Coronary artery disease

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Coronary artery disease (CAD) has various different names, including coronary heart disease and ischemic or atherosclerotic heart disease. CAD progresses through the build-up of plaque within the arteries of the heart, a process called atherosclerosis. Physical inactivity is a key risk factor for CAD. Exercise interventions can have powerful effects, even reversing the severity of the CAD in some cases and reducing mortality in many individuals with the disease. For cardiac rehabilitation, exercise recommendations include more physical activity, aerobic exercise and resistance-training.

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What is coronary artery disease?

Coronary artery disease (CAD) has various different names, including coronary heart disease (CHD) and ischemic or atherosclerotic heart disease. CAD progresses through the build-up of plaque within the arteries of the heart, a process called atherosclerosis. This build-up of plaque leads to narrowing of the coronary arteries and reduced blood-flow to the heart itself. However, in the absence of close medical examination, there are often few symptoms CAD progressing in otherwise healthy individuals. Indeed, the earliest symptoms may include angina (i.e. chest pains), reduced exercise tolerance and even heart attacks.

CAD is widely accepted to be the most common cause of death worldwide, being responsible for 7.2 million deaths in 2008, which is 12.7% of the total global mortality rate. However, the mortality associated with CAD varies widely between geographical locations, with the highest rates being found in the lower income countries and the lowest rates being observed in the higher income countries (Finegold et al.)


What are the risk factors for CAD?

The following studies have identified the common risk factors for developing CAD:

Study Description Finding
Choi  et al. The researchers investigated whether nonalcoholic fatty liver disease was a significant risk factor for CAD. They therefore recruited 134 subjects and allocated them into four groups according to coronary artery stenosis: insignificant, one-vessel disease, two-vessel disease, and three-vessel disease. The researchers used abdominal ultrasonography in order to assess the presence of a fatty liver. The researchers reported that among the patients who were classified as having CAD, 80.4% had evidence of a fatty liver. Additionally, the researchers reported that the grade of coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner. They concluded that nonalcoholic fatty liver disease is a significant, independent predictor of CAD.
Kim et al. The researchers wanted to see whether there was a association between metabolic syndrome score and the severity of CAD, as measured by coronary angiography. They therefore retrospectively recruited 632 patients for whom a coronary angiography was performed to assess the extent of CAD. The researchers also calculated a metabolic syndrome score following the National Cholesterol Education Program criteria with the waist criterion replaced by a Body Mass Index (BMI) of >25 kg/m2. The researchers found that 78.6% of the subjects had CAD and 44.8% were diagnosed with metabolic syndrome. However, out of all the individual components of metabolic syndrome, only high fasting blood glucose was a significant individual predictive factor for CAD. The researchers found that a combined measure including high fasting blood glucose, high blood pressure, and low high-density lipoprotein cholesterol (HDL-C) was able to predict CAD risk the best.
Yavuz et al. The researchers assessed the association between metabolic syndrome and the severity of CAD according to scoring following coronary angiography. The researchers evaluated metabolic syndrome score based on National Cholesterol Education Program Adult Treatment Panel III criteria. For subjects, the researchers recruited 634 male and 369 females with a mean age of 59 ± 11 years. The researchers observed metabolic syndrome in 25% of the subjects and CAD in 69% of the subjects. The researchers reported that they found a positive correlation between the severity of the score for metabolic syndrome and the severity of the score for CAD. The researchers also noted that the other significant risk factors for CAD were type II diabetes mellitus in males and hypertension in females.
Nakamura et al. The wanted to investigate the association between abnormal glucose tolerance, type II diabetes or hypertension and the risk of developing CAD in 474 consecutive patients with suspected CAD. The researchers assessed the association of these factors at baseline with the diagnosis of CAD and over a 2.5-year follow-up period in relation to the occurrence of ischemia. The researchers reported that at baseline coronary index and stenosis score were higher in subjects with type II diabetes mellitus as well as in subjects with impaired fasting glucose, and impaired glucose tolerance in comparison with subjects with normal glucose tolerance. The researchers reported that during the follow-up period, systolic blood pressure was significantly higher in those individuals who displayed an ischemic episode, indicating that hypertension is a risk factor for CAD. The researchers found that the risk of displaying an ischemic episode during this period was 1.7 times higher with each 10mmHg rise in systolic blood pressure. The researchers therefore concluded that managing both glucose tolerance and blood pressure is important for the prevention of CAD.
Bin-Miao et al. The researchers investigated the association between Chronic Obstructive Pulmonary Disease (COPD) and CAD. They therefore obtained the data of 354 patients for whom multi-detector computed tomography for suspected CAD had been obtained. The researchers found that those patients who had CAD had a significantly higher complication of COPD than those who did not have CAD (11.8 vs. 3.7%). The researchers therefore suggested that COPD may therefore be an important risk factor for the development of CAD.
Umul et al. The researchers wanted to see whether there was an association between erectile dysfunction and silent CAD. They therefore recruited 30 consecutive men with non-hormonal and non-psychogenic erectile dysfunction and with no obvious cardiac symptoms. The researchers used multi-detector computed tomography (MDCT) coronary angiography images under beta blockade to induce bradycardia and to detect signs of silent CAD. The researchers reported that there was a significant correlation between the presence of silent CAD and erectile dysfunction severity. Erectile dysfunction is therefore a risk factor for the development of CAD.
Siadat et al. The researchers investigated whether vitamin D deficiency was associated with CAD, while taking into account other cardiovascular risk factors. The researchers therefore measured 25 (OH) D serum levels in 57 patients with a diagnosis of CAD following coronary angiography in comparison with 62 age- and sex-matched controls. The researchers reported that individuals with vitamin D deficiency (defined as 25 (OH) D serum levels of < 30ng/ml) were 5.8 times more likely to have CAD, even after adjustment for other cardiovascular risk factors, including blood pressure, diabetes, smoking, obesity, extent of physical activity and high blood cholesterol.
Chae et al. The researchers investigated whether arterial stiffness, as measured by brachial ankle pulse wave velocity was associated with the presence and extent of CAD, as detected by conventional coronary angiography. The researchers therefore analyzed the data of 651 consecutive patients who had undergone both tests for suspected CAD between June 2010 and July 2011, at a single cardiovascular center. The researchers reported that the measurement of brachial ankle pulse wave velocity was one of the statistically meaningful predictors of significant CAD. However, they found that it was not a significant predictor of revascularization and was not able to differentiate between individuals with different grades of CAD.
Kivimäki et al. The researchers wanted to assess whether a healthy lifestyle would mitigate the adverse effects of job strain on coronary artery disease. They therefore set out to examine the association between job strain and lifestyle risk factors with the risk of developing CAD. The researchers obtained individual-level data from 7 different cohort studies comprising a total of 102,128 males and females, free of existing CAD at baseline. The researchers used basic questionnaires to assess job strain, smoking status, physical activity, alcohol drinking, and obesity. The researchers stratified the subjects by healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2 – 4 risk factors) to see which of the factors were most important for the risk of developing CAD. The researchers found that those living a healthy lifestyle were 2.55 less likely to develop CAD than those living an unhealthy lifestyle. They found that a healthy lifestyle was able to mitigate some but not all of the effects of job strain on CAD risk.
Briasoulis and Bakris The reviewers assessed whether Chronic Kidney Disease (CKD) was a risk factor for the development of CAD. They reported that there are substantial data from prospective cohort studies supporting the observation that dialysis patients as well as those with advanced stage CKD display a significantly increased risk for CAD and that this risk increases exponentially with declining kidney function. Additionally, the reviewers observed that cardiovascular disease (CVD) is responsible for >50% of deaths in patients with CKD. The reviewers conclude that CKD should be considered an independent risk factor for CAD.
Zen et al. The researchers wanted to see whether body fat and the distribution of body fat were differently associated the risk of CAD. They therefore performed a case-control study in 376 CAD patients, aged >40 years for whom coronary angiography was performed. The researchers also calculated Body Mass Index (BMI), waist circumference, waist-to-hip ratio and neck circumference. After controlling for age, sex, educational status, smoking, hypertension, HDL-cholesterol, type II diabetes mellitus, and overall adiposity, the researchers found that a high waist-hip ratio was associated with a 4 times greater risk of CAD, while neck circumference in the 90th percentile was associated with a 2 times greater risk of CAD. The researchers therefore concluded that neck circumference and waist-to-hip ratio are independent predictors of CAD, even taking into account traditional risk factors for CAD, including BMI and overall adiposity.
Hamagawa et al. The researchers wanted to see whether abdominal visceral fat was a significant risk factor for CAD. Using ultrasonography, the researchers measured maximum pre-peritoneal visceral fat thickness and minimum subcutaneous fat thickness in 185 patients for whom coronary angiography was also performed to determine the existence and extent of CAD. The researchers found that the 144 patients with confirmed CAD had larger maximum pre-peritoneal visceral fat thickness than those who did not have CAD (8.8 ± 3.6 vs. 6.4 ± 2.8mm) but there was no difference between the groups in respect of minimum subcutaneous fat thickness. The researchers therefore concluded that having a maximum pre-peritoneal visceral fat thickness >6.9 mm is associated with a 3.71 times greater risk of CAD.
Twig et al. The researchers investigated the association between white blood cell (WBC) count and CAD in a cohort of 29,120 apparently healthy, young male Israeli army personnel. The researchers followed the subjects, who had a normal baseline WBC count for an average of 7.5 ± 3.8 years to assess the development of CAD by coronary angiography. The researchers found that after adjusting for body mass index (BMI), LDL- and HDL-cholesterol, blood pressure, family history of CAD, physical activity, diabetes, triglycerides and smoking status, WBC levels >6,900 cells/mm3 were associated with a 2.17 times greater risk of developing CAD. The researchers found that each WBC increment of 1000 cells/mm3 was associated with a 17.4% increase in CAD risk. The researchers therefore conclude that high WBC count is a significant, independent risk factor for CAD.
Massierer et al. The researchers wanted to investigate the extent to which obstructive sleep apnea (OSA), as assessed by the Berlin Questionnaire, is a risk factor for CAD. The researches recruited cases from patients referred for elective coronary angiography and controls from the general population. The researchers reported that positive Berlin Questionnaire results for OSA  were identified in 41.2% of the CAD cases compared with 34.4% of the control subjects. The researchers found that the risk of suffering OSA was independently associated with CAD. The researchers therefore concluded that OSA greatly increases the risks of CAD.
Sorajja et al. The researchers assessed the association between obstructive sleep apnea (OSA) and the presence of subclinical CAD, as assessed by coronary artery calcification. The researchers recruited 202 consecutive patients with a median age of 50 years and a mean Body Mass Index of 32kg/m2. The researchers found that OSA was present in 76% of the subjects and CAC was present in 67% of those subjects with OSA but only in 31% of non-OSA subjects. The researchers reported that the median coronary artery calcification score increased with increasing OSA severity. The researchers therefore concluded that the presence and severity of OSA is independently associated with the presence and extent of coronary artery calcification and may therefore represent a modifiable risk factor.
Martinez et al. The researchers wanted to assess the performance of the Berlin Questionnaire for the diagnosis of obstructive sleep apnea (OSA) in individuals with angina complaints. The researchers found that a high risk in the Berlin Questionnaire for OSA was associated with a significantly increased risk (4.5 times) of the presence of CAD even after adjusting for the usual confounding factors of gender, age, and Body Mass Index (BMI).
Hoseini and Khosravi The researchers investigated the association between prevalent CAD and clinical periodontal disease in 152 consecutive CAD patients. The researchers found that CAD patients displayed higher average plaque index, Index of bleeding and mean adhesion than controls with normal coronary function. The researchers therefore concluded that gingival inflammation (periodontitis) is a significant risk factor for CAD.
Amabile et al. The researchers wanted to assess the association between the severity of the periodontal disease, inflammatory response and angiographic lesions extent in 131 patients with stable CAD. The researchers divided the subjects into one group displaying the presence of lesions and a second group displaying no lesions. The researchers then measured mean periodontal pocket depth and various other measures. The researchers found that mean periodontal pocket depth was significantly greater in patients with CAD than in controls and the systemic inflammatory response was also more pronounced in cases than in controls. The researchers concluded that periodontal disease severity was correlated with the extent of coronary lesions, independent of systemic inflammatory status.
Manninen et al. As part of the Helsinki Heart Study, which included over 4,000 subjects, the researchers assessed the correlation between baseline serum low-density lipoprotein (LDL) levels and high-density lipoprotein (HDL) and the risk of developing CAD. The researchers reported that in a population with elevated LDL levels, the lipoprotein fraction with the greatest predictive value for developing CAD was HDL cholesterol. They found that the size of the LDL levels did not provide any further predictive value for the development of CAD.
Wilson The reviewer assessed the various different risk factors for the development of CAD. The reviewer observed that the risk factors have traditionally been identified as age, serum total lipoproteins, serum high-density lipoprotein (HDL) cholesterol, blood pressure, cigarette smoking, type II diabetes mellitus, and left ventricular hypertrophy as measured by electrocardiography.
Kotecha et al. The researchers investigated the contemporary value of various different risk factors for the development of CAD in 328 of 539 patients referred for elective diagnostic coronary angiography. The researchers reported that only age, male sex, diabetes, chest pain and prior cardiovascular disease were independent predictors of CAD.
Wild et al. The researchers wanted to see whether androgen excess in females was associated with a greater risk of coronary artery disease. They therefore evaluated 102 women presenting for coronary artery catheterization for the signs and symptoms of androgen excess. The researchers reported that hirsutism was found more commonly in those women with confirmed CAD. Additionally, the researchers found that waist-to-hip ratio (an index of android fat distribution) was also associated with both hirsutism and CAD. The researchers therefore concluded that androgen excess in women may increase CAD risk.
Al-Nozha et al. The researchers wanted to assess the effect of smoking on CAD risk in the Kingdom of Saudi Arabia as part of the Coronary Artery Disease In Saudis (CADIS) study. The researchers collected data regarding smoking status from 17,350 adult male and female Saudis aged 30 – 70 years over a 5-year period from 1995 – 2000, of whom 2,217 were smokers. The researchers reported that smokers were significantly more likely to develop CAD than non-smokers.
Chouraki et al. The researchers assessed the extent to which abdominal obesity, as measured by waist circumference, is an important risk factor for CAD. They therefore recruited a cohort of 9,763 males, aged 50 – 59 years, without known CAD at baseline and followed them for 10 years. The researchers reported that the incidence of CAD increased across tertiles of waist circumference from never-smokers, to former-smokers, to current smokers. The researchers reported that after adjusting for age, center, educational level, alcohol intake and physical activity, the relative risk of CAD was between 1.14 – 1.28 greater for each standard deviation increase of waist circumference, depending on smoking status. However, the difference between tertiles was not significant. Therefore, the researchers concluded that smokers with abdominal obesity are at the highest absolute risk of developing CAD.
Lett et al. The reviewers assessed the association between depression and progression of CAD. The reviewers found that depression increases the risk of developing CAD by between 1.5 – 2.0 times in otherwise healthy individuals. The reviewers note that various explanations have been proposed for this association, including treatment adherence, lifestyle factors, traditional risk factors, alterations in autonomic nervous system and hypothalamic pituitary adrenal (HPA) axis functioning, platelet activation, and systemic inflammation.

Based on these studies, it appears that the main risk factors for coronary artery disease (CAD) are age, male gender, physical inactivity, high blood cholesterol, nonalcoholic fatty liver disease, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, type II diabetes, chest pain, prior cardiovascular disease, smoking, abdominal obesity and visceral adiposity, neck circumference, depression, erectile dysfunction, periodontal disease, obstructive sleep apnea, high white blood cell count, systemic inflammation, job strain, Chronic Kidney Disease, Chronic Obstructive Pulmonary Disease, Hypertension, and androgen excess in females.


Can exercise slow the progression of CAD?

The use of exercise for helping to slow the progression of CAD has been widely investigated, although many trials are difficult to interpret, as they involve combined lifestyle interventions (i.e. both diet and exercise and sometimes also stress-reduction). Such combined lifestyle interventions are often known as cardiac rehabilitation programs and are designed towards reducing the various coronary risk factors in patients with established heart disease in order to reduce subsequent morbidity and mortality as a result  of cardiovascular disease. However, some studies have been performed only examining the effects of exercise interventions on slowing the progression of CAD, as follows:

Study Description Finding
Hambrecht et al The researchers performed a randomized, controlled trial in order to investigate the effects of different amounts of leisure time physical activity on cardiorespiratory fitness and on the progression of coronary atherosclerotic lesions in 62 patients with coronary artery disease. The researchers randomly allocated the subjects to either to an intervention group or to a control group. The intervention group performed both individual and group exercise, while the control group received usual care. Before and after the 1-year intervention, the researchers performed a coronary angiography to assess the extent of coronary lesions. They also measured exercise capacity. The researchers reported that in the intervention group, there was regression of CAD in 28% of the patients, progression in 10%, and no change in 62%. However, in the control group there was regression of CAD in 6%, progression in 45% and no change in 49%. The researchers reported that they observed the lowest level of leisure time physical activity in patients with CAD progression (1,022 ± 142 kcal/week) and the greatest level of leisure time physical activity in patients with CAD regression (2,204 ± 237 kcal/week). The researchers therefore concluded that regression of CAD is observed only in patients expending around 2,200kcal/week in leisure time physical activity (i.e. 5 – 6 hours/week of exercise).
Schuler and Hambrecht The reviewers assessed the literature in respect of studies investigating the role of regular physical exercise for either slowing the progression of CAD or causing regression of CAD. The reviewers found that most of the available studies did not permit differentiation between the effects of physical exercise, pharmacological lowering of serum cholesterol levels, and stress management. However, the reviewers found that the combined lifestyle interventions led to either regression or slowed or halted progression of CAD while significant progression of CAD was noted in all of the control groups. The reviewers also noted that the intervention groups all displayed significant improvements in physical work capacity, myocardial perfusion, and reduction in anginal pain.

Based on these studies and reviews, exercise and physical activity appears to lead to either regression or slowed progression of CAD. Regression of CAD appears to be observed most frequently in patients expending around 2,200kcal/week in leisure time physical activity (i.e. 5 – 6 hours/week of exercise).


Can interval training improve cardiovascular fitness in CAD patients?

Cardiovascular fitness is considered to be an important factor for CAD patients, as VO2-max (the predominant measurement of cardiovascular fitness) has been found to be the single best predictor of death among cardiac patients (e.g. Kavanagh et al.). Therefore, researchers have suggested that improving cardiovascular fitness may help reduce mortality, morbidity and improve health-related quality of life in CAD patients. The following studies have assessed the ability of interval training exercise interventions for improving cardiovascular fitness in CAD patients:

Study Description Finding
Warburton et al. The researchers performed a randomized controlled trial to compare the effects of high-intensity interval exercise training with that of a usual care exercise-based cardiac rehabilitation program on maximal oxygen uptake (VO2-max), in 14 CAD patients. The usual care exercise-based cardiac rehabilitation program performed a standardized 10-minute warm-up, 30 minutes of continuous aerobic exercise at 65% of heart rate reserve, standardized resistance training, and a 10-minute cool-down period. The interval training group performed the same warm-up, resistance training, and cool-down procedures but instead of the steady-state training, the interval training group exercised using 2-minute, high-intensity work phases at 90% of heart rate reserve followed by 2-minute recovery bouts at 40% of heart rate reserve. Both groups performed the exercise protocol twice per week for 16 weeks. Additionally, the subjects were also required to perform 3 additional training days per week involving steady-state exercise at 65% of heart rate reserve. The researchers reported significant improvements in VO2-max, anaerobic threshold and time to exhaustion in an exercise test in both groups but the improvement in anaerobic threshold and time to exhaustion was greater in the interval training group.
Karlsen et al. The researchers compared the effects of normoxic and hyperoxic aerobic interval training on VO2-max in 21 CAD patients. The researchers allocated the subjects to either hyperoxic or normoxic groups who both took part in 30 supervised 44-minute treadmill walking interval training sessions at 85 – 95% of peak heart rate. The researchers found that peak oxygen uptake and stroke volume increased significantly in the hyperoxic and normoxic training groups (peak oxygen uptake by 16% and 17%, respectively and stroke volume by 16% and 18%, respectively). However, there were no significant differences between groups.
Cornish et al. The reviewers performed a systematic review of those studies assessing the benefits of interval training in CAD patients. The reviewers found 2 controlled trials and 5 randomized controlled trials involving a total of 213 participants. The reviewers reported that interval training prescribed in isolation or in combination with resistance-training produced significant and clinically important physiological adaptations, including cardiorespiratory fitness (i.e. VO2max), endothelial function, left ventricle morphology and function (e.g. ejection fraction) to a significantly greater extent than steady-state exercise training. Additionally, the reviewers observed that no adverse cardiac or other life-threatening events occurred in any of the studies included within the review.
Guiraud et al. The researchers observed that high-intensity interval exercise training has been shown to be more effective than steady-state exercise training for improving cardiovascular fitness, as measured by maximal oxygen uptake (VO2-max), in CAD patients. However, they noted no consensus regarding the optimum protocol. Therefore, the researchers performed a comparison of the acute cardio-pulmonary responses to 4 different single bouts of high-intensity interval training exercise in order to identify the optimal protocol in 19 CAD patients. In each case, the protocol involved an exercise intensity of 100% of maximal aerobic power but with differing durations (15s and 60s) and types of recovery (rest and 50% of maximal aerobic power). The researchers found that a complete rest during the recovery phase led to a longer time to exhaustion compared with an active recovery phase. In respect of rating of perceived exertion (RPE), the researchers found that patient comfort and time spent above 80% of VO2-max, short periods of work (15s) and passive rest periods were the optimal mode of interval training.

Based on the above studies and reviews, interval training improves VO2-max, anaerobic threshold and time to exhaustion in CAD patients. Such improvements are likely to be more significant than those achieved from steady-state aerobic training. Optimal interval training routines for adherence may include short durations of work followed by passive recovery.


Is resistance training useful for patients with CAD?

Resistance training for CAD patients was traditionally discouraged in the belief that it led to increases in blood pressure and consequently potentially adverse cardiovascular events. However, later studies have reported that resistance training appears to be safe in CAD patients and may be a useful adjunct to physical activity and cardiovascular training, as follows:

Study Description Finding
Ghilarducci et al. The researchers performed a study in order to assess the safety and efficacy of resistance-training program in 9 stable, aerobically-trained, male CAD patients. The resistance-training program was performed for 30 minutes, 3 days per week for a 10-week period and comprised lifting 80% of maximum voluntary contraction (MVC) of 5 movements, as follows: quadriceps extension, bench press, standing biceps curl, hamstring curl and military press in addition to 80% of the maximum number of sit-ups in 1 minute. Before and after the 10-week intervention, the researchers measured MVC for each movement as well as body composition. During the MVCs, the researchers observed an electrocardiogram to ensure that no adverse events were likely to occur. During all training sessions, the researchers also monitored heart rate and blood pressure. The researchers reported a significant (11%) increase in quadriceps girth but no other changes in body composition. However, they also noted increases in MVC strength of 17, 12, 19, 53 and 46% for bench press, military press, standing biceps curl, quadriceps extension and hamstring curl, respectively. Importantly, the researchers observed no signs or symptoms of ischemia or abnormal heart rate or abnormal blood pressure responses at any point during the resistance-training program. The researchers therefore concluded that resistance-training at 80% of MVC appears to be both safe and effective in stable, aerobically trained CAD patients.
Brochu et al. The researchers performed a study in order to assess whether 30 disabled older women with CAD were able to perform resistance-training at an intensity sufficient to improve physical function, as measured by the Continuous-Scale Physical Functional Performance Test (CSPFP Test), which assesses the ability to perform 15 different practical actions, including carrying groceries and climbing stairs. The researchers allocated the subjects to either a resistance-training group or to a control group. The researchers reported that in comparison with the controls, the resistance-training group displayed significant improvements in the physical function score on the CSPFP Test whereas the control group did not (+24 vs. +3%). Additionally, the researchers reported that the resistance-training group displayed significant improvements in upper body strength (+18 vs. +6%), lower body strength (+23 vs. +6%), endurance (+26 vs. +1%), balance and coordination (+29 vs. -2%), and 6-min walk (+15 vs. +7%) in comparison with the control group. The researchers concluded that disabled older women with CAD can perform resistance-training at a sufficient intensity to improve physical function.
Featherstone et al. The researchers performed a study to assess the safety of resistance-training in comparison with aerobic treadmill exercise in 12 male CAD patients. The researchers also wanted to assess the physiological responses to the two types of exercise. The subjects therefore performed resistance-training to fatigue at 40, 60, 80 and 100% of maximum voluntary contraction (MVC) force in the overhead press, biceps curl, quadriceps extension and supine press. The subjects also performed a maximal treadmill exercise test for comparison with the resistance-training protocols. While the subjects performed the lifts and the treadmill test, the researchers monitored an electrocardiogram continuously for safety. They also tracked heart rate and systolic and diastolic blood at rest and during peak exercise. The researchers reported that no symptoms or electrocardiographic evidence of ischemia occurred during the resistance training exercise. However, the researchers noted that 5 of the 12 patients displayed signs of ischemia during the treadmill test. Additionally, the researchers observed that the average peak heart rates during the resistance-training were significantly less than during the treadmill test, and while average peak systolic blood pressures were similar, average peak diastolic blood pressures were greater during resistance-training than during the treadmill test.
McCartney et al. The researchers performed a study to compare the effects of 10 weeks of combined aerobic exercise and resistance-training and aerobic exercise-only on strength and aerobic exercise capacity in 18 male CAD patients. The researchers reported that the aerobic exercise-only group displayed increases in 1RM single-arm biceps curl, single-leg press and single-knee extension of 13%, 4% and 5% while the combined aerobic exercise and resistance-training group displayed increases of 43%, 21% and 24%. Similarly, the researchers observed increases in maximal progressive incremental cycle ergometer power output of 2% in the aerobic-only group and by 15% in the combined aerobic exercise and resistance-training group. The researchers also observed that time-to-exhaustion at 80% of initial maximal power increased by 11% (which was not significant)  in the aerobic-only group and by 109% (which was significant) in the combined aerobic exercise and resistance-training group.
Faigenbaum et al. The researchers performed an study to investigate the acute physiological responses to moderate—to-heavy resistance-training in 15 male CAD patients who had recently completed 12 weeks of aerobic training without experiencing complications. Some of the patients were medicated with beta-blockers and some were not. The researchers carried out a graded exercise test and maximal voluntary contraction (MVC) tests on 7 upper-body Nautilus machines. Then, the subjects performed 2 sets of 7 repetitions at 75% of MVC for each exercise while the researchers measured symptomatic, hemodynamic, and electrocardiographic responses in the patients. The researchers reported that during the MVC and submaximal resistance-training trials, they did not detect any significant adverse hemodynamic change in respect of heart rate, systolic blood pressure, diastolic blood pressure, or rate pressure product. Additionally, they reported that none of the subjects complained of angina and none developed ischemic signs per the electrocardiogram. On the other hand, the researchers noted that during the graded exercise test, they observed 13 incidences of angina, ischemia, or premature ventricular contractions. The researchers therefore concluded that clinically stable, aerobically-trained patients with CAD are able to perform moderate-to-heavy resistance-training with a low risk of adverse events.
Marzolini et al. The researchers performed a study to compare resistance-training using either 1 set or 3 sets in combination with aerobic exercise versus aerobic exercise-only in 72 patients with CAD. The researchers randomly allocated the subjects to a 5-day per week aerobic exercise-only or combined 3-day per week aerobic exercise and either 1 set or 3 sets of resistance-training performed 2-days per week. The researchers measured VO2-max, anaerobic threshold, strength, endurance, body composition and adherence before and after a 29-week intervention. The researchers reported that VO2-max increased significantly by 11% in the aerobic exercise-only group, by 14% in the combined-1-set group and by 18% in the combined-3-sets group but the difference between groups was not significant. However, the increase in anaerobic threshold was significant only in the combined-3-sets group. Additionally, the combined-3-sets group increased lean mass by more than the aerobic exercise-only group but the combined-1-set group displayed similar increases to the aerobic exercise-only group. The researchers concluded that combined resistance-training and aerobic exercise protocols lead to superior physiological adaptations than aerobic exercise-only alone and multiple sets of resistance-training are better than single sets for this purpose.
Beniamini  et al. The researchers performed a randomized controlled study to find out whether adding a program of high-intensity resistance-training to an outpatient cardiac rehabilitation program would be a safe and effective means of increasing muscular strength and body composition in 38 cardiac patients. The researchers randomly allocated the subjects to either high-intensity resistance-training or flexibility training during a 12-week outpatient cardiac rehabilitation aerobic exercise program. Before and after the intervention, the researchers measured muscular strength, muscular endurance, joint flexibility, maximum treadmill tolerance time, and body composition. The resistance-training was performed with 80% of 1RM. The researchers reported that the resistance-training group displayed significantly greater increases in muscular strength and endurance and they also displayed greater losses in body fat (2.8 ± 2.0 versus 1.3 ± 2.0kg), greater gains in muscle mass (1.5 ± 2.3 versus 0.5 ± 1.2kg) and greater improvements in treadmill time to exhaustion than the flexibility group.
Beniamini et al. The researchers performed a randomized controlled study to find out whether adding a program of high-intensity resistance-training to an outpatient cardiac rehabilitation program would improve psychological well-being in 38 cardiac patients (29 men and 9 women). The researchers measured a variety of quality-of-life parameters before and after 12 weeks of high-intensity resistance-training or flexibility training in addition to a standard outpatient cardiac rehabilitation aerobic exercise program. The researchers reported that the subjects in the resistance-training group increased self-efficacy scores for lifting, push-ups, climbing and jogging in comparison with the flexibility group. Additionally, the researchers found that the resistance-training group displayed greater improvements in Profile of Mood States (POMS) dimensions of total mood disturbance, depression/dejection, and fatigue/inertia than the flexibility group. Finally, the researchers found that the Medical Outcome Survey Short Form 36 role emotional health domain scores were significantly improved in the resistance-training group in comparison with the flexibility group. The researchers therefore concluded that the addition of resistance-training to a cardiac rehabilitation program improves certain quality-of-life parameters.
Adams et al. The researchers performed a study to assess the effects and safety of an 8-week, high-intensity resistance-training program combined with a traditional aerobic-exercise cardiac rehabilitation program on muscular strength of 61 CAD patients, stratified by risk profile. The researchers tested 1RM for the horizontal leg press, shoulder press, leg extension, lat pull-down, and biceps curl. The subjects performed 2 sets of each exercise for 2 days per week at 60% of 1RM and progressed to 80% of 1RM over 4 weeks. For the second 4 weeks of the 8-week intervention, the relative loading was adjusted individually to maintain an 8RM per set. During the resistance-training, the researchers measured blood pressure and heart rate/rhythm responses and they also tracked muscle soreness and injury after 1RM testing. The researchers reported that all patient groups (across all risk profiles) made significant gains in muscular strength, increasing lower body strength by an average of 15.3% and upper body strength by an average of 16.7%. The researchers reported that no injury or significant muscle soreness occurred following 1RM testing and no abnormal heart rate/rhythm or blood pressure responses were detected. The researchers therefore concluded that CAD patients of varying risk profiles are able to improve muscular strength significantly through a program comprising both high-intensity resistance-training and aerobic exercise.

Based on these studies, resistance-training appears to be effective for improving muscular strength, muscular size, physical function, health-related quality of life and general quality of life in CAD patients. Moreover, researchers have reported few if any adverse events in the controlled trials that have been performed.


Can exercise help reduce mortality and morbidity as a result of CAD?

The use of exercise for helping to reduce mortality and morbidity following CAD has been widely investigated, although many trials are difficult to interpret, as they involve combined lifestyle interventions (i.e. both diet and exercise and sometimes also stress-reduction). However, some studies have been performed only examining the effects of exercise interventions on slowing the progression of CAD, as follows:

Study Description Finding
O’Connor et al. The reviewers assessed 22 randomized trials of cardiac rehabilitation using exercise after myocardial infarction involving 4,554 patients over a 3-year period. The researchers found that the odds ratio for sudden death as a result of myocardial infarction was significantly lower (37% lower) in the cardiac rehabilitation groups than in the control groups at 1 year and while the odds ratio was also lower in years 2 and 3, the reductions were not statistically significant. The researchers reported that there was no significant difference in respect of the odds ratio for nonfatal re-infarction at any point in the 3-year period.
Oldridge et al. The reviewers carried out a meta-analysis of 10 randomized clinical trials using exercise after myocardial infarction involving 4,347 CAD patients (2,145 control patients and 2,202 rehabilitation patients). The reviewers found that the rehabilitation group were significantly (24%) less likely to suffer all-cause death and 25% less likely to suffer cardiovascular death than the control group but they did not find any significant difference in respect of the risk of incurring a non-fatal recurrent myocardial infarction. The reviewers concluded that cardiac rehabilitation has a beneficial effect on both all-cause and cardiovascular mortality but not on non-fatal recurrent myocardial infarction.
Taylor et al. The reviewers performed a systematic review and meta-analysis of the effectiveness of exercise-based cardiac rehabilitation in patients with CAD. They found 48 trials with 8,940 patients. The reviewers found that exercise-based cardiac rehabilitation led to significantly reduced all-cause mortality (20%) and significantly reduced cardiovascular mortality (26%) but no significant differences in the rates of non-fatal myocardial infarction and revascularization. However, the reviewers also observed that exercise-based cardiac rehabilitation led to similar improvements in health-related quality of life compared to usual care.
Heran et al. The reviewers performed a Cochrane review to assess the effectiveness of exercise-based cardiac rehabilitation on all-cause and cardiovascular mortality, morbidity and health-related quality of life in CAD patients. The reviewers found 47 studies including a total of 10,794 subjects, randomized into either exercise-based cardiac rehabilitation or into usual care groups. The reviewers reported that in those trials including a 12+ month follow-up, exercise-based cardiac rehabilitation led to significant reductions in both all-cause and cardiovascular mortality (13% and 26%, respectively], as well as a significant reduction in hospital admissions (41%) up to 12 months. However, the reviewers also found that exercise-based cardiac rehabilitation did not reduce the risk of myocardial infarction, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty. Additionally, the reviewers reported that in 7 out of 10 trials reporting on health-related quality of life, there evidence of a significantly higher level of quality of life in patients undergoing exercise-based cardiac rehabilitation than in those undergoing usual care. The reviewers therefore reported that exercise-based cardiac rehabilitation is effective for reducing total and cardiovascular mortality (in 12+ month follow-ups) and hospital admissions (in <12 month follow-ups) but does not reduce the risk of myocardial infarction, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty.
Lawler et al. The reviewers performed a meta-analysis of randomized controlled trials in order to (1) investigate the effect of exercise-based cardiac rehabilitation on cardiovascular outcomes, and to (2) investigate the effect of exercise-based cardiac rehabilitation program characteristics on magnitude of the various benefits. The reviewers found 34 randomized controlled trials including 6,111 CAD patients. The reviewers reported that those patients who were randomized to exercise-based cardiac rehabilitation had a lower risk of re-infarction (47%), cardiac mortality (36%), and all-cause mortality (26%) and also displayed beneficial effects on cardiovascular risk factors. The reviewers found that the treatment effects were consistent regardless of the duration of the exercise-based cardiac rehabilitation interventions.
Joliffe et al. The reviewers performed a Cochrane review to asses the effectiveness of (1) exercise-only rehabilitation, (2) exercise plus other rehabilitation interventions (comprehensive cardiac rehabilitation), and (3) usual care on all-cause mortality, morbidity, health-related quality of life, and modifiable cardiac risk factors in CAD patients. The reviewers covered trials comprising a total of 7,683 patients (2,582 in exercise-only and 5,101 in comprehensive cardiac rehabilitation groups). The reviewers reported that the exercise-only group displayed a significant reduction in all-cause mortality (27%) in comparison with usual care. They noted that while comprehensive cardiac rehabilitation also reduced all cause mortality compared to usual care, the size of the reduction was smaller (13%). Similarly, the reviewers found that cardiovascular mortality was reduced by 31% and 26% in the exercise-only and comprehensive cardiac rehabilitation groups, respectively. Finally, the reviewers found that that neither exercise-only nor comprehensive cardiac rehabilitation interventions had any effect on the occurrence of non-fatal myocardial infarctions. The reviewers therefore concluded that exercise-based cardiac rehabilitation appears to be effective in reducing cardiac deaths but they did not feel able to conclude on which of exercise-only or comprehensive cardiac rehabilitation interventions were more beneficial.
Jolly et al. The reviewers performed a systematic review and meta-analysis of the effectiveness of home-based cardiac rehabilitation programs compared with (1) usual care, and (2) supervised center-based cardiac rehabilitation on mortality, health-related quality of life and modifiable cardiac risk factors of CAD patients. The reviewers found 18 trials assessing the difference between home and usual rehabilitation and 6 trials assessing the difference between home and supervised center-based rehabilitation. The reviewers reported that in comparison with usual care, home-based cardiac rehabilitation had a significantly (4mmHg) greater reduction in systolic blood pressure and a greater improvements in exercise capacity, total cholesterol, anxiety and depression. However, there was no significant difference in all-cause mortality between the groups.
Dalal et al. The reviewers performed a Cochrane review to compare the effects of home-based and supervised center-based cardiac rehabilitation on mortality and morbidity, health-related quality of life, and modifiable cardiac risk factors in CAD patients. The reviewers found 12 studies including 1,938 subjects. The reviewers reported that they did not find any significant difference between home-based and center-based cardiac rehabilitation for all-cause mortality, cardiac events, exercise capacity, modifiable risk factors, or health related quality of life, except for high density lipoprotein cholesterol and in fact, the reviewers found some evidence of superior adherence in the home-based subjects. The reviewers therefore concluded that both home- and center-based cardiac rehabilitation re equally effective for reducing mortality and improving clinical and health-related quality of life in CAD patients.
Shepherd and While The reviewers performed a systematic review to investigate the effects of cardiac rehabilitation interventions on health-related quality of life in CAD patients. The reviewers found 16 studies reporting on randomized controlled trials in 9 countries. The reviewers concluded that cardiac rehabilitation appears to improve physical well-being. They concluded that home-based interventions appears to be at least as effective as center-based interventions.

Based on these studies and reviews, it appears that exercise-based cardiac rehabilitation significantly reduces all-cause and cardiovascular mortality and improves health-related quality of life in CAD patients, but probably does not significantly reduce the risk of further non-fatal myocardial infarctions occurring.


Evidence-based recommendations for exercise

Some reviews have made evidence-based recommendations for exercise in the form of cardiac rehabilitation in the treatment of CAD that include non-pharmacological treatments, as follows:

Study Recommendation
Balady et al. The reviewers assert that exercise should be an integral part of cardiac rehabilitation. In this context, they note that incremental levels of regular physical activity are inversely proportional to long-term cardiovascular mortality up to at least 3,500kcal/week (or around 9 – 10 hours). Additionally, they note that higher levels of exercise tolerance are associated with significantly reduced subsequent cardiovascular mortality, emphasizing the importance of developing high maximum oxygen uptake (VO2-max).
Balady et al. The reviewers provided an update previous American Heart Association guidelines in respect of cardiac rehabilitation and secondary prevention programs. They assert that all such programs should contain specific core components that aim to optimize cardiovascular risk reduction, including exercise insofar as patients are judged capable. The reviewers advise that the program should encourage patients to accumulate 30 – 60 minutes per day of moderate-intensity physical activity 5 – 7 days of the week. They also advise that both aerobic exercise and resistance-training should be performed, where possible. For aerobic exercise, they recommend 3 – 5 days per week at 50 – 80% of exercise capacity, for 20 – 60 minutes, either walking, cycling, rowing, stair-climbing, arm or leg ergometry, using either steady-state or interval-training. For resistance-training, the reviewers recommend 2 – 3 days per week, using 1 – 3 sets of 10 – 15 repetitions per set to moderate fatigue of 8 – 10 upper and lower body exercises, making use bodyweight, elastic bands, machines or free weights.

Based on these guidelines, it appears that the general recommendation for patients with coronary artery disease CAD is to increase physical activity to 30 – 60 minutes per day most days of the week, and to perform both aerobic exercise up to 5 days per week and resistance-training up to 3 days per week. Benefits are thought to accrue in a dose-responsive fashion up to at least 10 hours per week of physical activity.


Conclusions

On the basis of these studies and reviews, the following conclusions might be drawn:

Area Conclusion
There are many risk factors for CAD The main risk factors for coronary artery disease (CAD) are age, male gender, physical inactivity, high blood cholesterol, nonalcoholic fatty liver disease, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, type II diabetes, chest pain, prior cardiovascular disease, smoking, abdominal obesity and visceral adiposity, neck circumference, depression, erectile dysfunction, periodontal disease, obstructive sleep apnea, high white blood cell count, systemic inflammation, job strain, Chronic Kidney Disease, Chronic Obstructive Pulmonary Disease, Hypertension, and androgen excess in females.
Exercise can help reverse CAD Exercise and physical activity appears to lead to either regression or slowed progression of CAD. Regression of CAD appears to be observed most frequently in patients expending around 2,200kcal/week in leisure time physical activity (i.e. 5 – 6 hours/week of exercise).
Interval training improves cardiovascular fitness in patients with CAD Interval training improves VO2-max, anaerobic threshold and time to exhaustion in CAD patients. Such improvements are likely to be more significant than those achieved from steady-state aerobic training. Optimal interval training routines for adherence may include short durations of work followed by passive recovery.
Resistance-training improves strength, muscle mass and function in patients with CAD Resistance-training appears to be effective for improving muscular strength, muscular size and physical function in CAD patients. Moreover, researchers have reported few if any adverse events in the controlled trials that have been performed.
Exercise reduces mortality in patients with CAD Exercise-based cardiac rehabilitation significantly reduces all-cause and cardiovascular mortality and improves health-related quality of life in CAD patients, but probably does not significantly reduce the risk of further non-fatal myocardial infarctions occurring.
Exercise recommendations include more physical activity, aerobic exercise and resistance-training The general recommendation for patients with coronary artery disease CAD is to increase physical activity to 30 – 60 minutes per day most days of the week, and to perform both aerobic exercise up to 5 days per week and resistance-training up to 3 days per week. Benefits are thought to accrue in a dose-responsive fashion up to at least 10 hours per week of activity.

In summary, CAD has a number of varied risk factors, including physical inactivity. However, exercise interventions can have powerful effects, even reversing the severity of the CAD in some cases and reducing mortality in individuals with the disease. For cardiac rehabilitation, exercise recommendations include more physical activity, aerobic exercise and resistance-training.


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