Thomas G. Allison

A CLINICAL TRIAL OF A CHEST-PAIN OBSERVATION UNIT FOR PATIENTS WITH UNSTABLE ANGINA

BACKGROUND Nearly half of patients hospitalized with unstable angina eventually receive a non-cardiac-related diagnosis, yet 5 percent of patients with myocardial infarction are inappropriately discharged from the emergency department. We evaluated the safety, efficacy, and cost of admission to a chest-pain observation unit (CPU) located in the emergency department for such patients. METHODS We performed a community-based, prospective, randomized trial of the safety, efficacy, and cost of admission to a CPU as compared with those of regular hospital admission for patients with unstable angina who were considered to be at intermediate risk for cardiovascular events in the short term. A total of 424 eligible patients were randomly assigned to routine hospital admission (a monitored bed under the care of the cardiology service) or admission to the CPU (where patients were cared for according to a strict protocol including aspirin, heparin, continuous ST-segment monitoring, determination of creatine kinase isoenzyme levels, six hours of observation, and a study of cardiac function). The CPU was managed by the emergency department staff. Patients whose test results were negative were discharged, and the others were hospitalized. Primary outcomes (nonfatal myocardial infarction, death, acute congestive heart failure, stroke, or out-of-hospital cardiac arrest) and use of resources were compared between the two groups. RESULTS The 212 patients in the hospital-admission group had 15 primary events (13 myocardial infarctions and 2 cases of congestive heart failure), and the 212 patients in the CPU group had 7 events (5 myocardial infarctions, 1 death from cardiovascular causes, and 1 case of congestive heart failure). There was no significant difference in the rate of cardiac events between the two groups (odds ratio for the CPU group as compared with the hospital-admission group, 0.50; 95 percent confidence interval, 0.20 to 1.24). No primary events occurred among the 97 patients who were assigned to the CPU and discharged. Resource use during the first six months was greater among patients assigned to hospital admission than among those assigned to the CPU (P<0.01 by the rank-sum test). CONCLUSIONS A CPU located in the emergency department can be a safe, effective, and cost-saving means of ensuring that patients with unstable angina who are considered to be at intermediate risk of cardiovascular events receive appropriate care.

Dual-Chamber Pacing for Hypertrophic Cardiomyopathy: A Randomized, Double-Blind, Crossover Trial

OBJECTIVES In a double-blind, randomized, crossover trial we sought to evaluate the effect of dual-chamber pacing in patients with severe symptoms of hypertrophic obstructive cardiomyopathy. BACKGROUND Recently, several cohort trials showed that implantation of a dual-chamber pacemaker in patients with severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms and decrease the severity of the left ventricular outflow tract gradient. However, the outcome of dual-chamber pacing has not been compared with that of standard therapy in a randomized, double-blind trial. METHODS Twenty-one patients with severely symptomatic hypertrophic obstructive cardiomyopathy were entered into this trial after baseline studies consisting of Minnesota quality-of-life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary exercise tests. Nineteen patients completed the protocol and underwent double-blind randomization to either DDD pacing for 3 months followed by backup AAI pacing for 3 months, or the same study arms in reverse order. RESULTS Left ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p < 0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of-life score and exercise duration were significantly improved from the baseline state after the DDD arm but were not significantly different between the DDD arm and the backup AAI arm. Peak oxygen consumption did not significantly differ among the three periods. Overall, 63% of patients had symptomatic improvement during the DDD arm, but 42% also had symptomatic improvement during the AAI backup arm. In addition, 31% had no change and 5% had deterioration of symptoms during the DDD pacing arm. CONCLUSIONS Dual-chamber pacing may relieve symptoms and decrease gradient in patients with hypertrophic obstructive cardiomyopathy. In some patients, however, symptoms do not change or even become worse with dual-chamber pacing. Subjective symptomatic improvement can also occur from implantation of the pacemaker without its hemodynamic benefit, suggesting the role of a placebo effect. Long-term follow-up of a large number of patients in randomized trials is necessary before dual-chamber pacing can be recommended for all patients with severely symptomatic hypertrophic obstructive cardiomyopathy.

Exercise Training and Cardiac Rehabilitation in Primary and Secondary Prevention of Coronary Heart Disease

Substantial data have established a sedentary lifestyle as a major modifiable risk factor for coronary heart disease (CHD). Increased levels of physical activity, exercise training, and overall cardiorespiratory fitness have provided protection in the primary and secondary prevention of CHD. This review surveys data from observational studies supporting the benefits of physical activity, exercise training, and overall cardiorespiratory fitness in primary prevention. Clearly, cardiac rehabilitation/secondary prevention (CRSP) programs have been greatly underused by patients with CHD. We review the benefits of CRSP programs on CHD risk factors, psychological factors, and overall CHD morbidity and mortality. These data support the routine referral of patients with CHD to CRSP programs. Patients should be vigorously encouraged to attend these programs.

Barriers to participation in cardiac rehabilitation

BACKGROUND Participation rates in cardiac rehabilitation after myocardial infarction (MI) remain low. Studies investigating the predictive value of psychosocial variables are sparse and often qualitative. We aimed to examine the demographic, clinical, and psychosocial predictors of participation in cardiac rehabilitation after MI in the community. METHODS Olmsted County, Minnesota, residents hospitalized with MI between June 2004 and May 2006 were prospectively recruited, and a 46-item questionnaire was administered before hospital dismissal. Associations between variables and cardiac rehabilitation participation were examined using logistic regression. RESULTS Among 179 survey respondents (mean age 64.8 years, 65.9% male), 115 (64.2%) attended cardiac rehabilitation. The median (25th-75th percentile) number of sessions attended within 90 days of MI was 13 (5-20). Clinical characteristics associated with rehabilitation participation included younger age (odds ratio [OR] 0.95 per 1-year increase), male sex (OR 1.93), lack of diabetes (OR 2.50), ST-elevation MI (OR 2.63), receipt of reperfusion therapy (OR 7.96), in-hospital cardiologist provider (OR 18.82), no prior MI (OR 4.17), no prior cardiac rehabilitation attendance (OR 3.85), and referral to rehabilitation in the hospital (OR 12.16). Psychosocial predictors of participation included placing a high importance on rehabilitation (OR 2.35), feeling that rehabilitation was necessary (OR 10.11), better perceived health before MI (excellent vs poor OR 7.33), the ability to drive (OR 6.25), and post-secondary education (OR 3.32). CONCLUSIONS Several clinical and psychosocial factors are associated with decreased participation in cardiac rehabilitation programs after MI in the community. As many are modifiable, addressing them may improve participation and outcomes.

Prognostic significance of exercise-induced systemic hypertension in healthy subjects

Exercise hypertension has been suggested to predict future resting hypertension, but its significance in terms of cardiovascular risk has not been defined. To assess the prognostic significance of exercise hypertension, 150 healthy, asymptomatic subjects with normal resting blood pressures and exercise systolic blood pressures > or =214 mm Hg (i.e., >90th percentile) on Bruce treadmill tests were identified retrospectively and age- and gender-matched with subjects with exercise systolic blood pressures of 170 to 192 mm Hg (40th to 70th percentiles). Subjects were contacted by survey a mean of 7.7+/-2.9 years after the index treadmill test. The survey response rate was 93%. There were 12 deaths, including 8 in the exercise hypertension group. A major cardiovascular event, defined as cardiovascular death, myocardial infarction, stroke, coronary angioplasty, or coronary bypass graft surgery occurred in 5 controls and 10 subjects with exercise hypertension. At follow-up, 13 controls and 37 subjects with exercise hypertension were now diagnosed as having resting hypertension. In multivariate analysis, exercise hypertension was not a significant predictor for death or any individual cardiovascular event, but was for total cardiovascular events and new resting hypertension. The multivariate risk ratio for exercise hypertension was 3.62 (p = 0.03) in predicting a major cardiovascular event. Other significant predictors included body mass index and age. For predicting new resting hypertension, the multivariate odds ratio for exercise hypertension was 2.41 (p = 0.02). These data suggest that exercise hypertension carries a small but significant risk for major cardiovascular events in healthy, asymptomatic persons with normal resting blood pressures.

Peak exercise blood pressure stratified by age and gender in apparently healthy subjects

OBJECTIVE To determine the peak blood pressure responses during symptom-limited exercise in a large sample of apparently healthy subjects, including both men and women over a wide range of ages. DESIGN We retrospectively studied the blood pressure response during maximal treadmill exercise testing with use of the Bruce protocol in apparently healthy subjects. MATERIAL AND METHODS Peak exercise blood pressures in 7,863 male and 2,406 female apparently healthy subjects who underwent a screening treadmill exercise test with the Bruce protocol between 1988 and 1992 were analyzed by age and gender. RESULTS In this large referral population of apparently healthy subjects, peak exercise systolic and diastolic blood pressures and delta systolic blood pressure (rest to peak exercise) were higher in men than in women and were positively associated with age. In men, the 90th percentile of systolic blood pressure increased from 210 mm Hg for the age decade 20 to 29 years to 234 mm Hg for ages 70 to 79 years; the corresponding increase among women was from 180 mm Hg to 220 mm Hg. Delta diastolic blood pressure also increased with advancing age. The difference in peak and delta systolic blood pressures between men and women seemed to decrease after age 40 to 49 years. Exercise hypotension, defined as peak exercise systolic pressure less than rest systolic pressure, occurred in 0.23% of men and 1.45% of women and was not significantly related to age. CONCLUSION Overall, peak exercise systolic and diastolic, as well as delta systolic, blood pressures were higher in men than in women and increased with advancing age. The reported data will enable clinicians to interpret more accurately the significance of peak exercise blood pressure response in a subject of a specific age and gender and will allow investigators to define exercise hypertension in statistical terms stratified by age and gender.

Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index

Background Recently, mild elevations in body mass index (BMI) have been related to better outcomes in patients with coronary heart disease. Our aim was to determine whether patients with coronary heart disease who are participating in cardiac rehabilitation would have improved outcomes if they lost weight and whether this would depend on initial BMI. Methods This is a prospective cohort study of 377 consecutive patients enrolled at a cardiac rehabilitation program, aged 30–85 years with a mean follow-up of 6.4 ± 1.8 years. We measured total mortality, acute cardiovascular events (fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, emergent revascularization in the setting of unstable angina, and hospitalization for congestive heart failure) and a composite outcome (mortality + acute cardiovascular events). Statistical testing used Cox Proportional Hazards Regression. Results On average, the weight loss group (n = 220) lost 3.6 ± 4.1 kg, and the nonweight loss group (n = 157) gained 1.5 ± 1.4 kg (P< 0.0001). The rate of the composite outcome was 24% (53/220) in those who did lose weight versus 37% (58/157) in those who did not lose weight. Weight loss was significantly associated with lower rate of the composite outcome after adjustment for age, sex, smoking, dyslipidemia, diabetes, hypertension, myocardial infarction, and obese status [hazard ratio (HR) = 0.62; P = 0.018]. Subgroup analysis showed that patients who lost weight had favorable outcomes both in patients with BMI ≤25 (HR = 0.32; P = 0.035) and those with BMI ≥ 25 kg/m2 (HR = 0.64; P = 0.032). Conclusions Weight loss in cardiac rehabilitation is a marker for favorable long-term outcomes, regardless of initial BMI.

Niacin-Induced Hepatitis: A Potential Side Effect With Low-Dose Time-Release Niacin

Hepatitis developed in five patients who were taking low dosages (3 g/day or less) of time-release niacin. In four of the five patients, clinical symptoms of hepatitis developed after the medication had been taken for a relatively short time (2 days to 7 weeks). This manifestation of hepatotoxicity seems to differ from that previously reported in association with use of crystalline niacin, which occurred with high dosage and prolonged usage of the medication. In view of the recent increased frequency of prescribing niacin for the treatment of hyperlipidemia, physicians should be aware of the potential for hepatotoxicity with even low-dose and short-term use of time-release niacin.

Comparison of numbers of circulating blood monocytes in men grouped by body mass index (<25, 25 to <30, ≥30)

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Cardiovascular mortality in Hispanics compared to non-Hispanic whites: A systematic review and meta-analysis of the Hispanic paradox

BACKGROUND Hispanics, the largest minority in the U.S., have a higher prevalence of several cardiovascular (CV) risk factors than non-Hispanic whites (NHW). However, some studies have shown a paradoxical lower rate of CV events among Hispanics than NHW. OBJECTIVE To perform a systematic review and a meta-analysis of cohort studies comparing CV mortality and all-cause mortality between Hispanic and NHW populations in the U.S. METHODS We searched EMBASE, MEDLINE, Web of Science, and Scopus databases from 1950 through May 2013, using terms related to Hispanic ethnicity, CV diseases and cohort studies. We pooled risk estimates using the least and most adjusted models of each publication. RESULTS We found 341 publications of which 17 fulfilled the inclusion criteria; data represent 22,340,554 Hispanics and 88,824,618 NHW, collected from 1950 to 2009. Twelve of the studies stratified the analysis by gender, and one study stratified people by place of birth (e.g. U.S.-born, Mexican-born, and Central/South American-born). There was a statistically significant association between Hispanic ethnicity and lower CV mortality (OR 0.67; 95% CI, 0.57-0.78; p<0.001), and lower all-cause mortality (0.72; 95% CI, 0.63-0.82; p<0.001). A subanalysis including only studies that reported prevalence of CV risk factors found similar results. OR for CV mortality among Hispanics was 0.49; 95% CI 0.30-0.80; p-value <0.01; and OR for all-cause mortality was 0.66; 95% CI 0.43-1.02; p-value 0.06. CONCLUSION These results confirm the existence of a Hispanic paradox regarding CV mortality. Further studies are needed to identify the mechanisms mediating this protective CV effect in Hispanics.