Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

BACKGROUND: The genetic influence on child obesity has not been fully elucidated. OBJECTIVE: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

Prenatal and early-life predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis Monitoring In earLY life (FAMILY) Study.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts.

OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary heart disease. We sought to determine ethnic differences in newborn adiposity comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two birth cohorts in Canada were analyzed. Pregnant women completed a health assessment including a 75-g oral glucose tolerance test to assess for dysglycemia. Birthweight, length, waist and hip circumference, and triceps and subscapular skinfold thickness (a surrogate measure of body adiposity) were measured in all newborns. Multivariate regression was used to identify maternal factors associated with newborn skinfold measurements. RESULTS: South Asian women were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns, South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn skinfold thickness included South Asian ethnicity (standardized estimate (s.e.): 0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight and have greater skinfold thickness, compared with White newborns, and this is influenced by maternal body fat and glucose. Interventions aimed at reducing body fat prior to pregnancy and gestational diabetes during pregnancy in South Asians may favorably alter newborn body composition and require evaluation.

Potentially modifiable risk factors associated with myocardial infarction in China: the INTERHEART China study.

BACKGROUND: Lifestyle changes associated with the rapidly developing economy increase cardiovascular disease (CVD), myocardial infarction (MI) and cardiovascular risk factors (CVRFs) in China. OBJECTIVE: To assess and compare regionally, and with other regions of the world, distribution of the nine INTERHEART CVRFs, their relationship to MI and the CVD epidemic in China in order to determine how this may influence the future of CVD in China. METHODS: Patients with first acute MI (n = 3030) and age- and sex-matched controls (n = 3056) were enrolled from 26 centres in China. RESULTS: Northern Chinese had higher rates of smoking and hypertension, whereas southern Chinese reported lower fruit and vegetable intake and higher rates of depression. Compared with other regions, participants from China were older, with lower body mass index and waist to hip ratios, lower total and low-density lipoprotein cholesterol levels, ApoB lipoprotein and ApoB to ApoA-1 ratios, but higher high-density lipoprotein cholesterol and ApoA-1. All nine INTERHEART CVRFs, education and income were significantly associated with MI in the Chinese cohort. There was significant heterogeneity in the strength of association between certain CVRFs and MI for China versus other regions, with stronger associations for the Chinese for diabetes (OR 5.10 vs 2.84), depression (2.27 vs 1.37) and permanent stress (2.67 vs 2.06); and lower for the Chinese for abdominal obesity (1.33 vs 2.62) (p for heterogeneity, all <0.001). CONCLUSIONS: Diabetes and psychosocial factors have strong associations with risk of MI in China, indicating that future increases in these risk factors with societal change in China may hasten rapid increases in CVD.

Ethnic differences in the relationships between obesity and glucose-metabolic abnormalities: a cross-sectional population-based study.

OBJECTIVES: To evaluate whether body mass index (BMI) and other anthropometric indices of visceral obesity vary by ethnic group in their distribution and their relationship to metabolic abnormalities. DESIGN: Cross-sectional study. PARTICIPANTS: Canadian men and women, aged 35-75 years, of South Asian (n=342), Chinese (n=317), European (n=326) and Aboriginal (n=301) descent were recruited using stratified random sampling. PRIMARY MEASURES: Anthropometric indices (BMI, waist to hip ratio (WHR) and waist circumference (WC)), metabolic markers (fasting glucose, HbA1c, the ratio of total cholesterol/HDL) and clinical markers (systolic blood pressure) were assessed. RESULTS: In subjects with BMI<30 kg/m2, the mean marker levels in people with elevated WC (>88 cm in women, >102 cm in men) vs people with normal WC were 6.16 vs 5.34 mmol/l for fasting glucose, 6.05 vs 5.66% for HbA1c and 5.46 vs 4.68 for the ratio of total cholesterol to HDL (P<0.001 in each case). At nearly every given level of BMI, non-European ethnic groups displayed significantly higher marker levels than Europeans. For example, for a given BMI, age and sex, the difference between European and non-European groups in HbA1c levels was 0.53% (95% confidence interval (CI): 0.37-0.69) for South Asians, 0.37% (95% CI: 0.2-0.54) for Chinese and 0.95% (95% CI: 0.78-1.12) for Aboriginal People. CONCLUSIONS: Uniform cut-points for the classification of obesity using BMI, WHR or WC result in marked variation in the levels of glucose-metabolic abnormalities between ethnic groups. Existing action thresholds for these anthropometric indices do not apply to non-European ethnic groups and warrant revision.

Acute precipitants of congestive heart failure exacerbations.

BACKGROUND: Few studies have prospectively and systematically explored the factors that acutely precipitate exacerbation of congestive heart failure (CHF) in patients with left ventricular dysfunction. Knowledge of such factors is important in designing measures to prevent deterioration of clinical status. The objective of this study was to prospectively describe the precipitants associated with exacerbation of CHF status in patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study. METHODS: We conducted a 2-stage, multicenter, randomized trial in 768 patients with CHF who had an ejection fraction of less than 40%. Patients were randomly assigned to receive enalapril maleate, candesartan cilexetil, or both for 17 weeks, followed by randomization to receive metoprolol succinate or placebo for 26 weeks. Investigators systematically documented information on clinical presentation, management, and factors associated with the exacerbation for any episode of acute CHF during follow-up. RESULTS: A total of 323 episodes of worsening of CHF occurred in 180 patients during 43 weeks of follow-up; 143 patients required hospitalization, and 5 died. Factors implicated in worsening of CHF status included noncompliance with salt restriction (22%); other noncardiac causes (20%), notably pulmonary infectious processes; study medications (15%); use of antiarrhythmic agents in the past 48 hours (15%); arrhythmias (13%); calcium channel blockers (13%); and inappropriate reductions in CHF therapy (10%). CONCLUSIONS: A variety of factors, many of which are avoidable, are associated with exacerbation of CHF. Attention to these factors and patient education are important in the prevention of CHF deterioration.

Randomised trials of secondary prevention programmes in coronary heart disease: systematic review.

OBJECTIVE: To determine whether multidisciplinary disease management programmes for patients with coronary heart disease improve processes of care and reduce morbidity and mortality. DATA SOURCES: Randomised clinical trials of disease management programmes in patients with coronary heart disease were identified by searching Medline 1966-2000, Embase 1980-99, CINAHL 1982-99, SIGLE 1980-99, the Cochrane controlled trial register, the Cochrane effective practice and organisation of care study register, and bibliographies of published studies. DATA EXTRACTION: Studies were selected and data were extracted independently by two investigators, and summary risk ratios were calculated by using both the random effects model and the fixed effects model. DATA SYNTHESIS: A total of 12 trials (9803 patients with coronary heart disease) were identified. Disease management programmes had positive impacts on processes of care. Patients randomised to these programmes were more likely to be prescribed efficacious drugs (risk ratio 2.14 (95% confidence interval 1.92 to 2.38) for lipid lowering drugs, 1.19 (1.07 to 1.32) for beta blockers, and 1.07 (1.03 to 1.11) for antiplatelet agents). Five out of seven trials evaluating risk factor profiles showed significantly greater improvements with these programmes in comparison with usual care (with effect sizes in the moderate range). Summary risk ratios were 0.91 (0.79 to 1.04) for all cause mortality, 0.94 (0.80 to 1.10) for recurrent myocardial infarction, and 0.84 (0.76 to 0.94) for admission to hospital. Five of the eight trials evaluating quality of life or functional status reported better outcomes in the intervention arms. Only three of these trials reported the costs of the intervention-the interventions were cost saving in two cases. CONCLUSIONS: Disease management programmes improve processes of care, reduce admissions to hospital, and enhance quality of life or functional status in patients with coronary heart disease. The programmes' impact on survival and recurrent infarctions, their cost effectiveness, and the optimal mix of components remain uncertain.

Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA).

BACKGROUND: The Total Occlusion Study of Canada (TOSCA) is a multicenter, randomized trial evaluating the effect of stenting with > =1 heparin-coated stent on long-term patency after percutaneous coronary intervention by balloon angioplasty of occluded coronary arteries. The purpose of the current study was to compare the effect of stenting and balloon angioplasty on global left ventricular ejection fraction (LVEF) and regional wall motion and to examine what clinical and angiographic factors may have an effect on left ventricular function in this setting. METHODS AND RESULTS: Analysis at the core angiographic laboratory of paired baseline and follow-up left ventricular angiograms, as well as target vessel patency, was possible in 244 of 410 cases. An improvement in LVEF was observed in the entire group (59.4% +/- 11% to 61.0% +/- 11%, P =.003). The LVEF change was +1.84 +/- 7.54 in the stent group (P =.009) and 1.28 +/- 8.16 in the percutaneous transluminal coronary angioplasty group (P =.085). There was no significant intergroup difference. Patients with duration of occlusion < or =6 weeks had an improvement in LVEF (+2.98 +/- 8.68, P =.0006), whereas those with an occlusion duration of > 6 weeks had no improvement (+0.48 +/- 7.01, P not significant). Multivariate analysis revealed baseline LVEF <60%, duration of occlusion < or =6 weeks, and Canadian Cardiology Society angina class I or II to be independent predictors of improvement in LVEF. CONCLUSIONS: The restoration of coronary patency of nonacute occluded coronary arteries is associated with a small but significant improvement in regional and global left ventricular function, especially in patients with recent occlusions and depressed left ventricular function. In spite of significant effect on long-term patency, stenting of nonacute coronary occlusions does not result in significantly better left ventricular function compared with balloon angioplasty in this setting.

A systematic review of randomized trials of disease management programs in heart failure.

PURPOSE: Disease management programs are often advocated for the care of patients with chronic disease. This systematic review was conducted to determine whether these programs improve outcomes for patients with heart failure. METHODS: Randomized clinical trials of disease management programs in patients with heart failure were identified by searching Medline 1966 to 1999, Embase 1980 to 1998, Cinahl 1982 to 1999, Sigle 1980 to 1998, the Cochrane Controlled Trial Registry, the Cochrane Effective Practice and Organization of Care Study Registry, and the bibliographies of published studies. We also contacted experts in the field. Studies were selected and data extracted independently by two investigators, and summary risk ratios (RR) and 95% confidence intervals (CI) were calculated using both the random and fixed effects models. RESULTS: A total of 11 trials (involving 2,067 patients with heart failure) were identified. Disease management programs were cost saving in 7 of the 8 trials that reported cost data and also appeared to have beneficial effects on prescribing practices. Hospitalizations (RR = 0.87, 95% CI: 0.79 to 0.96) but not all-cause mortality (RR = 0.94, 95% CI: 0.75 to 1.19) were reduced by the programs. However, there were considerable differences in the effects of various interventions on hospitalization rates; specialized follow-up by a multidisciplinary team led to a substantial reduction in the risk of hospitalization (RR = 0.77, 95% CI 0.68 to 0.86, n = 1366), whereas trials employing telephone contact with improved coordination of primary care services failed to find any benefit (RR = 1.15, 95% CI 0.96 to 1.37, n = 646). CONCLUSION: Disease management programs for the care of patients with heart failure that involve specialized follow-up by a multidisciplinary team reduce hospitalizations and appear to be cost saving. Data on mortality are inconclusive. Further studies are needed to establish the incremental benefits of the different elements of these programs.

Predicting and explaining cardiac rehabilitation attendance.

BACKGROUND: A variety of factors influence patients' health behaviour; these are patterns of practitioner practice, patient characteristics and availability of resources. OBJECTIVES: To examine patient-related factors (demographic, health, psychosocial characteristics) that may influence patients' attendance at cardiac rehabilitation programs and their subsequent behaviour change. PATIENTS AND METHODS: A prospective cohort design was used. Three hundred four acute myocardial infarction and/or coronary artery bypass graft surgery patients from a tertiary care centre in a Western Canadian city were enrolled to participate in telephone interviews at two weeks and again at approximately six months after their hospital discharge. Measures of self-efficacy and behaviour performance for cardiac health maintenance and role resumption, motivation and social support were used at both interview times. A survey focusing on factors influencing patients' choices to attend cardiac rehabilitation programs was also administered at the interview six months after discharge. RESULTS: Attendance at cardiac rehabilitation programs is not associated with patients' risk factor status, and elderly and rural-living patients are at particular risk for nonattendance. CONCLUSIONS: Systematic mechanisms to guide the appropriate referral of patients to this health care resource and administer secondary prevention initiatives to those with limited access to resources need to be a priority in cardiovascular health care.

Psychosocial components of cardiac recovery and rehabilitation attendance.

OBJECTIVE: To examine the relations between demographic factors, specific psychosocial factors, and cardiac rehabilitation attendance. DESIGN: Cohort, repeated measures design. SETTING: A large tertiary care centre in western Canada PATIENTS: 304 consecutive consenting patients discharged following acute myocardial infarction and/or coronary artery bypass graft surgery. MAIN OUTCOME MEASURES: The Jenkins self-efficacy expectation scales and activity checklists of behaviour performance for maintaining health and role resumption, modified version of the self-motivation inventory, and the shortened social support scale. RESULTS: Those who had higher role resumption behaviour performance scores at two weeks after discharge were significantly less likely to attend cardiac rehabilitation programmes. At six months after discharge, those who attended cardiac rehabilitation demonstrated higher health maintenance self-efficacy expectation and behaviour performance scores. Health maintenance self-efficacy expectation and behaviour performance improved over time. Women reported less social support but showed greater improvement in health maintenance self-efficacy expectation. Changes in self-efficacy scores were unrelated to-but changes in health maintenance behaviour performance scores were strongly associated with-cardiac rehabilitation attendance. CONCLUSIONS: Cardiac patients and practitioners may have misconceptions about the mandate and potential benefits of rehabilitation programmes. Patients who resumed role related activities early and more completely apparently did not see the need to "rehabilitate" while those who attended cardiac rehabilitation programmes enhanced their secondary prevention behaviours.

Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE)

BACKGROUND: Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese, and Europeans. METHODS: 985 participants were recruited from three cities (Hamilton, Toronto, and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured. FINDINGS: Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5%, and 2%, respectively, p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm), and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and LDL cholesterol, higher triglycerides, and lower HDL cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein (a), and plasminogen activator inhibitor-1. INTERPRETATION: Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.

Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Functional capacity in patients with congestive heart failure.

BACKGROUND: Six-minute walk distance (6MWd) is related to activities of daily living and is also an independent predictor of prognosis in patients with congestive heart failure (CHF). Therefore, it is important to determine factors that contribute to the variability of this test. METHODS AND RESULTS: We assessed the relationship between 6MWd and peak aerobic capacity (VO2) and dynamic muscle strength in 180 patients with CHF (age, 66+/-10 years; 146 men, 34 women; ejection fraction, .29+/-0.08). We also hypothesized that a measure of work performed during the walk test (6MWw) would be a better indicator of exercise capacity than 6MWd. The 6MWd had weak to moderate correlations with dynamic muscle strength (r = 0.33 to 0.41) and peak VO2 (r = 0.48). However, 6MWw was strongly related to dynamic muscle strength (r = 0.63 to 0.70) and peak VO2 (r = 0.77). Multivariate analysis indicated that a model combining dynamic muscle strength and peak VO2 explained 69% of the variance in 6MWw, more than with peak VO2 alone (R2 = 0.59). CONCLUSIONS: Compared with 6MWd, 6MWw correlates significantly better with peak VO2 and dynamic muscle strength, suggesting that 6MWw may be a better reflection of a patient's exercise capacity. Furthermore, these results suggest that an exercise program combining both aerobic and strength training in patients with CHF may improve 6MWw and therefore 6MWd.

Integrating clinical quality improvement strategies with nursing research.

Bridging the research-practice gap has been a focus of concern for nursing and other health care disciplines. The challenge in linking research and practice is for practitioners to use consistently the best available evidence in their clinical practice and for researchers to engage in clinically relevant research that provides practitioners with the evidence to do so. The authors of this article advocate that blending Clinical Quality Improvement (CQI) strategies with research methodology is a means of bridging the research-practice gap. The process of blending CQI strategies and nursing research is described in this article.

Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS).

BACKGROUND: We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction. METHODS AND RESULTS: Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053). CONCLUSION: These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.

Beta-blockers for congestive heart failure: what is the current consensus?

Despite the availability of angiotensin converting enzyme (ACE) inhibitors for patients with congestive heart failure (CHF), mortality and morbidity remains unacceptably high. CHF is thought to progress as a result of activation of endogenous neurohormonal systems which are activated by the initial myocardial injury. The 2 neurohormonal systems which seem to be important in CHF are the sympathetic nervous system (SNS), and the renin-angiotensin-aldosterone system (RAAS). While stimulation of the SNS has important circulatory support functions in the short term, long term activation appears to have deleterious effects on cardiac function and outcomes. The purpose of this article is to review the literature on the use of beta-blockers in patients with CHF. The published randomised clinical trials of beta-blockers in patients with CHF have shown very promising effects on mortality and morbidity. Several systematic overviews of these trials also suggest beneficial effects on mortality, hospitalisation for CHFE need for transplant, and ejection fraction. The effect of beta-blockers on exercise tolerance. New York Heart Association Function Class (NYHA-FC) and quality of life remain equivocal. The recent presentation of the results from several large-scale trials which were terminated early because of significant survival benefit, has removed any concern over the robustness of the mortality data. Available evidence suggests that a wide variety of patients with CHF, including the elderly, should be considered for beta-blocker therapy. Caution is warranted in the initiation and titration of therapy, as symptoms of CHF may transiently worsen. Whether all beta-blockers are equally efficacious remains unknown.