This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors.
Most cardiovascular ...clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease.
All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals.
The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked >or=150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 +/- 0.13 kg/m(2) to 29.3 +/- 0.23 kg/m(2) (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 +/- 0.49 mm Hg to 123 +/- 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 +/- 0.83 mg/dl to 72 +/- 0.88 mg/dl.
Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).
Novel Risk Factors for Atherosclerosis Kullo, Iftikhar J.; Gau, Gerald T.; Tajik, A. Jamil
Mayo Clinic proceedings,
04/2000, Letnik:
75, Številka:
4
Journal Article
Recenzirano
Odprti dostop
In the past several years, evidence has accumulated that factors other than conventional risk factors may contribute to the development of atherosclerosis. Conventional risk factors predict less than ...one half of future cardiovascular events. Furthermore, conventional risk factors may not have the same causal effect in different ethnic groups in whom novel risk factors may have a role. These newer risk factors for atherosclerosis include homocysteine, fibrinogen, impaired fibrinolysis, increased platelet reactivity, hypercoagulability, lipoprotein(a), small dense low-density lipoprotein cholesterol, and inflammatory-infectious markers. Identification of other markers associated with an increased risk of atherosclerotic vascular disease may allow better insight into the pathobiology of atherosclerosis and facilitate the development of preventive and therapeutic measures. In this review, we discuss the evidence associating these factors in the pathogenesis of atherosclerosis, the mechanism of risk, and the clinical implications of this knowledge.
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 ≥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.
We examined the degree of ventilatory constraint in patients with a history of chronic heart failure (CHF; n = 11; mean ± SE age, 62 ± 4 years; cardiac index CI, 2.0 ± 0.1; and ejection fraction EF, ...24 ± 2%) and in control subjects (CTLS; n = 8; age, 61 ± 5 years; CI, 2.6 ± 0.3) by plotting the tidal flow-volume responses to graded exercise in relationship to the maximal flow-volume envelope (MFVL). Inspiratory capacity (IC) maneuvers were performed to follow changes in end-expiratory lung volume (EELV) during exercise, and the degree of expiratory flow limitation was assessed as the percent of the tidal volume (Vt) that met or exceeded the expiratory boundary of the MFVL. CHF patients had significantly (p < 0.05) reduced baseline pulmonary function (FVC, 76 ± 4%; FEV1, 78 ± 4% predicted) relative to CTLS (FVC, 99 ± 4%; FEV1, 102 ± 4% predicted). At peak exercise, oxygen consumption ( V˙o2) and minute ventilation ( V˙e) were lower in CHF patients than in CTLS ( V˙o2, 17 ± 2 vs 32 ± 2 mL/kg/min; V˙e, 56 ± 4 vs 82 ± 6 L/min, respectively), whereas V˙e/carbon dioxide output was higher (42 ± 4 vs 29 ± 5). In CTLS, EELV initially decreased with light exercise, but increased as V˙e and expiratory flow limitation increased. In contrast, the EELV in patients with CHF remained near residual volume (RV) throughout exercise, despite increasing flow limitation. At peak exercise, IC averaged 91 ± 3% and 79 ± 4% (p < 0.05) of the FVC in CHF patients and CTLS, respectively, and flow limitation was present over > 45% of the Vt in CHF patients vs < 25% in CTLS (despite the higher V˙e in CTLS). The least fit and most symptomatic CHF patients demonstrated the lowest EELV, the greatest degree of flow limitation, and a limited response to increased inspired carbon dioxide during exercise, all consistent with V˙e constraint. We conclude that patients with CHF commonly breathe near RV during exertion and experience expiratory flow limitation. This results in V˙e constraint and may contribute to exertional intolerance.
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.
We ...retrospectively studied the blood pressure response during maximal treadmill exercise testing with use of the Bruce protocol in apparently healthy subjects.
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.
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&x0025; of men and 1.45&x0025; of women and was not significantly related to age.
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.
Ventilatory efficiency is the increase in ventilation relative to carbon dioxide production during exercise. Congestive heart failure (CHF) is associated with decreased ventilatory efficiency. ...β-blockers improve hemodynamics, prolong survival, and improve functional class in patients with CHF, though peak exercise performance may not improve. We hypothesized β-blockers increase ventilatory efficiency in patients with CHF.
The study group comprised 614 subjects with left ventricular ejection fraction ≤40% referred for cardiopulmonary exercise testing. Clinical and exercise data were reviewed and recorded. For comparison, subjects were divided into those treated with β-blockers (n
=
195) and those not treated (n
=
419). Subjects on β-blockers had lower minute ventilation (12 ± 4 versus 14 ± 4 L/min,
P < .001) at rest, which remained lower during submaximal and maximal exercise, by 4 and 6 L/min, respectively (
P
=
.001). Ventilatory efficiency was increased in subjects treated with β-blockers at submaximal (32 ± 6 versus 34 ± 7,
P
=
.002) and maximal (34 ± 7 versus 37 ± 10,
P
=
.005) exercise. Differences between treatment subgroups remained significant by covariate analysis; β-blockers were also independently associated with decreased minute ventilation by multiple regression.
β-Blockers may be associated with increased ventilatory efficiency in CHF patients, which may contribute to improved functional class and quality of life.
Objectives This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. Background ...Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. Methods All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. Results The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked ≥150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 ± 0.13 kg/m2 to 29.3 ± 0.23 kg/m2 (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 ± 0.49 mm Hg to 123 ± 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 ± 0.83 mg/dl to 72 ± 0.88 mg/dl. Conclusions Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657 )
Atherosclerosis is a systemic diffuse disease that may manifest as an anglographically localized coronary, cerebral, mesenteric, renal, and/or peripheral arterial stenosis or as diffuse ...atherosclerosis. While relief of organ ischemia is frequently possible with percutaneous or surgical revascularization, this in itself does not alleviate the long-term risks of disease recurrence or modify the metabolic derangements that promote atherosclerosis. It is critically important to recognize the need for treatment of dyslipidemia and to institute necessary therapies. The complex role of lipoprotein abnormalities is well understood and the use of lipid-lowering agents (90% statins) is reviewed in both primary and secondary prevention. The clinical interaction with novel risk factors and the practical problems in patient management are discussed.
The impact of stable, chronic heart failure on baseline pulmonary function remains controversial. Confounding influences include previous coronary artery bypass or valve surgery (CABG), history of ...obesity, stability of disease, and smoking history.
To control for some of the variables affecting pulmonary function in patients with chronic heart failure, we analyzed data in four patient groups, all with left ventricular (LV) dysfunction (LV ejection fraction LVEF ≤ 35%): (1) chronic heart failure, nonsmokers, no CABG (n = 78); (2) chronic heart failure, nonsmokers, CABG (n = 46); (3) chronic heart failure, smokers, no CABG (n = 40); and (4) chronic heart failure, smokers, CABG (n = 48). Comparisons were made with age- and gender-matched patients with a history of coronary disease but no LV dysfunction or smoking history (control subjects, n = 112) and to age-predicted norms.
Relative to control subjects and percent-predicted values, all groups with chronic heart failure had reduced lung volumes (total lung capacity TLC and vital capacityVC) and expiratory flows (p < 0.05). CABG had no influence on lung volumes and expiratory flows in smokers, but resulted in a tendency toward a reduced TLC and VC in nonsmokers. Smokers with chronic heart failure had reduced expiratory flows compared to nonsmokers (p < 0.05), indicating an additive effect of smoking. Diffusion capacity of the lung for carbon monoxide (Dlco) was reduced in smokers and in subjects who underwent CABG, but not in patients with chronic heart failure alone. There was no relationship between LV size and pulmonary function in this population, although LV function (cardiac index and stroke volume) was weakly associated with lung volumes and Dlco.
We conclude that patients with chronic heart failure have primarily restrictive lung changes with smoking causing a further reduction in expiratory flows.
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