Device-measured physical activity and cardiac structure by magnetic resonance.

BACKGROUND AND AIMS: Although extreme cardiac adaptions mirroring phenotypes of cardiomyopathy have been observed in endurance athletes, adaptions to high levels of physical activity within the wider population are under-explored. Therefore, in this study, associations between device-measured physical activity and clinically relevant cardiac magnetic resonance volumetric indices were investigated. METHODS: Individuals without known cardiovascular disease or hypertension were included from the UK Biobank. Cardiac magnetic resonance data were collected between 2015 and 2019, and measures of end-diastolic chamber volume, left ventricular (LV) wall thickness, and LV ejection fraction were extracted. Moderate-to-vigorous-intensity physical activity (MVPA), vigorous-intensity physical activity (VPA), and total physical activity were assessed via wrist-worn accelerometers. RESULTS: A total of 5977 women (median age and MVPA: 62 years and 46.8 min/day, respectively) and 4134 men (64 years and 49.8 min/day, respectively) were included. Each additional 10 min/day of MVPA was associated with a 0.70 [95% confidence interval (CI): 0.62, 0.79] mL/m2 higher indexed LV end-diastolic volume (LVEDVi) in women and a 1.08 (95% CI: 0.95, 1.20) mL/m2 higher LVEDVi in men. However, even within the top decile of MVPA, LVEDVi values remained within the normal ranges [79.1 (95% CI: 78.3, 80.0) mL/m2 in women and 91.4 (95% CI: 90.1, 92.7) mL/m2 in men]. Associations with MVPA were also observed for the right ventricle and the left/right atria, with an inverse association observed for LV ejection fraction. Associations of MVPA with maximum or average LV wall thickness were not clinically meaningful. Results for total physical activity and VPA mirrored those for MVPA. CONCLUSIONS: High levels of device-measured physical activity were associated with cardiac remodelling within normal ranges.

Interplay between physical activity volume and intensity with modeled life expectancy in women and men: A prospective cohort analysis.

BACKGROUND: There is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy. METHODS: Individuals from UK Biobank with wrist-worn accelerometer data were included. The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile. Mortality data were obtained from national registries. Adjusted life expectancies were estimated using parametric flexible survival models. RESULTS: 40,953 (57.1%) women (median age = 61.9 years) and 30,820 (42.9%) men (63.1 years) were included. Over a median follow-up of 6.9 years, there were 1719 (2.4%) deaths (733 in women; 986 in men). At 60 years, life expectancy was progressively longer for higher physical activity volume and intensity profiles, reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity, corresponding to 3.4 (95% confidence interval (95%CI): 2.4-4.4) additional years in women and 4.6 (95%CI: 3.6-5.6) additional years in men compared to those at the 10th centiles. An additional 10-min or 30-min daily brisk walk was associated with 0.9 (95%CI: 0.5-1.3) and 1.4 (95%CI: 0.9-1.9) years longer life expectancy, respectively, in inactive women; and 1.4 (95%CI: 1.0-1.8) and 2.5 (95%CI: 1.9-3.1) years in inactive men. CONCLUSION: Higher physical activity volumes were associated with longer life expectancy, with a higher physical activity intensity profile further adding to a longer life. Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy.

Age at onset of type 2 diabetes and prevalence of vascular disease and heart failure: Systematic review and dose-response meta-analysis.

AIM: To investigate the relationship between age at diagnosis of type 2 diabetes and the risk of macrovascular disease, heart failure, and microvascular disease. METHODS: In August 2022, PubMed/EMBASE were searched for articles reporting (i) coronary artery disease, cerebrovascular disease, peripheral vascular disease, amputation; (ii) heart failure; and (iii) retinopathy, neuropathy, nephropathy (albuminuria, chronic kidney disease [CKD], end-stage renal disease) by age at diagnosis of type 2 diabetes. Random effects, non-linear dose-response meta-analysis was undertaken for each outcome to assess the association with age at diagnosis (40 years = reference), using both crude and maximally adjusted odds ratios separately, with and without adjustment for current age (age at sampling). RESULTS: We identified 42 articles (230,003 to 3,465,590 participants; 1035 to 391,140 events). Age at diagnosis was positively associated with the risk of macrovascular diseases, heart failure, and CKD, independent of current age, and negatively associated with retinopathy. For other microvascular outcomes, when adjusting for current age, a "reverse U" relationship was observed (peak risk = 55-60 years). DISCUSSION: Retinopathy was negatively associated with age at diagnosis, highlighting the importance of retinopathy screening in early-onset type 2 diabetes. The implications of other associations were unclear due to the heterogeneity in methodologies and findings.

Walking pace and the time between the onset of noncommunicable diseases and mortality: a UK Biobank prospective cohort study.

PURPOSE: To estimate time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace. METHODS: In total, 391,744 UK Biobank participants were included (median age = 57 years; 54.7% women). Data were collected 2006-2010, with follow-up collected in 2021. Usual walking pace was self-defined as slow, steady, average, or brisk. Multistate modeling determined the transition rate and mean sojourn time in and across three different states (healthy, CVD or cancer, and death) upon a time horizon of 10 years. RESULTS: The mean sojourn time in the healthy state was longer, while that in the CVD or cancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer than a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVD or cancer. Similar results were seen in men. CONCLUSIONS: Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVD or cancer. AVAILABILITY OF DATA AND MATERIALS: Research was conducted using the UK Biobank resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available.

Long-term ambient air pollution exposure and prospective change in sedentary behaviour and physical activity in individuals at risk of type 2 diabetes in the UK.

BACKGROUND: Air pollution may be a risk factor for physical inactivity and sedentary behaviour (SED) through discouraging active lifestyles, impairing fitness and contributing to chronic diseases with potentially important consequences for population health. METHODS: Using generalized estimating equations, we examined the associations between long-term particulate matter with diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2) and annual change in accelerometer-measured SED, moderate-to-vigorous physical activity (MVPA) and steps in adults at risk of type 2 diabetes within the Walking Away from Type 2 Diabetes trial. We adjusted for important confounders including social deprivation and measures of the built environment. RESULTS: From 808 participants, 644 had complete data (1605 observations; 64.7% men; mean age 63.86 years). PM2.5, NO2 and PM10 were not associated with change in MVPA/steps but were associated with change in SED, with a 1 ugm-3 increase associated with 6.38 (95% confidence interval: 0.77, 12.00), 1.52 (0.49, 2.54) and 4.48 (0.63, 8.34) adjusted annual change in daily minutes, respectively. CONCLUSIONS: Long-term PM2.5, NO2 and PM10 exposures were associated with an annual increase in SED: ~11-22 min/day per year across the sample range of exposure (three standard deviations). Future research should investigate whether interventions to reduce pollution may influence SED.

Self-reported walking pace and 10-year cause-specific mortality: A UK biobank investigation.

OBJECTIVE: To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality. PATIENTS AND METHODS: In 391,652 UK Biobank participants recruited in 2006-2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland). RESULTS: Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (-45.8% [-58.3, -33.2] and - 45.9% [-54.8, -36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: -6.8% (-7.7, -5.8); men: -9.5% (-10.6, -8.4)]. CONCLUSION: Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP.

Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs, incretin mimetics) and dipeptidyl peptidase-4 inhibitors (DPP-4is, incretin enhancers) are glucose-lowering therapies with proven cardiovascular safety, but their effect on microvascular disease is not fully understood. Both therapies increase GLP-1 receptor agonism, which is associated with attenuation of numerous pathological processes that may lead to microvascular benefits, including decreased reactive oxygen species (ROS) production, decreased inflammation and improved vascular function. DPP-4is also increase stromal cell-derived factor-1 (SDF-1), which is associated with neovascularisation and tissue repair. Rodent studies demonstrate several benefits of these agents in the prevention or reversal of nephropathy, retinopathy and neuropathy, but evidence from human populations is less clear. For nephropathy risk in human clinical trials, meta-analyses demonstrate that GLP-1RAs reduce the risk of a composite renal outcome (doubling of serum creatinine, eGFR reduction of 30%, end-stage renal disease or renal death), whereas the benefits of DPP-4is appear to be limited to reductions in the risk of albuminuria. The relationship between GLP-1RAs and retinopathy is less clear. Many large trials and meta-analyses show no effect, but an observed increase in the risk of retinopathy complications with semaglutide therapy (a GLP-1RA) in the SUSTAIN-6 trial warrants caution, particularly in individuals with baseline retinopathy. Similarly, DPP-4is are associated with increased retinopathy risk in both trials and meta-analysis. The association between GLP-1RAs and peripheral neuropathy is unclear due to little trial evidence. For DPP-4is, one trial and several observational studies show a reduced risk of peripheral neuropathy, with others reporting no effect. Evidence in other less-established microvascular outcomes, such as microvascular angina, cerebral small vessel disease, skeletal muscle microvascular disease and autonomic neuropathies (e.g. cardiac autonomic neuropathy, gastroparesis, erectile dysfunction), is sparse. In conclusion, GLP-1RAs are protective against nephropathy, whereas DPP-4is are protective against albuminuria and potentially peripheral neuropathy. Caution is advised with DPP-4is and semaglutide, particularly for patients with background retinopathy, due to increased risk of retinopathy. Well-designed trials powered for microvascular outcomes are needed to clarify associations of incretin therapies and microvascular diseases.