Physical Activity, Muscle-Strengthening Activities, and Systemic Inflammation Among Retinopathy Patients

Data from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) was used. Study procedures were approved by the National Center for Health Statistics ethics review board, with informed consent obtained before data collection.

The NHANES is an ongoing survey conducted by the Centers for Disease Control and Prevention that uses a representative sample of non-institutionalized U.S. civilians selected by a complex, multistage, stratified, clustered probability design. The design consists of four stages, including the identification of counties, segments (city blocks), random selection of households within the segments, and random selection of individuals within the households. Further information on NHANES methodology and data collection is available on the NHANES website (www.cdc.gov/nchs/nhanes.htm).

The analyzed sample included 157 participants with complete data on the study variables who had evidence of mild or moderate-to-severe nonproliferative retinopathy and who did not have a physician’s diagnosis of coronary artery disease, congestive heart failure, heart attack, or stroke; participants were excluded if they had these conditions because these parameters may have confounded our investigated association between physical activity and systemic inflammation among those with retinopathy. The participants ranged in age from 40 to 85 years.

As we have described elsewhere (27,28), retinal imaging was performed using the Canon Non-Mydriatic Retinal Camera CR6-45NM (Canon, Tokyo, Japan). The presence of nonproliferative retinopathy (mild or moderate/severe retinopathy) was determined using the Early Treatment Diabetic Retinopathy Study grading criteria (29).

From a blood sample, CRP was assessed as a marker of systemic inflammation. High-sensitivity CRP concentration was quantified using latex-enhanced nephelometry.

Physical activity was assessed for up to 7 days using an ActiGraph 7164 accelerometer; activity counts/minute ≥2,020 defined participation in moderate-to-vigorous physical activity (MVPA) (30), with individuals having at least 4 days of ≥10 hours/day of monitoring included in the analyses. Non–wear-time was identified as ≥60 consecutive minutes of zero activity counts, with allowance for 1–2 minutes of activity counts between 0 and 100. Specific details regarding the NHANES accelerometer protocol have been previously published (31).

Participants were asked one to two questions related to engagement in MSA: 1) “Over the past 30 days, did you do any physical activities specifically designed to strengthen your muscles such as lifting weights, pushups, or sit-ups?” (response option: “yes” or “no”) and 2) individuals answering “yes” to the first question were then asked, “Over the past 30 days, how many times did you do these activities designed to strengthen your muscles such as lifting weights, pushups, or sit-ups?” These exact NHANES MSA items have provided evidence of convergent validity (e.g., were shown to be associated with cardiovascular-related parameters [32] and insulin sensitivity [33]). Further, we calculated knee extremity strength (using a Kin Com MP dynamometer) among individuals reporting and not reporting engagement in MSA (≥50 years of age); individuals reporting engagement in MSA (unweighted mean: 296.9 N) had greater knee extensor strength than individuals not reporting engagement in MSA (unweighted mean: 266.0 N) (P <0.05), providing some evidence of construct validity for this MSA item. Notably, these estimates were not from the NHANES cycle in the present study (2005–2006) but rather were from the 1999–2002 NHANES cycles because the 1999–2002 cycles are the only ones with lower-extremity strength data.

All statistical analyses, computed in Stata version 12 (StataCorp., College Station, Tex.), accounted for the complex survey design used in NHANES. A weighted multivariable linear regression was used, with the outcome variable being CRP and the main independent variables being accelerometer-assessed MVPA (minutes/day) and MSA (number of sessions/month). This model also included the following covariates: age (years; continuous), sex, race/ethnicity (Mexican American, non-Hispanic white, non-Hispanic black, other), self-reported smoking status (current, former, never-smoker), measured BMI (continuous; kg/m²), diabetes status (yes/no), physician-diagnosed hypertension (yes/no), objectively measured visual acuity (34) (normal vision, uncorrected refractive effort, and vision impairment), and objectively measured retinopathy status (mild/moderate-to-severe). With regard to diabetes status, participants were defined as having diabetes if they had a physician’s diagnosis, had a fasting blood glucose of ≥126 mg/dL, had an A1C ≥6.5%, or were taking any diabetes medications. Significance was set at P <0.05.

Table 1 displays the weighted characteristics of the sample. Participants, on average, were 56 years old; mean MVPA was 21.6 minutes/day; mean MSA was 5.1 sessions/month; mean CRP was 0.45 mg/dL; 70% had diabetes; and 87.7 and 12.3% had mild and moderate-to-severe retinopathy, respectively.

Regarding the main findings, only MVPA and not MSA was independently associated with lower CRP among individuals in the retinopathy sample. In a model that only included MVPA and MSA as independent variables, MVPA (β = –0.007, 95% CI –0.01 to –0.005, P <0.001) but not MSA (β = –0.001, 95% CI –0.003 to 0.0008, P = 0.23) was associated with CRP. In the adjusted model (Table 2), results were similar, in that MVPA (β = –0.004, 95% CI –0.007 to –0.001, P = 0.006) but not MSA (β = –0.0001, 95% CI –0.002 to 0.001, P = 0.86) was associated with lower CRP levels. For example, for a 1 minute/day increase in MVPA, there was a corresponding 0.004 mg/dL decrease in CRP. When expressed as a larger interval change (30 minutes/day), for a 30 minutes/day increase in MVPA, there was a corresponding 0.12 mg/dL decrease in CRP.

A follow-up analysis expressed CRP as a binary variable, categorized as elevated (≥0.3 mg/dL) or not (<0.3 mg/dL). In an adjusted logistic regression model, for a 1 minute/day increase in MVPA, retinopathy patients had a 7% reduced odds of having an elevated CRP (odds ratio [OR] 0.93, 95% CI 0.89–0.96, P = 0.001). When expressed as a larger interval change, for a 30 minutes/day increase in MVPA, there was a corresponding 88% reduced odds of having an elevated CRP (OR 0.12, 95% CI 0.04–0.39; P = 0.001).

Previous research highlights the attenuating benefit of physical activity on inflammatory mechanisms in healthy and diseased populations (17,19,25,26). Therefore, the purpose of our study was to extend this literature by examining the association of MSA and accelerometer-assessed physical activity on CRP among individuals with retinopathy because elevated systemic inflammation has been shown to facilitate the progression of retinopathy disease (14–16,35). Our main finding was that, among individuals engaging in higher levels of MVPA, CRP levels were reduced, whereas participation in MSA did not have a statistically significant influence on CRP.

Our findings demonstrate that even modest increases in physical activity may have a positive impact on retinopathic outcomes. For every additional 30-minute increase in MVPA, there was an associated 0.12 mg/dL decrease in CRP and an 88% reduced odds of having an elevated CRP. β-Adrenergic receptors are suggested to stimulate fat cells and increase pro-inflammation by way of cytokine mobilization (36,37). Physical activity may alter β-adrenergic receptor density and expression, curtailing their stimulatory effect on adipose tissue (38). Another possible mechanism by which this interaction may develop is the association between physical activity and stress reduction. High levels of stress may accelerate depression and anxiety, and the release of pro-inflammatory cytokines (39–41). A stronger clinical approach should perhaps focus on limiting retinopathy progression with physical activity in combination with individual stress-management strategies.

MSA data were self-reported, which augments the need for increased sample size to maximize potential for statistical significance, as questionnaire-based estimations tend to foreshadow weakened effect size (42). In addition to the risk of erroneous estimations in subjectively reported data, another potential explanation for the negligible influence of MSA on CRP status is the low frequency of resistance-training participation reported by participants in the present sample. On average, participants engaged in only five sessions of MSA per month, which is likely insufficient to favorably mitigate inflammation. The American College of Sports Medicine and the American Heart Association recommend engaging in at least two sessions of MSA per week for optimal health benefits, particularly among aging individuals (43,44). Future work should examine associations between MSA and retinopathy, with participant adherence to appropriate levels of activity closely monitored.

In conclusion, this study identifies the association between accelerometer-assessed MVPA participation and lower plasma measures of CRP among aging individuals with a nonproliferative retinopathy diagnosis. Our findings amplify important conclusions from previous research suggesting the multifactorial impact of physical activity on retinopathic biomarkers. We specifically examined the plausibility for aerobic-based, as well as resistance training, modalities to reduce concentration of plasma CRP among people with existing retinopathy. We identified a relationship between MVPA engagement and CRP reduction. This finding is noteworthy because elevated inflammation may facilitate retinopathy disease progression (14–16,35,45). Our use of a cross-sectional research design, in addition to self-reported MSA, are limitations that should be addressed in future longitudinal investigations.

E.F. and P.D.L. contributed to writing the manuscript, and P.D.L. computed the analyses. P.D.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis.

No potential conflicts of interest relevant to this article were reported.