Blood pressure and mortality risk in older people: comparison between African Americans and whites.

OBJECTIVES: To determine the risk from hypertension for all-cause mortality in a racially mixed sample of community-dwelling older adults. DESIGN: Baseline blood pressure was assessed between 1985 and 1986 in a sample of persons 65 years of age and older from five counties of the Piedmont of North Carolina (N = 4,162). All-cause mortality was monitored annually over the subsequent 6 years as part of the Established Populations for Epidemiologic Studies of the Elderly (EPESE) sponsored by the National Institute on Aging. SETTING: Eighteen percent of all respondents in the sample had a systolic blood pressure of > 160 (17% for whites and 18% for African Americans) and 16% had a diastolic blood pressure of >90 (14% for whites and 20% for African Americans). During the 6 years of follow-up, 29% of the sample died (with no difference in mortality rates between whites and African Americans). PARTICIPANTS: 4,000 community-dwelling people age 65 years and older; 1,846 were white and 2,154 were African American. MEASUREMENTS: Systolic and diastolic blood pressure and all-cause mortality. RESULTS: Systolic blood pressure positively related to mortality during the 6 years of follow-up (relative risk = 1.05). Among whites the relationship of diastolic pressure to mortality was nonlinear, with those at the upper and lower ends of the distribution at increased risk. Among African Americans, diastolic pressure was unrelated to mortality. The analyses were controlled for age; gender; education; body mass index (BMI); smoking history; taking a medication to manage blood pressure; a history of cancer, diabetes mellitus, heart attack, or stroke; poor subjective health; impaired functional status; and cognitive impairment. CONCLUSIONS: The findings confirm that among older adults there is a significant relationship overall between systolic blood pressure and mortality over 6 years of follow-up in both whites and African Americans. Diastolic pressure was a risk factor for whites only.

Ineffectiveness and potential proarrhythmia of atrial pacing for atrial fibrillation prevention after coronary artery bypass grafting.

BACKGROUND: Atrial pacing is often used empirically to suppress atrial ectopy and prevent atrial fibrillation after coronary artery bypass grafting. METHODS: To determine whether atrial overdrive pacing reduces atrial fibrillation and atrial ectopy after coronary artery bypass grafting, 100 patients were randomized to no atrial pacing (Control) versus AAI pacing at 10 beats/min or more above the resting heart rate (Paced), started by postoperative day 1 and continued through day 4. Major end points were new atrial fibrillation and frequency of atrial ectopy during the first 4 days after coronary artery bypass grafting. RESULTS: Atrial fibrillation occurred by day 4 in 13 of 51 (25.5%) Paced and in 14 of 49 (28.6%) Control patients, p = 0.90. Control patients who developed atrial fibrillation had significantly more atrial ectopy than those who did not. Atrial ectopy was paradoxically more frequent in the Paced group (2,106+/-428 versus 866+/-385 per 24 hours, p = 0.0001). Loss of capture, sensing, and consistent atrial pacing occurred frequently during atrial pacing. CONCLUSIONS: Contrary to prevailing opinion and practice, postoperative atrial overdrive pacing significantly increases atrial ectopy and does not reduce the likelihood of atrial fibrillation.

Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results.

Obsessive-compulsive disorder (OCD) has been linked to abnormal function of brain serotonin (5-HT) pathways. Since ondansetron is a highly selective 5-HT3 receptor antagonist, the present study was undertaken to investigate 5-HT3 function in OCD. We administered m-CPP (0.08 mg/kg i.v.) and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg i.v.), to 11 OCD patients. All of the subjects received four separate challenges (m-CPP + placebo, m-CPP + ondansetron, ondansetron + placebo and placebo + placebo). In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT3 receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in patients with OCD.

Prognostic significance of exercise-induced left bundle-branch block.

CONTEXT: Approximately 0.5% of all patients who undergo exercise testing develop a transient left bundle-branch block (LBBB) during exercise, but its prognostic significance is unclear. OBJECTIVE: To determine whether exercise-induced LBBB is an independent predictor of mortality and cardiac morbidity. DESIGN: Matched control cohort study. Between September 1990 and February 10, 1994, 17277 exercise stress tests were performed on patients. SETTING: Tertiary care, academic medical center. PATIENTS: From the cohort, 70 cases of exercise-induced LBBB were identified. The controls comprised 70 individuals without LBBB at rest or during exercise that matched the 70 cases based on age, test date, sex, prior history of coronary artery disease, hypertension, diabetes, smoking, and beta-blocker use. MAIN OUTCOME MEASURES: All-cause mortality, percutaneous coronary intervention, open heart surgery, nonfatal myocardial infarction, documented symptomatic or sustained ventricular tachydysrhythmia, or implantation of a permanent pacemaker or an implantable cardiac defibrillator. RESULTS: A total of 37 events (28 events from the exercise-induced LBBB cases and 9 from the control cohort) occurred in 25 patients (17 exercise-induced LBBB patients and 8 control patients) during a mean follow-up period of 3.7 (0.9 years) (median, 3.8 years [range, 0.9-5.2 years]). There were 7 deaths, of which 5 occurred among patients with exercise-induced LBBB. Four-year Kaplan-Meier event rates were 19% among exercise-induced LBBB patients and 10% among controls (log-rank chi2, 5.2; P=.02). After further adjusting for small differences in age, exercise-induced LBBB remained associated with a higher risk of primary events (adjusted relative risk, 2.78; 95% confidence interval, 1.16-6.65; P=.02). CONCLUSION: Exercise-induced LBBB independently predicts a higher risk of death and major cardiac events.

Biological and behavioral responses to D-amphetamine, alone and in combination with the serotonin3 receptor antagonist ondansetron, in healthy volunteers.

Evidence that serotonin3 (5-hydroxytryptamine3, 5-HT3) antagonists attenuate behavioral responses to D-amphetamine and cocaine suggests that 5-HT3 receptors modulate brain dopamine in animals. This study examined the potential interactions of the 5-HT3 antagonist ondansetron and D-amphetamine in 10 healthy human volunteers. After the subjects were pretreated with placebo or ondansetron (0.15 mg/kg, i.v.), 5-h challenge tests with oral D-amphetamine (0.5 mg/kg) were performed. As animal studies and early clinical studies with ondansetron have suggested nonlinear dose-response relationships, three subjects also underwent pilot studies with three doses of ondansetron (0.15, 0.05, and 0.015 mg/kg) before they received D-amphetamine. Administration of D-amphetamine increased plasma levels of cortisol, prolactin, growth hormone; elevated blood pressure, pulse, and temperature; and tended to increase self-ratings of activation/euphoria and anxiety. Amphetamine-induced increases in plasma prolactin were significantly reduced by ondansetron pretreatment, but the other neuroendocrine responses were unchanged. Diastolic blood pressure elevations were also significantly attenuated after administration of the lower ondansetron doses, but the other physiologic responses were unchanged. In subjects with minimal or moderate activation/euphoria responses, ondansetron pretreatment only minimally affected these effects of D-amphetamine. Preliminary data, however, indicate that those subjects with robust activation-euphoria responses to D-amphetamine had attenuated responses after ondansetron pretreatment. Taken together, these results suggest that some but not most of D-amphetamine's biological and behavioral effects may be modified by a 5-HT3 antagonist in healthy human volunteers.

Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder.

In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each. There were no significant differences between buspirone and placebo in obsessive-compulsive, depressive, or anxiety symptoms.

A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to i.v. mCPP.

In prior studies form three centers, an exacerbation of obsessive-compulsive disorder (OCD) symptoms was reported in some (55%-83%) patients with OCD receiving the serotonergic agonist m-chlorophenylpiperazine (m-CPP) orally, whereas intravenously administered mCPP produced anxiety but no OCD symptom exacerbation. In the present replication attempt, 27 OCD patients were given mCPP either orally (n = 17) or intravenously (n = 10) under double-blind conditions, using identical behavioral rating measures. OCD symptoms were significantly increased after intravenous mCPP (0.1 mg/kg), but not after oral mCPP (0.5 mg/kg). Anxiety and other ratings were markedly elevated after intravenous mCPP administration. After oral mCPP administration, anxiety and most other self-ratings were only slightly elevated in comparison to placebo administration, and behavioral rating increases were no different for the OCD patients compared to age-matched healthy controls. Pretreatment with the potent serotonin (5-HT) antagonist, metergoline, prior to intravenous mCPP was associated with essentially complete blockade of the exacerbation in OCD symptoms and the other behavioral responses in the OCD patients. These results suggest that the behavioral response of OCD patients to mCPP are variable and depend on the route and dose of mCPP. In addition, the ability of metergoline to antagonize the behavioral effects of intravenous mCPP suggests that these responses are mediated by 5-HT1/5-HT2 receptors.

Elevated antidepressant plasma levels after addition of fluoxetine.

Four patients treated with tricyclic antidepressants and one patient treated with trazodone all demonstrated marked increases in plasma levels of these drugs after the addition of fluoxetine. Such increases could increase adverse effects.

Premenstrual symptoms in black and white community samples.

Premenstrual syndrome specialty clinics are reported to be almost exclusively attended by white women. This racial discrepancy has raised the question of whether there is a lower prevalence or severity of symptoms during the premenstruum among black women. The authors evaluated selected premenstrual symptoms in a representative community-based sample and found no difference in the prevalence or severity of premenstrual symptoms reported by black and white women, except for a higher prevalence of food cravings among blacks. Exploration of broader sociocultural factors may explain the observed racial difference in seeking help for premenstrual complaints.