|Year : 2020 | Volume
| Issue : 3 | Page : 107-117
Plasma high-density lipoprotein cholesterol responses to endurance exercise training: A meta-analysis of randomized controlled trials
Manoj Kumar Choudhary MD 1, Sun Runlu MD 2, Shivir Sharma Dahal MD 3, Robin Bhattarai MS, PhD 4, Rajesh Nepal MD, DM 5, Zhang Yuling MD, PhD 6
1 Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar, Nepal; Department of Cardiovascular Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
2 Department of Cardiovascular Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
3 Department of Cardiovascular Medicine, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
4 Department of Neurosurgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
5 Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar, Nepal
6 Department of Cardiovascular Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China
|Date of Submission||13-Mar-2020|
|Date of Decision||02-Apr-2020|
|Date of Acceptance||12-Apr-2020|
|Date of Web Publication||26-Sep-2020|
Dr. Manoj Kumar Choudhary
Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar
Source of Support: None, Conflict of Interest: None
Background: Endurance exercise improves lipid and lipoproteins levels, while low high-density lipoprotein cholesterol (HDL-C) levels are risk factors for cardiovascular disease. There is a lack of evidence for the exercise characteristics in increasing lipids level, irrespective of the fact that endurance exercise increases lipids and lipoproteins level. The aim of this study was to clarify the effect and characteristics of endurance exercise in increasing HDL-C in randomized controlled trials. Methods: A search was performed for published studies between 1999 and 2014. Studies that assessed endurance exercise for ≥8 weeks and also reported the HDL-C levels pre- and post-training were included. The random effects model was used to measure the association between exercise and net change of HDL-C. Univariate regression analyses investigated the correlation of exercise characteristics. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity and the effect of potential confounders. The influence of pre-exercise lipid profile was assessed by meta-regression. Data were analyzed using Stata SE (12.0). Results: Fourteen studies with a total of 777 subjects were included. The mean HDL-C was reported to be increased and was statistically significant (weighted mean difference: 4.41 mg/dL; 95% confidence interval [CI]: 2.16–6.66 mg/dL, P < 0.001; I2 = 87.4%, P < 0.001). Univariate analysis indicated that exercise length was significantly associated with a net change of HDL-C (r = 0.56, P = 0.01). Nevertheless, there was no significant association between exercise frequency, duration, and total minutes. By subgroup analysis, exercise increased HDL-C level in Asia, Europe, and Africa and among all body mass index groups (P < 0.05). None of the studies omitted, in turn, seemed to substantially influence the effect of exercise on HDL-C by sensitivity analysis. Meta-regression showed that pre-exercise total cholesterol (TC) negatively correlated with net change of HDL-C (95% CI: 0.127, −0.018, r = −0073, P = 0.012). However, pre-exercise triglycerides, low-density lipoprotein cholesterol, and HDL-C did not correlate with a net change of HDL-C. Conclusions: Regular endurance exercise increases HDL-C level in any weight population. Exercise length of more than 8 weeks was the most important element of an exercise prescription. Among all lipid profiles, only the initial lower TC level responded better to exercise training and was more effective in increasing HDL-C level.
Keywords: Cardiovascular disease, endurance exercise, high-density lipoprotein cholesterol, lipids
|How to cite this article:|
Choudhary MK, Runlu S, Dahal SS, Bhattarai R, Nepal R, Yuling Z. Plasma high-density lipoprotein cholesterol responses to endurance exercise training: A meta-analysis of randomized controlled trials. J Clin Prev Cardiol 2020;9:107-17
|How to cite this URL:|
Choudhary MK, Runlu S, Dahal SS, Bhattarai R, Nepal R, Yuling Z. Plasma high-density lipoprotein cholesterol responses to endurance exercise training: A meta-analysis of randomized controlled trials. J Clin Prev Cardiol [serial online] 2020 [cited 2020 Oct 30];9:107-17. Available from: https://www.jcpconline.org/text.asp?2020/9/3/107/296187
| Introduction|| |
Previous epidemiological studies and clinical trials demonstrated an inverse association between the serum level of high-density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular events.,, Thus, HDL-C exerts potential antiatherogenic effects, which primarily include its capacity to efflux cholesterol from peripheral cells, but may also involve antioxidative, anti-inflammatory, anti-apoptotic, antithrombotic, anti-infectious, and antidiabetic activities. However, pharmacological strategies to increase HDL-C, either by niacin or inhibitors of cholesterol ester transport protein (CETP), did not improve cardiovascular outcomes despite significantly increasing the HDL level.,,,, Similarly, studies of genetic variants associated with HDL-C did not show a correlation with cardiovascular disease (CVD).
Apart from drugs, peoples are pursuing another way to raise plasma HDL-C levels. Endurance exercise also known as aerobic exercise is one of the lifestyle approaches that may improve HDL-C and other lipids and lipoproteins. It is cost-effective, and no pharmacological interference is required, while it is readily available to all.,, Endurance exercise done regularly not only increases the plasma HDL-C level but also reduces the risk of CVD., Studies have provided strong evidence that people who are more physically active have higher HDL-C levels., The importance of regular endurance exercise in increasing HDL-C level and reducing the risk of CVD has received extensive recognition.
Results of endurance exercise studies vary a lot, according to the exercise program (e.g., duration, exercise length, or frequency) and characteristics of subjects at baseline, possibly due to small sizes in studies. However, results vary in many studies of endurance exercise on increasing HDL-C level with nonsignificant improvement. Yamaoka and Tango's systemic review reported that the increased mean values were not significant for HDL-C (1.3 mg/dL; 95% confidence interval [CI]: 0.6–3.1) by random effects model. Therefore, we performed a meta-analysis of these studies to examine the effects of endurance exercise on plasma HDL-C level, as inconsistencies remain that require clarification. The purposes of this meta-analysis are to evaluate the efficiency of exercise on increasing HDL-C level; to determine the exercise characteristics most effective in raising HDL-C level; and to explore what characteristics of subjects had a significant effect on increasing HDL-C level by exercise. Clarifying these issues would help in establishing exercise programs to achieve better HDL-C level in clinical settings and promoting further study to evaluate HDL-C content with also HDL-C function.
| Methods|| |
A protocol for this review was prospectively developed, detailing the specific objectives, criteria for study selection, approach to assess study quality, outcomes, and statistical methods.
Data sources and literature search
To identify all available studies, a detailed search pertaining to endurance exercise and lipids and lipoproteins was conducted according to the PRISMA guidelines. A search was performed in the electronic databases (MEDLINE, EMBASE, Current Contents, Sports Discus, and Dissertation Abstract International), using the following search terms in all possible combinations: “physical activity,” “fitness,” “walking,” or “exercise,” crossed with “cholesterol,” “lipids,” “lipoproteins,” “HDL-C,” or “cardiovascular.” The first two authors (MKC and SRL), independent of each other, selected all studies. Disagreements were resolved by consensus.
We searched for all prospective studies that assessed potential associations between endurance exercise training and changing the level of HDL-C in adults (≥18 years of age at baseline). The inclusion criteria for this study were as follows: (1) adult humans aged 18 years and/or older including healthy adult but excluded subjects having specific medical problems in which treatments such as with drugs would influence the effect of exercise (history of cancer, hemodialysis treatment, and coronary heart disease); (2) studies that provided the following variables: total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG); (3) endurance exercise training period of at least 8 weeks as an intervention; (4) randomized controlled trials; (5) studies published between 1999 and 2014; and (6) studies that were published in the English language in the journals. Cointervention studies, such as those including a diet intervention, were excluded because the effect of exercise training itself would be obscured; observational studies, review articles, case reports, comment letters, animal studies, and training studies that did not have a comparative and/or randomized control group were also excluded.
Data abstraction, risk of bias, and validity assessment
We collected data on (1) study characteristics (year, country, and study quality); (2) subject characteristics (gender, age, and body mass index [BMI]); (3) exercise characteristics (exercise length, duration, frequency, and total minutes); and (4) pre- and post-exercise lipid and lipoprotein outcomes (HDL-C, TC, TG, and LDL-C). The Cochrane Collaboration's tool for assessing the risk of bias in randomized trials was used for assessing the quality of randomized trials  [Supplementary Table 1]. The risk of bias was evaluated under seven fields: random sequence generation, allocation concealment, blinding of participants and researchers, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. While the methodological quality of each included trial was assessed using the instrument described by Jadad et al. It is a three-item questionnaire instrument designed to assess bias, specifically, randomization, blinding, and withdrawals/dropouts. The minimum number of points possible is 0 and the maximum 5, with the higher number representing better quality. The majority of the included studies were considered to be of an acceptable quality with a total quality score of 3 [Supplementary Table 2].
The primary outcome measures were mean changes in HDL-C, TC, TG, and LDL-C. Net changes in lipids were calculated as the difference (exercise minus control) of changes (final minus initial) in the mean values from each study. The standard deviation (SD) of net changes in blood lipid was not reported in some literature. Therefore, they were calculated using the following formula.
SD 2 = SD 2pre + SD 2post − 2 × 0.5 × SDpre SDpost
where SDpre is the SD of pre-exercise value, SDpost is the pre-exercise value, and 0.5 is the correlation between the exercise and control group. We combined two subgroups into a single group if the study presented the outcomes separately for males and females. When a study had 2 or more exercise groups, we treated each group independently. For the net changes in all lipid and lipoprotein outcomes, pooled treatment effects were used by calculating weights equal to the inverse of the variance. The I2 statistic was used to assess the heterogeneity of effect size across interventions. A value >50% was considered evidence of heterogeneity. The random effects model was applied in our meta-analysis because there was significant heterogeneity among the studies.
Furthermore, we performed a cumulative meta-analysis, ranked by year and sample size. A univariate regression and a multivariate regression were performed to examine whether the change in HDL-C level was mediated by characteristics of exercise programs. Subgroup analysis was performed to examine the sensitivity of HDL-C outcome by limiting our analysis, based on the availability of data, to (1) exercise length (weeks), (2) subjects' status, (3) continent, (4) BMI, and (5) Jadad score. Meta-regression was used to examine the association between net changes in HDL-C and study quality, country, year, BMI, age, initial lipid, and lipoprotein levels. A sensitivity analysis was conducted to investigate the influence of a single study on the overall pool estimate by omitting one study in each study.
Publication bias was assessed using regression analysis to detect funnel plot asymmetry and also Begg's rank correlation test and Egger's linear regression test. Risk of bias was evaluated using a tool developed by Higgins et al. Study quality was assessed using a quality index developed by Jadad et al. We chose this index because of its stated validity and reliability. Descriptive statistics were reported as mean ± SD. Data were analyzed using Stata SE (version 12.0, StataCorp. College Station, Texas, USA).
| Results|| |
Literature search and study characteristics
The literature search yielded 267 potentially relevant papers (238 studies from the electronic database and 29 studies from hand searches). After duplicates removed, 139 potentially relevant studies remained. Finally, 14 original articles (20 trials) were included in the meta-analysis.,,,,,,,,,,,,, The literature selection criteria and the reason for exclusion are presented in [Figure 1].
The basic characteristics of all 14 studies published are summarized in [Table 1]. Among these eligible studies, four were conducted in Asia, three in North America, five in Europe, and two in the African continent. Three studies only included males and seven only included females, with rest four studies including both males and females. The included studies varied in sample size from 19 to 245, with a total of 777 subjects (mean age range, 21–81 years). The mean endurance exercise training period was 17.75 weeks. Subjects from different continents were not limited to particular ethnic groups, but most studies' information on ethnicity was lacking. Eleven studies reported the baseline mean BMI and two studies had baseline weight and height from which we calculated the BMI, making it in total 13 studies with BMI ranging from 21.00 to 32.80 kg/m 2.
|Table 1: Population, exercise, and lipid profile characteristics of included randomized clinical trials|
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The mean (SD) score of quality assessment of included studies was 2.9 (0.5) of a possible 5 points as shown in [Supplementary Table 2]. All of the 14 studies reported the number of withdrawals and their reason for withdrawals. In none of the 14 randomized controlled trials, methods of blinding for patients described.
Lipid assessment characteristics
Lipids and lipoproteins were assessed in the morning after an overnight fast that ranged between 12 h to 14 h. Exercise was avoided from 12 to 48 h before the assessment of lipids and lipoproteins.
Training program characteristic
These 14 studies assessed 20 interventions (some studies had more than one intervention group) and all were performed under supervision. The most common training modalities included brisk walking and jogging, endurance dance, running, or endurance cycling except that Callisthenic exercises, elastics bands and Tai Ji Quan were used in one study each. For studies that reported data, exercise length of training ranged from 8 to 32 weeks, frequency from 3.0 to 15.4 times per week, and duration ranged from 9.9 to 60 min per session. Total minutes of training (length × frequency × duration) ranged from 480 to 5657.6 min.
Effect of endurance exercises on high-density lipoprotein cholesterol and other lipids and lipoproteins
The overall net change in HDL-C level was increased significantly (weighted mean difference [WMD]: 4.41 mg/dL; 95% CI: 2.16–6.66 mg/dL; P < 0.001) as shown in [Figure 2]. It strongly suggested that the exercise group had higher HDL-C levels compared with the controls. Cumulative meta-analysis, ranked by year, revealed that a net change of HDL-C had become stable and statistically significant since 2010 as in [Supplementary Figure 1]a. Besides, cumulative meta-analysis ranked by sample size, showed that since the study of Zhang and Fu with the sample size of 20, the increase in HDL-C had been stable and statistically significant as described in [Supplementary Figure 1]b. Fourteen studies were included in the meta-analysis for TC and 12 studies for TG and LDL-C except for the study of Danladi et al. and Lamina et al. Compared with control, endurance exercises resulted in a significant reduction in TC (WMD: −6.13 mg/dL; 95% CI: −10.55, −1.71; P = 0.007) and TG (WMD: −18.13 mg/dL; 95% CI: −30.17, −6.10; P = 0.003), but a nonsignificant reduction in LDL-C (WMD: −3.20 mg/dL; 95% CI: −7.6, 1.19; P = 0.153) as shown in [Supplementary Figure 2]a, [Supplementary Figure 2]b, [Supplementary Figure 2]c.
|Figure 2: Forest plot of the meta-analysis for the association between exercise and HDL-C when random affects model were used. The size of the blank boxes for each outcome represents the weight given to that outcome. The overall mean difference was shown by the middle of the diamond while the left and right extremes of the diamond represent the corresponding 95% CI. The vertical red line represents the overall mean. Net change in HDL-C was calculated as the difference (exercise minus control) of changes (final minus initial) in the mean values from each study. HDL-C = High-density lipoprotein cholesterol, CI = Confidence interval|
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Effect of exercise characteristics on net change of high-density lipoprotein cholesterol level after exercise training
The correlation regression analysis was executed to determine which characteristic of exercise program (exercise length, frequency, duration, and total minutes) was the best predictor for an increase in HDL-C level [Figure 3]. Univariate analysis showed that exercise length (weeks) was the strongest predictor of the net change in HDL-C level (r = 0.56, P = 0.01). Interestingly, each 4 weeks increase in exercise length leads to an about 0.92 mg/dL reduction of the net change in HDL-C level. However, the HDL-C level was still increased, but the rate of increment was reduced. Briefly, with the increase of exercise length, the benefit of raising HDL-C became small. The net change of HDL-C was not associated with other exercise characteristics such as frequency, duration, and total minutes. Besides, multivariate analysis of exercise characteristics and net change in HDL-C levels were performed. When we controlled for the frequency, duration, and total minutes, the exercise length (in weeks) was still significantly correlated with a net change of HDL-C (r = −0.43, P = 0.006) through multivariate analysis. Univariate and multivariate analysis indicated that exercise length might be a good predictor of the net change in HDL-C.
|Figure 3: Association between exercise characteristics and net change of HDL-C. (a) Exercise length (weeks). (b) Frequency, sessions/week. (c) Duration, min/session. (d) Total minutes. This result shows exercise was best predictor of an increase in HDL-C level. Each trial was weighted by the inverse of the sample size of each exercise group. The circles represent each study. P < 0.05 is regarded as significance. The calculation of net change in HDL was the same with Figure 2. HDL-C = High-density lipoprotein cholesterol|
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Furthermore, we performed subgroup analysis by exercise length and duration as shown in [Table 2]. Exercise length of <13 weeks led to greater improvement in HDL-C (6.03 mg/dL) compared with the exercise length >13 weeks (2.63 mg/dL), which is consistent with the above regression results.
|Table 2: Subgroup meta-analysis of high density lipoprotein cholesterol level by exercise and subject characteristics|
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Association between subject characteristics and net change in high-density lipoprotein cholesterol by exercise training
According to subgroup analysis [Table 2] and meta-regression analysis [Figure 4], subject characteristics such as BMI, country, and initial lipids and lipoproteins affected the net change of HDL-C by exercise training. When interventions were stratified by person baseline BMI, the improvements in HDL-C were the greatest in BMI ranging from 18.5 to 24 kg/m 2 (7.19 mg/dL), following BMI ≥28 kg/m 2 (6.84 mg/dL). There was significant net change in HDL-C level in healthy subjects (6.60 mg/dL, P = 0.002) as well as subjects suffering from metabolic syndrome (3.44 mg/dL, P < 0.001). By continent, Asia and Africa had a greater improvement in HDL-C (7.44 mg/dL; 9.12 mg/dL) than North America and Europe (1.37 mg/dL; 2.56 mg/dL). Besides, studies with Jaded score ≥3 responded better to exercise. Meta-regression was performed to investigate which initial lipid or lipoprotein contributed to the net change in HDL-C level. [Figure 4]a showed that subjects with lower TC level responded better to exercise training, leading to a higher net change of HDL-C level (95% CI: 0.127 − 0.018, r = −0073, P = 0.012). However, there was no association between pre-exercise TG, LDL-C, and HDL-C and net change of HDL-C level (P > 0.05) as shown in [Figure 4]b. By contrast, year and age were not associated with a net change of HDL-C through meta-regression analysis.
|Figure 4: Univariate meta-regression between net change in HDL-C and lipid profile of pre-exercise. (a) Graph of meta-regression between net change in HDL-C and TC of pre-exercise. Lower pre-exercise TC level correlated with net change of HDL-C. Each circle represents each trial and its area is proportional to the study weight. (b) Table of univariate meta-regression between net change in HDL-C and TC, TG, LDL-C, HDL-C of pre-exercise. *Significance P < 0.05. The calculation of net change in HDL-C and TC was the same with Figure 2. Coef = Coefficient; Std Err = Standard error; 95% CI = 95% confidence interval, HDL-C = High-density lipoprotein cholesterol, TC = Total cholesterol, TG = Triglycerides|
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Sensitivity analysis and evaluation of publication bias
In the sensitivity analysis, none of the studies omitted in turn seemed to substantially influence the exercise effect [Figure 5]. There was no indication of publication bias for HDL-C and TC, TG, LDL-C through examination of funnel plots [Figure 6] and [Supplementary Figure 3]. Egger's and Begg's tests yielded similar results to funnel plots: HDL-C (Begg P = 0.770; Egger P = 0.550), TC (Begg P = 0.626; Egger P = 0.172), TG (Begg P = 0.112; Egger P = 0.844); and LDL-C (Begg P = 0.198; Egger, P = 0.525). Among all the included studies in this review, we found a low risk of bias for most of the domains. In the domain of blinding of participants and researchers, we found a high risk of bias in all studies. In the domain of other bias, most of the studies were unclear [Supplementary Table 1].
|Figure 5: Sensitivity analysis of included studies. None of the studies omitted influence the exercise effect|
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|Figure 6: Funnel plot for publication bias by HDL-C level. Blue points represent individual trials. Weighted mean difference in HDL-C change was plotted against its standard error. The funnel plot was roughly symmetrical with regard to the mean effect size (vertical line). HDL-C = High-density lipoprotein cholesterol|
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| Discussion|| |
The purpose of this study was to use the meta-analytic approach to examine the effects of endurance exercise on lipids and lipoprotein. While changes in the direction of benefit were observed in this study, an increase in HDL-C level and decrease in TG and TC remained statistically significant across all analyses except LDL-C, which was not statistically significant (P = 0.153). These findings of nonsignificant reduction in LDL-C level in our study are in contrast to previous studies, which found significant reductions in LDL-C as a result of endurance exercise programs. However, few studies are consistent with our finding of no significant change in LDL-C level.,,,, As little as 1% reduction in HDL-C has been associated with a 2%–3% increase in the risk of CVD. Assuming that the reverse is true, the approximate increase in our meta-analysis should decrease CVD by 6%–9%. Our meta-analysis indicated that the effect of endurance training resulted in a 4.41 mg/dL elevation in HDL-C [Figure 2]. In previous observational study , every 1 mg/dL rise in HDL-C level are associated with a 2%-3% decreased risk of CVD. For TG, elevated levels of TG are an independent risk factor for CVD. Studies have reported that with 1% reduction in TC level, it has been associated with 2% reduction in CVD.
This is of substantial importance in general public well-being, even though the influence of decreasing cardiovascular risk by raising HDL-C level might be smaller than that by the use of medications. However, the substantial rise in HDL-C level established by this analysis is of clinical significance and is not far from results of other studies., It is important from a clinical perspective, to scrutinize whether exercise training improves HDL-C level in subjects who have initial low level of HDL-C, or in subjects with HDL-C in the normal range. Nevertheless, few studies have reported the effect of the initial HDL-C level in increasing HDL-C level after endurance exercise., Moreover, due to phenomenon of regression to the mean, the increase in HDL-C levels in those with low HDL-C levels could be explained. Nishida et al. reported an increase in HDL-C level in a subject with a lower baseline HDL-C level, though our study was not statistically significant for the effect of initial HDL-C level on net change in HDL-C level. Our study showed that a low level of TC has significant effects on net change in HDL-C level, suggesting that those with a lower level of TC will gain the most from exercise. Further studies are needed to clarify the association between baseline HDL-C and the response to exercise training. Furthermore, the association and subgroup analyses between net change in HDL-C with BMI (normal, overweight, and obese) suggests that normal BMI peoples experience the greatest increase in net HDL-C from endurance exercise (7.19 mg/dL; P=0.04 and I 2=0%). Inaddition, our study all suggested that even overweight and obese peoples experience an increase in HDL-C (1.94 mg/dL and 6.84 mg/dL respectively) from regular endurance exercise. Besides, it is unknown whether the increases in HDL-C were a direct result of endurance exercise program itself and/or change in body BMI that also occurred because of the endurance program, which was statistically significant in all the groups (normal, overweight, and obese), with normal group BMI and obese having a higher net change in HDL-C level.
People have a higher increase in net HDL-C with exercise length of 8–13 weeks, and the rate of increment was reduced with that of more than 13 weeks of exercise experience, which was supported by findings of other studies as well. Even our study reported that each 4 weeks increase in exercise length leads to an increase of HDL-C, but the rate of increment was reduced. Our result suggested that 8 or more weeks of moderate-intensity interval training could elicit favorable changes in HDL-C, TC, and TG in hypertensive patients also. The finding of our study corresponds to previous studies where a significant reduction in LDL-C, TC, and TG and increase in HDL-C were recorded, though our study reported no significant change in LDL-C level, which may be due to lower number of cases included.,
Subjects who participated in an exercise training program in our study reported a lower BMI, TG level, and TC level and higher HDL-C and lower prevalence of self-reported diabetes and hypertension, which correlates with other studies too., Furthermore, exercise is confirmed to improve insulin sensitivity in insulin-resistant obese T2DM patients. In agreement with our results, Greene et al. also reported that obese middle-aged men and women participating in endurance exercise at 70% of VO2 max, 3 times per week for 12 weeks, had significant improvements in lipid profiles. Sung and Bae reported a similar finding in diabetic elderly men participating in walking exercise at 65%–75% of HRmax for 50 min a day, 3 times a week for 24 weeks. Taken together, endurance training was considered effective for inducing positive changes in blood lipid.
Before it was inconclusive, whether exercise characteristics (e.g., exercise length, duration, and frequency) effects change in HDL-C level. Consequently, we performed univariate analysis to examine the association between each exercise characteristic and change in HDL-C level. We found that exercise frequency and duration were not associated with net HDL-C change; this result indicates that vigorous exercise duration and frequency are not necessary for change in HDL-C. Controlling for weekly exercise, length (weeks) was positively associated with net HDL-C change [Figure 3]. This suggests that in improving blood HDL-C values, exercise length (weeks) of more than 8 weeks plays an important role in increasing HDL-C level. Exercise length of exercise might be a good predictor for elevating the HDL level.
Although HDL-C levels are a strong biomarker for assessing CVD risk, they do not predict either HDL functionality or composition. To date, HDL-based therapy to reduce the residual risk of CVD remains a largely unfulfilled promise. Although raising the level of functional HDL particles either by increasing their hepatic production or by HDL infusion appears promising, there is limited evidence that any of the clinical endpoints measured to date (plaque volume and inflammatory state of macrophages) are correlated with decreased events. There is increasing evidence that HDL-C levels are not necessarily directly correlated to HDL particle function. Since we know the structural components of HDL and the exact role of each component in the function of HDL, the traditional lipid panel research may be replaced by the measurement of HDL function or biomarker related to HDL dysfunction. There remains cautious optimism that CETP inhibition may be a viable option to reduce cardiovascular risk, but the concern that the inhibition of CETP might lead HDL to become dysfunctional has not yet been fully allayed.
Although our results are encouraging, endurance exercise alone may not be enough to achieve the recommended levels for those with lower than optimal levels of lipids and lipoproteins. Therefore, it would be suggested that in addition to endurance exercise, additional lifestyle  (such as vigilant diet and/or pharmacological such as statins) interventions are required to optimize blood lipid and lipoprotein levels in adults and reduce cardiovascular risk.
However, it must be noted that recent studies have found that the benefits of endurance exercise may not come from the improvement of blood lipid and lipoprotein levels, but from the change in the physical structure or the protein particles that carry cholesterol through the blood.
In a 24-week study, Kraus et al. investigated 111 sedentary, overweight men and women, who were randomly assigned to three intervention groups (12 miles walk per week, 12 miles jog per week, and 20 miles jog per week) or a control group. The authors found that endurance exercise increased large, low-density protein particles, which were unlikely to cause artery occlusion even if the TC of the subjects did not change. Although walking was similar to jogging 12 miles a week, jogging 20 miles a week can make a bigger difference.
The present meta-analysis has some limitations and evokes proposals for future studies. The first limitation of our meta-analyses was that it was limited to publish studies. Although we did not find evidence of publication bias, either graphically or statistically using the funnel plot and Egger's test, these tests do not necessarily have statistically sufficient power to detect the publication bias, as our number of studies included was less. Therefore, while we are confident that positive publication bias does not exist, we cannot rule it out entirely. In addition, in the study of exercise intervention, double-masking methods are fundamentally impossible.
Second, in most of the included trials, alcohol intake data were not considered, which might affect HDL-C levels. Third, as the effects of endurance exercise on lipids and lipoproteins may vary by race/ethnicity, future studies should be reported, and editors should publish complete information on race and ethnicity of subjects.
Our Study has several strengths. We used very strict inclusion criteria that allowed us to extract the true effect of endurance exercise from the confounding factors with minimal impact. For example, we only included studies where dietary intake did not change significantly. Therefore, we could more accurately assess the relationship between exercise itself and increase in HDL-C level than previous studies , that included trials with resistance training or studies with dietary modifications including change in energy intake during the intervention.
| Conclusions|| |
Regular endurance exercise increases the HDL-C level in any weight population. Exercise length of more than 8 weeks plays an important role in increasing HDL-C level and exercise length of more than 8 weeks should be an important element of an exercise prescription. Among all lipid profiles, only the initial lower TC level responded better to exercise training, leading to a higher net change of HDL-C level. Instruction for regular endurance exercise is of substantial importance in public health, for reducing cardiovascular risk.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]