OBJECTIVE Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes. RESEARCH DESIGN AND METHODS A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal weight nondiabetes as comparator. RESULTS Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96–1.56]; P = 0.1). CONCLUSIONS Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal weight diabetes.

Introduction Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. Methods 451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Results 5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p<0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p<0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Conclusions Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes.

the evaluation of clinical efficacy in clinical studies, however, this requires a hospital-based assessment. Physical activity, measured remotely, has been implemented in clinical studies as an indicator of exercise capacity. The relationships between daily physical activity and established measures of clinical risk are unknown. Methods Participants with PAH enrolled in the National Cohort Study of Idiopathic and Heritable PAH (NAIAD, NCT01907295) were implanted with an insertable cardiac monitor (ICM, LinQ-Medtronic), which provided a remote measure of physical activity from an embedded single axis accelerometer. Baseline indicators of clinical risk including WHO Functional Class (WHO FC)2,3, NTproBNP2,3, 6 Minute Walk Distance (6MWD)2,3, Incremental Shuttle Walk test Distance (ISWD)2, COMPERA 2.03 and EmPHasis-104 were compared with physical activity, heart rate variability (HRV), and night heart rate (NHR). Results Baseline demographics (mean±SD): idiopathic or heritable PAH (n=80); age 53±15 years; female sex 75.9%; BMI 30±7kg/m 2 ; years since diagnosis 8.1±5.3, baseline resting heart rate 75.1±12.2 beats per minute. Patients within the low-risk COMPERA2.0 category were used as a reference group. Table 1 shows statistically significant relationships for NHR, HRV and physical activity compared to clinical risk category (p<0.05). ICM-measured physical activity showed a higher sensitivity in distinguishing lowintermediate, within intermediate, and intermediate-high risk groups across WHO FC, COMPERA 2.0 and NTProBNP. Table 2 demonstrates that physical activity was reduced in those with intermediate and high-risk indicators compared to a low risk reference group (WHO-FC, ISWD. NT-proBNP, EmPHasis-10 and COMPERA 2.0 score). Physical activity was reduced in patients with increased indicators of clinical risk as measured by ISWD and COMPERA 2.0 (figure 2, table 2).Conclusion ICM-measured physical activity data, HRV and NHR correlates with existing risk measures and may be used for remote evaluation of physical risk in patients with PAH.

<p>  </p> <p><em>Objective</em></p> <p>Obesity and diabetes frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events and mortality in UK Biobank stratified by body mass index (BMI) and diabetes.</p> <p><em>Research design and Methods</em></p> <p>451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischemic stroke and cardiovascular death, with normal weight non-diabetes as comparator. </p> <p><em>Results</em></p> <p>5% of participants had diabetes (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-diabetes). In the non-diabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (p<0.005), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke and cardiovascular mortality rose across increasing BMI categories without diabetes (p<0.005); this was comparable in the diabetes groups (p-interaction>0.05). Normal weight diabetes had comparable adjusted cardiovascular mortality to obese non-diabetes (IRR 1.22 [95% confidence interval: 0.96-1.56]; p=0.1).</p> <p><em>Interpretation</em></p> <p>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. </p>

<p>  </p> <p><em>Objective</em></p> <p>Obesity and diabetes frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events and mortality in UK Biobank stratified by body mass index (BMI) and diabetes.</p> <p><em>Research design and Methods</em></p> <p>451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischemic stroke and cardiovascular death, with normal weight non-diabetes as comparator. </p> <p><em>Results</em></p> <p>5% of participants had diabetes (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-diabetes). In the non-diabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (p<0.005), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke and cardiovascular mortality rose across increasing BMI categories without diabetes (p<0.005); this was comparable in the diabetes groups (p-interaction>0.05). Normal weight diabetes had comparable adjusted cardiovascular mortality to obese non-diabetes (IRR 1.22 [95% confidence interval: 0.96-1.56]; p=0.1).</p> <p><em>Interpretation</em></p> <p>Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. </p>