Research ArticleArticles

Cardiopulmonary Rehabilitation, Exercise Training, and Preventive Cardiology: An Overview of a Decade of Research at the Ochsner Heart and Vascular Institute: Presented in part at Grand Rounds, Research Series, Ochsner Medical Institutions, May 17, 1999

Carl J. Lavie, Richard V. Milani, Mark M. Cassidy, Yvonne E. Gilliland and J. Alberto Bernal
Ochsner Journal October 1999, 1 (4) 177-186;

Abstract

A decade of research from the Ochsner Heart and Vascular Institute's cardiopulmonary rehabilitation and exercise training programs demonstrates the benefits of this therapy on coronary risk factors, exercise capacity, cardiopulmonary parameters, behavioral characteristics, and quality of life in various subgroups of patients, including the elderly, women, obese patients, and groups with dyslipidemia and psychological distress, as well as in patients with congestive heart failure or severe lung disease. Substantial data from our program support the idea that cardiopulmonary rehabilitation and exercise training programs are underemphasized and underutilized for the secondary prevention of coronary artery disease.

During the past 2 decades, significant declines in cardiovascular and, particularly, coronary mortality trends have been noted (1-3). Although various pharmacologic and aggressive interventional strategies are often credited for these major advances, lifestyle modifications account for a substantial percentage of the reduction in coronary artery disease (CAD) risk. Cardiac rehabilitation is one of various lifestyle modifying modalities which involve a multidisciplinary program of exercise and education designed to promote the development and maintenance of a desirable level of physical, social, and psychological function at the onset of an acute cardiovascular illness. The specific goals of cardiac rehabilitation and exercise training programs include risk stratification, improving emotional well-being, decreasing symptoms, improving functional capacity, and decreasing morbidity and mortality (1-6).

Table 1 lists the phases of cardiac rehabilitation. Substantial evidence has demonstrated the benefits of phase II cardiopulmonary rehabilitation and exercise training programs in patients after major CAD events (Table 2). Significant improvements in exercise capacity and in risk factor reduction (such as increasing levels of high-density lipoprotein cholesterol [HDL-C], and reducing triglycerides, low-density lipoprotein cholesterol [LDL-C], and obesity indices) have been associated with psychosocial benefits, reduced subsequent hospitalization costs, and reduced major CAD morbidity and mortality (1-6). However, despite this evidence, substantial data indicate that cardiopulmonary rehabilitation programs are underutilized nationally (less than 10% of eligible patients attend these programs, and only 25% of eligible Ochsner patients attend), due to multiple reasons, including lack of physician referrals (which is not a problem at our institution, with >95% referral), inadequate “strength” of the referral (or lack of physician encouragement), as well as geographic and financial barriers and lack of patient interest.

View this table:
Table 1.

Phases of Cardiac Rehabilitation

View this table:
Table 2.

Benefits of Phase II Cardiopulmonary Rehabilitation and Exercise Training Programs

During the past decade, we have followed a large number of patients in our phase II cardiac rehabilitation and exercise training programs at the Ochsner Heart and Vascular Institute. We assessed exercise capacity and cardiopulmonary parameters, plasma lipids, obesity indices, various behavioral characteristics (including scores for depression, hostility, anxiety, and somatization) using the Kellner Symptom Questionnaire, and quality of life (QoL) using the Medical Outcomes Study (MOS) short form survey (SF-36), to evaluate the benefits in several subgroups of patients listed in Table 3. We have also demonstrated benefits in work-site primary prevention settings.

Elderly

We recently compared benefits of cardiac rehabilitation and exercise training programs in 199 elderly CAD patients and 259 younger patients (7). At baseline, as previously demonstrated in a similar cohort of patients (8,9), elderly patients had nearly 30% lower exercise capacity, and had lower triglycerides, body mass indices (BMI), hostility scores, and overall function scores, as well as higher percent body fat and higher levels of HDL-C than did the younger patients. The two groups were statistically similar regarding all other major baseline factors. Following formal cardiac rehabilitation and exercise training programs, this large elderly cohort demonstrated modest, but statistically significant, improvements in total cholesterol and LDL-C (-2% and-3%, respectively), HDL-C (+3%), and LDL/HDL ratio (-5%). The elderly, however, showed dramatic improvements in estimated exercise capacity (+43%) and modest improvements in obesity indices. Almost all behavioral components and QoL improved significantly in the elderly patients after cardiac rehabilitation. Improvements in most of the parameters were statistically similar in older and younger patients; however, the elderly had statistically greater improvements in both estimated exercise capacity (+43% versus +32%; p<0.01) and in mental health scores (+5% versus +2%; p=0.05) than did younger patients.

In our study of a small cohort of very elderly patients over the age of 75 (n=74), CAD risk factors, behavioral characteristics, and QoL components improved significantly (10). Compared with patients younger than 60, the very elderly had greater relative improvements in exercise capacity, overall QoL, well-being, and hostility scores, and had similar improvements in all other parameters. These studies further support the fact that the elderly, including groups of patients well over the age of 75, should not only be referred to, but should be vigorously encouraged to attend formal cardiac rehabilitation and exercise training programs following major CAD events. Since the very elderly had greater than 40% lower exercise capacity at baseline compared with younger patients, the improvements may be even more “clinically significant” in the older compared with younger patients, who had fairly good baseline exercise capacity.

View this table:
Table 3.

Subgroups Proven to Benefit from Cardiopulmonary Programs at Ochsner Heart and Vascular Institute.

We recently reported that elderly patients also had small, but statistically significant, improvements in cardiopulmonary parameters, including peak oxygen consumption (VO2) (+13%; p<0.0001) and anaerobic threshold (AT) (+11%; p=0.03) (11). Although the younger patients had greater improvements in cardiopulmonary parameters than did elderly patients, the elderly had significantly greater improvements in function scores (+27% versus +20%; p=0.02) and total QoL scores (+20% versus =14%; p=0.03), showing the disparate effects of cardiac rehabilitation programs on improvements in exercise capacity and QoL in young and elderly patients with CAD. As we had previously demonstrated in a cohort of 50 CAD patients (12), we found that estimating exercise capacity using standard published formulas greatly overestimates the exercise capacity previously determined by cardiopulmonary stress testing. This overestimation is more marked in the younger compared with the elderly patients, and in both groups the overestimation is even more notable after the exercise training program (11). These data support the benefits of precisely measuring functional capacity by cardiopulmonary stress testing.

Women

On average, women develop CAD 10 years later than men, yet this disease remains the leading cause of morbidity and mortality in women, and there is substantial evidence that women with CAD, particularly older women, often are not referred to cardiac rehabilitation and exercise training programs and are not vigorously encouraged to attend these programs (1,2,13-15). However, we have recently found quite significant improvements in CAD risk factors, exercise capacity, behavioral characteristics, and QoL parameters after cardiac rehabilitation and exercise training in women (3,4,16). Even more recently, we demonstrated the effects of cardiac rehabilitation and exercise training in a cohort of 83 women and 375 men (17). At baseline, women with CAD had lower exercise capacity, lower IDL/HDL ratios, and lower scores for energy, function, and total QoL. The women, however, had higher levels of total cholesterol, LDL-C, percent body fat, and HDL-C than their male counterparts. After cardiac rehabilitation and exercise training, women improved their exercise capacities and lipid levels, as well as anxiety and somatization scores. However, improvements in depression and hostility scores did not reach statistical significance in women. Male patients with CAD appeared to have two times greater improvements in both depression and somatization scores than did women, although these relative differences were not quite statistically significant. With the exception of mental health scores, all QoL parameters improved significantly in women after cardiac rehabilitation and exercise training programs, including total QoL scores. We concluded that women also have significant benefits from cardiac rehabilitation and exercise training programs and should therefore be routinely referred to these programs after major CAD events and vigorously encouraged to pursue them. Since women had significantly lower exercise capacities, as well as scores for energy, function, and total QoL at baseline, the relative clinical benefit may be even greater for them.

Elderly women are probably the largest growing segment in society and in cardiovascular practices, and members of this group are the least likely to be referred to, and to attend, cardiac rehabilitation programs. We recently analyzed results of cardiac rehabilitation in 70 elderly women (mean age >71) and compared the effects of this therapy with that of 574 other patients (91% men, mean age approximately 60) (18). At baseline, elderly women had 26% lower exercise capacity and 7% higher body mass index (BMI), higher percentage of body fat (+29%), and higher levels of total cholesterol, LDL-C, and HDL-C than did the other patients. Both groups were statistically similar regarding other parameters studied. Following the cardiac rehabilitation and exercise training program, elderly women had significant (30%) improvements in exercise capacity, obesity indices (BMI-2% and percent body fat-10%), and in LDL/HDL ratio (-12%), and borderline improvements in triglycerides (-13%; p=0.08). For most parameters, improvements after cardiac rehabilitation were statistically similar in elderly women and other patients. However, elderly women had significantly greater improvements in obesity indices, including BMI (-2% versus 0%; p<0.03), and percent body fat (-10% versus-5%; p<0.01), compared with the other patients. These improvements were particularly noteworthy since obesity seems to be a stronger CAD risk factor in women than in men. Elderly women also had significant improvements in anxiety, somatization, and total QoL and six other QoL components studied, as well as borderline improvements in depression scores (-31%, p=0.07) following cardiac rehabilitation.

Obesity

In addition to the adverse effects of obesity on other CAD risk factors, including unfavorable plasma lipid levels (particularly elevated triglyceride levels and low levels of HDL-C), insulin resistance, promoting a sedentary lifestyle, elevated arterial blood pressure, and the development of left ventricular hypertrophy (LVH), numerous studies indicate that obesity is an independent risk factor for CAD events (19-26). We assessed the benefits of cardiac rehabilitation and exercise training programs in 116 obese coronary patients (defined as BMI ≥ 27.3 kg/m2 in women and ≥ 27.8 kg/m2 in men) (26). Unfortunately, the prevalence of obesity changed only minimally after cardiac rehabilitation programs (37% to 33%), and the prevalence of severe obesity (defined as BMI ≥ 35 kg/m2) also improved only slightly (3.5% to 2.5%). However, the obese patients did show significant improvements in lipid values, including significant reductions in total cholesterol levels (-2%), LDL-C (-4%), triglycerides (-6%), and LDL/HDL ratios (-10%), and increases in HDL-C (+6%). The obese patients had improvements in BMI (-3%; p<0.0001), percent body fat (-5%; p<0.0001), and estimated exercise capacity (+24%; p<0.001). However, when the relative benefits of the cardiac rehabilitation and exercise training programs were compared, the obese had significantly less improvements in estimated exercise capacity than did non-obese coronary patients (+24% vs +36%; p<0.01). In a more recent study (27), 235 obese patients also had significant improvements in behavioral characteristics and QoL parameters following cardiac rehabilitation. In obese patients with at least 5% weight reduction, improvements in exercise capacity (+34% versus +26%; p<0.001), total cholesterol (-7% versus-2%; p=0.03), HDL-C (+11% versus + 2%; p<0.001), LDL-C (-7% versus-4%; p=0.02), and LDL/HDL (-16% versus-7%; p<0.0001) were significantly greater than in obese patients who did not lose weight (27). Therefore, we feel that greater emphasis on successful weight reduction programs could further enhance CAD risk factor reduction in the nearly 40% of CAD patients who meet the criteria for obesity. In a small study of obese hypertensive patients with LVH, high doses of a drug used for depression, sertraline, which is a serotonin uptake inhibitor, significantly lowered body weight and produced modest, but significant, improvements in blood pressure and LVH (28).

Very recently, we analyzed cardiopulmonary parameters in 99 obese patients and 76 lean patients before and after cardiac rehabilitation (29). At baseline, obese patients had significantly lower peak VO2 and AT compared with lean patients, whereas both groups were statistically similar regarding peak VO2 corrected for lean body mass (LBM) and work efficiency ($DL Watts/$DL VO2), which is a marker of peripheral work mechanics. Whereas both obese and lean patients had significant improvements in all cardiopulmonary parameters after cardiac rehabilitation, peak VO2 and AT adequately described exercise capacity in the lean patients, but exercise capacity was best described by peak VO2corrected for LBM (+11%; p<0.001) and work efficiency (+35%; p<0.0001) in obese patients (29,30).

Patients with High Baseline Exercise Capacity

Some experts have suggested that patients with very good baseline exercise capacity may not obtain significant benefits from cardiac rehabilitation programs and could enroll in less intensive and, therefore, less expensive programs. We reviewed and compared the benefits of cardiac rehabilitation and exercise training programs in 163 patients with a high baseline exercise capacity (≥ 6 estimated metabolic equivalents [METs]; mean 8.8 METs) with 125 patients having a low baseline exercise capacity (<6 estimated METs; mean 4.5 METs) (31). Those with a high baseline exercise capacity revealed significant improvements in total cholesterol (-2%), LDL-C (-4%), triglycerides (-10%), LDL/HDL ratio (-10%), HDL-C (+7%), and estimated exercise capacity (+22%; p<0.0001). Although patients with lower baseline exercise capacity had greater relative improvements in estimated exercise capacity after the exercise training programs (+48% versus +22%; p<0.0001), the group with high baseline exercise capacity, for reasons that have not been totally explained, had significantly greater reductions in both LDL-C (-4% versus 0%; p<0.05) and LDL/HDL ratio (-10% versus-4%; p<0.01). Improvements in all other parameters were statistically similar in the two groups. Therefore, we believe that these data support the potential benefits of cardiac rehabilitation programs, even in patients with relatively preserved baseline exercise capacity.

Diabetic Patients

In a study of 291 patients with CAD (70 diabetics, or 24% of the cohort) before and after cardiac rehabilitation (32), diabetic patients were more likely to be female (p=0.08), hypertensive (p=0.05), and obese (p=0.08). Additionally, diabetics had lower exercise capacity (-19%; p<0.01), HDL-C (-10%; p<0.01) and LDL-C (-10%; p=0.02) and had higher triglycerides (+26%; p=0.04) than did those not suffering from diabetes. Diabetic patients also had a higher prevalence of depression (26% versus 14%; p<0.03) and had more somatization (p=0.05) and significantly lower scores for QoL (-7%; p<0.01). Following cardiac rehabilitation and exercise training programs, diabetic patients had marked improvements in exercise capacity, obesity indices, lipids, behavioral characteristics, and QoL. Moreover, after cardiac rehabilitation, the incidence of depression was reduced in diabetic patients by 67% (p=0.01) and ultimately equaled the 9% prevalence for the non-diabetic group. These diabetic patients also had marked benefits in scores for anxiety, somatization, and total QoL and its components.

Patients with Psychological Distress

Baseline psychological factors help predict improvements in exercise capacity following cardiac rehabilitation and exercise training programs (33-37). However, the medical and cardiovascular communities have greatly under-emphasized the importance of psychological distress in patients with CAD, and substantial data indicate that psychological distress is a risk factor for CAD and adversely affects recovery following CAD events (36,37). In cohorts with CAD, as well as in elderly CAD patients, the prevalence of depression approached 20% and the prevalence of depression in women with CAD was 23% (38-40). Depressed patients will generally have lower exercise capacity and have more adverse baseline CAD risk profiles and lower QoL scores compared with patients without depression. Following cardiac rehabilitation programs, the prevalence of depression was reduced by more than 50%, and the rest of the cardiovascular profile improved markedly in depressed patients. High levels of hostility, or unexpressed anger, were present in nearly 15% of patients with CAD, who also had more abnormal baseline CAD risk profiles and more adverse behavioral characteristics and lower QoL than patients without high hostility scores (41). Likewise, the prevalence of high hostility following cardiac rehabilitation was reduced 40%, and marked improvements were noted in the other CAD risk factors, behavioral characteristics, and QoL. These data indicate that patients with depression and high hostility have marked benefits following cardiac rehabilitation and exercise training programs. In addition, we believe that greater attention in general should be directed at behavioral characteristics and psychological distress, particularly depression and hostility, to enhance both the primary and secondary prevention of CAD.

Patients with Dyslipidemia

Considerable evidence during the past 2 decades has indicated the importance of lipids, including LDL-C, HDL-C, and triglycerides, in contributing to atherosclerosis and, particularly, CAD (42-45). Several years ago, the National Cholesterol Education Program (NCEP) made firm recommendations regarding lipid assessment and treatment, which were mostly aimed at LDL-C levels (46). However, in our review of 238 patients with CAD, nearly half had ideal levels of total cholesterol and LDL-C (46), fewer than 25% had a high-risk LDL-C, originally defined as LDL-C ≥ 160 mg/dl. Nearly 50% of our patients, however, had high-risk HDL-C values of < 35 mg/dl, and 25% of our CAD patients had extremely low HDL-C (<30 mg/dl) (46,47). Although, as mentioned above, elderly patients had higher HDL-C levels than did younger patients, low HDL-C levels were considerably more prevalent than high-risk LDL-C levels both before and after a cardiac rehabilitation and exercise training program, even in the elderly patients (48). Therefore, we concluded several years ago that the NCEP should reassess the pivotal role of HDL-C in its assessment and treatment guidelines, particularly in patients with established CAD, since emphasis on both LDL-C and HDL-C is needed for optimal CAD prevention.

Substantial evidence in the literature suggests that patients with “isolated” low levels of HDL-C are extremely resistant to both pharmacologic and non-pharmacologic treatments (49). This is of critical importance, since approximately 25% of our patients with CAD have “isolated” low HDL-C levels and relatively normal levels of LDL-C and triglycerides. We recently demonstrated that these patients have quite dramatic responses to vigorous non-pharmacologic therapy, including significant increases in HDL-C (+17%; p<0.001) and LDL/HDL ratios (-11%; p<0.0001) (42). In fact, patients with “isolated” low HDL-C levels had greater improvements in both HDL-C and LDL/HDL ratios than did other coronary patients after cardiac rehabilitation and exercise training programs.

Considerable controversy remains regarding the role that triglycerides play in the atherosclerotic process (42,50). Although physicians generally believe that patients with high levels of triglycerides often respond better to vigorous non-pharmacologic therapy than patients with low baseline triglycerides, recent data strongly dispute this. In fact, in a comparison of patients with hypertriglyceridemia (≥250 mg/dl) with patients having normal triglyceride levels (<150 mg/dl), patients with low baseline triglyceride levels had statistically greater improvements in both IDL-C and LDL/HDL ratios (50). In multivariable analyses, a low baseline triglyceride value is one of the strongest independent predictors for improving both LDL-C and LDL/HDL ratio after a vigorous non-pharmacologic program. In addition, since nearly half of our coronary patients have low levels of HDL-C, we also showed that a low baseline triglyceride value was one of the strongest independent predictors for improving both LDL-C and LDL/HDL ratio in a study of nearly 250 patients with HDL-C < 35 mg/dl (51). Therefore, contrary to popular belief, patients with hypertriglyceridemia are actually more resistant to non-pharmacologic therapy, at least with regard to improving levels of LDL-C and LDL/HDL ratios; therefore, these patients are even more likely than patients with low triglyceride levels to require drug treatment aimed at reducing LDL-C values (40-51).

Our large experience in using various lipid therapies in CAD patients (52-57) included the use of sustained-release niacin preparations to treat patients with CAD and low levels of HDL-C (58-62). Using a mean dose of niacin of approximately 2.4 g/d (62), we demonstrated that in patients with very low baseline HDL-C levels (<30 mg/dl), significant improvements in total cholesterol levels (-11%; p<0.005), LDL-C (-20%; p<0.01), HDL-C (+30%; p<0.0001), and LDL/HDL ratio (-37%; p<0.0001) occurred after niacin therapy. Although patients with hypertriglyceridemia responded even better to sustained-release niacin therapy than did patients with normal triglyceride levels (including 25% reduction in triglycerides, 35% reduction in LDL-C, 41% increase in HDL-C, and 56% reduction in LDL/HDL ratio), improvements after niacin therapy were still quite significant in the total cohort of patients, as well as in those with “isolated” low levels of HDL-C (greater than 25% increase in HDL-C and greater than 25% reduction in LDL/HDL ratio).

Other CAD Risk Factors

Cardiac rehabilitation and exercise training may affect other CAD risk factors, including levels of dehydroepiandrosterone sulfate (DHEA-S), homocysteine, parameters of blood viscosity and rheology, as well as therapy with omega-3 fatty acids (fish oils). Some studies have suggested that high levels of DHEA-S are associated with reduced atherosclerosis and CAD. Unfortunately, levels of DHEA-S did not increase after our cardiac rehabilitation and exercise training programs (63). Substantial data also indicate that high levels of homocysteine may damage endothelium and enhance coagulation, and high levels have been associated with increased CAD, peripheral vascular disease, and cerebral vascular disease events (64, 65). Although we recently demonstrated only small and non-statistically significant reductions in homocysteine levels following exercise training in a cohort of 76 CAD patients, a subgroup of 11 patients with elevated levels of homocysteine (>15 mmol/L) had significant (-12 %; p<0.02) reductions in levels in homocysteine after an exercise training program (64). Several studies have indicated that elevated blood viscosity is associated with increases in cardiovascular disease events (66). Recently, we noted that CAD patients had considerably higher levels of blood and plasma viscosity and decreased plasma conductance compared with control patients; these abnormalities markedly normalized after a 12-week program of cardiac rehabilitation and exercise training (66). Considerable evidence also points to the benefits of using fish oils in the prevention and treatment of various cardiovascular disorders (53,67,68). This therapy resulted in reductions of approximately 25% in mean arterial blood pressure and systemic vascular resistance, modest reductions in LVH, and modest improvements in left ventricular diastolic filling in cardiac transplant patients with cyclosporine-induced hypertension (69,70). Fish oil therapy also resulted in greater than 50% reductions in the levels of tumor necrosis factor and greater than 70% reductions in interleukin-1 levels, which were associated with significant improvements in percent body fat in patients with end-stage CHF and cardiac cachexia (71-74).

Congestive Heart Failure (CHF)

We have evaluated exercise training in patients with CHF, as well as the value of cardiopulmonary stress testing to assess prognosis and need for transplantation (75-77). Although 15-20 years ago CHF was considered a contraindication to cardiac rehabilitation and exercise training, the safety and efficacy of the therapy was previously noted in a small study of 20 patients post myocardial infarction (MI) with a mean ejection fraction of only 20% (78). In a small study of cardiac rehabilitation and exercise training in 20 patients with severe CHF, there were very minimal improvements in peak VO2, but marked improvements in work efficiency (+34%; p=0.03) following exercise training, which correlated with very significant improvements (+13%; p=0.02) in parameters of QoL (79). In another small study of 15 patients with severe CHF, a 12-week exercise training program was associated with marked improvements in Q-Tc and other indices of ventricular repolarization dispersion, which may decrease the risk of malignant ventricular dysrhythmias and sudden death (80). Along with our colleagues in cardiac transplantation, we are beginning to evaluate the benefits of cardiac rehabilitation in a prospective, randomized study on the effect of this therapy on major CHF morbidity and mortality.

Chronic Obstructive Lung Disease (COLD)

Although cardiopulmonary rehabilitation programs in patients with COLD resulted in only minimal improvements in peak VO2 in patients with severe lung disease, major morbidity and subsequent medical costs were reduced by this therapy (81). Compared with CAD patients (81), those with COLD (n=25) had minimal improvements in peak VO2 (+5%; p<0.001) but much more marked improvements in work efficiency (+36%; p<0.001). Like in patients with CHF, improvements in work efficiency correlated strongly with QoL improvements in patients with COLD.

Primary Prevention Work-site Programs

In a multidisciplinary program aimed at primary worksite interventions in individuals at high risk of medical utilization (82,83), depression, anxiety, and somatization, scores were reduced more than 30% and hostility scores 47%, along with significant improvements in other cardiovascular risk factors and high-risk characteristics in 164 participants, whereas we noticed no improvements in 161 “control” subjects from the same worksite who did not receive specific intervention. Most of the treatment group with high-risk clinical profiles crossed over into a low-risk profile. When followed for 1 year, the intervention group had marked reductions in outpatient, inpatient, and total medical costs, which approached nearly $1,000 per patient per year. Further studies are needed to demonstrate the clinical benefits and “cost-effectiveness” of many primary and secondary preventive strategies.

Conclusions

During the last decade, numerous studies from our program have demonstrated the marked benefits of cardiopulmonary rehabilitation and exercise training programs in preventive cardiology, including marked benefits on exercise capacity, cardiopulmonary parameters, CAD risk factors, behavioral characteristics, and QoL. Our challenge for the next decade is to increase referrals and attendance to these highly effective but underutilized services and to find ways to deliver these therapies more efficiently and cost-effectively (84,85).

Acknowledgments

The authors greatly appreciate the help of our interventional and medical colleagues for referring their patients and for vigorously encouraging them to attend our phase II cardiopulmonary rehabilitation and exercise training programs. In addition, our nurses, exercise physiologists, and dietitians provided invaluable help during patient care and data collection. Finally, Mr. Mario Vaz prepared and edited this article.

References

  1. 1.
    1. Friesenger GC
    1. Lavie CJ,
    2. Milani RV
    Cardiac rehabilitation and preventive cardiology in the elderly Friesenger GC editor Cardiovascular Disease in the Elderly, Volume 17 1 233 242 1999
    OpenUrl
  2. 2.
    1. Wenger NK
    1. Lavie CJ,
    2. Milani RV
    Cardiac rehabilitation in the aged patient Wenger NK editor Cardiovascular Disease: Recognition and Management of the Octogenarian and Beyond London: Martin Dunitz Publishers 1999: Chapter 17, 227 236
  3. 3.
    1. Lavie CJ,
    2. Milani RV,
    3. Ventura HO
    (1995) Cardiac rehabilitation, exercise training, and preventive cardiology research at Ochsner Heart and Vascular Institute. Tex Heart Inst J 22:44–52, pmid:7787470. et al.
    OpenUrlPubMed
  4. 4.
    1. Brown DC
    1. Lavie CJ,
    2. Milani RV
    Cardiac rehabilitation Brown DC editor Cardiac Intensive Care Philadelphia: W. B. Saunders Company 1998: 329 335
  5. 5.
    1. Lavie CJ,
    2. Milani RV,
    3. Squires R
    (1992) Exercise and the heart: good, benign, or evil? Postgrad Med 91:130–134, 143–150, pmid:1738734. et al.
    OpenUrlPubMed
  6. 6.
    1. Maines TY,
    2. Lavie CJ,
    3. Milani RV
    (1997) Effects of cardiac rehabilitation and exercise programs on exercise capacity, coronary risk factors, behavior, and quality of life in patients with coronary artery disease. South Med J 90:43–49, pmid:9003823. et al.
    OpenUrlPubMed
  7. 7.
    1. Lavie CJ,
    2. Milani RV
    (1995) Effects of cardiac rehabilitation programs on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in a large elderly cohort. Am J Cardiol 76:177–179, pmid:7611156.
    OpenUrlCrossRefPubMed
  8. 8.
    1. Lavie CJ,
    2. Milani RV,
    3. Littman AB
    (1993) Benefits of cardiac rehabilitation and exercise training in secondary coronary prevention in the elderly. J Am Coll Cardiol 22:678–683, pmid:8354798.
    OpenUrlFREE Full Text
  9. 9.
    1. Lavie CJ,
    2. Milani RV,
    3. Cassidy MM
    (1995) Benefits of cardiac rehabilitation and exercise training in older patients. Am J Geriatr CAR Cardiol 4:42–48. et al.
    OpenUrl
  10. 10.
    1. Lavie CJ,
    2. Milani RV
    (1996) Effects of cardiac rehabilitation programs in patients ≥ 75 years of age. Am J Cardiol 78:675–677, pmid:8831404.
    OpenUrlCrossRefPubMed
  11. 11.
    1. Lavie CJ,
    2. Milani RV
    Disparate effects of improving exercise capacity and quality of life following cardiac rehabilitation in young and elderly coronary patients, (abstract) J Am Coll Cardiol 1999 33( 2 505A
    OpenUrl
  12. 12.
    1. Milani RV,
    2. Lavie CJ,
    3. Spiva H
    (1995) Limitations of estimating metabolic equivalents in exercise assessment in patients with coronary artery disease. Am J Cardiol 75:940–942, pmid:7733007.
    OpenUrlCrossRefPubMed
  13. 13.
    1. Banks BC,
    2. Lavie CJ,
    3. Milani RV
    Analysis of risk status in elderly and young in-patients with acute coronary syndromes (abstract) Chest 1992 102 (Suppl): 57S
    OpenUrl
  14. 14.
    1. Banks BC,
    2. Milani RV,
    3. Lavie CJ
    (1992) Gender differences in risk status in patients hospitalized with acute coronary syndromes (abstract). Chest 102(Suppl):56S.
    OpenUrl
  15. 15.
    1. Banks BC,
    2. Milani RV,
    3. Lavie CJ
    (1993) Age and gender related differences in psychological variables in patients with acute coronary syndromes (abstract). Clin Res 41:226A.
    OpenUrl
  16. 16.
    1. Lavie CJ,
    2. Milani RV,
    3. Boykin JC
    et al. Gender differences in patients referred for cardiac rehabilitation and exercise training (abstract) J Cardiopulm Rehabil 1992 12: 348
  17. 17.
    1. Lavie CJ,
    2. Milani RV
    (1995) Effects of cardiac rehabilitation and exercise training on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in women. Am J Cardiol 75:340–343, pmid:7856524.
    OpenUrlCrossRefPubMed
  18. 18.
    1. Lavie CJ,
    2. Milani RV
    (1997) Benefits of cardiac rehabilitation and exercise training in elderly women. Am J Cardiol 79:664–666, pmid:9068528.
    OpenUrlCrossRefPubMed
  19. 19.
    1. Wenger NK,
    2. Smith LK,
    3. Frolicher ES,
    4. Composs PM
    1. Lavie CJ,
    2. Milani RV
    (1999) in Cardiac Rehabilitation: A Guide to Practice in the 21st Century, Exercise training in special populations: Obesity, eds Wenger NK, Smith LK, Frolicher ES, Composs PM (Marcel Dekker, New York, NY, and Basel, Switzerland), pp 151–154.
  20. 20.
    1. Lavie CJ,
    2. Ventura HO,
    3. Messerli FH
    (1988) Cardiopathy of obesity. Intern Med Specialist 9:57–71.
    OpenUrl
  21. 21.
    1. Lavie CJ,
    2. Ventura HO,
    3. Messerli FH
    (1991) Regression of increased left ventricular mass by antihypertensives. Drugs 42:945–961, pmid:1724641.
    OpenUrlPubMed
  22. 22.
    1. Lavie CJ,
    2. Ventura HO,
    3. Messerli FH
    (1992) Left ventricular hypertrophy: its relationship to obesity and hypertension. Postgrad Med 91:131–143, pmid:1534169.
    OpenUrlPubMed
  23. 23.
    1. Lavie CJ,
    2. Ventura HO,
    3. Messerli FH
    (1993) Hypertension, obesity, left ventricular hypertrophy, complex ventricular ectopic activity, and increased risk for sudden death: review of Ochsner studies and the literature. J Cardiopulm Rehabil 13:264–270.
    OpenUrl
  24. 24.
    1. Lavie CJ,
    2. Ventura HO,
    3. Messerli FH
    (1994) Left ventricular hypertrophy in the elderly. Cardiol Elderly 2:362–369.
    OpenUrl
  25. 25.
    1. Tresch DD,
    2. Aronow WS
    1. Lavie CJ,
    2. Milani RV,
    3. Mehra MR
    (1999) in Cardiovascular Disease in the Elderly Patient, Hypertension and left ventricular hypertrophy in the elderly, eds Tresch DD, Aronow WS (Marcel Dekker, New York, NY, and Basel, Switzerland), 2nd ed. pp 109–127. et al.
  26. 26.
    1. Lavie CJ,
    2. Milani RV
    (1996) Effects of cardiac rehabilitation and exercise training in obese patients with coronary artery disease. Chest 109:52–56, pmid:8549217.
    OpenUrlCrossRefPubMed
  27. 27.
    1. Lavie CJ,
    2. Milani RV
    (1997) Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in obese coronary patients. Am J Cardiol 79:397–401, pmid:9052338.
    OpenUrlCrossRefPubMed
  28. 28.
    1. Jordan J,
    2. Messerli FH,
    3. Lavie CJ
    (1995) Reduction of weight and left ventricular mass with serotonin uptake inhibition in obese patients with systemic hypertension. Am J Cardiol 75:743–744, pmid:7900678. et al.
    OpenUrlCrossRefPubMed
  29. 29.
    1. Lavie CJ,
    2. Milani RV
    Effects of cardiac rehabilitation and exercise training on peak aerobic capacity and work efficiency in obese patients with coronary artery disease Am J Cardiol 1999 83 1477 1480, A7. pmid:10335765
    OpenUrlCrossRefPubMed
  30. 30.
    1. Milani RV,
    2. Lavie CJ
    (1998) The effects of body composition changes to observed improvements in cardiopulmonary parameters after exercise training with cardiac rehabilitation. Chest 113:599–601, pmid:9515831.
    OpenUrlCrossRefPubMed
  31. 31.
    1. Lavie CJ,
    2. Milani RV
    (1994) Patients with high baseline exercise capacity benefit from cardiac rehabilitation and exercise training programs. Am Heart J 128:1105–1109, pmid:7985590.
    OpenUrlCrossRefPubMed
  32. 32.
    1. Milani RV,
    2. Lavie CJ
    (1996) Behavioral differences and effects of cardiac rehabilitation in diabetic patients following cardiac events. Am J Med 100:517–523, pmid:8644763.
    OpenUrlCrossRefPubMed
  33. 33.
    1. Milani RV,
    2. Littman AB,
    3. Lavie CJ
    (1993) Depressive symptoms predict functional improvement following cardiac rehabilitation and exercise program. J Cardiopulm Rehab 13:406–411.
    OpenUrlCrossRef
  34. 34.
    1. Milani RV,
    2. Lavie CJ,
    3. Littman AB
    (1992) Hostility and depression indices predict functional improvement following cardiac rehabilitation and exercise (abstract). Clin Res 40:348A.
    OpenUrl
  35. 35.
    1. Milani RV,
    2. Lavie CJ
    (1991) Factors predicting improvement in exercise capacity following cardiac rehabilitation and exercise program (abstract). Circulation 84(Suppl II):11–220.
    OpenUrl
  36. 36.
    1. Messerli FH
    1. Milani RV,
    2. Littman AB,
    3. Lavie CJ
    Psychological factors influence prognosis of cardiovascular disease In Messerli FH editor Cardiovascular Disease in the Elderly, 2nd ed. Norwell, MA: Kluwer Academic Publishers 1993: 401 412
  37. 37.
    1. Lavie CJ,
    2. Milani RV
    Benefits of cardiac rehabilitation and exercise training Chest 1999 in press.
  38. 38.
    1. Milani RV,
    2. Lavie CJ,
    3. Cassidy MM
    (1996) Effects of cardiac rehabilitation and exercise training programs on depression in patients after major coronary events. Am Heart J 132:726–732, pmid:8831359.
    OpenUrlCrossRefPubMed
  39. 39.
    1. Milani RV,
    2. Lavie CJ
    (1998) Prevalence and effects of cardiac rehabilitation on depression in the elderly with coronary heart disease. Am J Cardiol 81:1233–1236, pmid:9604957.
    OpenUrlCrossRefPubMed
  40. 40.
    1. Lavie CJ,
    2. Milani RV,
    3. Cassidy MM
    (1999) Effects of cardiac rehabilitation and exercise training programs in women with depression. Am J Cardiol 83:1480–1483, pmid:10335766. et al.
    OpenUrlCrossRefPubMed
  41. 41.
    1. Lavie CJ,
    2. Milani RV
    Effects of cardiac rehabilitation and exercise training programs in coronary patients with hostility symptoms Mayo Clin Proc. In press, 1999
  42. 42.
    1. Lavie CJ
    (1993) Lipid and lipoprotein fractions and coronary artery disease [editorial]. Mayo Clin Proc 68:618–619, pmid:8497140.
    OpenUrlPubMed
  43. 43.
    1. Lavie CJ,
    2. Gau GT,
    3. Squires RW
    (1988) Management of lipids in primary and secondary prevention of cardiovascular diseases. Mayo Clin Proc 63:605–621, pmid:3287024. et al.
    OpenUrlPubMed
  44. 44.
    1. Lavie CJ,
    2. O'Keefe JH,
    3. Blonde L
    et al. High-density lipoprotein cholesterol. Recommendations for routine testing and treatment Postgrad Med 1990 87 36- 44 47, 51 pmid:2188240
    OpenUrlPubMed
  45. 45.
    1. Milani R,
    2. Lavie CJ
    (1992) Recommendations for managing patients with low HDL-cholesterol levels. J Myocardial Ischemia 4:27–46.
    OpenUrl
  46. 46.
    1. Lavie CJ,
    2. Milani RV
    (1991) National Cholesterol Education Program's recommendations, and implications of “missing” high-density lipoprotein cholesterol in cardiac rehabilitation programs. Am J Cardiol 68:1087–1088, pmid:1927923.
    OpenUrlCrossRefPubMed
  47. 47.
    1. Mailander L,
    2. Lavie CJ,
    3. Milani RV
    (1993) Emphasis on high-density lipoprotein cholesterol in patients with coronary artery disease. South Med J 86:508–512, pmid:8488395. et al.
    OpenUrlPubMed
  48. 48.
    1. Lavie CJ,
    2. Milani RV
    (1994) High-density lipoprotein cholesterol and coronary risk in the elderly (editorial). Cardiology in the Elderly 2:251–252.
    OpenUrl
  49. 49.
    1. Milani RV,
    2. Lavie CJ
    (1995) Prevalence and effect of nonpharmacologic treatment of “isolated” low-HDL cholesterol in patients with coronary artery disease. J Cardiopulm Rehabil 15:439–444, pmid:8624971.
    OpenUrlPubMed
  50. 50.
    1. Lavie CJ,
    2. Milani RV
    (1994) Effects of cardiac rehabilitation and exercise training on low-density lipoprotein cholesterol in patients with hypertriglyceridemia and coronary artery disease. Am J Cardiol 74:1192–1195, pmid:7977088.
    OpenUrlCrossRefPubMed
  51. 51.
    1. Lavie CJ,
    2. Milani RV
    (1996) Effects of nonpharmacologic therapy with cardiac rehabilitation and exercise training in patients with low levels of high-density lipoprotein cholesterol. Am J Cardiol 78:1286–1289, pmid:8960593.
    OpenUrlCrossRefPubMed
  52. 52.
    1. Messerli FH
    1. Milani RV,
    2. Lavie CJ
    (1996) in Cardiovascular Drug Therapy, Gemfibrozil, ed Messerli FH (W. B. Saunders Company, Philadelphia) editor, 2nd edition, pp 1098–1101.
  53. 53.
    1. Messerli FH
    1. Lavie CJ,
    2. Milani RV
    (1996) in Cardiovascular Drug Therapy, Fish oils, ed Messerli FH (W. B. Saunders Company, Philadelphia) editor, 2nd edition, pp 1608–1613.
  54. 54.
    1. Messerli FH
    1. Milani RV,
    2. Lavie CJ
    Antioxidants Messerli FH editor Cardiovascular Drug Therapy, 2nd edition Philadelphia: W. B. Saunders Company, 1996 324 330
  55. 55.
    1. Stapleton DD,
    2. Mehra MR,
    3. Dumas D
    (1997) Lipid-lowering therapy and long-term survival in heart transplantation. Am J Cardiol 80:802–805, pmid:9315598. et al.
    OpenUrlCrossRefPubMed
  56. 56.
    1. Mehra MR,
    2. Vivekananthan K,
    3. Uber PA
    (1999) The immunomodulatory role of simvastatin and pravastatin on cardiac allograft rejection: a prospective randomized trial (abstract). J Am Coll Cardiol 33:205A. et al.
    OpenUrl
  57. 57.
    1. Lavie CJ,
    2. O'Keefe JH,
    3. Mehra M
    (1995) Potential role of antioxidants in the primary and secondary prevention of atherosclerosis in the elderly. Cardiol Elderly 3:21–25. et al.
    OpenUrl
  58. 58.
    1. Dearing BD,
    2. Lavie CJ,
    3. Lohmann TP
    (1992) Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med 152:861–863, pmid:1558449. et al.
    OpenUrlCrossRefPubMed
  59. 59.
    1. Lavie CJ
    (1993) Sustained-release niacin for low levels of high-density lipoprotein cholesterol (letter). Mayo Clinic Proceedings 68:201–202, pmid:8481196.
    OpenUrlPubMed
  60. 60.
    1. Lavie CJ,
    2. Milani RV
    (1994) Safety and side effects of sustained-release niacin. JAMA 272:513–515, pmid:8046796.
    OpenUrlPubMed
  61. 61.
    1. Messerli FH
    1. Lavie CJ,
    2. Milani RV
    (1996) in Cardiovascular Drug Therapy, Nicotinic acid, ed Messerli FH (W. B. Saunders Company, Philadelphia) editor, 2nd edition, pp 1061–1067.
  62. 62.
    1. Lavie CJ,
    2. Mailander L,
    3. Milani RV
    (1992) Marked benefit with sustained-release niacin therapy in patients with “isolated” very low levels of high-density lipoprotein cholesterol and coronary artery disease. Am J Cardiol 69:1083–1085, pmid:1561983.
    OpenUrlCrossRefPubMed
  63. 63.
    1. Milani RV,
    2. Lavie CJ,
    3. Barbee RW
    (1995) Lack of effect of exercise training on dehydroepiandrosterone-sulfate. Am J Med Sci 310:242–246, pmid:7503104. et al.
    OpenUrlPubMed
  64. 64.
    1. Ali A,
    2. Mehra MR,
    3. Lavie CJ
    (1998) Modulatory impact of cardiac rehabilitation on hyperhomocysteinemia in patients with coronary artery disease and “normal” lipid levels. Am J Cardiol 82:1543–1545, A8, pmid:9874065. et al.
    OpenUrlCrossRefPubMed
  65. 65.
    1. Lavie CJ,
    2. Milani RV,
    3. O'Keefe JH Jr..
    (1996) Update on new coronary risks factors (editorial). Chest 110:583–584, pmid:8797390.
    OpenUrlCrossRefPubMed
  66. 66.
    1. Church TS,
    2. Lavie CJ,
    3. Kirby GS
    et al. Beneficial effects of cardiac rehabilitation and exercise training programs on blood rheology in patients with coronary artery disease (abstract). Circulation 1997 96( 8 1 637
    OpenUrl
  67. 67.
    1. Lavie CJ,
    2. Squires RW,
    3. Gau GT
    (1987) Preventive cardiology-what is the role of fish and fish oils in primary and secondary prevention. J Cardiopulm Rehabil 7:526–533.
    OpenUrl
  68. 68.
    1. Lavie CJ,
    2. Squires RW,
    3. Gau GT
    (1987) Prevention of cardiovascular disease. Of what value are risk factor modification, exercise, fish consumption, and aspirin therapy? Postgrad Med 81:52–4, 59–72.
    OpenUrl
  69. 69.
    1. Ventura HO,
    2. Lavie CJ,
    3. Messerli FH
    (1994) Cardiovascular adaptation to cyclosporine-induced hypertension. J Hum Hypertens 8:233–237, pmid:8021902. et al.
    OpenUrlPubMed
  70. 70.
    1. Ventura HO,
    2. Milani RV,
    3. Lavie CJ
    et al. Cyclosporine-induced hypertension: efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circulation 1993 88 5 part 2 II281- 285 pmid:8222166
    OpenUrlPubMed
  71. 71.
    1. Milani RV,
    2. Endres S,
    3. Ventura HO
    (1994) Suppression of tumor necrosis factor synthesis by n-3 fatty acids in end-stage congestive heart failure (abstract). J Am Coll Cardiol 23(Special Issue):453A. et al.
    OpenUrl
  72. 72.
    1. Milani RV,
    2. Mehra MR,
    3. Endres S
    et al. Clinical relevance of circulating TNF-A in decompensated advanced heart failure (abstract). Circulation 1995 92( 8 1 208 pmid:7788902
    OpenUrlAbstract/FREE Full Text
  73. 73.
    1. Milani RV,
    2. Endres S,
    3. Mehra MR
    et al. Modulation of tumor necrosis factor (alpha) in advanced heart failure with cachexia is associated with anabolic effects (abstract). J Am Coll Cardiol 1996 27( 2 70A 71A
    OpenUrl
  74. 74.
    1. Milani RV,
    2. Mehra MR,
    3. Endres S
    (1996) The clinical relevance of circulating tumor necrosis factor-alpha is not elevated in acute decompensated chronic heart failure without cachexia. Chest 110:992–995, pmid:8874257. et al.
    OpenUrlCrossRefPubMed
  75. 75.
    1. Milani RV,
    2. Mehra MR,
    3. Lavie CJ
    (1996) Ventilation/carbon dioxide production ratio in early exercise predicts poor functional capacity in congestive heart failure. Heart 76:393–396, pmid:8944583. et al.
    OpenUrlAbstract/FREE Full Text
  76. 76.
    1. Mehra MR,
    2. Lavie CJ,
    3. Milani RV
    (1996) Predicting prognosis in congestive heart failure. Use of exercise indices (editorial). Chest 110:310–312, pmid:8697822.
    OpenUrlCrossRefPubMed
  77. 77.
    1. Richards DR,
    2. Mehra MR,
    3. Ventura HO
    (1997) Usefulness of peak oxygen consumption in predicting outcome of heart failure in women versus men. Am J Cardiol 80:1236–1238, pmid:9359563. et al.
    OpenUrlCrossRefPubMed
  78. 78.
    1. Squires RW,
    2. Lavie CJ,
    3. Brand TR
    (1987) Cardiac rehabilitation in patients with severe ischemic left ventricular dysfunction. Mayo Clin Proc 62:997–1002, pmid:3669777. et al.
    OpenUrlPubMed
  79. 79.
    1. Milani RV,
    2. Mehra MR,
    3. Lavie CJ
    et al. Improvements in work efficiency result in enhanced functional status and quality of life following exercise training in heart failure (abstract). J Am Coll Cardiol 1998 31( 2 Suppl A 198A
    OpenUrl
  80. 80.
    1. Ali A,
    2. Mehra M,
    3. Malik FS
    (1999) Effects of aerobic exercise training on indices of repolarization in patients with chronic heart failure. Chest 116:83–87, pmid:10424508. et al.
    OpenUrlCrossRefPubMed
  81. 81.
    1. Milani RV,
    2. Lavie CJ
    (1998) Disparate effects of out-patient cardiac and pulmonary rehabilitation programs upon work efficiency and peak aerobic capacity in patients with coronary disease or severe obstructive pulmonary disease. J Cardiopulm Rehabil 18:17–22, pmid:9494878.
    OpenUrlCrossRefPubMed
  82. 82.
    1. Milani RV,
    2. Lavie CJ
    (1995) Reductions in coronary risk profile and total medical costs with comprehensive work-site primary prevention programs (abstract). Circulation 92:I–510.
    OpenUrl
  83. 83.
    1. Milani RV,
    2. Lavie CJ
    (1997) Marked reductions in outpatient, inpatient, and total medical costs with comprehensive work-site primary prevention programs (abstract). J Am Coll Cardiol 29(2 Suppl A):49A, pmid:8996294.
    OpenUrlCrossRefPubMed
  84. 84.
    1. Lavie CJ,
    2. Milani RV
    (1995) Cardiac rehabilitation and health-care reform. Chest 107:1189–1190, pmid:7750303.
    OpenUrlCrossRefPubMed
  85. 85.
    1. Lavie CJ,
    2. Legwold G
    (1997) Coronary heart disease. From early defeats to current victories, the battle continues. Postgrad Med 2:210–215, pmid:9270710.
    OpenUrlPubMed
Back to top

In this issue

Print
Download PDF
Email Article
Citation Tools

Jump to section