Clinical profile and outcomes of obese patients in cardiac rehabilitation stratified according to National Heart, Lung, and Blood Institute criteria.

PURPOSE: Obesity is a major health problem and must be evaluated and treated in cardiac rehabilitation patients. The purpose of this study was to identify the scope of this problem in an urban-based cardiac rehabilitation program by evaluating the prevalence of obesity, and comparing the clinical and risk factor profiles and outcomes of patients stratified according to National Heart, Lung, and Blood Institute (NHLBI) weight classifications. METHODS: Four hundred forty-nine consecutive cardiac rehabilitation patients, aged 57 +/- 11 years, were stratified according to the NHLBI criteria as: normal (body mass index [BMI] 18-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), class I/II obese (BMI 30-39.9 kg/m2), and class III morbidly obese (BMI > or = 40 kg/m2). Baseline cardiac risk factors and dietary habits were identified, and both pre- and postexercise training measurements of exercise tolerance, weight, and lipid profile were obtained. RESULTS: Overweight and obesity (BMI > or = 25 kg/m2) were present in 88% of patients. Compared to normal weight patients, obese patients were younger and had a greater adverse risk profile (higher prevalence of diabetes and hypertension, larger waist circumference, lower exercise capacity, lower high-density lipoprotein cholesterol level) at entry. After 10 weeks, all groups had a significant increase in exercise capacity, and on average obese patients in each category lost weight (Class I/II--4 lbs and Class III--12 lbs). Dropout rates were similar among the groups. CONCLUSION: Overweight and obesity are highly prevalent in cardiac rehabilitation. Overweight and obese patients had a greater adverse cardiovascular risk profile, including a lower exercise capacity in the latter. Thus, targeted interventions toward weight management in contemporary cardiac rehabilitation programs are important. Although short-term outcomes appear promising, greater efforts to improve these outcomes and to support long-term management are needed.

Accuracy of a pretest questionnaire in exercise test protocol selection.

Proper exercise test protocol selection is essential to allow adequate time for observation of subjective and physiologic responses to exercise, as well as provider-patient interaction and patient comfort. This study evaluates the accuracy of a pretest questionnaire in predicting exercise capacity for exercise test protocol selection and compares the accuracy of this questionnaire when ramp versus step protocols are used.

Comparison of ramp versus step protocols for exercise testing in patients > or = 60 years of age.

To evaluate whether individualized ramp protocols may be better than step protocols in patients > or = 60 years of age referred for exercise testing, peak cardiopulmonary responses and accuracy in prediction of oxygen uptake (VO2) for individualized ramp and step protocols (Bruce or modified Bruce) were compared. Twenty-four subjects (67+/-3 years) with known or suspected coronary artery disease performed both tests in random order. Protocols were selected based on estimated exercise capacity using a pretest activity questionnaire. No differences were observed between peak VO2 (19.3+/-6.3 and 19.1+/-6.4 ml/kg/min), heart rate (127+/-15 and 126+/-16 beats/min), rate-pressure product (24.0+/-4.8 and 23.4+/-4.9 beats/min x mm Hg x 10(3)) and anaerobic threshold (16.6+/-3.7 and 16.0+/-4.7 ml/kg/min) for the ramp and step protocols, respectively. The relation between measured submaximal VO2 and American College of Sports Medicine (ACSM)-predicted VO2 during the ramp protocol is demonstrated by the regression coefficient (beta), where beta = 0.92 (95% confidence intervals [CI] 0.85 to 0.99) and for the step protocols where beta = 1.02 (95% CI 0.84 to 1.20). Peak cardiopulmonary responses in the elderly are similar during individualized ramp and step protocols when appropriately selected based on a pretest activity questionnaire. Both protocols appear to provide clinically reasonable estimates of VO2 when gas exchange analysis is not used.

Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols.

The purpose of this study was to evaluate whether individual ramp protocol treadmill testing is superior to frequently used step protocols in eliciting peak cardiopulmonary responses in obese women. The main findings indicate that protocol selection based on predicted pretest individual exercise capacity is more important than whether a ramp or step protocol is used.

Regulation of genomic imprinting by gametic and embryonic processes.

Parental genomic imprinting refers to the phenomenon by which alleles behave differently depending on the sex of the parent from which they are inherited. In the case of the murine transgene RSVIgmyc, imprinting is manifest in two ways: differential DNA methylation and differential expression. In inbred FVB/N mice, a transgene inherited from a male parent is undermethylated and expressed; a transgene inherited from the female parent is overmethylated and silent. Using a series of RSVIgmyc constructs and transgenic mice, we show that the imprinting of this transgene requires a cis-acting signal that is principally derived from the repeat sequences that make up the 3' portion of the murine immunoglobulin alpha heavy-chain switch region. Such imprinting is relatively independent of the site of transgene insertion but is influenced by the structure of the transgene itself. Imprinting is also modulated by genetic background. Detailed studies indicate that the paternal allele is undermethylated and expressed in inbred FVB/N mice and in heterozygous F1 FVB/N/C57Bl/6J mice but is overmethylated and silent in inbred C57Bl/6J mice. Consequently, the FVB/N genome appears to carry alleles of modulating genes that dominantly block methylation and permit expression of the paternally imprinted transgene. Furthermore, our results suggest that overmethylation is the default status of both parental alleles and that the paternal allele can be marked in trans by polymorphic factors that act in postblastocyst embryos.

Induction of immediate early genes by Ca2+ influx requires cAMP-dependent protein kinase in PC12 cells.

Agents that activate cAMP-dependent protein kinase (PKA) as well as agents that increase intracellular calcium induce the expression of certain immediate early genes (IEGs). Recently, it has been demonstrated that the same cis-acting element in the 5' region of the c-fos gene has the ability to mediate both cAMP- and calcium-induced c-fos expression in PC12 cells (Sheng, M., McFadden, G., and Greenberg, M. (1990) Neuron 4, 571-582). Here we demonstrate that both cAMP- and calcium-mediated induction of c-fos and egr1 are dependent on PKA activity. Addition of either depolarizing concentrations of KCl or the calcium ionophore, ionomycin, to PC12 cells increased the expression of both c-fos and egr1, but these inductions were dramatically reduced in three PKA-deficient cell lines, 123.7, AB.11, and A126-1B2. Furthermore, pretreatment of PC12 cells with 20 microM H89, a specific inhibitor of PKA, inhibited forskolin, dibutyryl cAMP, and KCl-induced c-fos and egr1 induction, while having no effect on NGF induction. Likewise, in the PKA-deficient cells, NGF or an activator of protein kinase C induced c-fos and egr1 normally. To determine if PKA deficiency modifies the ability of Ca2+ to activate calcium-dependent kinases, autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) in response to Ca2+ influx was determined. In parental PC12 cells, PC12 cells pretreated with H89, and PKA-deficient cell lines, CaM kinase was activated equivalently in response to KCl depolarization. These results suggest that PKA is not required for Ca(2+)-induced increase in CaM kinase activity and that the induction of IEGs in response to Ca2+ influx is PKA-dependent. Thus, the requirement for PKA resides at a point distal to the activation of calmodulin-dependent processes.