Paul Corey

Prediction of Long-Term Prognosis in 12 169 Men Referred for Cardiac Rehabilitation

Background—Predicting the risk of cardiac and all-cause death in patients with established coronary heart disease is important in counseling the individual and designing risk-stratified rehabilitation and secondary prevention programs. Cox proportional hazards and Kaplan-Meier survival curves were thus completed on initial assessment data obtained from patients referred to an outpatient cardiac rehabilitation center. Methods and Results—A single-center prospective observational design took peak cardiorespiratory exercise test data for 12 169 male rehabilitation candidates aged 55.0±9.6 years (7096 myocardial infarctions [MIs], 3077 coronary artery bypass grafts [CABGs], and 1996 documented cases of ischemic heart disease [IHD]). A follow-up of 4 to 29 years (median, 7.9) yielded 107 698 man-years of experience. Entry data were tested for associations with time to cardiac and all-cause death. We recorded 1336 cardiac deaths (953 MI, 225 CABG, and 158 IHD) and 2352 all-cause deaths. A powerful predictor of cardiac and all-cause mortality was measured peak oxygen intake (&OV0312;o2peak). For the overall sample, values of <15, 15 to 22, and >22 mL/kg per minute yielded respective multivariate adjusted hazard ratios of 1.00, 0.62, and 0.39 for cardiac and 1.00, 0.66, and 0.45 for all-cause deaths. For the separate diagnostic categories, apart from &OV0312;o2peak, the only other significant predictors of cardiac death common to all 3 were smoking and digoxin, and for all-cause death, age, smoking, digoxin, and diabetes. Conclusions—Exercise capacity, as determined by direct measurement of &OV0312;o2peak, exerts a major long-term influence on prognosis in men after MI, CABG, or IHD and can play a valuable role in risk stratification and counseling.

Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.

Insights Into the Mechanisms and Mediators of the Effects of Air Pollution Exposure on Blood Pressure and Vascular Function in Healthy Humans

Fine particulate matter air pollution plus ozone impairs vascular function and raises diastolic blood pressure. We aimed to determine the mechanism and air pollutant responsible. The effects of pollution on heart rate variability, blood pressure, biomarkers, and brachial flow-mediated dilatation were determined in 2 randomized, double-blind, crossover studies. In Ann Arbor, 50 subjects were exposed to fine particles (150 &mgr;g/m3) plus ozone (120 parts per billion) for 2 hours on 3 occasions with pretreatments of an endothelin antagonist (Bosentan, 250 mg), antioxidant (Vitamin C, 2 g), or placebo. In Toronto, 31 subjects were exposed to 4 different conditions (particles plus ozone, particles, ozone, and filtered air). In Toronto, diastolic blood pressure significantly increased (2.9 and 3.6 mm Hg) only during particle-containing exposures in association with particulate matter concentration and reductions in heart rate variability. Flow-mediated dilatation significantly decreased (2.0% and 2.9%) only 24 hours after particle-containing exposures in association with particulate matter concentration and increases in blood tumor necrosis factor &agr;. In Ann Arbor, diastolic blood pressure significantly similarly increased during all of the exposures (2.5 to 4.0 mm Hg), a response not mitigated by pretreatments. Flow-mediated dilatation remained unaltered. Particulate matter, not ozone, was responsible for increasing diastolic blood pressure during air pollution inhalation, most plausibly by instigating acute autonomic imbalance. Only particles from urban Toronto additionally impaired endothelial function, likely via slower proinflammatory pathways. Our findings demonstrate credible mechanisms whereby fine particulate matter could trigger acute cardiovascular events and that aspects of exposure location may be an important determinant of the health consequences.

Acute blood pressure responses in healthy adults during controlled air pollution exposures

Exposure to air pollution has been shown to cause arterial vasoconstriction and alter autonomic balance. Because these biologic responses may influence systemic hemodynamics, we investigated the effect of air pollution on blood pressure (BP). Responses during 2-hr exposures to concentrated ambient fine particles (particulate matter < 2.5 μm in aerodynamic diameter; PM2.5) plus ozone (CAP+O3) were compared with those of particle-free air (PFA) in 23 normotensive, non-smoking healthy adults. Mean concentrations of PM2.5 were 147 ± 27 versus 2 ± 2 μg/m3, respectively, and those of O3 were 121 ± 3 versus 8 ± 5 ppb, respectively (p < 0.0001 for both). A significant increase in diastolic BP (DBP) was observed at 2 hr of CAP+O3 [median change, 6 mm Hg (9.3%); binomial 95% confidence interval (CI), 0 to 11; p = 0.013, Wilcoxon signed rank test] above the 0-hr value. This increase was significantly different (p = 0.017, unadjusted for basal BP) from the small 2-hr change during PFA (median change, 1 mm Hg; 95% CI, −2 to 4; p = 0.24). This prompted further investigation of the CAP+O3 response, which showed a strong association between the 2-hr change in DBP (and mean arterial pressure) and the concentration of the organic carbon fraction of PM2.5 (r = 0.53, p < 0.01; r = 0.56, p < 0.01, respectively) but not with total PM2.5 mass (r ≤ 0.25, p ≥ 0.27). These findings suggest that exposure to environmentally relevant concentrations of PM2.5 and O3 rapidly increases DBP. The magnitude of BP change is associated with the PM2.5 carbon content. Exposure to vehicular traffic may provide a common link between our observations and previous studies in which traffic exposure was identified as a potential risk factor for cardiovascular disease.

The impact of excluding non-leisure energy expenditure on the relation between physical activity and mortality in women.

The purpose of this study was to examine the relation between physical activity and mortality in a 7-year follow-up of a sample of women more than 30 years of age (N = 6,620) from the Canada Fitness Survey cohort, which was initiated in 1981. Age-adjusted relative risks relating quartiles of average daily energy expenditure (kilocalories per kilogram of body weight per day) to mortality were estimated using logistic regression. Compared with the least active, the risk of all-cause mortality was 0.73 for those in the highest quartile (P for trend = 0.03). The associations were stronger for cardiovascular disease mortality (odds ratio = 0.51; P for trend = 0.01) and fatal myocardial infarction (odds ratio = 0.61; P for trend = 0.04) for those in the highest quartile. These relations were due mainly to the contribution of non-leisure (household chores) energy expenditure, which represented, on average, 82% of womens total activity. The accompanying study on the same cohort by Villeneuve et al reported estimates based on a subset of leisure-time physical activity only, which underestimates the activity of many women (Villeneuve PJ, Morrison HI, Craig CL, Schaubel DE. Physical activity, physical fitness, and risk of dying. Epidemiology 1998; 9;632–635). The resulting bias illustrates the importance of including non-leisure energy expenditure in the assessment of total activity. These data support the hypothesis that physical activity is inversely associated with risk of death in women. (Epidemiology 1998; 9:632–635)

Individual correlates of health service utilization and the cost of poor adjustment to chronic illness.

It was conjectured that a small group of chronically ill in tertiary ambulatory clinics consume a large amount of health resources and that, from the perspective of the patient, psychosocial rather than disease variables would most explain their health service utilization and subsequent cost. New referrals with a chronic illness (N = 215) to one of three clinics (oncology, rheumatology, and gastroenterology) consented to participate in a subsequent trial of a psychosocial intervention designed to promote their adjustment to illness and, conceivably, to reduce their health service utilization. At baseline an inventory to describe the disease, treatment, functional capacity, prognosis, and socioeconomic situation of consenting subjects was completed. In addition, subjects completed the Psychosocial Adjustment to Illness Inventory (PAIS-SR), the Family Assessment Device (FAD), the Meaning of Illness Questionnaire (MIQ), and a Health Service Utilization Inventory designed to assess direct and indirect costs of health resources. These data were entered into a concurrent analytic survey design. Participating subjects represented a more socioeconomically advantaged and better-adjusted group of chronically ill patients compared with others referred to the tertiary clinics. They were representative of all new referrals in their use of the majority of health services. However, once hospitalized, participating subjects stayed longer and used specialists less. There was no important relationship between disease severity or prognosis and any type of service utilization, including hospitalization. Because the strongest correlate of all types of health services consumed was psychosocial adjustment to illness (r = 0.28 to 0.33), patients were partitioned into one of three categories of adjustment to illness: good, fair, and poor. The total annual cost per patient was

Influence of an employee fitness programme upon fitness, productivity and absenteeism

23,883, if poorly adjusted, compared with

Development and validation of Transfusion Risk Understanding Scoring Tool (TRUST) to stratify cardiac surgery patients according to their blood transfusion needs.

9,791 if well adjusted. If cash transfers (benefits paid by different types of insurance) are added, the average 1987 annual cost per poorly adjusted subject was

Increases in HIV incidence among men who have sex with men undergoing repeat diagnostic HIV testing in Ontario, Canada.

31,291 per patient, compared with

Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations

13,771 for a patient well adjusted to the illness. There was a statistically significant and economically important linear gradient in 1987 treatment costs per category of adjustment. The possible economic implications for psychosocial intervention are highlighted.