Value of cardiac rehabilitation Prof. Dr. L Vanhees

Session: At the interface of hypertension and coronary heart disease haemodynamics, heart and hypertension Value of cardiac rehabilitation Prof. Dr. L Vanhees ESC Stockholm August 2010

Introduction There is a strong and frequent association between arterial hypertension (HT) and coronary heart disease (CHD): Magnitude of HT has an impact on the incidence of CHD: i.e. there is a direct, strong, independent and continuous relation between BP and cardiovascular mortality and morbidity and this from 115/75 mmhg on 1. CHD is primary cause of mortality in hypertensive patients 25-43% of patients in secondary prevention trials have HT (CARE, LIPID, 4S) 2 Mortality rate of CHD is 2.3 times greater when HT is present 1 1 Lewington et al. Lancet 2002 2 Escobar E. J Hum Hypertens 2002

Treatment of hypertension General principles for the treatment of hypertension fully apply to patients with CHD and HT. However, treatment of hypertension in patients with CHD must be more aggressive than in the absence of CHD. Risk of a recurrent coronary event in this population is very high and all efforts should be expended in order to lower BP Reducing BP is cornerstone of strategies to reduce the number of fatal and no-fatal cardiovascular events both in patients with or withhout CHD Focus on CR and Exercise Training in this talk

Joint Associations of Physical Activity and Aerobic Fitness on the Development of Incident Hypertension Coronary Artery Risk Development in Young Adults An inverse, graded association between fitness category and the development of hypertension Carnethon M.R. et al., Hypertension. 2010

Joint Associations of Physical Activity and Aerobic Fitness on the Development of Incident Hypertension Coronary Artery Risk Development in Young Adults Carnethon M.R. et al., Hypertension. 2010

Kokkinos et al. Hypertension 2009; 53: 494-499 Role of Physical Fitness: HT, PF and Mortality

Exercise Capacity and Mortality in Hypertensive Men With and Without Additional Risk Factors Kokkinos P. et al., Hypertension;2009

Kokkinos et al. Am J Hypertens 2009; 22: 735-741 Role of Physical Fitness: Pre-HT, PF and Mortality

Exercise Capacity and All-Cause Mortality in Prehypertensive Men Cumulative survival for entire cohort Kokkinos P. et al., Am J Hypertens. 2009

Exercise Capacity and All-Cause Mortality in Prehypertensive Men Cumulative survival for individuals 60 years of age Cumulative survival for individuals >60 years of age -> A strong, inverse and graded association between exercise capacity and all-cause mortality. -> More protective effects of increased fitness in younger individuals age should be more closely considered when assessing fitness and mortality relationships. Kokkinos P. et al., Am J Hypertens. 2009

Role of Physical fitness CHD, PF and mortality 6213 men referred for ET Mean FU: 6.2 ±3.7 yrs Two groups: Normal subjects with normal test and no CV history Subjects with abnormal test and/or history of CV disease End-point: overall mortality Myers J et al. NEJM 2002; 346: 793-801

Role of Physical fitness CHD, PF and mortality 12.169 rehabilitation candidates (CABG, MI, IHD that completed an exercise test Median FU: 7.9 yrs (4-29 yrs) End-point: all-cause and cardiac mortality 15 yr survival rates for peakvo 2 of <15, 15 to 22, and > 22ml/min/kg were 65%, 81% and 88%. when treated as a continuous variable, a 1ml/min/kg increments in peakvo 2 could be equated with a 9% improvement in prognosis Kavanagh et al. Circulation 2002; 106: 666-671

Definition Cardiac Rehabilitation Sum of activity and interventions required to ensure the best possible physical, mental and social conditions so that patients with chronic or post-acute cardiovascular disease may, by their own efforts, preserve or resume their proper place in society and lead an active life 1 How: programme of prescribed exercise and interventions designed to modify coronary risk factors with the use of optimised drug therapy and appropriate lifestyle changes. Exercise therapy is a central element in CR as identified by international clinical guidelines. 1 World Health Organ Tech Rep Ser 1993; 831: 1-122.

Endurance Exercise and Hypertension Number of studies 72 (study groups: 105; 28 optimal pressure, 46 prehypertension; 31 hypertension) Number of participants: randomized: 3.936 (median: 32; range: 8-357) analysed: 3.394 (overall: 88.7%; range: 51-100) Demographic characteristics gender: ~ 57% male Age: median 46.6 yrs (range: 21-83) Cornelissen VA and Fagard RH, Hypertension 2005; 46: 667-675

Endurance Exercise and Hypertension Duration (weeks): 16 (4-52) Frequency (n/week): 3 (1-7) Intensity (%HRres): 65 (30-87.5) Duration/session (min)*: 40 (15-63) Mode: predominantly walking, jogging, running or cycling Values are median (range) *without warming-up and cool-down Increase in peakvo 2 +4.0 ml/min/kg (95% CL: 3.5 to 4.5) Cornelissen VA and Fagard RH, Hypertension 2005; 46: 667-675

Endurance Exercise and Hypertension effect on BP Training frequency, intensity, duration and mode are not significantly related to the BP response to training Cornelissen VA and Fagard RH, Hypertension 2005; 46: 667-675

Endurance Exercise and Hypertension Effect on Hemodynamics Cornelissen VA and Fagard RH, Hypertension 2005; 46: 667-675

Resistance Exercise and BP Number of studies (RCTs): 25 Number of study groups: 30 (optimal pressure: 12; prehypertension: 14; hypertension: 4) Number of participants: randomized: 961 (median 30, range 15-143) analysed: 860 (overall 91% range 63-100%) Demographic characteristics gender: median 28% men (range 0-100) Mean age: median 53 yrs (range 19-84 yrs) V. Cornelissen, R. Fagard, L. Vanhees. Unpublished data

Resistance Exercise and BP Variable N studies Median Range Duration (wks) 30 16 6-52 Frequency (times/wk) 30 3 2-3 Intensity (% 1RM) 26 76 30-100 Exercises (#) 28 8 1-14 Sets (#/exercise) 27 3 1-6 Repetitions/set (#) 29 10 6.5-30 Progressive 26 Supervised 23 Significant increase in peak VO 2 = 2.7 ml/min/kg (0.81 to 4.56)

CCornelissen et al. Unpublished data Resistance Exercise and BP: SBP weighted for the inverse of the variance

Resistance Exercise and BP: SBP weighted for the n of trained participants CCornelissen et al. Unpublished data

Resistance Exercise and BP: DBP weighted for the inverse of the variance CCornelissen et al. Unpublished data

Resistance Exercise and BP: DBP weighted for the n of trained participants CCornelissen et al. Unpublished data

Resistance Exercise and BP Variable N Net change (95% CL) I² SBP (mmhg) - normotension 26-2.84 (-4.98; -0.70) 37 - hypertension 4-1.73 (-5.48; +2.02) 0 DBP (mmhg) -normotension 26-3.29 (-4.65; -1.93) 22 - hypertension 4-1.11 (-3.13; +0.91) 0 CCornelissen et al. Unpublished data

Resistance exercise and BP: role of training intensity Changes in SBP and DBP, adjusted for control data, versus training intensity (% 1RM) for 26 study groups that reported data. The weighted meta-regression coefficients are r=0.048 (P=0.82) for SBP and r=0.12 (P=0.57) for DBP. CCornelissen et al. Unpublished data

Number of patients Distribution of changes in peak VO 2 (%) after Cardiac Rehabilitation 250 200 150 100 50 0-40 -20 0 20 40 60 80 100 120 Change in peak oxyen uptake (% ) Vanhees et al, Eur J Cardiovasc Prevention Rehab, 2004.

Probability for cardiovascular mortality (%) Probability for cardiovascular mortality (%) Exercise capacity and it s change by ET on CV mortality 40 35 30 25 20 15 10 5 0 Mean Plus 95 % CL Min 95 % CL 10 20 30 40 35 30 25 20 15 10 5 0 Mean Plus 95 % CL Min 95 % CL -400 0 400 800 1200 1600 Peak Oxygen Uptake (ml/min/kg) Delta Peak Oxygen Uptake (ml/min) L. Vanhees et al. JACC, 1994 L. Vanhees et al. Am J Cardiol 1995

Value of Cardiac Rehabilitation: CHD effect on total mortality Meta-analyses of randomized controlled trials which assessed the effects of exercise training alone or in combination with psychological or eductional interventions: Oldridge (1988), Jolliffe et al (2001) and Taylor et al (2004). - 48 trials - 8.940 patients with CHD Taylor et al. Am J Med 2004; 116: 682-692

Effect on Total Mortality 0.80 (0.68; 0.93) Taylor et al. Am J Med 2004; 116: 682-692

Value of Cardiac Rehabilitation: CHD effect on cardiac mortality 0.74 (0.61; 0.90) Taylor et al. Am J Med 2004; 116: 682-692

Value of Cardiac Rehabilitation: CHD effect on BP Taylor et al. Am J Med 2004; 116: 682-692

Aim: Value of Cardiac Rehabilitation: CHD and Hypertension to investigate whether the effect of cardiac rehabilitation differs between CHD patients with and without HT Study population: 2.392 patients with a diagnosis of acute myocardial infarction, CABG, PCI or patients with chronic angina who were referred to our CR unit and completed an exercise test at baseline and following 3 months of CR. Cardiac Rehabilitation Programme: - Optimal medical treatment - Risk factor management - Nutritional counseling - Psychosocial management - Exercise therapy Own data; unpublished

Value of Cardiac Rehabilitation: CHD and hypertension Exercise intervention: supervised Mode: endurance training (cycling, running, arm ergometry, rowing, dynamic calisthenics) followed by relaxation Duration: approximately 100 minutes/session Frequency: on average 2.27 (SD 0.47) exercise sessions weekly during 3 months Intensity: 80.7 ±19.6 % HRpeak Own data; unpublished

Patient Characteristics CHD without HT CHD with HT N of patients 1688 (71%) 704 (29%) Men n (%) 1576 (93%) 622 (88%) Age (years) 55.8±9.4 58.4±9 * Drug therapy -Beta-blockers -Antiplatelets -ACE-inhibitors -AII-antagonists -diuretics -Ca- antagonists -other vasodilators 1345 (80%) 1277 (76%) 297 (17.6%) 9 (0.53%) 77 (4.5%) 185 (11%) 328 (19.4) 590 (84%)* 553 (79%) 181 (26%)* 14 (2%)* 63 (9%)* 116 (16%)* 167 (24%)* *, <0.05 Own data; unpublished

Baseline Characteristics CHD without HT CHD with HT P-value Weight (kg) 75.9±11.0 78.3±11.9 <0.001 BMI (kg/m²) 25.5±3.1 26.5±3.5 <0.001 Ejection Fraction 59.0±13.9 58.7±15.4 NS HRrest (bpm) 67.2±12.2 68.2±12.2 NS SBPrest (mmhg) 127.6±18.1 138.6±19.7 <0.001 DBP rest (mmhg) 76.8±11.5 81.5±12.9 <0.001 VO 2 peak (ml/min) 1720±487.7 1598±474.7 <0.001 Oxygen pulse (ml/beat) 13.4±3.25 12.8±3.2 <0.001 HRpeak (bpm) 129.4±21.5 125.0±20.9 <0.001 RER 1.13±0.11 1.14±0.12 NS EqO2 37.3±7.0 37.8± 7.1 NS Own data; unpublished

Results: exercise capacity Own data; unpublished

Results: exercise capacity * P<0.001 within group Own data; unpublished

Results: other characteristics Absolute Change Relative Change (%) CHD CAHD with HT CHD CHD with HT Oxygen pulse (ml/beat) +2.0±2.19** 2.30±6.26** +18.72±19.7** 20.83±20.51** HRpeak (bpm) +8.43±15.86** +7.51±14.76** +7.69±14.13** 6.78±12.42** HRrest (bpm) -2.29±10.69** -3.42±10.66**$ -2.11±15.6** -3.82±14.72**$ SBPrest (mmhg) -0.95±16.36* -2.91±19.29**$ +0.11±12.91-1.1±14.05*$ DBPrest (mmhg) -1.04±10.12** -1.98±10.91**$ -0.37±14.25-1.41±13.82* Data are expressed as mean + SD. * P< 0.05; **P<0.001 for within group changes; $ P<0.05 for between group changes Own data; unpublished

Conclusions There is a dose-response relation between physical fitness and all-cause and cardiac mortality in both hypertensive patients and CHD patients with and without HT Both endurance and dynamic resistance training result in a significant increase in peakvo 2 and induce a significant reduction in SBP and DBP. CR including exercise results in a significant larger reduction in all-cause and cardiac mortality and a greater reduction in BP, although only significant for SBP. In CHD patients with HT, CR induces a significant larger reduction in SBP and HR compared to patients without HT. No differences could be observed with regard to the effect on peak VO 2