First study to quantify benefits of exercise on CHD risk Dose Response Between Physical Activity (15/day, 150, 300, 750-week minutes) and Risk of Coronary Heart Disease [reduced 14-25%]
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www.theheart.org Aug 2, 2011
Boston, MA - The first meta-analysis to specifically examine the dose-response relationship between physical activity and risk reduction for coronary heart disease (CHD) has found that those engaging in the equivalent of 150 minutes of moderate-intensity exercise per week-the basic minimum as recommended by 2008 US federal guidelines-had a 14% lower CHD risk, and those who achieved 300 minutes per week had a 20% lower risk of CHD, compared with those who were sedentary .
Dr Jacob Sattelmair (Harvard School of Public Health, Boston, MA) and colleagues report their findings online August 1, 2011 in Circulation.
"Although it is well-established that physical activity helps prevent CHD, a lot of the literature compares active vs inactive individuals or qualitative concepts, such as 'high,' 'medium,' and 'low' amounts of exercise," Sattelmair explained to heartwire. "We wanted to look at studies done recently that assessed physical activity quantitatively. Generally, the 'industry-standard' quote is that if you are physically active, you will lower your CHD risk by 20% to 30%. We wanted to see, if you follow the US federal guidelines, what does that mean? What are the risk reductions for CHD?
The conclusion is that even a little bit of physical activity is beneficial and more is better, but the biggest bang for your buck happens at the lower end of the spectrum.
"Overall, the conclusion is that even a little bit of physical activity is beneficial and more is better, but the biggest bang for your buck happens at the lower end of the spectrum. The majority of the population in the US is inactive, so if you start by doing something, that's a great first step, and you'll start to realize the benefits. If you're doing nothing, you don't have to start by running a marathon to see the benefit; even walking briskly for 15 minutes a day was associated with a significant reduction in CHD risk," he observes. This is, he says, in line with the US guidelines, which encourage any amount of activity for those unable to meet the minimum recommended.
Findings support US federal physical-activity guidelines
Sattelmair and colleagues included in their review 26 studies published in English since 1995, nine of which allowed for quantitative estimates of leisure-time physical activity. The researchers performed initial analyses comparing high and low physical activity, which included all 26 studies, and the findings were similar to those of the primary analysis, which included only the nine studies.
As well as the 14% and 20% CHD risk reduction observed with the minimum and advanced recommended amounts of exercise, the researchers found that those who were physically active at levels lower than the minimum recommended also had a significantly lower risk of CHD, compared with those who did nothing.
So although meeting the basic guideline "is associated with a lower risk reduction than that which is generally ascribed to being physically active, meeting the advanced guideline-300 minutes of moderate-intensity exercise per week-is associated with a risk reduction that is pretty much in line with the benefit that has generally been ascribed to physical activity," he notes.
And those who engaged in more than the advanced amount of exercise saw additional benefits-those able to participate in 750 minutes per week of moderate intensity exercise (five times the minimum recommended amount) had around a 25% reduction in risk of CHD, Sattelmair said.
The researchers also found that the cardiovascular benefits of exercise appeared to be stronger in women than in men but say they don't have any plausible explanation for this finding. And there were insufficient data to examine the effect of age at baseline or race on the relationship between physical activity and CHD risk.
Nevertheless, "These findings provide quantitative data that support the 2008 US physical-activity guidelines," they say, and indicate that the most benefit for CHD risk occurs at the lower end of the activity spectrum-ie, very modest, achievable levels of physical activity.
Future studies that quantitatively assess the dose-response relation between leisure-time physical activity and CHD risk will help clarify the upper end of the dose-response curve, they note, "and enable additional quantitative evaluations in future reviews, such as exploring potential differences by age and race."
Dose Response Between Physical Activity and Risk of Coronary Heart Disease - Federal Exercise Guidelines attached
Circulation. 2011; 124: 789-795 Published online before print August 1, 2011
"This meta-analysis is the first to quantify the dose-response relation between physical activity and CHD risk with regard to both physical activity amount and magnitude of lower CHD risk. We found that individuals who met the basic US physical activity guideline for health9 had a 14% lower risk of CHD compared with those with no LTPA[leisure-time physical activity]. Those meeting the advanced guideline had a 20% lower risk of CHD. At higher levels of physical activity, modest increments of risk reduction were observed. We also noted lower RRs among persons who were physically active below the basic guideline, supporting the guideline's assertion that some physical activity is better than none.....
Individuals who met the basic guideline had a 14% lower risk of CHD than those who engaged in no LTPA (RR, 0.86; 95% CI, 0.77 to 0.96), whereas those who met the advanced guideline had a 20% lower risk (RR, 0.80; 95% CI, 0.74 to 0.88). Additionally lower risks of moderate magnitude were observed among those with higher physical activity levels; eg, there was a 25% lower risk for those active at 5 times the basic guideline (750 minutes). Among persons who were physically active at half the basic guideline level (275 kcal/wk), we found a 14% lower risk of CHD (RR, 0.86; 95% CI, 0.76 to 0.97)."
Jacob Sattelmair, Jeremy Pertman, Eric L. Ding, Harold W. Kohl III, William Haskell and I-Min Lee
From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (J.S., J.P.); Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Department of Nutrition, Harvard School of Public Health, Boston, MA (E.L.D.); Division of Epidemiology, Genetics and Environmental Health Sciences, University of Texas Health Science Center-Houston, Department of Kinesiology and Health Education, University of Texas at Austin (H.W.K.); Stanford Center for Research in Disease Prevention, Stanford Medical School, Stanford, CA (W.H.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Department of Epidemiology, Harvard School of Public Health, (I.-M.L.).
Background No reviews have quantified the specific amounts of physical activity required for lower risks of coronary heart disease when assessing the dose-response relation. Instead, previous reviews have used qualitative estimates such as low, moderate, and high physical activity.
Methods and Results We performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of CHD. We included prospective cohort studies published in English since 1995. After reviewing 3194 abstracts, we included 33 studies. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Among the 33 studies, 9 allowed quantitative estimates of leisure-time physical activity.
Individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 US federal guidelines) had a 14% lower coronary heart disease risk (relative risk, 0.86; 95% confidence interval, 0.77 to 0.96) compared with those reporting no leisure-time physical activity.
Those engaging in the equivalent of 300 min/wk of moderate-intensity leisure-time physical activity (2008 US federal guidelines for additional benefits) had a 20% (relative risk, 0.80; 95% confidence interval, 0.74 to 0.88) lower risk.
At higher levels of physical activity, relative risks were modestly lower.
People who were physically active at levels lower than the minimum recommended amount also had significantly lower risk of coronary heart disease.
There was a significant interaction by sex (P=0.03); the association was stronger among women than men.
Conclusions These findings provide quantitative data supporting US physical activity guidelines that stipulate that "some physical activity is better than none" and "additional benefits occur with more physical activity."
Although prevalence and incidence rates of coronary heart disease (CHD) mortality have declined since the 1960s, it is estimated that ≈17 million people in the United States are living with CHD in 2010.1 Coronary heart disease causes ≈425 000 annual deaths in the United States, making it the leading cause of mortality nationwide.1 Identifying and characterizing modifiable risk factors for CHD remain important for public health and clinical medicine.
Clinical Perspective on p 795
The independent role of physical activity in the primary prevention of CHD is well established and has been assessed in numerous reviews or meta-analyses.2-8 Although all reviews agree that physical activity is associated with a 20% to 30% lower risk of CHD,7,8 no work to date has designated quantitative assessments of the amount of physical activity required for these lower risks, referring instead to qualitative levels of physical activity (eg, high versus low).8 Public health guidelines on the amount of physical activity required for health benefits have relied on individual studies rather than a systematic assessment of the overall evidence.9
Many early studies that assessed the relation between physical activity and CHD dichotomized participants according to their activity levels (eg, active versus inactive); however, more recent studies have grouped participants into multiple quantitatively designated categories of specific types of physical activity8 (eg, quartiles of leisure-time physical activity [LTPA]), making it possible to assess and describe in detail the dose-response relation. The purpose of this meta-analysis is to pool results from prospective cohort studies to quantify the dose-response relationship between physical activity and risk of CHD, including both the amount of physical activity required and the magnitude of benefit to CHD risk.
Guidelines from the 2008 US physical activity guidelines were used to assign the first 2 doses of physical activity at which to assess RR.9 These guidelines recommend 150 minutes of moderate-intensity (3 to <6 METs) physical activity per week as a minimum amount for health enhancement (referred to hereafter as basic) and 300 min/wk for additional health benefits (advanced). Alternatively, guidelines recommend equivalent expenditure from vigorous-intensity (≥6 METs) physical activity (75 and 150 min/wk, respectively) or any combination of moderate- and vigorous-intensity activity that results in energy expenditure equivalent to either regimen. The cutoffs associated with the basic and advanced guidelines, converted into approximate units of kilocalories per week, were 550 and 1100 kcal/wk, respectively, for both sexes combined, 600 and 1200 kcal/wk for men, and 500 and 1000 kcal/wk for women (based on population norms for weight). These intervals were used as a guide to extend analyses to higher levels of LTPA to fit the available data; higher doses were assigned to balance model parsimony and goodness of fit.
In a sensitivity analysis, we examined lower doses of physical activity (eg, 275 kcal/wk for both sexes combined) to test the statement in the 2008 US guidelines that, in addition to recommending levels of physical activity, says, "All adults should avoid inactivity. Some physical activity is better than none, and adults who participate in any amount of activity gain some health benefits."9
The initial search produced 1545 articles using PubMed and 1649 articles using EMBASE; 87 and 129 studies were selected for further evaluation from PubMed and EMBASE, respectively. On the basis of information from abstracts, 68 studies warranted further assessment. Inclusion or exclusion was determined after a detailed evaluation of the study design, population, physical activity assessment, and CHD assessment. An additional 7 studies were identified by a manual search through references of recent reviews.7,8 Finally, 33 prospective cohort studies were selected for analysis14-46 (see Figure 1 for selection flow and Tables I and II in the online-only Data Supplement for characteristics of all studies selected for analysis) from which 30 assessments of LTPA were analyzed, 10 of which provided quantitative estimates of LTPA categories
To relate our findings to past reviews, we first compared the highest and lowest (or referent) categories of physical activity for each type of physical activity using random effects pooled RRs (the Table). The majority of physical activity types were associated with significantly lower risks of CHD, which varied between 6% and 51%. The summary risk among all studies that assessed LTPA indicated a 26% risk reduction (RR, 0.74; 95% CI, 0.69 to 0.78).
Within each type of physical activity, pooled RRs were also provided for each sex (when there were ≥2 studies for each sex). For the majority of physical activity types, the RR among the most active women was lower than the corresponding value among men by ≈0.10. Among all studies that assessed LTPA, those conducted in men showed a 22% lower risk (RR, 0.78; 95% CI, 0.73 to 0.82) comparing most with least active and those conducted in women showed a 33% lower risk (RR, 0.67; 95% CI, 0.61 to 0.74).
Within each type of physical activity, RRs were also provided for the subset of studies that included quantitative assessments of physical activity (when there were ≥2 studies). These quantitative studies tended to demonstrate RRs of magnitudes similar to those observed when all studies were included (the Table).
Plots of the dose-response relation between LTPA, assessed categorically, and CHD risk (30 comparisons [26 studies] of 56 comparisons [33 studies] included data on LTPA) are shown in Figure 1. Studies that allowed quantitative estimates of LTPA demonstrated trends similar to those of studies that assessed LTPA only qualitatively.
Plots of the dose-response relation between quantitative estimates of LTPA in kilocalories per week and CHD risk14-22 (10 comparisons; 9 studies), including a trend line derived from random effects, 1-stage GLST spline analysis for both sexes combined, is shown in Figure 2. Pooled results indicated the expected inverse relation between LTPA and CHD risk. Individuals who met the basic guideline had a 14% lower risk of CHD than those who engaged in no LTPA (RR, 0.86; 95% CI, 0.77 to 0.96), whereas those who met the advanced guideline had a 20% lower risk (RR, 0.80; 95% CI, 0.74 to 0.88). Additionally lower risks of moderate magnitude were observed among those with higher physical activity levels; eg, there was a 25% lower risk for those active at 5 times the basic guideline. Among persons who were physically active at half the basic guideline level (275 kcal/wk), we found a 14% lower risk of CHD (RR, 0.86; 95% CI, 0.76 to 0.97).
Using GLST spline models, we observed significant interaction by sex (P=0.03). Figure 3 shows trend lines from gender-specific GLST spline analysis. Men who met the basic and advanced guidelines were at 9% (RR, 0.91; 95% CI, 0.79 to 1.04) and 18% (RR, 0.82; 95% CI, 0.74 to 0.91) lower risk of CHD, respectively, than men with no LTPA. Minimally lower risk was observed among men who participated in higher levels of LTPA; eg, there was a 21% lower risk among men who were physically active at 5 times the basic guideline. Women who met the basic guideline were at 20% lower risk (RR, 0.80; 95% CI, 0.69 to 0.92) of CHD than women who engaged in no LTPA; women who met the advanced guideline were at 28% lower risk (RR, 0.72; 95% CI, 0.63 to 0.83). Among women, no added lower risks were observed at higher levels of LTPA until 5 times the basic guideline, which was associated with a 48% lower risk (RR, 0.52; 95% CI, 0.40 to 0.67).
We observed no interaction by geographic region, adjustment strategy for confounding variables, or CHD outcome (data not shown). Because the interaction assessment with spline models had low power, as a secondary analysis, we assessed potential interaction using quadratic models. We found significant interaction by sex, adjustment for confounding, and CHD outcome (all P<0.05). Despite the low power, we found that among studies that controlled for plausible biological intermediates (eg, body mass index, hypertension, and diabetes mellitus), CHD RRs were higher by ≈0.1 than those from studies that did not, indicating that additional adjustment for plausible intermediates attenuated the observed associations. We observed no effect modification by geography. We found no evidence for publication bias using the Begg test (with funnel plot) (P=0.21).
This meta-analysis is the first to quantify the dose-response relation between physical activity and CHD risk with regard to both physical activity amount and magnitude of lower CHD risk. We found that individuals who met the basic US physical activity guideline for health9 had a 14% lower risk of CHD compared with those with no LTPA. Those meeting the advanced guideline had a 20% lower risk of CHD. At higher levels of physical activity, modest increments of risk reduction were observed. We also noted lower RRs among persons who were physically active below the basic guideline, supporting the guideline's assertion that some physical activity is better than none.
Interestingly, we observed a significant interaction by sex such that the association of physical activity and CHD risk was stronger in women than in men. We were unable to assess whether the association differed by race or age because of insufficient variation among studies. Geographic region of origin did not influence the association.
It is unclear why we observed a significant interaction by sex. Possible explanations include biological differences, methodological considerations, or some combination of both. Previous evidence does not support more favorable effects of habitual physical activity on CHD risk factors (including blood pressure, lipid levels, vascular indicators, cardiorespiratory fitness, and metabolic syndrome) among women compared with men.8 The type or intensity of physical activity contributing to total LTPA energy expenditure may differ between men and women (eg, men favor vigorous activities and women are more likely to engage in moderate activities).17,43 However, this does not explain the stronger effects in women because there are limited data suggesting that vigorous-intensity physical activity may be associated with additional cardiovascular benefits beyond its contribution to energy expenditure.47
Methodological issues may explain a portion of the difference. For instance, women have lower CHD rates1; thus, the presence of imprecisely measured or unmeasured plausible confounders (such as smoking habit and diet) may have a smaller effect in women than men.
There may be sex differences in the reporting of physical activities. However, it is unlikely that such misclassification would be greater among men than women because vigorous-intensity activities (in which men are more likely to engage) tend to be better reported than activities of lesser intensity.48 Of the studies included, longer duration of follow-up was more likely in studies of men, leading to greater potential for misclassification of energy expenditure. However, analyzing a subset of studies with comparable follow-up in men and women did not change our main results.
The primary strength of this study was the quantification of physical activity amount in analyses, enabling assessments of the risk associated with specific quantitative levels of LTPA. We chose to quantify physical activity in units of kilocalories per week (and accounting for the different average weights of men and women) because they were more frequently reported in studies and are more easily understood than other units. We also assessed potential effect modification by numerous variables and reported sex-specific results.
Although the selection of studies that included quantitative estimates of physical activity allowed this more quantitative approach, it also limited the number of studies that could be included. In a secondary analysis, we included several additional studies for which we were able to crudely estimate quantitative levels of LTPA; findings were similar to those of the main analyses. We also examined the potential influence of single studies and found that no single study changed results.
This study was limited by inclusion of only English language studies, possibly resulting in bias because statistically significant results may be more likely to be published in English. However, it is unclear whether inclusion of only English language articles causes bias.49,50 By designating meta-analytic methods a priori, we aimed to minimize any potential investigator bias caused by preconceptions. However, it is possible that the a priori designations and subsequent interpretations were subject to personal biases. Because this is a meta-analysis of observational studies, the potential for residual confounding and bias cannot be addressed through pooling. A primary source of potential residual confounding is likely to stem from confounding variables that were either unmeasured or insufficiently measured in the individual studies themselves. For instance, dietary intake was rarely assessed in the studies reviewed. In all studies included, physical activity was assessed by self-report; some misclassification of activity levels is probable, and quantitative characterizations should therefore be considered approximate in nature.
We were able to conduct our primary analysis on LTPA on only 9 of 26 of potential studies. As result, there were insufficient data to assess potential interaction by several important factors (eg, baseline age and race). Among women alone, it appeared that there was a marked and sudden decline in risk at 5 times the minimally recommended level of physical activity (Figure 3). However, this data point was based on only 2 studies.
We contacted the authors of the remaining 17 studies to request unpublished quantitative physical activity data; however, little additional usable information was obtained because many of these studies used qualitative categories to assess physical activity. The inclusion of only the 9 studies for quantitative analyses was unlikely to have biased results because these 9 studies appeared representative of the broader group of 26 eligible studies. In initial analyses comparing high and low physical activity, which included all 26 studies, findings were similar to those including only the 9 studies. Furthermore, in a comparison of our findings with previous reviews, which quantified only the magnitude of lower RRs but not the amount of physical activity required, the results are comparable. Our comparison of high and low physical activity yielded an RR of 0.75 for CHD, similar in magnitude to several past reviews.2,3,7,8
The present study provides quantitative data supporting the 2008 Physical Activity Guidelines for Americans, which recommend the equivalent of 150 min/wk of moderate-intensity physical activity for health and 300 min/wk for additional health benefits and encourage any amount of activity for those unable to meet the minimum. Future studies that quantitatively assess the dose-response relation between LTPA and other types and features of physical activity and CHD risk will help clarify the upper end of the dose-response curve and enable additional quantitative evaluations in future reviews such as exploring potential differences by age and race. Additionally, individual participant meta-analyses conducted via collaboration among research groups, although resource intensive, can use existing studies to further clarify dose-response relationships.51