A treadmill exercise sestamibi stress test (TESST) was performed in 609 consecutive diabetic persons with a mean age of 70 years and no history of coronary artery disease (CAD) who were referred for a TESST because of chest pain or dyspnea. Of 609 patients, 301 (49%) had a predicted exercise capacity ≤85% (group A) and 308 (51%) had a predicted exercise capacity >85% (group B). Group A patients had a higher prevalence of myocardial ischemia (43% vs 30%, P =.0005), 2- or 3-vessel obstructive CAD (38% vs 18%, P =.001), myocardial infarction (17% vs 9%, P =.004), death (10% vs 4%, P =.008), and myocardial infarction or stroke or death at 47-month follow-up (21% vs 12%, P =.001). Stepwise Cox regression analysis showed that the only significant independent predictor for the time to development of myocardial infarction or stroke or death was a predicted exercise capacity >85% (hazard ratio, 0.52; 95% confidence interval, 0.34–0.78; P =.002). Diabetic persons with a predicted exercise capacity >85% had a 48% lower chance of myocardial infarction, stroke, or death than those with a predicted exercise capacity ≤85%. Prev Cardiol. 2010;13:14–17. © 2009 Wiley Periodicals, Inc.
A cardiac patient is considered to be a poor candidate for an exercise-based rehabilitation program either because coronary disease and/or comorbid conditions limit the ability to exercise vigorously enough to achieve a training effect or because low-level exercise is associated with adverse signs or symptoms (eg, ischemic ST-segment depression [≥1 mm], angina pectoris, threatening ventricular arrhythmias) that are considered potentially dangerous.1 It is helpful to be able to predict which patients will derive substantial physiologic and/or clinical benefits from participation in an exercise training program and which ones will show little or no improvement. The latter, although poor candidates for improved exercise tolerance, may achieve psychological benefits, cardiovascular risk reduction, or ongoing surveillance that improves medical management: outcomes that are vital to their overall rehabilitation. In some cases, patients who are unlikely to profit from a physical conditioning program may be referred for more intensive medical management (such as drug therapy) and considered for cardiac catheterization and coronary revascularization prior to initiation of exercise training. Previous studies have suggested that several variables may influence functional capacity, expressed as metabolic equivalents (METs; 1 MET=3.5 mL O2/kg/min), or the improvement in cardiorespiratory fitness subsequent to regular exercise training. These include initial patient profile and history; clinical cardiac status; left ventricular impairment; response to graded exercise testing; cardioprotective medications; the exercise prescription; time from the acute cardiac event; and patient compliance. Although the extent of exercise-induced cardiovascular improvement among healthy individuals generally shows an inverse relationship with age, habitual physical activity, and initial maximal oxygen consumption (VO2max), in cardiac patients the relationship is more complex. Improvements in exercise capacity may not show an inverse relationship with initial VO2max. Apparently, some patients with low baseline fitness levels are limited because they are deconditioned and thus have great potential to improve, whereas others are limited by residual left ventricular dysfunction, acute myocardial ischemia, the severity of coronary artery disease, and related symptoms (eg, dyspnea on exertion). Habitually sedentary individuals, in particular, should be strongly encouraged to engage in regular exercise so they can move out of the least fit, least active, “high-risk” cohort (bottom 20%).2 Despite demonstration of a significant correlation (r=−0.68) between VO2max and infarct size, the latter has been shown to be a poor predictor of the patient’s VO2max or the ability to improve aerobic capacity with exercise training.3 Moreover, numerous studies have now demonstrated the discordance between resting left ventricular function, aerobic capacity, and exercise trainability.4-6 Although cardiovascular mortality appears to be directly related to the degree of left ventricular dysfunction, the training-induced improvement in aerobic capacity is not necessarily attenuated by a reduced prerehabilitation ejection fraction.7 Poor candidates for exercise training often demonstrate reduced inotropic and/or chronotropic reserve, electrical instability, symptomatic or asymptomatic myocardial ischemia, and a markedly reduced level of cardiorespiratory fitness, adjusted for age and sex. It has been previously suggested that exercise training regimens do not lead to improvements in cardiac patients on β-blockade;8 however, numerous reports have now shown that patients with cardiovascular disease may derive considerable physiologic benefit from an exercise training program in the presence of long-term β-blockade therapy despite therapeutic doses and a reduced training heart rate.9 Improvement in aerobic capacity with exercise training generally shows a positive correlation to the prescribed frequency, intensity, and duration, the latter expressed as minutes per exercise session as well as the length of the training program in weeks or months.1 A marked improvement in VO2max in some studies, despite a relatively low training intensity, suggests that the interrelationship among the training intensity, frequency, and duration may permit a decrease in the intensity to be partially or totally compensated for by increases in the exercise duration or frequency or both. Thus, the improvement in aerobic capacity may depend more on the total amount of exercise accomplished or calories expended than on the specific exercise frequency, intensity, or duration. It also appears that the minimum or threshold intensity for training in coronary patients to enhance the VO2max is lower than previously thought. An analysis of 23 training studies suggested that ∼45% of the oxygen uptake “reserve” (∼69% of maximal heart rate) should be considered the minimal effective intensity for improving cardiorespiratory fitness in this population.10 Finally, lack of improvement with exercise training may be due to intercurrent illness, exacerbation of disease (eg, acute coronary syndrome), injury (eg, orthopedic complications), inadequate adherence to the exercise prescription, poor patient compliance, or combinations thereof. The study by Kakos and colleagues11 published in the current issue of Preventive Cardiology extends these analyses to older adults enrolled in a 3-session-per-week exercise-based cardiac rehabilitation program to determine whether patients with evidence of cognitive dysfunction at baseline may derive less benefit from their course of treatment. Forty-four participants (mean±SD age, 67.6±9.3 years; 29.5% women) were administered a neuropsychological test battery, using the Trail Making Test Part-B (TMT-B) to evaluate cognitive functioning, and the Short Form–36 physical and mental component scales (MCS) to evaluate quality of life before and after a 12-week exercise/education program. All participants also completed the Mini-Mental Status Exam and the Reading subtest from the Wide Range Achievement Test (WRAT-3 Reading Score), to provide additional assessments of cognitive function and reserve. The exercise program consisted of a warm-up, a cool-down, stretching, and a 40-minute, 5-station circuit training regimen using a variety of upper/lower extremity exercise devices at a progressive, escalating, intensity (40%–70% VO2max), based on the patient’s initial physical work capacity, expressed as METs. Cardiorespiratory fitness was determined from a peak or symptom-limited treadmill test, using a ramp protocol, with the achieved METs estimated from the highest treadmill speed, grade, and duration, using previously published equations.12 Participants completed an average of 34.4±8.4 sessions, substantiating a high level of compliance, and demonstrated a significant postconditioning improvement in aerobic capacity (from 7.8 to 10.3 METs) and MCS score (from 49.9 to 54.2). Nevertheless, poorer TMT-B test performance was associated with significantly lower METs and MCS scores at program completion, despite adjustments for age, WRAT-3 Reading Score, and baseline METs and MCS scores. The authors concluded that patients with cognitive impairment may experience reduced benefit from an exercise-based cardiac rehabilitation program, perhaps due to suboptimal adherence to prescribed lifestyle changes, exercise, medications, and/or associated neural responses. It was suggested that cardiac rehabilitation programs consider expanding their baseline functional and risk factor screening to include an assessment of cognitive functioning to help identify patients at greatest risk for poor outcomes. Although the results are unique and provocative, these data should be interpreted with caution in view of the relatively small sample (n=44), the limited number of women (n=13), the short-term nature of the exercise intervention (eg, up to 12 weeks), and the lack of data regarding numerous other potential confounding variables (eg, smoking history, comorbid conditions, medications, body mass index, duration of coronary disease, left ventricular ejection fraction, leisure-time activities). A significant component of age-related dementia, cognitive dysfunction, and Alzheimer’s disease is vascular in origin.13 Others suggest that cardiovascular disease can cause memory lapses and cognitive challenges prior to the onset of stroke or dementia.14-16 Recently, investigators examined the effect of coronary history and duration in 10,308 participants (33% women), aged 35 to 55 years at baseline, on cognitive performance.17 Although time since the first coronary event varied considerably, among men the trend suggested progressively lower scores on reasoning, vocabulary, and semantic fluency among those with longer duration coronary disease. In women, associated cognitive deficits were noted for phonemic and semantic fluency. Silbert and associates18 reported preexisting cognitive impairment in 35% of patients presenting for coronary artery bypass graft surgery, with the most severe deficits occurring for verbal memory learning and executive function. These findings appear to challenge the notion that postoperative cognitive deficit relates directly to the surgical intervention and suggest that it may be associated with poor preexisting cognition. Cognitive impairment is also common among patients with congestive heart failure, with odds ratios ranging from 1.6 to 4.5 (vs matched controls).19-21 The relationship of myocardial infarction severity to deficits in recall and learning suggest that ischemic cardiomyopathy may be a significant factor in the development of cognitive impairment in heart failure.21 Collectively, these data suggest that the severity and duration of cardiovascular disease may be harbingers of cortical derangements in middle-aged and older adults and that risk factor reduction, including dietary modifications and regular exercise,22, 23 may be viable interventions for preventing or favorably modifying age-related cognitive deterioration. The finding that reduced cognitive function portends limited gains in aerobic fitness and poorer outcomes following exercise-based cardiac rehabilitation, as suggested by Kakos and associates, requires additional validation in a larger and more diverse study population. The methodology used to answer this question should also better address the myriad of potential confounding variables as well as the mechanisms that may link cognitive impairment with a diminished benefit from structured secondary prevention. Despite these limitations, this provocative preliminary study, and previous reports,13-21 raise important questions regarding a likely “cognitive-cardiac” vascular connection that is worthy of future investigation.
A treadmill exercise sestamibi stress test (TESST) was performed in 609 consecutive diabetic persons with a mean age of 70 years and no history of coronary artery disease (CAD) who were referred for a TESST because of chest pain or dyspnea. Of 609 patients, 301 (49%) had a predicted exercise capacity 85% (group B). Group A patients had a higher prevalence of myocardial ischemia (43% vs 30%, P=.0005), 2- or 3-vessel obstructive CAD (38% vs 18%, P=.001), myocardial infarction (17% vs 9%, P=.004), death (10% vs 4%, P=.008), and myocardial infarction or stroke or death at 47-month follow-up (21% vs 12%, P=.001). Stepwise Cox regression analysis showed that the only significant independent predictor for the time to development of myocardial infarction or stroke or death was a predicted exercise capacity >85% (hazard ratio, 0.52; 95% confidence interval, 0.34-0.78; P=.002). Diabetic persons with a predicted exercise capacity >85% had a 48% lower chance of myocardial infarction, stroke, or death than those with a predicted exercise capacity
Cardiovascular risk factors have utility in risk prediction but have limitations in predicting individual risk. Identifying an individual's risk remains a challenge. Emerging technologies such as carotid artery ultrasonography and measures of carotid intima-media thickness (CIMT) may be useful in identifying the susceptible patient who may benefit from more aggressive preventive therapy. This screening test is noninvasive, reproducible, inexpensive, and radiation-free. Recent data have improved our understanding of the application of CIMT as a screening tool for cardiovascular disease. CIMT measurement may place an individual into a higher- or lower-risk category, allowing for appropriate institution of preventive strategies.
To the Editor: Clinical trials of preventive cardiology often use sonographically evaluated carotid intima-media thickness, a representative surrogate marker for cardiovascular diseases, as a study end point. A recent example is the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6—HDL and LDL Treatment Strategies (ARBITER 6-HALTS) trial for statin-treated patients, which reported the superiority of extended-release niacin over ezetimibe in suppressing the intima-media thickness progression (a primary end point).1 The assessment method appears to be a valid trial methodology (eg, the single operator in a blinded manner, a confirmation on reproducibility of measurements).1 However, the resolution of sonography equipment may not make it possible to obtain a significant level of accuracy as reported in a previous trial (−0.0007 mm in the ezetimibe group and −0.0142 mm in the niacin group in the changes observed at 14-months: an expression in four decimal points)1 in considering the actual situation where at least one or two decimal points are clinically applicable. It is necessary to accept the fact that, even if the results are considered to reach a level of statistical significance, the basic nature of such data must still be acknowledged.2–4 The images obtained depend on the settings of the sonography devices (the gain and/or the time gain compensation) and the sound attenuation of the body/tissue. These factors are examiner- and examinee-dependent, respectively; thus, such data can vary greatly due to both factors. The errors also tend to increase in manually operated measurements. Moreover, the repeated measurement of data at specific intervals with such background may potentially induce further problems, even though the same sites of the same arteries were examined. Therefore, based on the above-described factors that may negatively influence the accuracy of the sonographic findings, it is important to carefully and prudently interpret sonography data, especially when there is a slight level of change.
This study examined the relationships among health-related quality of life and risk factors of coronary artery disease (CAD) and all-cause mortality in high-risk cardiac patients seen in a cardiology prevention clinic. At baseline, 1785 patients (age, 53.4+/-13.4 years; 58.8% men) had a medical history, physical examination, and laboratory tests. They completed the Medical Outcomes Study Short Form-36-Item Health Survey (SF-36). Analyses were conducted on associations of 2 SF-36 domain scores (overall physical health [OPH] and overall mental health [OMH]) with CAD biomarkers and all-cause mortality. Lower OPH scores were associated with CAD risk factors including smoking; history of hypertension, diabetes, and peripheral artery disease; the metabolic syndrome; and other novel CAD biomarkers. Lower OMH scores showed similar but weaker associations with CAD risk factors. OPH significantly predicted 5-year mortality in multivariable survival analysis. SF-36, especially OPH, was associated with many risk factors of CAD and significantly predicted mortality.
The Framingham Risk Score (FRS) has become the standard tool to determine coronary heart disease (CHD) risk. Recent studies have demonstrated that FRS underestimates CHD risk in a number of patient populations. One strategy that has been proposed to improve the diagnostic accuracy of FRS is to use imaging of subclinical atherosclerosis to define a "vascular age" and use this age to calculate FRS. Both computed tomography assessment of coronary artery calcium (CAC) and ultrasonographic assessment of carotid intima-media thickness (CIMT) have been proposed as modalities that can be employed to assess vascular age. In the present study, the authors compared CAC vs CIMT for the assessment of vascular age and adjustment of FRS. In the cohort as a whole, CAC- and CIMT-derived vascular age correlated well. Further study is needed to verify the accuracy of vascular age-adjusted FRS using both CAC and CIMT and to determine whether there are specific patient demographics that favor either imaging modality.
The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4+/-12.3 vs 65.6+/-11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.
The authors investigated the use of warfarin at hospital discharge in 557 consecutive patients, mean age 76 years, with nonvalvular atrial fibrillation (AF) at a university hospital. Of 557 patients with AF, 116 (21%) had contraindications to warfarin. Of patients eligible for warfarin, warfarin was used in 8 of 30 patients (27%) with a CHADS(2) score of 0, in 82 of 132 patients (62%) with a CHADS(2) score of 1, in 121 of 175 patients (70%) with a CHADS(2) score of 2, in 72 of 77 patients (94%) with a CHADS(2) score of 3, and in 27 of 27 patients (100%) with a CHADS(2) score of 4 to 6. Warfarin was used in 123 of 168 patients (73%) older than 75 years, in 74 of 79 patients (94%) aged 65 to 75 years, and in 23 of 32 patients (72%) younger than 65 years. Warfarin was used in 80 of 116 patients (69%) with a glomerular filtration rate < 60 mL/min/1.73 m(2) and in 140 of 163 patients (86%) with a glomerular filtration rate ≥ 60 mL/min/1.73 m(2) . There was no significant difference in use of warfarin between men and women and between whites and nonwhites.
Controlling low-density lipoprotein cholesterol is one of the major focuses of cardiovascular care. However, the twin global pandemics of obesity and diabetes are promoting an increased prevalence of associated cardiometabolic risk factors. These factors include mixed dyslipidemia, which is prevalent among several important subgroups of the overall population. Cardiovascular risk increases as women reach and extend beyond menopause, partly reflective of dyslipidemia. In addition, women with polycystic ovary syndrome display a cluster of risk factors reminiscent of the metabolic syndrome. Certain ethnic groups are also at increased risk for type 2 diabetes or the metabolic syndrome. Dyslipidemia contributes significantly to overall cardiovascular risk in the elderly, and the frequency of children and adolescents presenting with type 2 diabetes or metabolic syndrome is increasing worldwide. Physicians should be aware of the possibility of mixed dyslipidemia in patients at elevated cardiometabolic risk. However, while combination therapy may successfully correct the associated dyslipidemia, it remains to be established whether the addition of a second agent improves coronary risk beyond statin monotherapy.
This study characterized the determinants of carotid atherosclerosis in a large contemporary sample of current smokers. Associations between risk factors, carotid intima-media thickness (CIMT), and carotid plaque presence were determined by multivariable regression. Participants included 1504 current smokers (58% female) who were a median (interquartile range) of 44.7 (38-53) years old and smoked 25 (15-40) pack-years; 55% had plaque. Pack-years, age, male sex, nonwhite race, body mass index, systolic blood pressure, small low-density lipoproteins (LDLs), and total high-density lipoproteins were independently associated with CIMT (model R(2) =0.434, P<.001). Pack-years (odds ratio [OR], 1.14 per 10 pack-years; P=.001), age (OR, 1.75 per 10 years; P<.001), body mass index (OR, 0.91 per 5 kg/m(2) ; P=.035), and small LDLs (OR, 1.11 per 100 nmol/L; P<.001) were independently associated with carotid plaque presence (model χ(2) =210.7, P<.001). The association between pack-years and carotid plaque was stronger in women (OR, 1.09 per 10 pack-years, P(interaction) =.018).
