Lipid lowering in the cardiac rehabilitation setting.

PURPOSE: The authors determined the frequency and effectiveness of pharmacologic lipid lowering, guided by the recommendations of the National Cholesterol Education Program (NCEP) before and after institution of a systematic lipid assessment performed at the time of the cardiac rehabilitation entry evaluation. METHODS: The systematic lipid evaluation included a full lipid profile and a dietary evaluation at which time an active approach to pharmacologic lipid therapy was taken. Therapy was guided by the NCEP guidelines, with the collaboration of the referring physician. The frequency of lipid therapy change (starting or changing therapy) from the baseline evaluation to a 3-month follow-up visit was the primary study outcome variable. The control group consisted of 51 patients with coronary heart disease (CHD) seen in 1995 at cardiac rehabilitation, who agreed to have their serum lipids measured in a double-blinded fashion. There was no systematic lipid lowering intervention. The intervention group consisted of 187 patients with CHD who participated in cardiac rehabilitation in 1996 to 1997. RESULTS: At baseline, a similar percentage of patients in each group were on lipid lowering therapy: 38% (19/51) in controls versus 35% (65/187) in intervention patients. Among patients with a baseline low-density lipoprotein (LDL) cholesterol of > or = 130 mg/dL, therapy was modified in 18% (4/22) of control patients compared with 52% (35/68) of intervention patients (P < 0.05). Among patients with a baseline LDL cholesterol of > or = 160, therapy was altered in 22% (2/9) control patients compared with 72% (18/25) intervention patients (P < 0.01). In both risk strata of > or = 130 mg/dL and > or = 160 mg/dL, LDL cholesterol measures were lowered to a greater degree in the intervention group. CONCLUSIONS: The performance of a systematic lipid review at the time of cardiac rehabilitation entry, with an active stance toward pharmacologic therapy, results in a threefold increase in pharmacologic modifications and lower LDL cholesterol values for cardiac rehabilitation participants.     

Primary care anticoagulant clinic management using computerized decision support and near patient International Normalized Ratio (INR) testing: routine data from a practice nurse-led clinic

BACKGROUND: Increasing indications for warfarin therapy has led to increased pressure on primary care to undertake therapeutic monitoring. OBJECTIVE: This study evaluates a primary care model of oral anticoagulation monitoring which utilises computerized decision support (CDSS) and near patient testing (NPT) within a practice nurse-led clinic. Whilst this has been shown to be a successful model under trial conditions, this paper reports the first data from a long-standing clinic, outside a formal study. METHOD: A prospective evaluation of therapeutic and clinical control of all patients taking warfarin within one inner city general practice. Data were collected via CDSS. RESULTS: 29 patients were seen in 208 appointments. The mean percentage of patients within therapeutic range was 72%. The costs to the practice were pound sterling 1751. The costs the practice would have incurred had these patients been seen at the hospital with the same frequency would have been pound sterling 2290. CONCLUSIONS: The use of CDSS and NPT for nurse-delivered oral anticoagulation monitoring could enable the safe transfer of the majority of patients from secondary to primary care. Funding mechanisms to support the transfer of costs will be essential for most practices, as will be the maintenance of adequate staff training and quality assurance.      

Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women

INTRODUCTION: Genetic variants affecting adrenoceptors have been suggested to influence body fatness. A putative gain-of-function polymorphism in the beta(1)-adrenoceptor was recently discovered (Gly389Arg ADRB1). We examined the association between Gly389Arg ADRB1 and obesity status in a large cohort of well-characterized individuals. METHODS: First, a large cohort of 931 Caucasian women (55.0+/-12.2 y) were genotyped for Gly389Arg ADRBbeta1 and we examined the association of the Arg allele with body weight and BMI (Gly/Gly, n=54; Gly/Arg, n=360; Arg/Arg, n=517). To further examine phenotypes regulating energy balance and body fatness, we examined the contribution of the Arg allele to body composition (DEXA), fat distribution (CT scan), resting energy expenditure, energy and macronutrient intake, maximal oxygen capacity, and physical activity in a subsample of 214 women from the main cohort that had been carefully characterized (Gly/Gly, n=19; Gly/Arg, n=82; Arg/Arg, n=113). RESULTS: In the entire cohort (n=931), allele frequencies were 0.25 and 0.75 for the Gly and Arg alleles, respectively. In this cohort, we found that each Arg allele was associated with greater body weight of 2.91 kg (P=0.01) and BMI of 0.86 kg/m(2) (P=0.05). Accordingly, in the subsample of women, each Arg allele was associated with greater fat mass (3.71 kg; P=0.008). Other phenotypes were not significantly associated with the presence of the Arg allele. CONCLUSIONS: This is the first study to investigate the relationship between the Gly389Arg ADRB1 variant and obesity. We found that the Arg allele is associated with greater body weight and BMI in Caucasian women due to a greater fat mass.     

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220- expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.     

Modest effects of exercise training alone on coronary risk factors and body composition in coronary patients

BACKGROUND: Cardiac rehabilitation programs have evolved to become secondary prevention centers. However, the independent effect of exercise alone on coronary risk factors and body composition in patients with coronary artery disease has not been well studied. OBJECTIVE: The aim of this study was to determine the effect of exercise training alone, without modification of dietary intake, on coronary risk factors and body composition in a coronary population. METHODS: The authors studied 82 coronary patients (23 females and 59 males) aged 61.2 +/- 12.2 years (mean +/- SD) before and after a 3-month exercise training program. Outcome variables included serum lipid values, glucose, insulin, body composition, body fat distribution, macronutrient intake, and peak aerobic capacity. RESULTS: Neither male nor female patients experienced a significant overall improvement in plasma cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose, or insulin levels after the 3-month exercise training program. Dietary macronutrient intake was unaltered during the study period. Peak aerobic capacity increased by 3.4 +/- 4.7 ml/kg/min (17%, P < 0.0001) and high-density lipoprotein (HDL)-cholesterol increased from 38 +/- 10 to 41 +/- 11 mg/dL (8%, P < 0.001) after the rehabilitation program. Patients with baseline triglyceride levels over 200 mg/dL experienced a 22% decrease (from 374 +/- 205 to 293 +/- 190 mg/dL; P < 0.05) after conditioning. Patients with baseline HDL-cholesterol levels under 35 mg/dL also improved overall by 17% (from 29 +/- 3 to 34 +/- 5 mg/dL; P < 0.0001). Exercise-induced changes in plasma HDL-cholesterol were more related to changes in body composition and/or body fat distribution, rather than changes in peak aerobic capacity. CONCLUSION: Exercise conditioning alone resulted in relatively modest risk factor improvements in coronary patients after 3 months. High-density lipoprotein cholesterol measures increased by 3 +/- 8 mg/dL (8%). Patients with baseline triglyceride elevations experienced a 22% decrease. On the other hand, there were no overall effects on body weight, total cholesterol, LDL-cholesterol, triglycerides, glucose, or insulin levels. For most patients, exercise effects were minimal and nutritional and medical therapy will need to be used more aggressively to attain nationally recognized risk factor goals.     

Coronary risk profiles in men with coronary artery disease: effects of body composition, fat distribution, age and fitness

BACKGROUND: Few studies have investigated the influence of body composition, abdominal obesity, age and fitness on coronary risk factors in populations of patients with coronary heart disease (CHD). We investigated whether abdominal obesity or generalized adiposity is a better predictor of cardiovascular risk in men with coronary artery disease (CAD), and the effects of exercise training on coronary risk factors in younger and older patients with CAD. METHODS: The study population consisted of 81 male patients aged 33-83 years (mean +/- SD 60.0 +/- 13.3 years) with established CAD. We studied the relationships among body composition, body fat distribution, dietary intake, peak aerobic capacity, lipid concentrations, and plasma glucose and insulin concentrations. We subsequently measured the influence of exercise training on these components. RESULTS: The study population was characterized by a high prevalence of obesity, particularly in younger patients. Body mass index, rather than body fat distribution, was the best anthropometric predictor of plasma triglyceride concentrations (r2 = 0.11, P < 0.05) and cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (r2 = 0.13, P < 0.01). Body weight, rather than body fat distribution, was the best predictor of plasma HDL-C concentration (r2 = 0.14, P < 0.01) and fasting glucose concentrations (r2 = 0.10, P < 0.05). Fat mass was the best anthropometric predictor of fasting plasma insulin concentrations (r2 = 0.38, P < 0.0001) and for the glucose-insulin ratio (r2 = 0.39, P < 0.0001) in men with CAD. Younger patients tended to have greater improvements in HDL-C concentrations and the cholesterol:HDL-C ratio than did older individuals, as a result of exercise training. CONCLUSION: In men with CAD, general measures of obesity, such as body weight, body mass index, and fat mass are better predictors of coronary risk factors than body fat distribution. Younger and older men with CAD experienced similar improvements in body composition and body fat distribution after an exercise training program.     

Epstein-Barr virus and familial Hodgkin's disease

Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV in familial HD (FHD). Among 60 FHD patients from 27 families with two or more cases per family, we tested available paraffinized tumor tissues from 46 cases by in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate of EBV positivity was evaluated among 34 first-degree related pairs from 17 families for which both cases had available paraffinized tumor tissues. Only two of 17 pairs were concordant for EBER1 positivity. There was no excess of positive concordance (P = .18). Serologically, FHD patients had higher geometric mean antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA- D). There was no difference in seroprevalence between patients and control groups, nor was there concordance in elevated serology among 15 pairs of first-degree related FHD cases. Young adult unaffected family members (UFM) may not react to EBV in the same way as the general population as evidenced by the lower titer of VCA, although not statistically significant, and significantly lower titers of EA-D, compared with age-matched controls. While EBV might have some role in a subset of HD, lack of concordance of EBER1 expression and EBV serology among the FHD cases in the same family suggest that EBV does not play an important role in FHD.     

Energy expenditure and requirements in aging humans.

Although physical activity is frequently recommended for the elderly individual, its influence on energy intake and energy expenditure is unclear. The use of indirect calorimetry techniques and stable isotopes make it possible to examine the effects of physical activity on total daily energy expenditure and its components. In this review, the influence of physical activity on adaptive changes in energy intake, daily energy expenditure, resting metabolic rate and the energy expenditure of physical activity during nonexercising time was examined. Recent findings show that moderate physical activity can increase resting metabolic rate and energy intake in the elderly. Vigorous exercise, however, did not increase total daily energy expenditure because of a compensatory decline in physical activity during nonexercising time. These findings should prompt investigators to re-examine the influence of different levels of endurance exercise on total daily energy expenditure in an attempt to maximize the energy expending properties of physical exercise in older persons. A second objective was to examine the current status of methodology to predict energy requirements in older persons. Current recommendations for energy lack specificity and have not considered the influence of physical activity and body composition. Energy needs of older persons need to be re-examined based on the measurement of total daily energy expenditure. It will then be important to identify biological markers of total daily energy expenditure that take into account the variation in physical activity and body composition.