Abstract
The protective effect of physical activity on arteries is not limited to coronary vessels, but extends to the whole arterial system, including arteries, in which endothelial dysfunction and atherosclerotic changes are one of the key factors affecting erectile dysfunction development. The objective of this study was to report whether the endurance training intensity and training-induced chronotropic response are linked with a change in erectile dysfunction intensity in men with ischemic heart disease. A total of 150 men treated for ischemic heart disease, who suffered from erectile dysfunction, were analyzed. The study group consisted of 115 patients who were subjected to a cardiac rehabilitation program. The control group consisted of 35 patients who were not subjected to any cardiac rehabilitation. An IIEF-5 (International Index of Erectile Function) questionnaire was used for determining erectile dysfunction before and after cardiac rehabilitation. Cardiac training intensity was objectified by parameters describing work of endurance training. The mean initial intensity of erectile dysfunction in the study group was 12.46 ± 6.01 (95% confidence interval [CI] = 11.35-13.57). Final erectile dysfunction intensity (EDI) assessed after the cardiac rehabilitation program in the study group was 14.35 ± 6.88 (95% CI = 13.08-15.62), and it was statistically significantly greater from initial EDI. Mean final training work was statistically significantly greater than mean initial training work. From among the parameters describing training work, none were related significantly to reduction of EDI. In conclusion, cardiac rehabilitation program–induced improvement in erection severity is not correlated with endurance training intensity. Chronotropic response during exercise may be used for initial assessment of change in cardiac rehabilitation program–induced erection severity.
Keywords
Introduction
Numerous studies have confirmed a correlation between erectile dysfunction (ED) and risk factors for atherosclerosis. Glucose and lipid metabolism disorders, obesity, smoking, and low level of leisure time physical activity have a substantial and proven impact on the development of ED (Bacon et al., 2006; Chao et al., 2012; Derby et al., 2000; Gandaglia et al., 2013).
Therefore, a concentration of these factors observed in the population of patients with cardiovascular disease (CVD) makes this group especially exposed to ED (Guo et al., 2010). Actions undertaken as part of secondary prevention should lead to a limitation of the impact of risk factors and thereby have a positive effect on erection quality in patients with CVD. One of the elements of prevention programmes for cardiovascular patients is kinesiotherapy, which is a crucial element of cardiac rehabilitation (CR) and—as confirmed by various studies—has a beneficial effect on modifiable risk factors (Achatziefstratiou, Giakoumidakis, & Brokalaki, 2013). For patients with coronary artery disease, kinesiotherapy is a form of general exercise regimen overseen by a specialist. The protective effect of physical activity on arteries is not limited to coronary vessels, but extends to the whole arterial system, including arteries, in which endothelial dysfunction and atherosclerotic changes are one of the key factors affecting ED development (Haskell et al., 1994; Niebauer et al., 1997).
Risk of complications from the cardiovascular system and individual exercise capacity determines individual exercise training intensity safe for each patient. Exercise training causes various intensity effects, which include a positive effect on erection quality in men with ischemic heart disease (IHD; Belardinelli, Lacalaprice, Faccenda, Purcaro, & Perna, 2005; Kalka et al., 2013).
Considering the above, the authors attempted to answer the question whether endurance training intensity and training-induced chronotropic response are linked with a change in erection severity in men with IHD and ED.
Material and Method
A total of 150 men treated for IHD (107 percutaneous coronary intervention, 43 coronary artery bypass graft), who scored ≤21 points in the initial IIEF-5 (International Index of Erectile Function) test were analyzed. The study group consisted of 115 patients (mean age 62.12 ± 8.71 years) who were subjected to a CR Phase 3 program. The control group consisted of 35 patients (mean age 61.43 ± 8.68 years) who were not subjected to CR Phase 3 program. Because of the documented beneficial influence of CR, no typical randomization was performed (Piepoli et al., 2014). To intentionally prevent the subjects from participating in CR would have been unethical. The authors tried to enroll as many participants as possible. However, some of the approached patients were reluctant and did not agree to participate. The patients who were reluctant to participate gave distance from the facility and the bother of having to attend exercises daily as reasons of their refusal. Thus, the great disproportions in the volume of the study groups. The two groups were statistically equivalent on all outcomes and potential covariates with the exception of Left ventricular end-diastolic dimension (LVEDD; Table 1).
Inclusion Criteria.
All patients gave their informed content to the study and completed the initial and final IIEF-5 tests fully (all categories). For patients from the study group, an inclusion criterion for the study was participation in at least 90% of exercises during the CR program.
All patients were married and had the same sex partner for a long time. The inclusion criteria are given in Table 1.
In all patients from the study group and the control group, a pharmacological treatment as per IHD treatment standards was applied. The treatment for IHD also included nonpharmacological protocols aimed at eliminating IHD risk factors, in particular at introducing prohealth physical activity and pharmacological treatment employing the use of acetylsalicylic acid and/or other antiplatelet drugs, IHD medication (short-acting nitrates, beta-adrenergic blocking agents, calcium antagonists), and hypolipidemic agents (statins, fibrates). As a result of concurrence of arterial hypertension, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), and diuretics were administered (Jankowski et al., 2013).
The criterion for exclusion of a patient from the study was a necessary dosage adjustment of drugs with a proven negative effect on erection and of drugs affecting the chronotropic reaction, carried out during the 6-month study.
The inclusion and exclusion criteria were assessed by a therapeutic team in charge of CR (one internal diseases specialist, one cardiologist, and two physiotherapists). The participants’ case histories and results of additional tests were analyzed. If case of doubt, additional specialists were invited to consult. All respondents were informed of the study procedure and the key aspects of the studied issue and have given their written informed consent.
There were no severe ventricular arrhythmias or conduction disturbances found in any of the patients in a 24-hour electrocardiograpic monitoring (Holter monitor).
Characteristics of the patients with IHD making up the study group and the control group are outlined, respectively, in columns 2 and 2 of Table 2.
Clinical Characteristics of the Study Groups (Patients With IHD and ED).
Note. IHD = ischemic heart disease; BMI = body mass index; Hb = hemoglobin; TC = total cholesterol; eGFR = estimated glomerular filtration rate; MDRD = modification of diet in renal diseases; TG = triglyceride; LDL-C = low-density lipoprotein; HDL-C = high-density lipoprotein; LVEDD = left ventricular end-diastolic dimension; EF = ejection fraction; LA = left atrial dimension; RVEDD = right ventricular end-diastolic dimension; PTCA = percutaneous transluminal coronary angioplasty; CABG = coronary artery bypass graft; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blockers; CVD = cardiovascular disease.
Inadequate physical activity means <1000 kilocalories per week.
p < .05.
The exercise training program was carried out over 6 months and included endurance trainings on cycle ergometers, general rehabilitation exercises, and elements of resistance training (Figure 1). The duration of the rehabilitation (early rehabilitation at an outpatient facility) was typical and consistent with European Society of Cardiology guidelines (Piepoli et al., 2014). A stress test was performed prior to commencing a rehabilitation cycle and after its completion. The initial cardiac stress test allowed the establishment of individual permissible heart rate values for each subject.
Cardiac rehabilitation cycle.
The endurance trainings were carried on ERGOLINE ER 900 cycle ergometer (GmbH CoKG 72457, Bitz). In the applied cycle ergometer training (which lasted 45 minutes at a time), loads were increased at 4-minute intervals until halfway through the training, when they achieved their peak, and then they were declined to their initial values, interrupted by 2-minute recovery periods with a maintained load of 0 to 5 W. Each training started with a 2-minute warm-up and ended with a 3-minute cool-down period with no load. The peak load of the initial trainings was established at 40% to 70% of the load achieved during the initial cardiac stress test and it was increased not more than by 10 W for each interval every 12 endurance trainings on the cycle ergometer by the proper adaptation of patients for exertion (subjective assessment and declining trend of heart rate increment on the exertion peak). Heart rate was monitored continuously and blood pressure was measured automatically during endurance training on cycle ergometers at the beginning and end of each interval.
Cardiac training intensity was objectified by parameters describing work of endurance training. Additionally, individual heart rate change—the cardiovascular system’s response to cardiac training (the chronotropic response)—was analyzed.
Initial training work (IW), final training work (EW), training work growth (ΔW), and mean training work were analyzed (Table 3).
Training Work Formulas.
Chronotropic response was analyzed by estimating heart rate before training (HRmin), heart rate at peak exercise (HRmax), and heart rate growth (ΔHR), which is the difference between HRmax and HRmin. These parameters were estimated at the beginning (1) and end (2) of the program by averaging their value from the first three and the last three trainings within the CR program. A model of the interval training, with indicated chronotropic response parameters, is presented in Figure 2.
Cardiac rehabilitation scheme.
General rehabilitation training consisted of standard breathing, relaxation, stretching, balance, and skill exercises performed in groups. Gym exercises were supplemented with elements of resistance training, which included 8 to 10 various resistance exercises involving different muscle groups. All exercises were performed in a series of 12 to 15 repetitions. All patients performed the same sets of exercises. During exercise, the 13th fatigue level, according to the 15-point Borg scale, was not exceeded (15-20). During general rehabilitation exercises, heart rate was monitored continuous using a Polar S720i heart rate monitor (0.2 Hz sampling rate). CR was performed as per recommendations of the European Society of Cardiology (Giannuzzi et al., 2003).
The control group—not subjected to any CR—received, as part of health-promoting education, information about the necessity to maintain an active lifestyle, with individual recommendations concerning the type, intensity, and desired dose of leisure time physical activity.
Because of the fact that it was Phase 3 of CR for all the subjects, education on prohealth lifestyle had been introduced prior and modifiable CVD risk factors had already been modified. All subjects stated they were adhering to the nonpharmacological protocols for IHD, which had been introduced in Phases 1 and 2 of CR.
An abridged IIEF-5 questionnaire was used for determining erectile dysfunction. It contained five questions with answers scored from 0 to 5 assessed collectively in the score scale 0 to 25.
ED was diagnosed if the total score in the questionnaire was ≤21. Sexual intercourses that were not had after taking PDE-5 inhibitors were assessed.
The IIEF is a widely used, multidimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of ED and for diagnostic evaluation of ED severity (Rosen, Cappelleri, & Gendrano, 2002). Validity and sensitivity of the abridged scale were evaluated by analyses of patients with ED from four placebo-controlled trials of sildenafil, as well as with a control group of men without ED (Cappelleri, Siegel, Osterloh, & Rosen, 2000; Cappelleri & Stecher, 2008; Rosen, Cappelleri, Smith, Lipsky, & Peña, 1999).
In the group of patients with IHD who were subjected to CR, the IIEF-5 test was performed twice, at the beginning and after the program. In the control group, the test was also performed twice, with a 6-month interval corresponding to the duration of the program.
The analyzed parameter was the total score (EQ) in the IIEF-5 questionnaire. Assessed was its initial value (EQ1), end value (EQ2), and change in erection severity (ΔEQ), which was the difference between EQ2 and EQ1.
Credibility of data from the IIEF-5 questionnaire was verified by comparing in 32 randomly selected patients the total test score in the initial and control tests (interval of at least 7 days).
The study was conducted as part of a project approved by the Local Bioethics Committee (95/WIM/2005, KB-433/2010). All participants gave their informed consent to the study.
Statistical Analysis
Because of the unmet condition of normal distribution of one of the main parameters (EQ), the median was the basic measurement for the central tendency used in this study. Maximum and minimum values were used to describe the dispersion of variables.
The Mann–Whitney U test for independent samples was used for testing the significance of differences for the two subgroups. Wilcoxon paired sample rank test was used for dependent samples, in order to test the influence of chosen factors on the analyzed parameters.
The strength of the relationship between the variables was measured with Spearman’s rank correlation coefficient.
Student’s t test was used for testing the significance of mean differences within two subgroups (for independent samples). For dependent samples, the same test was used for testing the impact of chosen factors on the behaviour of the analyzed parameters. Levene’s test was used for testing the hypothesis of equality of group variances in the population. The result of the test determined using an appropriate formula of the t test.
Correlation between two dichotomous variables was determined using the chi-square test or Fisher’s exact test. The value of p < .05 was taken as the level of statistical significance. All statistical calculations were made using the STATISTICA statistical programme package (data analysis software system), Version 10, StatSoft, Inc. (2011).
Study Results
From among the analyzed clinical parameters, the test group was characterized by a significantly lower left ventricular diastolic diameter; however, for both groups mean values were within normal limits.
Mean EQ1 in the study group was 12.46 ± 6.01 (95% CI = 11.35-13.57). EQ2 assessed after the cardiac training program in the study group was 14.35 ± 6.88 (95% CI = 13.08-15.62). In the control group, EQ2 was not different from EQ1.
The value for EQ1 median for the study group was 14 (0-21) and was not statistically significantly different from the value for the control group, which was 13 (4-21). The EQ2 median for the study group, assessed after a series of cardiac exercise, amounted to 16 (0-24) and was statistically significantly different from EQ1 (Figure 3). For the control group, there was no statistically significant difference between EQ1 and EQ2. Median ΔEQ for the study group amounted to 2 (−1 − 5) and was significantly different from the control group, where ΔEQ amounted to 0 (−2 − 2).
Erectile dysfunction intensity (EQ) before (1) and after (2) cardiac rehabilitation into study (E) and control (C) groups; NS indicates not significant.
Initial ED severity (EQ1) in the study group was statistically significantly related to age (r = −0.755802), eGFR (estimated glomerular filtration rate) value (r = 0.405996), high-density lipoprotein cholesterol (HDL)-C concentration (r = 0.219874), and triglyceride concentration (r = −0.207723).
Body mass index (BMI), echocardiographic parameters LVEDD and ejection fraction (EF), hemoglobin concentration, and low-density lipoprotein (LDL-C) concentration had no statistically significant relation to EQ1.
From among the analyzed dichotomic parameters, a significantly lower EQ1 was determined by hypertension, diabetes, and treatment with ACEIs and/or ARBs. Type of invasive treatment, smoking, excess weight, obesity, lipid disorders, low level of leisure time physical activity (<1000 kcal/week), myocardial infarction, and pharmacotherapy with beta-blockers, diuretics, statins, and/or fibrates did not determine EQ1 significantly.
ΔEQ value for the study group had a statistically significant relation with age (r = −0.481027), height (r = 0.194464), EQ1 (r = 0.537467), EQ2 (r = 0.693708), eGFR (r = 0.193217), high density lipprotein (HDL-C; r = 0.242143), and triglyceride (r = −0.205950) concentration.
From among the analyzed dichotomic parameters, a significantly lower ΔEQ was determined by hypertension, hyperlipidemia, myocardial infarction, and treatment with ACEIs and/or ARBs. The other analyzed clinical parameters were not significantly related to ΔEQ and had no significant impact on its value.
Mean final training work (EW) was statistically significantly greater than mean initial training work (IW). From among the parameters describing training work, none were related significantly to ΔEQ.
Mean resting heart rate at end of program (HRmin2) was statistically significantly lower than the corresponding heart rate at beginning of program (HRmin1). Mean peak heart rate at end of program (HRmax2) was not statistically significantly different from corresponding heart rate at beginning of program (HRmax1). From among the parameters describing chronotropic response, HRmax1, ΔHR1, HRmax2, and ΔR2 are statistically significantly related to ΔEQ. Figure 4 presents a graph of the linear correlation between ΔHR1 and ΔEQ.
A graph of the linear correlation between ΔHR1 and ΔEQ.
The test of credibility of data from the IIEF-5 questionnaire showed no statistically significant differences between the initial and the control completion of the questionnaire.
Discussion
Cardiovascular diseases are one of the major causes of ED in men. It applies especially to men older than 50 years, in whom as much as 40% of ED is related to vascular disorders with an underlying atherosclerotic process associated with the concentration of major risk factors, such as diabetes, hypertension, smoking, and low level of leisure time physical activity (Kaiser et al., 1988; Maroto-Montero et al., 2008).
As a result of its popularity, potential ease, and low costs of positive modification, there has been a growing interest of medical professionals in leisure time physical activity. Its substantial and independent correlation with ED was confirmed by an analysis performed in a population of 2,126 men by Selwin, Burnett, and Platz (2007) under the National Health and Nutrition Examination Survey.
Moreover, a study performed by Derby et al. (2000) on a group of 593 men confirmed the influence of physical activity on ED development. At the same time, it stressed that physical activity is the only factor whose positive modification, even if initiated in midlife, may reduce the risk of ED.
An analysis, performed in the study group, of the risk factors and of clinical parameters considered as favoring the development of endothelial dysfunction and atherosclerosis in the test group indicates that they have a negative effect both on EQ1 and ΔEQ. It confirms the influence of factors, such as age, hypertension, diabetes, lipid disorders, and low level of leisure time physical activity on ED development in a population of patients with IHD (Chao et al., 2012; Derby et al., 2000; Feldman, Goldstein, Hatzichristou, Krane, & McKinlay, 1994).
Intensification of physical activity in the study group as part of the CR had a beneficial effect on erection quality. No such effect was observed in the control group, which was not subjected to any CR.
CR is specific in that training intensity is selected individually depending on different risks of complications during physical exercise. Cardiac training intensity is determined based on an assessment of the risk of complications associated with physical exercise. It contains an assessment of physical capacity and an analysis of the degree of left ventricular damage, together with an assessment of the hitherto course of IHD. It determines the intensity of initial cardiac training, which is then modified depending on how the patient adapts to physical exercise (Giannuzzi et al., 2003).
However, activities that limit training intensity may also limit the beneficial effects of CR, including change in erection severity.
Patients from the test group were subjected to the CR program in accordance with the applicable standard, with different individually selected CR intensity. The parameter that both differentiated and objectified training intensity was work performed by the patient during a single endurance training on a cycle ergometer. Exercise tolerance that developed in the test group as a result of the 6-month cardiac training allowed to significantly increase cardiac training work. Therefore, initial training work, final training work, training work growth, and mean training work were analyzed. None of the above parameters were statistically significantly related to ΔEQ. This observation, in the context of recommendations for patients concerning the need for a physically active lifestyle, seems to have a very significant practical dimension, indicating that intensity of physical activity is not the key element determining efficiency of applied physical exercise in improving erection quality.
As part of the assessment of cardiac training intensity, the cardiovascular system’s response to training load was also analyzed.
Analysis of individual training-induced change in heart rate is the easiest to record and measure index (regulated by the autonomic nervous system) of the cardiovascular system’s response to exercise.
Systematic cardiac training in the study group led to adaptive and beneficial changes in heart rate. In the study group, there was a statistically significant reduction of (resting) heart rate, which, according to the observations made to date, is the result of modification of the autonomic system activity (Arai et al., 1989; Klabunde, 2005; Leitch et al., 1997).
From the physiological point of view, the training-induced chronotropic response observed in patients from the test group resulted from a cooperative interaction of the two subsystems of the autonomic system, which are also involved in the initiation of erection. Furthermore, as confirmed in various studies, patients with IHD suffer from sympathetic and parasympathetic activity balance disorders (Eckberg, Drabinsky, & Braunwald, 1971). Therefore, the statistically significantly negative relations observed between training-induced change in erection quality (ΔEQ) and heart rate at peak exercise (HRmax) and heart rate growth dynamics (ΔHR) may be associated with the disturbed balance between sympathetic and parasympathetic activity, which is involved both in control of the dynamics of chronotropic response and in penile erection.
The conclusion that ED accompanies postexercise dysfunction of the autonomic nervous system (affecting chronotropic response) was presented by Dogru, Basar, and Haciislamoglu (2010) after an analysis carried out in a group of 135 men, of which 65 was diagnosed with ED.
The gap between ΔEQ and HRmax and ΔEQ and ΔHR decreasing as a result of the cardiac training program confirms a favorable trend indicating a decrease in the strength of the observed correlations, which may be associated with the training program-induced improvement in the balance between sympathetic and parasympathetic activity (Blumenthal et al., 1990; Malfatto et al., 1998).
Therefore, CR-induced improvement in erection quality in patients with IHD and ED may depend not only on the effect on modification of endothelial mechanisms, as suggested by other authors, but also on a beneficial modifying effect of physical activity on the balance between sympathetic and parasympathetic activity (Kratz et al., 2014; Penedo & Dahn, 2005; Solomon, Man, & Jackson, 2003).
Application of multiple regression analysis allows to assess ΔEQ based on ΔHR1. It allows, theoretically already at the beginning of the program, the assessment of potential improvement in erection quality achieved through the training program and to single out a group in which poor prognosis should trigger off radicalization of the fight with risk factors that have a proven negative effect on the erection process.
By analysing the obtained data, we can conclude that apart from a beneficial effect on erection quality, physical activity also provides information useful in making a decision on necessary intensification of preventive actions undertaken with respect to patients with IHD and ED.
In conclusion, cardiac training program-induced improvement in erection quality is not correlated with endurance training intensity. Chronotropic response during exercise may be used for initial assessment of change in cardiac training program–induced erection quality.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.