Selected Abstracts [*].

MAJOR CORONARY DISEASE RISK FACTORS ARE STRONG CONTRIBUTORS IN PREDICTING FUTURE RISK, EVEN IN YOUNG MEN

Navas-Nacher EL, Colangelo L, Beam C, et al: Risk factors for coronary heart disease in men 18 to 39 years of age. Ann Intern Med 2001; 134:433-439

This prospective cohort study included 11,016 men aged 18 to 39 (mean age, 29.7 years), and 8,955 men aged 40 to 59 years at baseline served as the reference group. The main measurement was death from coronary heart disease. All major risk factors (age, serum cholesterol level, systolic blood pressure, and cigarette smoking) were significantly associated with death from coronary heart disease over 20 years in young men. Relative risks for the major risk factors were generally similar in young and middle-aged men. The results indicate that coronary risk factors in men 18 to 39 years of age have a powerful effect on long-term risk of death from coronary disease.

HORMONE REPLACEMENT THERAPY MAY HAVE SPECIFIC COGNITIVE EFFECTS IN WOMEN WITH MENOPAUSAL SYMPTOMS

LeBlanc ES, Janowsky J, Chan BK, et al: Hormone replacement therapy and cognition. JAMA 2001; 285:1489-1499

These randomized, controlled trials and cohort studies were reviewed for the effects of hormone replacement therapy (HRT) on cognitive decline. Cohort and case-control studies were reviewed for dementia risk. There were no randomized controlled trials identified with regard to dementia risk. Twenty studies were included. Women symptomatic from menopause showed improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. No benefits were seen in asymptomatic women. A meta-analysis of observational studies indicated that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval [CI], 0.53-0.82). Limitations of these studies include possible biases and lack of control for potential confounders limiting interpretation of these studies. They also did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or length of therapy.

POSTMENOPAUSAL WOMEN WHO USE ESTROGEN REPLACEMENT THERAPY FOR 10 OR MORE YEARS HAVE AN INCREASED RISK OF OVARIAN CANCER MORTALITY

Rodriguez C, Patel AV, Calle EE, et al: Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA 2001; 285:1460-1465

This prospective US cohort study included 211,581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. The main outcome measures included ovarian cancer mortality compared among women who never used estrogen replacement therapy (ERT), users of ERT at baseline, former users, and the number of years of estrogen use. During 14 years of follow-up, 944 ovarian cancer deaths were recorded. Women who were using ERT at baseline had higher death rates from ovarian cancer than women who didn't take the therapy (rate ratio [RR], 1.51; 95% CI, 1.16-1.96). The risk was slightly, but not significantly, increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). The duration of use was associated with an increased risk in both baseline and former therapy users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17). Former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). A mong ERT users with 10 or more years of use, risk decreased with time since the last use reported at study entry (RR for last use [less than]15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use [greater than or equal to]15 years ago, 1.31; 95% CI, 0.79-2.17).

EFFECTS OF VITAMIN E ON LIPID PEROXIDATION IN HEALTHY ADULTS ARE QUESTIONABLE

Meagher EA, Barry OP, Lawson JA, et al: Effects of vitamin E on lipid peroxidation in healthy persons. JAMA 2001; 285:1178-1182

This randomized, double-blind, placebo-controlled trial conducted from March 1999 to June 2000 included 30 healthy men and women aged 18 to 60 years. The participants were randomly assigned to receive a placebo or [alpha]-tocopherol dosages of 200, 400, 800, 1,200, or 2,000 IU/day for 8 weeks (n = 5 in each group), followed by an 8-week washout period. No significant effect of vitamin E on levels of urinary 4-hydroxynonenal (4-HNE) or either of two isoprostanes was seen. Mean (SEM) baseline versus week-8 levels of [iPF.sub.2[alpha]]-III were 154 (20.1) versus 168 (22.3) pg/mg of creatinine for subjects taking placebo, 165 (19.6) versus 234 (30.1) pg/mg for those taking 200 IU/day of vitamin E, and 195 (26.7) versus 213 (40.6) pg/mg for subjects taking 2,000 IU/day. Corresponding [iPF.sub.2[alpah]] levels were 1.43 (0.6) versus 1.62 (0.4) ng/mg of creatinine for those taking a placebo, 1.64 (0.3) versus 1.24 (0.8) ng/mg for those taking 200 IU/day of vitamin E, and 1.83 (0.3) versus 1.94 (0.9) ng/mg for those taking 2,000 IU/ day.

HUMAN EMBRYONIC DOPAMINE-NEURON TRANSPLANTS SURVIVE IN PATIENTS WITH SEVERE PARKINSON'S DISEASE AND SHOW SOME CLINICAL BENEFIT IN YOUNGER PATIENTS

Freed CR, Greene PE, Breeze RE, et al: Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001; 344:710-719

Forty patients aged 34 to 75 years of age with severe Parkinson's disease (mean duration, 14 years), were randomly assigned to receive a transplant of nerve cells or undergo sham surgery. All patients were observed in a double-blind manner for 1 year. Cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally in the transplant recipients. Holes were drilled in the skulls of the patients who had sham surgery, but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of the disease, scored on a scale of -3.0 to 3.0 at 1 year. Negative scores indicated a worsening of symptoms and positive ones an improvement. The mean ([+ or -]SD) scores on the global rating scale for improvement or deterioration at 1 year were 0.0 [+ or -] 2.1 in the transplantation group, and scores in the sham-surgery group were -0.4 [+ or -] 1.7. In the younger patients (60 years old or younger), standardized tests of Parkinson's disease showed significa nt improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P = .01 for scores on the Unified Parkinson's Disease Rating Scale; P = .006 for the Schwab and England score). No significant improvement was observed in older patients in the transplantation group.

ERADICATION OF HELICOBACTER PYLORI IS AS EFFECTIVE AS MAINTENANCE THERAPY WITH OMEPRAZOLE IN PREVENTING RECURRENT UPPER GASTROINTESTINAL BLEEDING IN PATIENTS TAKING LOW-DOSE ASPIRIN

Chan FK, Chung SC, Suen BY, et al: Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001; 344:967-973

The study included 400 patients (250 taking aspirin and 150 taking other nonsteroidal anti-inflammatory drugs [NSAIDs]) with upper gastrointestinal bleeding confirmed by endoscopy. Their ulcers were healed with daily treatment of 20 mg of omeprazole for 8 weeks or longer. Those who had been treated with aspirin were given 80 mg of aspirin daily, and those who had taken other NSAIDs were given 500 mg of naproxen twice daily for 6 months. The patients in each group were then randomly assigned separately to 20 mg of omeprazole daily for 6 months or 1 week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all administered four times daily followed by a placebo for 6 months. Among those taking aspirin, the probability of recurrent bleeding during the 6-month period was 1.9% for patients who received eradication therapy and 0.9% for those who received omeprazole (absolute difference, 1.0%; 95% CI, --1.9%-3.9%). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8% for patients receiving eradication therapy and 4.4% for those treated with omeprazole (absolute difference, 14.4%; 95% CI, 4.4%-24.4%; P = .005).

NO RELATIONSHIP HAS BEEN FOUND BETWEEN THE MAGNITUDE OF CHOLESTEROL REDUCTION AND NON-ILLNESS MORTALITY

Muldoon MF, Manuck SB, Mendelsohn AB, et al: Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials. BMJ 2001; 322:11-15

This meta-analysis of non-illness mortality outcomes of large, randomized clinical trials of cholesterol-lowering treatments included data from 19 trials. The main outcome measures were deaths from suicides, accidents, and violence in treatment groups compared with control groups. The odds ratio of non-illness mortality in the treated groups relative to control groups was 1.18 (95% CI, 0.91-1.52; P = .20). The odds ratios were 1.28 (0.94-1.74; P = .12) for primary prevention trials and 1.00 (0.65-1.55; P = .98) for secondary prevention trials. Randomized clinical trials using statins did not show a treatment-related rise in non-illness mortality (0.84, 0.50-1.41; P = .50). However, a trend toward increased deaths from suicide and violence was found in trials of dietary interventions and non-statin drugs (1.32,0.98-1.77; P = .06).

BEHAVIORAL FACTORS AND CARDIOVASCULAR RISK FACTORS ARE ASSOCIATED WITH MAINTENANCE OF GOOD HEALTH IN OLDER ADULTS

Burke GL, Arnold AM, Bild DE, et al: Factors associated with healthy aging: The Cardiovascular Health Study. J Am Geriatr Soc 2001; 49:254-262

Behavioral factors, such as physical activity, smoking, and obesity, and cardiovascular risk factors, such as diabetes, high-density lipoprotein (HDL) cholesterol, and blood pressure, are associated with maintenance of good health in older adults. This longitudinal cohort study included 5,888 participants aged 65 years and older in the Cardiovascular Health Study to identify factors associated with remaining healthy. The presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. A number of cardiovascular disease risk factors and subclinical disease measures were associated with continued health, including higher HDL cholesterol, lack of diabetes, thinner common carotid intimal medial thickness, lower blood pressure, lower C-reactive protein value, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, lack of smoking, and not taking aspirin remained significant predictors of health even after controlling for cardiovascular disease risk factor s and subclinical disease in older adults.

INHALED BECLOMETHASONE DIPROPIONATE REDUCES BONE MINERAL DENSITY IN EARLY POSTMENOPAUSAL BUT NOT PREMENOPAUSAL ASTHMATIC PATIENTS

Fujita K, Kasayama S, Hashimoto J, et al: Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women. J Bone Miner Res 2001; 16:782-787

This study examined the effect of inhaled beclomethasone dipropionate (BDP) on bone mineral density (BMD) and biochemical markers of bone metabolism in premenopausal and early postmenopausal asthmatic women. The study included 36 (17 premenopausal and 19 early postmenopausal) asthmatic women and 45 healthy controls (24 premenopausal and 21 early postmenopausal). All of the asthmatic women were given BDP (542 [+ or -] 298 [micro]g/day; 100 to 1,200 [micro]g/day) without any systemic administration of corticosteroids for at least 1 year. In the premenopausal women, BMD as well as the biochemical markers of bone metabolism did not differ between the control patients and BDP-treated asthmatic patients. On the other hand, in early postmenopausal women, BMD was significantly lower in BDP-treated asthmatic patients than in the control subjects.

(*.) Originally prepared for presentation on Southern Medical Association's Web site (http://www.sma.org) by Elaine McClellan-Holm.