and the probability of producing such a
response depends on interactions between the behavioral situation and the
individual involved. Thus there is a danger that a psychological stressor
will be defined according to the stress response it causes rather than its
structural characteristics. The characteristics that enhance the likelihood
that a psychological stressor will cause a stress response are its novel,
challenging, or threatening aspects that engage a subject in continuous
active mental effort. The intensity of the stress response depends on the
intensity of mental effort exerted to meet a challenging situation, whether
or not that situation is perceived as threatening. The behavioral response
to a psychological stressor also has been defined. It includes somatomotor,
neuroendocrine, and cardiovascular components. The somatomotor response to
stressful psychological events includes purposeful active coping to counter
the challenge or threat posed by the stressor. The neuroendocrine response
includes a combination of pituitary-adrenal cortical and
hypothalamic-sympathetic-adrenal medullary secretions. The cardiovascular
response includes a combination of increased rate and force of cardiac
contraction, skeletal muscle vasodilation, venoconstriction, splanchnic
vasoconstriction, renal vasoconstriction, and decreased renal excretion of
sodium. Of all the modifiers that influence the stress response to a
psychological stressor, family history is the one most likely to have an
effect. A family history of essential hypertension increases the likelihood
that a subject will respond to a psychological stressor with a
cardiovascular stress response pattern. Other predisposing characteristics
that increase the likelihood of a stress response include behavioral
patterns of response to challenge or threat but may also include anatomic
or biochemical characteristics that increase susceptibility to neurogenic
activation of central aminergic mechanisms.
Background. Actinic keratoses are premalignant lesions and are a sensitive and important manifestation of sun-induced skin damage. Studies in animals have shown that dietary fat influences the ...incidence of sun-induced skin cancer, but the effect of diet on the incidence of actinic keratosis in humans is not known. Methods. We randomly assigned 76 patients with nonmelanoma skin cancer either to continue their usual diet (control group) or to eat a diet with 20 percent of total caloric intake as fat (dietary-intervention group). For 24 months, the patients were examined for the presence of new actinic keratoses by physicians unaware of their assigned diets. Results. At base line, the mean (+/- SD) percentage of caloric intake as fat was 40 +/- 4 percent in the control group and 39 +/- 3 percent in the dietary-intervention group. After 4 months of dietary therapy the percentage of calories as fat had decreased to 21 percent in the dietary-intervention group, and it remained below this level throughout the 24-month study period. The percentage of calories as fat in the control group did not fall below 36 percent at any time. The cumulative number of new actinic keratoses per patient from months 4 through 24 was 10 +/- 13 in the control group and 3 +/- 7 in the dietary-intervention group (P = 0.001). Conclusions. In patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the incidence of actinic keratosis
Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial ...and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained ≥160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (± cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, ΔMLD −0.028 versus −0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, ΔMLD −0.024 versus −0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.
The POST CABG (Post Coronary Artery Bypass Graft) Trial showed that aggressive lowering of low-density lipoprotein (LDL) cholesterol levels reduced the progression of atherosclerosis in saphenous ...vein grafts. In the extended follow-up phase, aggressive lowering of LDL cholesterol levels was associated with reduced rates of clinical events. Low-dose anticoagulation therapy did not reduce the progression of atherosclerosis. We conducted this analysis to determine the effects of both lipid-lowering and low-dose anticoagulation therapy on health-related quality of life (HRQL).
Randomized clinical trial, factorial design.
Outpatients in five tertiary care medical centers.
A cohort of 852 patients enrolled in the POST CABG Trial completed an HRQL questionnaire at baseline, and at the year 2 and year 4 follow-up visits.
Aggressive LDL cholesterol lowering vs moderate LDL cholesterol lowering, and low-dose warfarin vs placebo.
Domains included emotional status, basic physical and social functioning, perceived health status, symptoms of pain, a variety of physical symptoms, and global life satisfaction.
Overall, there were no indications of systematic differences among treatment groups for any of the HRQL parameters at baseline, year 2, or year 4.
These data indicate that patients did not experience detrimental or beneficial effects on HRQL parameters while receiving LDL cholesterol-lowering therapy that had demonstrable benefits for treatment of atherosclerosis.
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