Carotid atherosclerosis is the leading cause of ischemic stroke.1 At the population level, early detection of carotid plaque formation is possible through the routine use of Doppler ultrasound.2,3 Carotid intima–media thickness (cIMT) is a marker of vascular structure and a well-established surrogate of atherosclerosis.4–6 Epidemiological studies have indicated that an increase in cIMT is present in the general population, especially in middle-aged and older adults. Li et al7 reported that among 14,322 participants, the mean cIMT was 0.74 (0.11) mm, with almost 40% of the participants having cIMT >1 mm and early atherosclerotic lesions.
Evidence shows that the use of pharmacological agents and lifestyle interventions reduces the rate of increase in cIMT.8–10 It is well-known that a cIMT ≥0.7 mm is associated with an increased risk for cardiovascular disease.11,12 cIMT can be used to evaluate cardiovascular disease risk in asymptomatic adults.13,14 In nonpharmacological treatments, the regression of atherogenesis, as demonstrated by cIMT, has been observed in trials of lifestyle interventions.15–17 Lifestyle modification may be key to treating subclinical atherosclerosis as it affects vascular and endothelial function.18,19 Meanwhile, the separate effect of exercise on cIMT, an important component of lifestyle intervention, remains unclear. Conflicting results have been obtained among the studies. Glodzik et al20 reported that controlled aerobic exercise reduced cIMT in healthy adults, whereas Bjarnegard et al21 found that the effect of exercise on cIMT was negligible. Although several previous systematic reviews and meta-analyses have explored exercise interventions, they only focused on a particular form of exercise (such as tai chi, yoga, or walking) and extensively evaluated a particular outcome, such as quality of life and cardiovascular events.22–25
In this systematic review and meta-analysis, we aimed to summarize the current evidence regarding the effects of exercise on cIMT in adults and determine the impact of the 3 characteristics of exercise (duration, intensity, and type) on cIMT. We hope to provide a basis for the development of appropriate exercise prescriptions for adults.
Methods
This meta-analysis was conducted based on the recommendations of the Preferred Reporting Items for Systematic Reviews statement.26
Eligibility Criteria
Populations
Adult participants (aged ≥ 18 y) who were not restricted by health status were eligible.
Interventions
Studies that treated PA as a single intervention as opposed to a component of a broader intervention were eligible. Furthermore, studies that included the intervention and control groups, where the only difference between the 2 groups was the addition of exercise in the intervention group, were included. We excluded studies that combined exercise with cognitive training, diet control, or drug therapy to assess the independent effect of exercise on cIMT. We classified the exercise included in the studies into 5 types: aerobic exercise, resistance exercise, combined aerobic and resistance exercise (CARE), high-intensity interval exercises (HIIE), moderate-intensity continuous exercise (MICE), and endurance exercise.
Comparisons
Studies in which the control group received usual care (allowed participation in unplanned, unstructured, daily exercises) were eligible. Sedentary behavior is reportedly associated with increased cIMT.27–29 Therefore, we excluded studies in which individuals who had a sedentary lifestyle were used as controls.
Outcomes
Studies in which the outcome was cIMT of the participants and those in which there were no restrictions on the band of the measuring instrument and measuring sites (the common carotid artery, internal carotid artery, common carotid artery bifurcation, and carotid bulb) were all eligible.
Information Sources and Search Strategy
We searched the PubMed, Cochrane Library, Embase, and Web of Science databases until October 11, 2021. The reference lists in relevant reviews and meta-analyses were another source of information. Two researchers (H. Wu and J. Wu) independently searched the electronic databases using the same search strategy. The complete search strategy for PubMed is presented in Table S1 (see Supplementary Material [available online]), the other databases were searched using the same index terms.
Selection Process
We imported records from the database searches into EndNote and deleted duplicate records. For initial screening of the eligible studies, 2 researchers (Y. Wang and Wei) independently reviewed the titles and abstracts of all records and discussed inconsistencies until they reached a consensus. To determine the studies to be included, 2 researchers (Wei and Sun) independently screened the full texts according to the inclusion criteria and discussed disagreements with other researchers until they reached an agreement. Only studies published in English were included.
Data Collection Process
We designed an extraction form into which 2 researchers (Y. Wang and JW) independently inputted data extracted from the included studies. Other researchers examined and resolved the conflicting data. The information extracted from each included study were as follows: (a) characteristics of the articles (first author, year of publication, and the country where the study was carried out), (b) characteristics of the participants (health status, male/female, sample size, and mean age), (c) characteristics of exercise (type, form, duration of session, frequency, intensity, and duration of exercise), and (d) effects of treatment.
Data Items
We extracted the mean and SD of the cIMT in the intervention and control groups after the intervention. With the participant in the supine position, the thickness of the intima and media of the carotid artery wall was measured using B-mode sonography. The measurement sites included the common, internal, and external carotid arteries, bifurcation of the common carotid artery, and carotid bulb. The final recorded result was the measurement of 1 vascular site or the average of measurements at multiple sites.
Study Risk of Bias Assessment
Two review authors (Y. Wang and Sun) independently assessed the quality of the included studies using the Cochrane risk-of-bias tool30 and resolved any differences through discussions with other authors. The tool evaluates each study based on the areas of randomized controlled trials related to deviations: selection, performance, detection, attrition, reporting, and other biases. Based on the description in a study, it was evaluated as having “low,” “unclear,” or “high” risk of bias in these areas.
Synthesis Methods
Statistical analyses were performed using Stata (version 15.0, Stata Corporation).
In different studies, consistent methods were used to measure cIMT, and the units were all in millimeters. Therefore, we expressed the effect measures as weighted mean differences (WMDs) and 95% confidence intervals (CIs). An individual study group was used as the unit of analysis. Studies that reported multiple intervention groups and a single control group were treated as multiple studies. To avoid double counting, we referred to the method described by Coventry et al31 and divided the sample size of the control group equally.
The I2 statistic was calculated to assess the heterogeneity among studies and select the effect model. A random-effects model was selected if I2 was >50%, indicating statistical heterogeneity among the studies. Otherwise, a fixed-effects model was used. Meta-regression analysis was used to examine the causes of heterogeneity. Forest plots were used to graphically demonstrate the meta-analysis results. Egger regression analysis was performed to assess potential publication bias and visually inspect the funnel plots.
Results
Study Selection
We searched 4 electronic databases and reference lists (6 citations) and identified 1681 citations. After removal of duplications, titles and abstracts were screened, and 204 records were identified for full-text review. Finally, 26 studies20,21,32–55 (32 study groups) that met the eligibility criteria were included in the meta-analysis. The detailed selection process and reasons of exclusion of some studies are presented in the Preferred Reporting Items for Systematic Reviews flow diagram (Figure 1).
—Flowchart of study selection for the meta-analysis.
Citation: Journal of Physical Activity and Health 19, 12; 10.1123/jpah.2022-0372
Study Characteristics
Twenty-six studies identified 32 study groups with 1370 participants, and all study groups were included in the meta-analysis. Most of the studies were conducted in Asia (n = 14), the United States (n = 6), and Europe (n = 5). Twenty-four study groups evaluated participants with diseases. The duration of the intervention ranged from 2 to 12 months for the intervention arms, but lasted ≤6 months20,33–35,38–40,42–44,46,49–55 for most studies. The effect of aerobic exercise was reported in 9 of the 32 study groups. Fifteen study groups reported that exercise reduced cIMT in adults. However, 17 study groups maintained that exercise did not affect the cIMT. The relevant characteristics of these studies are summarized in Table 1.
Characteristic of Included Studies
Studies | Country | Health status | Male/female | Exercise | Control | Types | Forms | Session duration | Frequency (times/wk) | Intensity | Duration | Effect | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | Age | n | Age | |||||||||||
Adams et al49 | Canada | TCS | 63/0 | 35 | 44.0 (11.6) | 28 | 43.3 (9.9) | HIIE | Treadmill walk/running | 35 min | 3 | 75%–95% VO2peak | 12 wk | Decrease |
Bjarnegard et al21 | Sweden | Nonsmoking | 0/42 | 21 | 34 (7) | 21 | 35 (6) | Aerobic | Cycling | 45–60 min | 3 | High effort | 12 mo | NS |
Byrkjeland et al48 | Norway | T2DM | 115/22 | 61 | 63.5 (8.0) | 62 | 63.2 (7.2) | Aerobic and resistance | — | 60 min | 2 | RPE ≥ 15 | 12 mo | NS |
Croymans et al51 | United States | Obese young men | — | 28 | 21.5 (2.22) | 8 | 21.72 (1.57) | Resistance | DB | 60 min | 3 | 6–8 RM | 12 wk | Decrease |
Donley et al33 | United States | Metabolic syndrome | 8/14 | 11 | 46 (4) | 11 | 44 (3) | Aerobic | Treadmills | 60 min | 3 | 85% HRmax | 8 wk | NS |
Healthy adults | 6/15 | 11 | 41 (4) | 10 | 40 (4) | Aerobic | Treadmills | 60 min | 3 | 85% HRmax | 8 wk | NS | ||
Farahati et al52 | Iran | Overweight | 0/20 | 11 | 43.90 (3.80) | 9 | 44.22 (3.63) | MICE | Treadmill walk/running | 30 min | 3 | 85%–95% HRmax | 12 wk | NS |
0/19 | 10 | 42.80 (2.69) | 9 | 44.22 (3.63) | HIIE | Treadmill walk/running | 47 min | 3 | 60%–70% HRmax | 12 wk | NS | |||
Ghardashi-Afousi et al53 | Iran | T2DM | 41/28 | 30 | 55.10 (6.07) | 29 | 54.10 (5.68) | HIIE | Cycling | — | 3 | 85%–90% HRmax | 12 wk | Decrease |
Glodzik et al20 | Poland | Healthy adults | 31/14 | 31 | 44.3 (5.57) | 14 | 45.0 (3.41) | Aerobic | Cycling | 40–60 min | 3 | 40%–65% HRR | 12 wk | Decrease |
Hafner et al35 | United States | Healthy adults | — | 14 | 20.4 (1.6) | 11 | 19.4 (1.1) | ET | Marathon | — | 4 | — | 16 wk | NS |
Kadoglou et al38 | Sweden | T2DM | 13/32 | 21 | 58.3 (5.4) | 24 | 57.9 (7.2) | Aerobic | Walking/cycling | 60 min | 4 | 60%–75% HRmax | 6 mo | Decrease |
14/33 | 23 | 56.1 (5.3) | 24 | 57.9 (7.2) | Resistance | — | 60 min | 4 | 60%–80% 1 RM | 6 mo | Decrease | |||
12/34 | 22 | 57.9 (6.5) | 24 | 57.9 (7.2) | Aerobic and resistance | Walking/cycling | 60 min | 4 | 60%–75% HRmax /60%–80% 1 RM | 6 mo | Decrease | |||
Kim et al46 | Korea | Abdominal obese | 0/62 | 32 | 41.1 (5.5) | 30 | 40.8 (6.2) | Aerobic and resistance | Walking/elastic band | 50–80 min | 5 | 60%–70% HRmax /RPE 13–15 | 12 wk | Decrease |
Kim et al34 | Korea | Older adults | — | 14 | 65 (1) | 11 | 63 (2) | HIIE | Treadmill | 40 min | 4 | 90% HRpeak | 8 wk | NS |
— | 13 | 65 (2) | 11 | 63 (2) | MICE | Treadmill | 47 min | 4 | 70% HRpeak | 8 wk | NS | |||
Kitzman et al40 | United States | HFPEF | 15/48 | 32 | 70 (7) | 31 | 70 (7) | ET | Walking/cycling | 60 min | 3 | 70% HRmax | 16 wk | NS |
Lee et al50 | United States | Breast cancer | 30/0 | 15 | 49.1 (7.9) | 15 | 44.7 (11.2) | HIIE | Cycling | 45 min | 3 | 90% VO2peak | 8 wk | NS |
Magalhães et al47 | Portugal | T2DM | 18/20 | 16 | 60.4 (6.8) | 22 | 60.8 (7.5) | MICE | Cycling | 45 (7.1) min | 3 | 40%–60% HRR | 1 y | Decrease |
T2DM | 20/15 | 13 | 58.9 (7.5) | 22 | 60.8 (7.5) | HIIE | Cycling | 33.1 (64) min | 3 | 70%–90% HRR | 1 y | Decrease | ||
Miyachi et al55 | Japan | Healthy adults | 28/0 | 14 | 22 (1) | 14 | 22 (1) | Resistance | — | 45 min | 3 | 80% 1 RM | 4 mo | NS |
Olson et al54 | United States | Overweight | 0/30 | 15 | 38 (1) | 15 | 38 (2) | Resistance | — | — | 2 | — | 12 mo | NS |
Park44 | Korea | Healthy older adults | 30/0 | 15 | 73.1 (3.0) | 15 | 70.9 (3.9) | Resistance | Elastic bands | 30–50 min | 3 | — | 24 wk | NS |
Park et al43 | Korea | Obese older | 0/50 | 25 | 73.5 (7.1) | 25 | 74.7 (5.1) | CARE | Elastic bands/walking | 50–80 min | 5 | RPE ≥ 15 | 24 wk | Decrease |
Park et al39 | Japan | Obese older | 0/20 | 10 | 66.1 (3.1) | 10 | 67.7 (5.2) | CARE | Walking/elastic bands | 70 min | 3 | RPE 12–13 | 12 wk | NS |
Park et al43 | Korea | Obese older | 0/41 | 21 | 68.4 (2.6) | 20 | 70.4 (4.5) | CARE | Elastic bands | 40–80 min | 5 | RPE 5–6 | 6 mo | Decrease |
Park et al45 | Korea | Obese older adults | 0/20 | 10 | 70.7 (0.7) | 10 | 71.3 (0.6) | CARE | Walking/dance | 45 min | 3 | 60%–70% HRmax | 12 wk | Decrease |
Rahbar et al37 | Iran | T2DM | — | 13 | 48.31 (5.02) | 15 | 48.60 (4.80) | Aerobic | Treadmill | 30 min | 3 | 50%–70% HRmax | 8 wk | Decrease |
Saboo et al41 | India | Prediabetes | 85/165 | 125 | — | 125 | — | Aerobic | Yoga | 46 min | 6 | — | 6 mo | Decrease |
Shin et al36 | Korea | Rheumatoid arthritis | 0/43 | 29 | 64.0 (5.4) | 14 | 62.7 (5.9) | Aerobic | Tai chi | 60 min | 1 | — | 3 mo | NS |
Tanahashi et al32 | Japan | Postmenopausal | 0/30 | 10 | 62 (6) | 20 | 61 (7) | Aerobic | Cycling | 40–60 min | 3 | 65%–80% HRmax | 12 wk | NS |
Abbreviations: CARE, combined aerobic and resistance exercise; DB, dumbbell; ET, endurance exercise; HFPEF, have preserved left ventricular ejection fraction; HIIE, high-intensity interval exercise; HRmax, maximal heart rate; HRpeak, peak heart rate; HRR, heart rate reserve; MICE, moderate-intensity continuous exercise; NS, no significant; RM, repetition maximum; RPE, rated perceived exertion; T2DM, type 2 diabetes mellitus; TCS, testicular cancer survivors; VO2peak, peak aerobic fitness.
Risk of Bias in Studies
Details of the quality assessment using the Cochrane Collaboration tool are presented in Table S2 (see Supplementary Material [available online]). No included study provided a clear explanation for the concealment of allocation, and most of them did not mention blinding of the evaluator. Although blinding of participants and personnel was not feasible in this setting, we assessed all studies as having a high risk of performance to avoid potential bias.
Results of Syntheses
In the pooled analyses, exercise (WMD −0.02; 95% CI, −0.03 to −0.01; I2 = 90.1%), compared with usual care controls had a more significant effect on cIMT in adults, which presented substantial heterogeneity (Figure 2). We conducted a random-effects meta-regression to explore the heterogeneity among the studies (Table S3, see Supplementary Material [available online]). A subgroup analysis was performed based on the variables included in the meta-regression model. We used a random-effects model to calculate total and subgroup effects.
—Forest plot of included studies. CI indicates confidence interval; WMD, weighted mean difference.
Citation: Journal of Physical Activity and Health 19, 12; 10.1123/jpah.2022-0372
Subgroup Analysis
Duration of Exercise
Subgroup analyses by duration showed a variation in the effects of different durations of exercise on cIMT. Figure 3 shows that studies with a higher exercise duration (>6 mo; WMD −0.02; 95% CI,−0.02 to −0.02; I2 = 0.0%) reported a more significant effect on cIMT. Studies with a lower exercise duration (≤6 mo; WMD −0.02; 95% CI, −0.04 to −0.00; I2 = 91.1%) reported a tendency toward reduction in cIMT at the end of the intervention.
—Forest plot according to duration of intervention. CI indicates confidence interval; WMD, weighted mean difference.
Citation: Journal of Physical Activity and Health 19, 12; 10.1123/jpah.2022-0372
Exercise Types
In the subgroup analysis by type, aerobic exercise showed a more significant effect on cIMT compared with the other types of exercise. The results of the meta-analysis of the different types of exercise were as follows: aerobic exercise (WMD −0.02; 95% CI, −0.04 to −0.00; I2 = 52.7%), resistance exercise (WMD −0.01; 95% CI, −0.02 to −0.00; I2 = 38.5%), CARE (WMD −0.01; 95% CI, −0.02 to −0.00; I2 = 0.0%), HIIE (WMD −0.03; 95% CI, −0.09 to 0.02; I2 = 95.6%), MICE (WMD −0.02; 95% CI, −0.09 to 0.05; I2 = 59.4%), and endurance exercise (WMD −0.04; 95% CI, −0.13 to 0.05; I2 = 73.4%; Figure 4).
—Forest plot according to physical activity types. CI indicates confidence interval; WMD, weighted mean difference.
Citation: Journal of Physical Activity and Health 19, 12; 10.1123/jpah.2022-0372
Intensity of Exercise
The effects of medium- to low-intensity exercise (WMD −0.02; 95% CI, −0.04 to −0.00; I2 = 59.4%) on cIMT were little or no different from those of medium to high-intensity exercise (WMD −0.02; 95% CI, −0.04 to 0.00; I2 = 59.8%; Figure 5).
—Forest plot according to the intensity of intervention. CI indicates confidence interval; WMD, weighted mean difference.
Citation: Journal of Physical Activity and Health 19, 12; 10.1123/jpah.2022-0372
Participant Characteristics
Subgroup analyses were used to explore the impact of study location, participant health status, age, and mean cIMT at baseline in the intervention group. cIMT ≥0.7 mm is reportedly associated with an increased risk for cardiac events; therefore, we selected 0.7 mm as the cut-off value.13,20,56–58 A detailed description of the characteristics of each participant is provided in Table 2.
Subgroup Analysis According to Study Characteristics
Heterogeneity | |||||
---|---|---|---|---|---|
Subgroups | Study groups, n | Effects model | Overall effect, WMD (95% CI) | I2, % | P |
All | 32 | Random | −0.02 (−0.03 to −0.01) | 90.1 | .006 |
Study location | |||||
Asia | 16 | Random | −0.00 (−0.01 to 0.01) | 58.9 | .788 |
Europe | 8 | Random | −0.02 (−0.03 to −0.01) | 0.0 | .000 |
North America | 8 | Random | −0.03 (−0.05 to −0.01) | 93.9 | .005 |
Participant’s health status | |||||
Participants with diseases | 24 | Random | −0.02 (−0.04 to −0.01) | 88.0 | .003 |
Healthy participants | 8 | Random | −0.01 (−0.03 to 0.01) | 88.2 | .575 |
Mean/median age, y | |||||
<60 | 20 | Random | −0.03 (−0.04 to −0.01) | 90.2 | .001 |
≥60 | 12 | Random | −0.00 (−0.02 to 0.01) | 69.7 | .692 |
Mean cIMT at baseline of exercise group, mm | |||||
<0.7 | 19 | Random | −0.01 (−0.03 to 0.00) | 93.9 | .000 |
≥0.7 | 13 | Random | −0.03 (−0.04 to −0.01) | 32.5 | .122 |
Abbreviations: CI, confidence interval; cIMT, carotid intima–media thickness; I2, I square; WMD, weighted mean difference.
Sensitivity Analysis
A sensitivity analysis was performed by sequentially excluding each study to test the reliability of the results. We found that the combined results were not affected by the exclusion of any single data set (Figure S1, see Supplementary Material [available online]).
Risk of Publication Bias
We used a funnel plot to assess publication bias, which showed no apparent asymmetry (Figure S2, see Supplementary Material [available online]). Egger test (P = .246) provided evidence of no publication bias (Figure S3, see Supplementary Material [available online]).
Discussion
This systematic review and meta-analysis included 26 studies with 1396 participants. The pooled effects of the included studies demonstrated the beneficial effect of exercise on cIMT. However, a significant heterogeneity was observed among the included studies. We used subgroup analysis and a random-effects model to examine the effect of exercise prescription variables on the population. The studies included in this review included various types of exercise (eg, aerobic and resistance exercise), and a more detailed discussion of each factor is beyond the scope of this review.
Exercise Prescription Variables
Duration of Exercise
Our meta-analysis demonstrated interesting findings regarding the duration of exercise as follows: exercise for >6 months was associated with a greater decline in cIMT than exercise for ≤6 months in adults. Similarly, Elitok et al59 reported that changes in cIMT were related to exercise duration. One possible reason for this is that cIMT is slowly modified, and the effects do not appear until the exercise intervention has continued for a prolonged period. Additionally, a previous study demonstrated that the effect of exercise on cIMT does not persist after the exercise is terminated60; therefore, exercise must be continued for sustained benefit. In general, changes in cIMT were correlated with the duration of exercise, suggesting that focusing on the temporal inflection point of the exercise effect is important for determining the optimal duration of exercise prescriptions.
Exercise Types
We also examined the effect of exercise type on cIMT. The results showed that aerobic exercise, resistance exercise, and CARE were associated with a reduction in cIMT; however, the magnitude of the reduction was more pronounced with aerobic exercise. A possible explanation for this is that aerobic exercise reduces age-related arterial inflammation and the production of tumor necrosis factor and interleukin.61,62 Aerobic exercise also normalizes blood pressure and lipid levels, which are crucial factors in the development of cIMT.63,64
Regular resistance exercise increases the incidence of arteriosclerosis and blood pressure, although endothelial function remains intact.65–67 Our results showed that resistance exercise improved cIMT, although the effect was not as significant as that of aerobic exercise. A previous meta-analysis showed that high-intensity resistance exercise was associated with increased arterial stiffness in younger participants with low baseline levels of arterial stiffness.23,65–67 The results of the current review demonstrated that resistance exercise may not be suitable for all populations.
Another interesting finding from our study is that CARE did not reduce cIMT to a greater extent than resistance exercise. However, Kawano et al68 showed that synchronized aerobic exercise prevented carotid arteriosclerosis caused by resistance exercise in healthy young men. These results should be interpreted with caution, as there are relatively fewer studies on the various exercise types, except for aerobic exercise.
Exercise Intensity
Although some studies have suggested that high-intensity exercise for cardiac rehabilitation produces better results,69–71 our findings did not demonstrate substantial declines in cIMT with high-intensity exercise.
Previously, researchers believed that high-intensity exercise generally involved lower training volumes than traditional aerobic and resistance exercises, making it a time-saving strategy.70 However, Quindry et al72 reviewed previous studies and found that high-intensity activities were not better than moderate-intensity activities in reducing risk factors for cardiovascular disease. Our results are consistent with these findings. This may be due to the fact that although the intensity of moderate-intensity exercise is low and its effect is not as strong as that of high-intensity exercise over a short period of time, moderate-intensity exercise often requires a longer period of activity to achieve effects similar to those of high-intensity exercise.73,74 Despite the similar effects of the different exercise intensities, there are differences in exercise compliance and safety.75,76 Therefore, when selecting exercise intensity, it is necessary to consider the health status of the individual.
Participant Characteristics
The results of our study showed that exercise may not be effective in reducing cIMT in a relatively healthy population with a well-preserved physiological and cardiovascular status. Similar to our results, a nonrandomized controlled trial of lifestyle intervention in Germany showed significant differences in subgroup analyses of participants with a higher baseline mean cIMT.56 This beneficial effect of exercise was more pronounced in participants with a high baseline cIMT. This may be because certain diseases (such as diabetes and hypertension) are risk factors for the progression of cIMT,77 while the cIMT of healthy individuals does not increase beyond the normal level. However, this population could benefit from exercise in other aspects such as improved physical fitness, body composition, lipid profiles, and fasting blood glucose levels.78,79
Exercise was less effective in improving cIMT in the older subgroup, which may be because exercise does not reduce age-related increases in cIMT.33,80 Therefore, the older adults’ population may require a combination of drug therapy and exercise to achieve a positive effect on cIMT.
Limitations and Strengths
The strength of this meta-analysis is that we analyzed the independent effect of exercise on cIMT, after excluding interference from other interventions (eg, drugs and diet). However, owing to the heterogeneity of exercise regimens, such as varying duration and intensity, it was difficult to definitively identify the most appropriate and effective exercise type, duration, and intensity that will reduce cIMT.
In addition, our meta-analysis has some limitations. First, the included studies did not report the safety indicators with exercise. The choice of exercise type was guided by its effectiveness and safety. Second, this meta-analysis only included publicly available documents and excluded unpublished documents, which may have affected the comprehensiveness of the data. Third, in the subgroup analysis, some subgroups included fewer studies and had higher heterogeneity; therefore, our findings should be interpreted with caution.
Future studies should further evaluate the details of the optimal exercise prescription, the inflection point of the intervention time, and differences in the optimal interventions for the older and young populations. Additional research is needed to verify the results of this meta-analysis.
Conclusions
The results of this systematic review and meta-analysis suggest that aerobic exercise with a minimum duration of 6 months should be an effective method of improving the state of atherosclerosis markers in adults. However, our findings were limited by the mixed risk of bias among the significant studies. Evidence supporting the effectiveness of exercise as an additional health measure remains ambiguous. Additional atherosclerosis biomarkers are required as the outcome of trials to confirm the effectiveness of exercise.
Acknowledgments
The study was funded by the Nature Science Foundation of China (No. 71904127). All data supporting the results of this study are included in this article (and its Supplementary Material [available online]). Author Contributions: Y. Wang, X. Wu, and J. Wu were responsible for this study’s conception, design, and hypothesis. Y. Wang, H. Wu, Sun, and J. Wu performed the systematic search, data extraction, and risk of bias assessment. Y. Wang, Sun, J. Wang, and Li completed all statistical analyses and wrote the first draft of this manuscript. All authors discussed the study results and drafted the manuscript and its revision.
References
- 1.↑
Murphy SJ, Werring DJ. Stroke: causes and clinical features. Medicine. 2020;48:561–566. doi:10.1016/j.mpmed.2020.06.002
- 2.↑
Onut R, Balanescu AP, Constantinescu D, Calmac L, Marinescu M, Dorobantu PM. Imaging atherosclerosis by carotid intima-media thickness in vivo: how to, where and in whom? Maedica. 2012;7:153–162.
- 3.↑
Faust O, Acharya UR, Sudarshan VK, et al. Computer aided diagnosis of Coronary Artery Disease, Myocardial Infarction and carotid atherosclerosis using ultrasound images: a review. Phys Med. 2017;33:1–15. doi:10.1016/j.ejmp.2016.12.005
- 4.↑
Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. ARBITER: Arterial biology for the investigation of the treatment effects of reducing cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation. 2002;106:2055–2060. doi:10.1161/01.cir.0000034508.55617.65
- 5.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340:14–22. doi:10.1056/NEJM199901073400103
- 6.↑
Crouse JR 3rd, Raichlen JS, Riley WA, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297:1344–1353. doi:10.1001/jama.297.12.1344
- 7.↑
Li J, Guo L, Liu L, et al. Effect of age stratification on the association between carotid intima-media thickness and cognitive impairment in Chinese hypertensive patients: new insight from the secondary analysis of the China Stroke Primary Prevention Trial (CSPPT). Hypertens Res. 2021;44:1505–1514. doi:10.1038/s41440-021-00743-w
- 8.↑
Wang JG, Staessen JA, Li Y, et al. Carotid intima-media thickness and antihypertensive treatment: a meta-analysis of randomized controlled trials. Stroke. 2006;37:1933–1940. doi:10.1161/01.STR.0000227223.90239.13
- 9.
Geng DF, Jin DM, Wu W, Fang C, Wang JF. Effect of alpha-glucosidase inhibitors on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials. Atherosclerosis. 2011;218:214–219. doi:10.1016/j.atherosclerosis.2011.05.004
- 10.↑
Huang Y, Li W, Dong L, Li R, Wu Y. Effect of statin therapy on the progression of common carotid artery intima-media thickness: an updated systematic review and meta-analysis of randomized controlled trials. J Atheroscler Thromb. 2013;20:108–121. doi:10.5551/jat.14001
- 11.↑
Maki KC, Davidson MH, Dicklin MR, Bell M, Witchger M, Feinstein SB. Predictors of anterior and posterior wall carotid intima media thickness progression in men and women at moderate risk of coronary heart disease. J Clin Lipidol. 2011;5:141–151. doi:10.1016/j.jacl.2011.02.003
- 12.↑
Liu S, Wang J, Wu S, et al. The progression and regression of metabolic dysfunction-associated fatty liver disease are associated with the development of subclinical atherosclerosis: a prospective analysis. Metabolism. 2021;120:154779. doi:10.1016/j.metabol.2021.154779
- 13.↑
Polak JF, O’Leary DH. Carotid intima-media thickness as surrogate for and predictor of CVD. Glob Heart. 2016;11:295–312.e3. doi:10.1016/j.gheart.2016.08.006
- 14.↑
van den Oord SC, Sijbrands EJ, ten Kate GL, et al. Carotid intima-media thickness for cardiovascular risk assessment: systematic review and meta-analysis. Atherosclerosis. 2013;228:1–11. doi:10.1016/j.atherosclerosis.2013.01.025
- 15.↑
Wildman RP, Schott LL, Brockwell S, Kuller LH, Sutton-Tyrrell K. A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries. J Am Coll Cardiol. 2004;44:579–585. doi:10.1016/j.jacc.2004.03.078
- 16.
Marshall D, Elaine W, Vernalis M. The effect of a one-year lifestyle intervention program on carotid intima media thickness. Mil Med. 2011;176:798–804. doi:10.7205/milmed-d-10-00447
- 17.↑
Elkoustaf RA, Aldaas OM, Batiste CD, et al. Lifestyle interventions and carotid plaque burden: a comparative analysis of two lifestyle intervention programs in patients with coronary artery disease. Perm J. 2019;23:31634108. doi:10.7812/TPP/18.196
- 18.↑
Kadoglou NP, Iliadis F, Liapis CD. Exercise and carotid atherosclerosis. Eur J Vasc Endovasc Surg. 2008;35:264–272. doi:10.1016/j.ejvs.2007.08.022
- 19.↑
Spring B, Moller AC, Colangelo LA, et al. Healthy lifestyle change and subclinical atherosclerosis in young adults: Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation. 2014;130:10–17. doi:10.1161/CIRCULATIONAHA.113.005445
- 20.↑
Glodzik J, Rewiuk K, Adamiak J, et al. Controlled aerobic training improves endothelial function and modifies vascular remodeling in healthy adults with high normal blood pressure. J Physiol Pharmacol. 2018;69:699–707. doi:10.26402/jpp.2018.5.04
- 21.↑
Bjarnegard N, Hedman K, Lanne T. Vascular adaptation to indoor cycling exercise in premenopausal women. Int J Sports Med. 2019;40:245–252. doi:10.1055/a-0800-1640
- 22.↑
Huang C, Wang J, Deng S, She Q, Wu L. The effects of aerobic endurance exercise on pulse wave velocity and intima media thickness in adults: a systematic review and meta-analysis. Scand J Med Sci Sports. 2016;26:478–487. doi:10.1111/sms.12495
- 23.↑
Miyachi M. Effects of resistance training on arterial stiffness: a meta-analysis. Br J Sports Med. 2013;47:393–396. doi:10.1136/bjsports-2012-090488
- 24.
Jhamnani S, Patel D, Heimlich L, King F, Walitt B, Lindsay J. Meta-analysis of the effects of lifestyle modifications on coronary and carotid atherosclerotic burden. Am J Cardiol. 2015;115:268–275. doi:10.1016/j.amjcard.2014.10.035
- 25.↑
Tomoto T, Liu J, Tseng BY, et al. One-year aerobic exercise reduced carotid arterial stiffness and increased cerebral blood flow in amnestic mild cognitive impairment. J Alzheimers Dis. 2021;80:841–853. doi:10.3233/JAD-201456
- 26.↑
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. doi:10.1016/j.ijsu.2021.105906
- 27.↑
Zheng C, Zhang X, Sheridan S, et al. Effect of sedentary behavior interventions on vascular function in adults: a systematic review and meta-analysis. Scand J Med Sci Sports. 2021;31:1395–1410. doi:10.1111/sms.13947
- 28.
Patterson R, McNamara E, Tainio M, et al. Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta-analysis. Eur J Epidemiol. 2018;33:811–829. doi:10.1007/s10654-018-0380-1
- 29.↑
Garcia-Hermoso A, Martinez-Vizcaino V, Recio-Rodriguez JI, et al. Sedentary behaviour patterns and carotid intima-media thickness in Spanish healthy adult population. Atherosclerosis. 2015;239:571–576. doi:10.1016/j.atherosclerosis.2015.02.028
- 30.↑
Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M. Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. Cochrane; 2021.
- 31.↑
Coventry PA, Brown JE, Pervin J, et al. Nature-based outdoor activities for mental and physical health: systematic review and meta-analysis. SSM Popul Health. 2021;16:100934. doi:10.1016/j.ssmph.2021.100934
- 32.↑
Tanahashi K, Akazawa N, Miyaki A, et al. Aerobic exercise training decreases plasma asymmetric dimethylarginine concentrations with increase in arterial compliance in postmenopausal women. Am J Hypertens. 2014;27:415–421. doi:10.1093/ajh/hpt217
- 33.↑
Donley DA, Fournier SB, Reger BL, et al. Aerobic exercise training reduces arterial stiffness in metabolic syndrome. J Appl Physiol. 2014;116:1396–1404. doi:10.1152/japplphysiol.00151.2014
- 34.↑
Kim H-K, Hwang C-L, Yoo J-K, et al. All-extremity exercise training improves arterial stiffness in older adults. Med Sci Sports Exerc. 2017;49:1404–1411. doi:10.1249/mss.0000000000001229
- 35.↑
Hafner NM, Womack CJ, Luden ND, Todd MK. Arterial adaptations to training among first time marathoners. Cardiovasc Ultrasound. 2016;14:19. doi:10.1186/s12947-016-0063-6
- 36.↑
Shin JH, Lee Y, Kim SG, Choi BY, Lee HS, Bang SY. The beneficial effects of Tai Chi exercise on endothelial function and arterial stiffness in elderly women with rheumatoid arthritis. Arthritis Res Ther. 2015;17:380. doi:10.1186/s13075-015-0893-x
- 37.↑
Rahbar S, Naimi SS, Rezasoltani A, et al. Changes in vascular structure in diabetic patients after 8 weeks aerobic physical exercise: a randomized controlled trial. Int J Diabetes Dev Ctries. 2018;38:202–208. doi:10.1007/s13410-017-0579-9
- 38.↑
Kadoglou NPE, Fotiadis G, Kapelouzou A, Kostakis A, Liapis CD, Vrabas IS. The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with Type 2 diabetes. Diabet Med. 2013;30:E41–E50. doi:10.1111/dme.12055
- 39.↑
Park J, Nakamura Y, Kwon Y, Park H, Kim E, Park S. The effect of combined exercise training on carotid artery structure and function, and vascular endothelial growth factor (VEGF) in obese older women. Jpn J Phys Fit Sports Med. 2010;59:495–503. doi:10.7600/jspfsm.59.495
- 40.↑
Kitzman DW, Brubaker PH, Herrington DM, et al. Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction a randomized, controlled, single-blind trial. J Am Coll Cardiol. 2013;62:584–592. doi:10.1016/j.jacc.2013.04.033
- 41.↑
Saboo N, Kacker S, Rathore J. Effect of six months yoga intervention on metabolic profile and carotid intima media thickness in prediabetes. J Clin Diagn Res. 2021;15:CC01–CC05. doi:10.7860/jcdr/2021/47146.14699
- 42.↑
Park J, Park H. Effects of 6 months of aerobic and resistance exercise training on carotid artery intima media thickness in overweight and obese older women. Geriatr Gerontol Int. 2017;17:2304–2310. doi:10.1111/ggi.12972
- 43.↑
Park J, Kwon Y, Park H. Effects of 24-week aerobic and resistance training on carotid artery intima-media thickness and flow velocity in elderly women with sarcopenic obesity. J Atheroscler Thromb. 2017;24:1117–1124. doi:10.5551/jat.39065
- 44.↑
Park J. Effects of 24-week resistance exercise training on carotid peak systolic and end diastolic flow velocity in healthy older adults. J Phys Ther Sci. 2016;28:2793–2797.
- 45.↑
Park J-H, Park H, Lim S-T, Park J-K. Effects of a 12-week healthy-life exercise program on oxidized low-density lipoprotein cholesterol and carotid intima-media thickness in obese elderly women. J Phys Ther Sci. 2015;27:1435–1439. doi:10.1589/jpts.27.1435
- 46.↑
Kim DK, Jee JH, Park WH. Effects of aerobic and resistance exercise training on carotid intima-media thickness in abdominal obese women. Metab Syndr Relat Disord. 2021;19:200–204. doi:10.1089/met.2020.0118
- 47.↑
Magalhães JP, Melo X, Correia IR, et al. Effects of combined training with different intensities on vascular health in patients with type 2 diabetes: a 1-year randomized controlled trial. Cardiovasc Diabetol. 2019;18:34. doi:10.1186/s12933-019-0840-2
- 48.↑
Byrkjeland R, Stensaeth KH, Anderssen S, et al. Effects of exercise training on carotid intima-media thickness in patients with type 2 diabetes and coronary artery disease. Influence of carotid plaques. Cardiovasc Diabetol. 2016;15:13. doi:10.1186/s12933-016-0336-2
- 49.↑
Adams SC, DeLorey DS, Davenport MH, et al. Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: a phase 2 randomized controlled trial. Cancer. 2017;123:4057–4065. doi:10.1002/cncr.30859
- 50.↑
Lee K, Kang I, Mack WJ, et al. Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study. Breast Cancer Res Treat. 2019;177:477–485. doi:10.1007/s10549-019-05332-7
- 51.↑
Croymans DM, Krell SL, Oh CS, et al. Effects of resistance training on central blood pressure in obese young men. J Hum Hypertens. 2014;28:157–164. doi:10.1038/jhh.2013.81
- 52.↑
Farahati S, Hosseini SRA, Moazzami M, Daloee MH, Daloee SH. The impact of high-intensity interval training versus moderate-intensity continuous training on carotid intima-media thickness and ankle-brachial index in middle-aged women. Int J Prev Med. 2020;11:62. doi:10.4103/ijpvm.IJPVM_524_18
- 53.↑
Ghardashi-Afousi A, Davoodi M, Hesamabadi BK, et al. Improved carotid intima-media thickness-induced high-intensity interval training associated with decreased serum levels of Dkk-1 and sclerostin in type 2 diabetes. J Diabetes Complications. 2020;34:107469. doi:10.1016/j.jdiacomp.2019.107469
- 54.↑
Olson TP, Dengel DR, Leon AS, Schmitz KH. Moderate resistance training and vascular health in overweight women. Med Sci Sports Exerc. 2006;38:1558–1564. doi:10.1249/01.mss.0000227540.58916.0e
- 55.↑
Miyachi M, Kawano H, Sugawara J, et al. Unfavorable effects of resistance training on central arterial compliance: a randomized intervention study. Circulation. 2004;110:2858–2863. doi:10.1161/01.CIR.0000146380.08401.99
- 56.↑
Koeder C, Hahn A, Englert H. Effect of a 6-month controlled lifestyle intervention on common carotid intima-media thickness. J Nutr Health Aging. 2021;25:869–877. doi:10.1007/s12603-021-1628-0
- 57.
Chen Y, Xu B, Sun W, et al. Impact of the serum uric acid level on subclinical atherosclerosis in middle-aged and elderly Chinese. J Atheroscler Thromb. 2015;22:823–832. doi:10.5551/jat.26260
- 58.↑
Xu M, Bi Y, Chen Y, et al. Increased C-reactive protein associates with elevated carotid intima-media thickness in Chinese adults with normal low density lipoprotein cholesterol levels. J Atheroscler Thromb. 2013;20:575–584. doi:10.5551/jat.15172
- 59.↑
Elitok A, Emet S, Bayramov F, et al. Effect of bariatric surgery on flow-mediated dilation and carotid intima-media thickness in patients with morbid obesity: 1-year follow-up study. Anatol J Cardiol. 2020;23:218–222. doi:10.14744/AnatolJCardiol.2019.85249
- 60.↑
Willenheimer R, Rydberg E, Cline C, et al. Effects on quality of life, symptoms and daily activity 6 months after termination of an exercise training programme in heart failure patients. Int J Cardiol. 2001;77:25–31. doi:10.1016/s0167-5273(00)00383-1
- 61.↑
Sloan RP, Shapiro PA, Demeersman RE, et al. Aerobic exercise attenuates inducible TNF production in humans. J Appl Physiol. 2007;103:1007–1011. doi:10.1152/japplphysiol.00147.2007
- 62.↑
Lesniewski LA, Durrant JR, Connell ML, et al. Aerobic exercise reverses arterial inflammation with aging in mice. Am J Physiol Heart Circ Physiol. 2011;301:H1025–H1032. doi:10.1152/ajpheart.01276.2010
- 63.↑
Qu B, Qu T. Causes of changes in carotid intima-media thickness: a literature review. Cardiovasc Ultrasound. 2015;13:46. doi:10.1186/s12947-015-0041-4
- 64.↑
Thompson PD. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease. Arterioscler Thromb Vasc Biol. 2003;23:1319–1321. doi:10.1161/01.ATV.0000087143.33998.F2
- 65.↑
Kollet DP, Marenco AB, Belle NL, et al. Aerobic exercise, but not isometric handgrip exercise, improves endothelial function and arterial stiffness in patients with myocardial infarction undergoing coronary intervention: a randomized pilot study. BMC Cardiovasc Disord. 2021;21:101. doi:10.1186/s12872-021-01849-2
- 66.
Kawano H, Tanimoto M, Yamamoto K, et al. Resistance training in men is associated with increased arterial stiffness and blood pressure but does not adversely affect endothelial function as measured by arterial reactivity to the cold pressor test. Exp Physiol. 2008;93:296–302. doi:10.1113/expphysiol.2007.039867
- 67.↑
Grigoriadis G, Rosenberg AJ, Lefferts WK, Wee SO, Schroeder EC, Baynard T. Similar effects of acute resistance exercise on carotid stiffness in males and females. Int J Sports Med. 2020;41:82–88. doi:10.1055/a-1044-2321
- 68.↑
Kawano H, Tanaka H, Miyachi M. Resistance training and arterial compliance: keeping the benefits while minimizing the stiffening. J Hypertens. 2006;24:1753–1759. doi:10.1097/01.hjh.0000242399.60838.14
- 69.↑
Luo L, Meng H, Wang Z, et al. Effect of high-intensity exercise on cardiorespiratory fitness in stroke survivors: a systematic review and meta-analysis. Ann Phys Rehabil Med. 2020;63:59–68. doi:10.1016/j.rehab.2019.07.006
- 70.↑
Keteyian SJ, Hibner BA, Bronsteen K, et al. Greater improvement in cardiorespiratory fitness using higher-intensity interval training in the standard cardiac rehabilitation setting. J Cardiopulm Rehabil Prev. 2014;34:98–105. doi:10.1097/HCR.0000000000000049
- 71.↑
Rognmo O, Hetland E, Helgerud J, Hoff J, Slordahl SA. High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease. Eur J Cardiovasc Prev Rehabil. 2004;11:216–222. doi:10.1097/01.hjr.0000131677.96762.0c
- 72.↑
Quindry JC, Franklin BA, Chapman M, Humphrey R, Mathis S. Benefits and risks of high-intensity interval training in patients with coronary artery disease. Am J Cardiol. 2019;123:1370–1377. doi:10.1016/j.amjcard.2019.01.008
- 73.↑
Grediagin MA, Cody M, Rupp J, Benardot D, Shern R. Exercise intensity does not effect body composition change in untrained, moderately overfat women. J Am Diet Assoc. 1995;95:661–665.
- 74.↑
Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lot of gain? Exerc Sport Sci Rev. 2008;36:58–63.
- 75.↑
Worcester MC, Hare DL, Oliver RG, Reid MA, Goble AJ. Early programmes of high and low intensity exercise and quality of life after acute myocardial infarction. BMJ. 1993;307:1244–1247. doi:10.1136/bmj.307.6914.1244
- 76.↑
Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. J Physiol. 2012;590:1077–1084.
- 77.↑
Johnson HM, Douglas PS, Srinivasan SR, et al. Predictors of carotid intima-media thickness progression in young adults: the Bogalusa Heart Study. Stroke. 2007;38:900–905. doi:10.1161/01.STR.0000258003.31194.0a
- 78.↑
Brochu M, Poehlman ET, Savage P, Ross S, Ades PA. Coronary risk profiles in men with coronary artery disease: effects of body composition, fat distribution, age and fitness. Coron Artery Dis. 2000;11:137–144. doi:10.1097/00019501-200003000-00008
- 79.↑
Dehghanzadeh Suraki R, Mohsenzade M, Tibana RA, Ahmadizad S. Effects of CrossFit training on lipid profiles, body composition and physical fitness in overweight men. Sport Sci Health. 2021;17:855–862.
- 80.↑
Rhodes JB Jr. Carotid intima-media thickness and physical and cognitive function in elderly men and women: role of physical activity. 2009. https://digitalcommons.lsu.edu/gradschool_theses/2802