Cardiovascular disease is the leading cause of mortality and morbidity in Portugal, making atherosclerotic disease an important public health issue that requires measures for primary and secondary prevention.1,2

The 2008 Framingham general cardiovascular risk profile identified the main risk factors for cardiovascular disease (CVD) as age, gender, total cholesterol, high-density lipoprotein (HDL) cholesterol, systolic blood pressure, diabetes and smoking.3 Of these, most are modifiable, offering a window of opportunity to significantly reduce the global burden of CVD.

Exercise-based cardiac rehabilitation programs (CRP) are an important element in the prevention and treatment of CVD and in the control of cardiovascular risk factors.4

A significant factor in the effectiveness of CRP is their positive effect on patients’ functional capacity, which results in improved prognosis and survival after diagnosis of CVD. Functional capacity following a cardiovascular event is known to be a strong independent predictor of mortality.5

Participation in a CRP has been shown to improve exercise tolerance, raise ischemic threshold, help control cardiovascular risk factors and improve general health.6,7

The objective of the present study is to determine the cardiovascular risk factors that predict changes in functional capacity in patients who have completed a CRP.

We performed a cross-sectional descriptive retrospective study of consecutive patients diagnosed with ischemic heart disease referred for a multidisciplinary exercise-based CRP between January 2008 and December 2013.

The sample included 1399 patients, mean age 61±11 years (Table 1), 1068 (76%) male. Analysis of cardiovascular risk factors showed 71% had dyslipidemia, 38% diabetes and 61% hypertension. Body mass index (BMI) was <25 kg/m2 (low or normal weight) in 33%, 25–30 kg/m2 (overweight) in 49% and ≥30 kg/m2 (obese) in 18%; 31% of the sample were smokers (Table 2).

According to the responses to the IPAQ, most of the population (63%) had low levels of physical activity before the CRP; only 3% reported vigorous activity. In the last two years of the study period, the prevalence of sedentary behavior increased, with rates of 72% and 76% in 2012 and 2013, respectively (Table 3).

The most frequent reason for referral (62%) to the program was acute coronary syndrome (ACS) (Table 4).

Of the initial sample of 1399 participants, complete data at the end of the CRP were only available for 1125, mainly because of patients lost to follow-up or leaving the program for medical or personal reasons. However, these losses did not significantly alter the prevalence of risk factors in the population (Table 5).

Analysis of the influence of cardiovascular risk factors on changes in functional capacity was thus limited to these 1125 patients.

The mean gain in functional capacity on completion of the program was 1.45±1.19 METs; the maximum gain was 7.8 METs (Table 6). Functional capacity improved in 93% of participants (Table 7).

A multivariate logistic regression model was used to determine the influence of different cardiovascular risk factors on changes in functional capacity as assessed by exercise testing. Although the goodness of fit was low (R=0.213; R2=0.045), patients with diabetes showed significantly less improvement in functional capacity than those without diabetes.

Another risk factor associated with changes in functional capacity was age. Patients aged 45–64 and over 65 more often had improved functional capacity than those aged <45. Furthermore, those referred for a CRP following coronary artery bypass grafting (CABG) had significantly greater mean improvement in functional capacity (0.44 METs) than those admitted for ACS. By contrast, those who had undergone elective angioplasty and those referred for control of cardiovascular risk factors showed less improvement in functional capacity than those referred following ACS.

No significant differences were seen between the groups in the other variables (Table 8).

Multivariate analysis in this study identifies three predictors of changes in functional capacity following CRP: age, diabetes and reason for referral.

There is a statistically significant relation between the presence of diabetes and smaller gains in functional capacity during CRP. There is evidence in the literature that patients with diabetes have skeletal muscle dysfunction associated with microvascular disease, leading to reduced functional capacity. This dysfunction is reflected in loss of phosphocreatine, decreased pH and more rapid deoxygenation of skeletal muscle during exercise and slower recovery.10,11 There is also evidence that myocardial oxygen demand is higher in patients with diabetes than in non-diabetic individuals.11 The increased availability of fatty acids in diabetes results in increased absorption and oxidation in the mitochondria of cardiac muscle and increases mitochondrial expression of uncoupling proteins, both of which reduce the quantity of ATP produced per molecule of oxygen consumed.12,13

In view of the above, diabetic patients can be expected to show less improvement. It may therefore be advantageous to focus greater efforts on these patients, by increasing the number of CRP sessions per week or by encouraging better adherence to home-based exercise protocols outside the formal sessions.

Age was also a statistically significant predictor of changes in functional capacity in our study, with middle-aged (45–65) and older (over 65) patients achieving greater improvement than younger patients (aged <45). These findings are in agreement with those of similar studies, which report higher gains in functional capacity in older patients.14,15 Functional capacity declines by 8–10% per decade in non-athletes, largely due to reduced peak heart rate and peak aerobic capacity.16 However, older patients who undergo an appropriate individualized CRP present the same benefits as other individuals, and in fact their gains can be greater, perhaps due to their initially lower baseline functional capacity.

For these reasons, more older patients should be referred for these programs, due to their clear benefits in terms of functional capacity.

Overweight and obesity were not statistically significant predictors of changes in functional capacity in our study. This conflicts with the results of other studies in which obesity was associated with reduced exercise performance during each phase II session, ultimately resulting in smaller gains in functional capacity by the end of the program.17 An inverse relation between obesity and functional capacity has also been reported,18 with studies showing that excessive body adiposity leads to lower oxygen uptake by skeletal muscle and hence worse functional capacity.19 In addition, type II muscle fibers are increased and type I fibers are decreased in obese individuals, which is also associated with a significant reduction in oxygen uptake.20 The fact that obese individuals in our study did not, as might be expected, present worse performance can be explained by the individualized interventions that they underwent in terms of exercise and diet throughout the program.

Patients referred for the CRP following CABG showed greater improvement in functional capacity than those referred following ACS without surgery. This may be explained by the lower baseline functional capacity of the CABG patients, and thus greater benefit.

There was no statistically significant evidence of a gender influence on changes in functional capacity, which is in agreement with similar studies.21

Hypertension was not shown to affect changes in functional capacity, although there is evidence in the literature of an inverse relation between functional capacity and hypertension.22,23 Hypertensive patients would be expected to have worse baseline functional capacity, but to improve with regular exercise over the course of a CRP. While this was not observed in our study, it should be borne in mind that all patients on a CRP are closely monitored in terms of cardiovascular risk factors and medication, and so the influence of hypertension on functional capacity in our sample may have been minimized by blood pressure control and optimization of drug therapy, together with control of diet, particularly salt intake.

Dyslipidemia also did not influence functional capacity. Several studies have shown a strong correlation between improved functional capacity and reductions in total cholesterol, total triglycerides and low-density lipoprotein and increases in HDL.24,25

Smoking status at the beginning of the CRP did not appear to influence functional capacity. Smoking is known to be inversely related to functional capacity, but it has also been shown that functional capacity can at least partially recover in the long term following smoking cessation. If long-term follow-up data were analyzed, a positive relation would probably be found between smoking cessation and improvement in functional capacity.26,27

Sedentary behavior as assessed by the IPAQ was not shown to be a predictor of changes in functional capacity. It is associated with peripheral alterations, including loss of skeletal muscle and impaired muscle oxidative capacity, that reduce functional capacity.28,29 There is also evidence of a relation between sedentary behavior and vascular dysfunction, possibly due to reduced endothelium-dependent vasodilation and increased endothelial cell damage.30,31 The lack of influence of level of physical activity on changes in functional capacity in the different IPAQ categories may be explained by the fact that patients who already took moderate or vigorous exercise would tend to improve less, since they were in better physical condition before the program. All the factors associated with sedentary behavior act together to limit the gains achieved by sedentary patients on a phase II CRP.

The proportion of sedentary patients entering the CRP rose over the years, reaching a peak of 76% in 2013. This trend is worrying in view of the finding in various studies of a significant relationship between low levels of physical activity and greater risk of cardiovascular events.32 The World Health Organization has identified physical inactivity as the fourth leading risk factor for global mortality.33

Finally, irrespective of the cardiovascular risk factors presented and their prevalence in the study sample, improvements in functional capacity were seen in 93% of the 1125 participants by the end of the program. This finding reinforces the importance of such programs for improving patients’ prognosis and survival.

This study highlights the importance of CRP in secondary prevention of CVD, showing that most participants achieve a significant improvement in functional capacity; it also identifies patient subgroups whose response is less positive, underscoring the need for individualized approaches.

The authors have no conflicts of interest to declare.