| |
Exercise Reduces Inflammation Markers CRP & IL-6 - new study
|
| |
| |
Download the PDF here
"Remaining physically active in midlife linked with lower CRP, IL-6 levels".... original article & pdf below....Circulation. published online August 13, 2012
from Jules: I have said we need a real, well-designed & well-conducted exercise & diet study in the ACTG or by the NIH
theheart.org August 13, 2012 Marlene Busko
"In summary, the results show that physically active participants maintain lower levels of inflammatory markers over a 10 year period. Thus, physical activity may be important in preventing the pro-inflammatory state seen with ageing.....The main findings show that physically active participants at baseline had lower CRP and IL-6 levels and this difference remained stable over time. Secondly, maintenance of physical activity over the 10 years follow-up period was associated with lower levels of both inflammatory markers at followup......Crucially, the associations observed between physical activity and inflammatory markers were independent of adiposity, which is an important confounder of the association between physical activity and inflammatory markers as physically active participants tend to have lower levels of adiposity, and adipose tissue is a key production site for several inflammatory markers......Physical activity, inflammation and health are linked together in a complex fashion. Cytokines are secreted transiently in large doses by several metabolically active tissues during exercise; namely from the muscle during contraction and adipose tissue via exercise-related mechanisms. Paradoxically, regular (chronic) exercise training has been consistently associated with lower levels of systemic inflammatory markers5 and reduced adipose tissue inflammation.......In comparison to participants that rarely adhered to physical activity guidelines through follow up, the high adherence group displayed lower loge CRP (B coefficient=-0.07, 95% CI, -0.12, -0.02) and loge IL-6........Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hrs/wk displayed lower loge CRP (B coefficient =- 0.05, 95% CI, -0.10, -0.001) and loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.03) at follow up after adjustment for age, gender, hours/week of moderate to vigorous physical activity at phase 5, smoking, employment grade, BMI, and chronic illness."
"Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP ( =-0.07, 95% CI, -0.12, -0.02) and logeIL-6 ( =-0.07, 95% CI, -0.10, -0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =-0.05, 95% CI, -0.10, -0.001) and loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.03) at follow up. Conclusions - Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing."
London, UK - In a large, prospective UK study, participants who kept physically active during their 50s had lower levels of C-reactive protein (CRP) and interleukin-6 (IL-6)-inflammatory markers that increase with age and are linked to cardiovascular disease [1]. The findings reinforce the importance of staying active as one ages, say the researchers, led by Dr Mark Hamer (University College London, UK).
"What these data specifically show for the first time is the chronicity of physical activity," Hamer told heartwire. "People who were consistently active over a 10-year period had much more favorable inflammatory markers.
"We know that inflammatory markers are important for heart health. This suggests that the way physical activity is possibly working is through the inflammatory pathway," he added. Clinicians need to "encourage regular, moderate physical activity. . . . The most popular moderate physical activity in this age group is, in fact, brisk walking."
The study is published online August 13, 2012 in Circulation.
Walking to heart health
Most existing evidence of the cardiovascular benefits of exercise is derived from cross-sectional studies or research that lasted less than six months, Hamer said. To examine the relationship between physical activity and inflammatory markers in an aging cohort, the team scrutinized data from the Whitehall II study, an ongoing, prospective cohort study in participants from the British civil service.
The current study included 3092 men and 1197 women with mean age of 49.2 years at baseline (1991 to 1993) who were assessed at approximately five and 10 years thereafter.
The database included serum CRP and IL-6 values and results of a self-reported questionnaire about exercise.
The team determined whether the participants met the recommended guidelines for physical activity validated for cardiovascular health: at least 2.5 hours a week of moderate to vigorous physical activity such as cycling, sports, gardening, housework, and home maintenance.
They found that 50% of participants met these guidelines at baseline. The rate reached 83.7% at the second time point (approximately five years) and 83.3% at the third time point (approximately 10 years).
Nearly a quarter of the cohort (681 participants) rarely met the guidelines (ie, at one or fewer time points), whereas about half (2105 participants) met the guidelines at all three time points.
Compared with individuals who did not habitually engage in 2.5 hours of physical activity over the 10 years, those who did had, on average, a 0.18-mg/L-lower CRP level and a 0.2-pg/mL-lower IL-6 level.
The association between physical activity and inflammatory markers remained after correcting for adiposity (body-mass index).
Many of the civil servants would have taken early retirement at aged 55 years, which might explain the jump in physical activity seen at the second time point, when participants were around that age. "Maybe we have to check in another 10 years to see what happens as they age after retirement-whether they sustain that, or is it just a blip?" Hamer said.
Asked to comment on this research, Dr Gerald Fletcher (Mayo Clinic College of Medicine, Jacksonville, FL), a spokesperson for the American Heart Association, said that "the study gives us more scientific data on what we know and believe is good with physical activity." It emphasizes that "cardiologists need to spend at least a few minutes each patient visit to discuss the importance of proper lifestyle and physical activity in the prevention and control of cardiovascular disease." The activity can be walking to work, walking up stairs, playing with the grandchildren, or standing instead of sitting at a computer, he added.
Source
1. Hamer M, Sabia S, Batty GD, et al. Physical activity and inflammatory markers over 10 years: Follow-up in men and women from the Whitehall II cohort study. Circulation 2012;
------------------------
Physical Activity and Inflammatory Markers Over 10 Years: Follow-Up in Men and Women from the Whitehall II Cohort Study
Circulation. published online August 13, 2012
Abstract
Background-Inflammatory processes are putative mechanisms underlying the cardio-protective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period.
Methods and Results-Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP (ß=-0.07, 95% CI, -0.12, -0.02) and logeIL-6 (ß=-0.07, 95% CI, -0.10, -0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =-0.05, 95% CI, -0.10, -0.001) and loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.03) at follow up.
Conclusions-Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing.
The anti-inflammatory effects of exercise are thought to be one of the mechanisms that explain the well-documented cardio-protective effects of physical activity.1-4 Evidence from epidemiological studies has demonstrated an inverse association between physical activity and markers of low grade systemic inflammation.5 However, the majority of existing evidence is drawn from cross-sectional analyses and few studies have examined the association between long-term physical activity behaviour and low grade inflammation prospectively. Cross-sectional data make it difficult to discount reverse causation effects. For example, some evidence suggests low grade inflammation is a marker of sarcopenia,6 thus functional limitations might explain associations between systemic inflammation and low activity in ageing populations.7 Tracking low-grade inflammation is particularly relevant in an ageing population, as inflammatory markers gradually rise with increasing age and this pro-inflammatory status underlies biological mechanisms responsible for cardiovascular disease (CVD) and other age-related diseases.8-10
Since the majority of health benefits from exercise are established through chronic training adaptations, it is difficult to draw firm conclusions from short-term exercise trials often lasting less than 6 months. Indeed, this might partly explain the equivocal nature of clinical trial data on exercise and inflammatory markers.11 Thus, in the present study we examined the association between physical activity and inflammatory markers over a 10-year follow-up period using a well characterised population based cohort study.
Discussion
Given that the majority of existing data on physical activity and markers of systemic inflammation is cross-sectional, the aim of this study was to explore the longitudinal association between physical activity and inflammatory markers over a 10-year follow-up period. The main findings show that physically active participants at baseline had lower CRP and IL-6 levels and this difference remained stable over time. Secondly, maintenance of physical activity over the 10 years follow-up period was associated with lower levels of both inflammatory markers at followup.
An increase in physical activity was also associated with lower levels of both inflammatory markers at follow up. Crucially, the associations observed between physical activity and inflammatory markers were independent of adiposity, which is an important confounder of the association between physical activity and inflammatory markers as physically active participants tend to have lower levels of adiposity, and adipose tissue is a key production site for several inflammatory markers.19 Previous data from the Whitehall II study have demonstrated that increases in BMI and waist circumference over time were associated with higher levels of inflammatory markers at follow up,20 although the present findings were independent of changes in body composition. Another important finding showed that basal systemic inflammation was associated with reduction in physical activity over follow up, after adjusting for confounders such as BMI and chronic illness. Given that inflammatory processes are thought to be involved in sarcopenia and functional decline,6,7 this explains why systemic inflammation may result in decreased activity in ageing populations.
Physical activity, inflammation and health are linked together in a complex fashion. Cytokines are secreted transiently in large doses by several metabolically active tissues during exercise; namely from the muscle during contraction and adipose tissue via exercise-related mechanisms. Paradoxically, regular (chronic) exercise training has been consistently associated with lower levels of systemic inflammatory markers5 and reduced adipose tissue inflammation.21
The expression of exercise-regulated muscle genes, such as the transcriptional co-activator PGC1a, is thought to promote anti-inflammatory effects through a transient release of cytokines,22 and possibly explains some of the systemic and beneficial effects of exercise in nonmuscle tissue.21-25 In contrast, chronically elevated levels of low grade systemic inflammation have been linked to the development of many diseases associated with inflammation including CVD, sarcopenia, neurodegeneration and depression.6-10, 26, 27 Thus, the transient fluctuations of cytokines following exercise might contribute to the beneficial effects of exercise on organs other than muscle in a hormone-like fashion, whereas chronic, low grade elevation of many of these same molecules is almost certainly pro-inflammatory and detrimental.
A notable strength of this study is the repeated serial measures taken over a 10-year follow-up period in a well characterised cohort. This allowed us to track changes in physical activity, inflammatory markers and other important clinical variables. Self-reported measures of physical activity are prone to reporting bias although the questionnaire used in the present study is well validated and has demonstrated convergent validity in predicting mortality in the Whitehall II study.15 In addition, among a sub-cohort of 394 Whitehall II participants, we recently demonstrated that self-reported physical activity was associated with objectively (accelerometry) assessed activity at 10-year follow-up across various activity categories.28 Although there was only modest correlation between physical activity measures at different phases of data collection, we did observe an upward trend in physical activity. This might be explained by the fact many participants from Whitehall II were in the transition to retirement during this period. This is consistent with recent data from the GAZEL cohort 4 years before and 4 years after retirement showing that leisure-time physical activity increased by 36% in men and 61% in women during the transition to retirement.29 Our findings on the association between baseline inflammatory markers and change in physical activity over follow up should be interpreted with caution as we were unable to account for presence of sarcopenia. Nevertheless, the analyses were adjusted for chronic illness that incorporates factors such as functional limitations and history of CVD.
In summary, the results show that physically active participants maintain lower levels of inflammatory markers over a 10 year period. Thus, physical activity may be important in preventing the pro-inflammatory state seen with ageing.
Results
At baseline 7366 participants had available data on all variables although after excluding participants with missing data through follow-up the final analytic sample comprised 4289 participants (3092 men and 1197 women). Participants excluded were slightly older (50.1 vs. 49.2 yrs, p<0.001), less physically active (3.3 vs. 3.6 hrs/wk moderate to vigorous physical activity, p=0.003), and had higher baseline loge CRP values (0.87 vs. 0.75, p<0.001) compared with those included. However, these absolute differences in characteristics between the groups were trivial, only attaining statistical significance owing to the large sample size. Approximately half the sample (49%) adhered to the physical activity recommendation (2.5 hrs per week moderate to vigorous physical activity) across all assessments (50% at phase 3 [baseline]; 83.7% at phase 5; 83.3% at phase 7). Participants that 'always' met the physical activity guidelines were more likely to be men, from higher employment grades, and had lower BMI (Table 1).
Baseline physical activity and change in inflammatory markers
Meeting the physical activity guideline at baseline was inversely associated with baseline loge CRP (coefficient = -0.04, 95% CI, -0.07, -0.01, p=0.007) and loge IL-6 (coefficient = -0.04, 95% CI, -0.06, -0.02, p=0.001) after adjustments for age, gender, smoking, employment grade, BMI, and chronic illness (Table 2). On average, there was an increase in both inflammatory markers from baseline to follow-up: loge CRP increased from 0.75 to 0.94 (p<0.001) and loge IL-6 from 0.93 to 1.08 (p<0.001), corresponding to a change of 0.44 mg/l (21%) in CRP and 0.41 pg/ml (16%) in IL-6 over 10 years. There was no statistically significant association between baseline physical activity and change in loge CRP (p=0.10) or loge IL-6 (p=0.39) over follow-up (Table 2), suggesting that the difference in inflammation levels persisted but did not increase across time (Figure 1).
Habitual physical activity over 10 years and inflammatory markers at follow up
In comparison to participants that rarely adhered to physical activity guidelines through follow up, the high adherence group displayed lower loge CRP (B coefficient=-0.07, 95% CI, -0.12, -0.02) and loge IL-6 (B coefficient =-0.07, 95% CI, -0.10, -0.03) at follow up after adjustment for age, gender, smoking, employment grade, BMI, and chronic illness (Table 3). These coefficients corresponded to a fully adjusted difference of 0.18 mg/l in CRP and 0.20 pg/ml in IL-6 between individuals who adhered consistently compared to those that did not adhere to physical activity guidelines over 10 years. When we adjusted for waist circumference as a marker of central adiposity (instead of BMI) the effect estimate was slightly attenuated for loge CRP (B coefficient=-0.04, 95% CI, -0.10, 0.01) but changed little for loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.02). Participants that were consistently physically active over follow up gained less weight compared to those rarely active (average BMI increase, 1.4 ± 1.8kg/m2 vs. 1.6 ± m2, p=0.04). However, when we adjusted for change in BMI during follow-up (instead of BMI at baseline) this did not alter the association between physical activity and inflammatory markers.
We examined the associations for change in physical activity (Table 4). In order to retain consistency we calculated changes in activity between phases 5 and 7 when the same questionnaire was used. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hrs/wk displayed lower loge CRP (B coefficient =- 0.05, 95% CI, -0.10, -0.001) and loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.03) at follow up after adjustment for age, gender, hours/week of moderate to vigorous physical activity at phase 5, smoking, employment grade, BMI, and chronic illness. There was no difference in inflammatory markers between participants that reported a reduction in physical activity compared with those remaining stable.
| |
| |
| |
|
|
|
