Risk Of Cardiovascular Disease In Older Adults Research Articles

Sex-Related Differences in Vascular Function Among Older Adults with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a sleep disorder associated with hypertension and cardiovascular disease (CVD) risk. Endothelial dysfunction and altered shear stress are implicated in OSA-related CVD pathogenesis, however, their contributions to CVD risk in males vs females remains unclear. We obtained measures of resting blood pressure (BP), brachial artery flow-mediated dilation (FMD), brachial artery diameter, and shear stress in 71 older adults (F=30, M=41; age=66.9±7.7) diagnosed with mild, moderate, or severe OSA based on oxygen desaturation index (ODI) score. All were prospective participants in an ongoing clinical trial (NCT04932447). Group differences (mean ± SD) were assessed with two-way ANOVAs (sex X severity) and associations between ODI score, baseline diameter, relative FMD, shear stress, and BP were assessed with Pearson correlations. We hypothesized that a) regardless of sex, individuals with greater OSA severity exhibit lower relative FMD and mean shear stress, greater baseline diameter and higher BP, and b) for a given OSA severity, females have greater relative FMD and mean shear stress and lower baseline diameter and BP compared to males. In line with our hypotheses, we found greater mean shear stress in females compared to males (F=69.6±26.9 s−1, M=53.5±16.7 s−1, p=0.035) and among females, those with mild OSA had higher mean shear stress than those with severe OSA (mild=77.6±26.1 s−1, severe= 44.4±8.5 s−1, p=0.009). Contrary to expectations, mean shear stress did not differ as a function of OSA severity in male subjects, nor was there any difference in FMD or BP across OSA severity between males and females. In subjects with moderate OSA, FMD was greater in females than males (F=6.07±3.89%, M=3.07±2.39%, p=0.047). On average, baseline diameters were larger in adults with severe OSA compared to moderate OSA (moderate=3.66±0.59 mm, severe=4.33±0.61 mm, p=0.003), and females with mild (F=3.20±0.47 mm, M=4.73±0.50 mm, p<0.001) and moderate (F=3.31±0.42 mm, M=3.91±0.57 mm, p=0.007) OSA had smaller baseline diameters than their male counterparts. There were no differences in baseline diameter between males and females with severe OSA. We report a negative correlation between mean shear stress and BP (systolic BP, r=-0.48, p=0.011; diastolic BP, r=-0.55, p=0.002) and a positive correlation between ODI score and baseline diameter (r=0.54, p=0.003) in females but not males. Conversely, ODI score and relative FMD were positively correlated in male subjects (r=0.45, p=0.009), but not females. Overall, our findings highlight sex-specific vascular differences in older adults with OSA. Relative to males, females with mild OSA exhibit greater mean shear stress and lower baseline diameters, which may confer a cardiovascular advantage. In contrast, males and females with severe OSA exhibit similar vascular characteristics. Our findings provide new insights into the impact of sex and OSA severity on vascular function and CVD risk in older adults. This work is supported by NIH/NIA grant number: 1R01AG065346. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort

IntroductionThe impact of residential green spaces on cardiovascular health in older adults remains uncertain. MethodsCohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF‐15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). ResultsAfter adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of −5.56 % (95 %CI: −9.77; −1.35), −5.05 % (-9.58; −0.53), −4.24 % (-8.19, −0.19), and −4.16 % (-7.59; −0.74), respectively; and mean differences in hs-TnT among diabetic participants of −8.03 % (95 %CI: −13.30; −2.77), −9.52 % (-16.08; −2.96), −8.05 % (-13.94, −2.16) and −5.56 % (-10.75; −0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. ConclusionIncreased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Assessing the effect of regular swimming exercise on the micro- and macrovascular physiology of older adults (ACELA II study).

Introduction: Cardiovascular disease (CVD) remains the main cause of death in the Western world. Our recent findings demonstrate potential CVD risk reduction in older adults who undertake regular swimming exercise. Nevertheless, it remains unknown whether an exercise intervention based on swimming is feasible and effective prior to a wider implementation of a CVD risk prevention strategy. Methods: This was a pragmatic, two-group, randomised controlled trial. A total of 40 older adults were randomly split into two groups (n = 20 per group). The swimming exercise group consisted of participants who engaged in swimming exercise (2-3days/week, for 8weeks). The control group did not perform any exercise. Flow-mediated dilation (%FMD) was the primary outcome. Secondary outcomes included raw cutaneous vascular conductance. Feasibility outcomes (e.g., recruitment, adherence, and attrition rates) were also assessed. Results: Statistically significant macrovascular (%FMD; swimming group: 9.8% ± 4.2%, p <0.001; control group: 4.6% ± 2.5%) and microvascular function (raw cutaneous vascular conductance; swimming group: 4.1 ± 0.9, p <0.01; control group: 3.2 ± 1.1) improvements were observed in the swimming group compared to the control group. Compliance to twice and thrice weekly in an 8-week swimming exercise was 92.6% and 88.4%, respectively, with no dropouts. Conclusion: Our 8-week, community-based, pragmatic swimming exercise intervention is a feasible and effective exercise programme that could be implemented in older adults for the prevention of age-related CVD. These findings suggest that swimming exercise could significantly reduce CVD risk in older adults, and a large research clinical trial is warranted to establish these findings.

Biological sex influences aortic hemodynamic responses to maximal exercise in healthy older adults

Aging is associated with stiffening of large elastic arteries resulting in early wave reflection, which increases aortic systolic blood pressure (BP) and left ventricular afterload. These age-related alterations predispose older adults to cardiovascular disease (CVD). Exercise is recommended for reducing CVD risk in older adults, but the acute aortic hemodynamic responses to exercise have not been fully described. We have previously shown that exercise intensity influences acute aortic hemodynamic responses to submaximal exercise in older adults, however, the responses to maximal exercise have not been investigated. In young adults, the influence of maximal exercise on aortic wave characteristics is impacted by sex. Therefore, the objective of this study was to investigate the acute effects of maximal exercise on aortic wave characteristics in healthy older adults and to test the hypothesis that the acute aortic hemodynamic responses to maximal exercise will be influenced by sex. Twenty-two older men and postmenopausal women (66.4±1.0 yrs, mean±SE, 11M/11W) completed the study. Research participants were free of major clinical disease, were not using hormone replacement therapy or participating in endurance exercise training. Aortic wave characteristics were assessed using wave separation analysis (SphygmoCor XCEL) before and immediately after maximal exercise, based on a modified Balke treadmill test. We found that wave reflection, assessed as augmentation index (AIx) at heart rate of 75 bpm (AIx@75), was not different between older men and women prior to maximal exercise ( P=0.2). Following maximal exercise, AIx@75 increased in older men (21.1±2.6 vs. 28.2±2.4 %, pre- vs. post-exercise, P=0.02) and women (27.4±3.3 vs. 33.9±3.2 %, P=0.03), but the response was not influenced by sex ( P=0.9 for sex × time interaction). Aortic systolic and diastolic BP (AoSBP and AoDBP) were not different in older men compared with women prior to maximal exercise ( P≥0.4). In response to maximal exercise, AoSBP and AoDBP significantly increased in older men (AoSBP: 113±3 vs. 118±2 mmHg, P=0.01 and AoDBP: 75±2 vs. 80±2 mmHg, P&lt;0.01), but not in women (AoSBP: 113±4 vs. 113±4 mmHg, P=0.9; P=0.04 for sex × time interaction and AoDBP: 73±2 vs. 74±2 mmHg, P=0.054; P=0.02 for sex × time interaction). In conclusion, sex influences the aortic BP response to maximal exercise, but not the wave reflection response in older adults. This finding suggests that left ventricular afterload remains elevated during recovery from maximal exercise in older men which may differentially expose them to a transient risk of experiencing a cardiac complication. This work was supported by National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiovascular disease risk and all-cause mortality associated with accelerometer-measured physical activity and sedentary time ‒ a prospective population-based study in older adults

BackgroundLow levels of physical activity (PA) and high sedentary time (ST) are common in older adults and lack of PA is a risk factor for cardiovascular disease (CVD). Knowledge about associations with accelerometer-measured PA, ST and CVD risk in older adults is insufficient. This study examines the associations of accelerometer-measured PA and ST with cardiovascular risk measured using the Framingham risk score (FRS) and all-cause mortality in older adults.MethodsA population-based sample of 660 (277 men, 383 women) older people (mean age 68.9) participated in the Oulu45 cohort study from 2013‒2015. PA and ST were measured with wrist-worn accelerometers at baseline for two weeks. Ten-year CVD risk (%) was estimated with FRS. The data for all-cause mortality were identified from the Digital and Population Data Services Agency, Finland after an average of 6.2 years follow-up. The associations between moderate to vigorous physical activity (MVPA), light physical activity (LPA), ST and FRS were analyzed using the multivariable linear regression analysis. Associations between LPA, ST and mortality were analyzed using the Cox proportional-hazard regression models.ResultsEach 10 min increase in MVPA (β = -0.779, 95% CI -1.186 to -0.371, p < 0.001) and LPA (β = -0.293, 95% CI -0.448 to -0.138, p < 0.001) was negatively associated with FRS while a 10 min increase in ST (β = 0.290, 95% CI 0.158 to 0.421, p < 0.001) was positively associated with FRS. After adjustment for waist circumference, only ST was significantly associated with FRS. Each 10 min increase in LPA was associated with 6.5% lower all-cause mortality risk (HR = 0.935, 95% CI 0.884 to 0.990, p = 0.020) and each 10 min increase in ST with 5.6% increased mortality risk (HR = 1.056, 95% CI 1.007 to 1.108, p = 0.025).ConclusionA higher amount of daily physical activity, at any intensity level, and avoidance of sedentary time are associated with reduced cardiovascular disease risk in older people. Higher time spent in light physical activity and lower sedentary time are associated with lower all-cause mortality.

Physical Function and Subsequent Risk of Cardiovascular Events in Older Adults: The Atherosclerosis Risk in Communities Study.

BackgroundReduced physical function, a representative phenotype of aging, has been associated with cardiovascular disease (CVD). However, few studies have comprehensively investigated its association with composite and individual CVD outcomes in community‐dwelling older adults and its predictive value for CVD beyond traditional risk factors.Methods and ResultsWe studied 5570 participants (mean age 75 [SD 5] years, female 58%, Black 22%) at visit 5 (2011–2013) of the ARIC (Atherosclerosis Risk in Communities) study. Physical function was evaluated with the Short Physical Performance Battery (SPPB), which incorporates a walk test, chair stands, and balance tests. The SPPB score was modeled categorically (low [0–6], intermediate [7–9], and high [10–12]) and continuously. We assessed the associations of SPPB score with subsequent composite (coronary heart disease, stroke, or heart failure) and individual CVD outcomes (components within composite outcome) using multivariable Cox models adjusting for major CVD risk factors and history of CVD. We also evaluated improvement in C‐statistics by adding SPPB to traditional CVD risk factors in the Pooled Cohort Equation. Among the study participants, 13% had low, 30% intermediate, and 57% high SPPB scores. During a median follow‐up of 7.0 (interquartile interval 5.3–7.8) years, there were 930 composite CVD events (386 coronary heart disease, 251 stroke, and 529 heart failure cases). The hazard ratios of composite CVD in low and intermediate versus high SPPB score were 1.47 (95% CI, 1.20–1.79) and 1.25 (95% CI, 1.07–1.46), respectively, after adjusting for potential confounders. Continuous SPPB score demonstrated independent associations with each CVD outcome. The associations were largely consistent across subgroups (including participants with prevalent CVD at baseline). The addition of SPPB to traditional CVD risk factors significantly improved the C‐statistics of CVD outcomes (eg, ΔC‐statistic 0.019 [95% CI, 0.011–0.027] for composite CVD).ConclusionsReduced physical function was independently associated with the risk of composite and individual CVD outcomes and improved their risk prediction beyond traditional risk factors in community‐dwelling older adults. Although confirmatory studies are needed, our results suggest the potential usefulness of SPPB for classifying CVD risk in older adults.

Antihypertensive treatment effect on exercise blood pressure and exercise capacity in older adults.

An exaggerated blood pressure (BP) response to exercise and low exercise capacity are risk factors for cardiovascular disease (CVD). The effect of pharmacological antihypertensive treatment on exercise BP in older adults is largely unknown. This study investigates these effects accounting for differences in exercise capacity. Participants enrolled in the Southall and Brent Revisited (SABRE) study undertook a 6-min stepper test with expired gas analysis and BP measured throughout exercise. Participants were stratified by antihypertensive treatment status and resting BP control. Exercise systolic and diastolic BP (exSBP and exDBP) were compared between groups using potential outcome means [95% confidence intervals (CIs)] adjusted for exercise capacity. Exercise capacity was also compared by group. In total, 659 participants were included (mean age ± SD: 73 ± 6.6 years, 57% male). 31% of normotensive and 23% of hypertensive older adults with controlled resting BP had an exaggerated exercise BP. ExSBP was similar between normotensive and treated/controlled individuals [mean (95%CI): 180 (176 184) mmHg vs. 177 (173 181) mmHg, respectively] but was higher in treated/uncontrolled and untreated/uncontrolled individuals [mean (95% CI): 194 (190 197) mmHg, P < 0.001 and 199 (194 204) mmHg, P < 0.001, respectively]; these differences persisted after adjustment for exercise capacity and other confounders. Exercise capacity was lower in treated vs. normotensive individuals [mean (95% CI) normotensive: 16.7 (16.0,17.4) ml/kg/min]; treated/controlled: 15.5 (14.8,16.1) ml/kg/min, P = 0.009; treated/uncontrolled: [15.1 (14.5,15.7) ml/kg per min, P = 0.001] but was not reduced in untreated/uncontrolled individuals [mean (95% CI): 17.0 (16.1,17.8) ml/kg per min, P = 0.621]. Irrespective of resting BP control and despite performing less exercise, antihypertensive treatment does not fully mitigate an exaggerated BP response to exercise suggesting residual CVD risk in older adults.

Inflammatory phenotype and T‐cell mitochondrial reactive oxygen species in young adults with major depressive disorder

BackgroundMajor depressive disorder (MDD) is prevalent in young adults and projected to rise further with the COVID pandemic. Notably, MDD is associated with an increased risk of cardiovascular disease (CVD) and mortality. Although the mechanisms are unclear, evidence supports chronic systemic inflammation as a major contributor to CVD risk in older adults with MDD. However, whether an inflammatory phenotype is present in young adults with MDD prior to the onset of CVD and other comorbidities is equivocal. Recent work has implicated the sympathetic nervous system and specifically norepinephrine as a potent driver of inflammation via stimulating an increase in T‐cell mitochondrial reactive oxygen species (T‐cell mitoROS). Given previous findings of elevated plasma norepinephrine and inflammation in MDD, the purpose of this study was to examine the potential for a T‐cell mitoROS pro‐inflammatory pathway in young otherwise healthy adults with MDD. We hypothesized that young adults with MDD but otherwise free of clinical disease would have augmented circulating pro‐inflammatory cytokines and T‐cell mitoROS compared to young healthy adults without MDD (HA).MethodsAll participants underwent a structured diagnostic neuropsychiatric interview to determine the presence or absence of MDD based on the DSM‐5 diagnostic criteria for MDD. Systemic pro and anti‐inflammatory cytokines and T‐cell mitoROS were measured in 14 healthy young adults with MDD of mild‐to‐moderate severity (non‐medicated; age: 23±2 years) and 11 HA (age: 22±1 years). Serum cytokines were detected using LEGENDplex Human Essential Immune Response panel and assessed by flow cytometry. Seven serum cytokines related to the norepinephrine‐T‐cell mitoROS‐inflammation pathway were measured. Immune cells were isolated from whole blood by red blood cell lysis. T‐cell mitoROS was measured by labeling with antibodies against CD3+ (total T cells) and mitoROS targeted fluorogenic dye (MitoSoxRED) and assessed by flow cytometry. All data are expressed as mean ± SE.ResultsFor pro‐inflammatory cytokines, there were no differences between MDD and HA for IL‐6 (41±18 pg/mL; 92± 66 pg/mL, P=0.66), IL‐17A (7±3 pg/mL; 17±8 pg/mL, P=0.13), TNF‐α (19±9 pg/mL; 36±18 pg/mL, P=0.20), IFNγ (120±70 pg/mL; 201±137 pg/mL, P=0.34) or IL‐2 (5±2 pg/mL; 13±6 pg/mL, P=0.25), respectively. Likewise, no differences were found in anti‐inflammatory cytokines between MDD and HA for IL‐10 (18±9 pg/mL; 78±57 pg/mL, P=0.19) or IL‐4 (33±15 pg/mL; 95±46 pg/mL, P=0.13), respectively. In contrast, T‐cell mitoROS was significantly elevated in MDD (34402±13353 a.u) compared to HA (6258±2942 a.u, P&lt;0.05).ConclusionThese preliminary findings suggest T‐cell mitoROS but not circulating cytokine profiles are different between young adults with and without MDD. Thus, an elevated T‐cell mitoROS may represent an early marker of immune system alterations and inflammation in MDD.

Longer-term soy nut consumption improves vascular function and cardiometabolic risk markers in older adults: Results of a randomized, controlled cross-over trial

Soy foods may contribute to the beneficial health effects of healthy plant-based diets on the risk to develop cardiovascular disease (CVD). However, their effects on vascular function have hardly been studied. To investigate longer-term effects of soy nut consumption on vascular function and cardiometabolic risk markers in healthy older men and women. Twenty-three healthy participants (age: 60-70 years; BMI: 20-30kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67g/day of soy nuts providing 25.5g protein and 174mg isoflavones) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Adults followed the Dutch food-based dietary guidelines. No serious adverse events were reported and the soy nut regime was well tolerated. Body weights remained stable during the whole study. A higher protein (3.1 energy percent [En%]) and a lower carbohydrate intake (2.0 En%) was observed during the intervention period. Total fat intake was comparable, but that of saturated (-1.3 En%), cis-monounsaturated (-1.5 En%) and cis-polyunsaturated fatty acids (+1.9 En%) differed. Serum isoflavone concentrations were higher after the intervention as compared with the control period (daidzein: 127.8ng/mL; 95% CI: 74.3-181.3ng/mL; p<0.001 and genistein: 454.2ng/mL; 95% CI: 266.6-641.8ng/mL; p<0.001). Brachial artery flow-mediated vasodilation was 1.48 percent points (pp; 95% CI: 0.08-2.89 pp; p=0.040) higher following soy nut intake. The carotid artery reactivity response and arterial stiffness did not differ. Serum LDL-cholesterol was lower (0.17mmol/L; 95% CI: 0.02-0.32mmol/L; p=0.027), while HDL-cholesterol and triacylglycerol concentrations were comparable. Mean arterial pressure (MAP) was lower (3mmHg; 95% CI: 0-6mmHg; p=0.035). Longer-term soy nut intake as part of a healthy diet improved endothelial function, LDL-cholesterol concentrations and MAP levels, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Registered under ClinicalTrials.gov Identifier no. NCT03627637.

The aortic-femoral arterial stiffness gradient is blood pressure independent in older adults: the atherosclerosis risk in communities (ARIC) study.

Aortic arterial stiffness is a strong independent predictor of cardiovascular disease (CVD); however, its dependence on mean arterial pressure (MAP) limits its clinical utility. The aortic-femoral arterial stiffness gradient (af-SG), a novel marker of CVD risk, may be a promising alternative, but its dependence on MAP is not known. The aim of this study was to determine the relationship between MAP and the af-SG in healthy older adults and those with established disease, including hypertension and diabetes. We evaluated the dependency of the af-SG on MAP in healthy older adults (n = 694, aged 74 ± 5 years), and adults with hypertension (n = 2040, aged 76 ± 5 years), and diabetes (n = 1405, aged 75 ± 5 years) as part of the community-based Atherosclerosis Risk in Communities (ARIC) Study. Carotid-femoral pulse-wave velocity (cfPWV), femoral-ankle PWV (faPWV) and blood pressure were measured using standardized protocols. The af-SG was calculated as faPWV divided by cfPWV. Multivariable regression analysis was performed to test the independent association of MAP with af-SG, with adjustments for known confounders, including age, sex, BMI, blood glucose and heart rate. There was no significant relationship between the af-SG and MAP in healthy (β = 0.002, P = 0.301), hypertension (β = -0.001, P = 0.298) or diabetes (β = -0.001, P = 0.063) population groups, with MAP explaining less than 0.1, less than 0.1 and 0.2% of the variance in the af-SG, respectively. These findings suggest that the af-SG may be regarded as a MAP independent index of arterial health and CVD risk in older adults.

SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions.

The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions. Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk. The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.

Longer-Term Soy Nut Consumption Improves Vascular Function and Cardiometabolic Risk Markers in Older Adults: Results of a Randomized, Controlled Cross-Over Trial

Abstract Objectives Soy foods may contribute to the beneficial effects of plant-based diets on cardiovascular disease (CVD) risk. However, their effects on vascular function have hardly been investigated. The objective was to investigate if longer-term soy nut consumption improves vascular function and cardiometabolic health in older adults. Methods Twenty-three apparently healthy participants (60–70 years; BMI between 20–30 kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67 g of soy nuts daily providing 25.5 g soy protein) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Volunteers followed the Dutch food-based dietary guidelines. At baseline and at 8 and 16 weeks anthropometric measurements and fasting blood samples were collected. Markers of vascular function (i.e., endothelial function, arterial stiffness, and microvascular structure) were assessed at week 16. Results No serious adverse events were reported and the soy nut regime was well tolerated. Body weight remained stable. Serum isoflavone concentrations, a marker of compliance, increased after the intervention period (daidzein: 128.3 ng/mL; 95% CI: 72.6–183.9 ng/mL; P &amp;lt; 0.001 and genistein: 439.8 ng/mL 95% CI: 246.7–632.9 ng/mL; P &amp;lt; 0.001). The brachial artery flow-mediated vasodilation (FMD) response increased by 1.49 pp (95% CI: 0.03–2.95 pp; P = 0.046) following the soy intervention, but no effect was found on the carotid artery reactivity (CAR) response. Arterial stiffness, assessed by carotid-to-femoral pulse wave velocity (PWVc-f), was unchanged. Retinal arteriolar calibers (CRAE), a measure for microvascular structure, tended to improve by 1.42 mm (95% CI: −0.05–2.90 mm; P = 0.059). Soy consumption also lowered serum LDL-cholesterol concentrations by 0.17 mmol/L (95% CI: 0.02–0.32 mmol/L; P = 0.027). HDL-cholesterol and triacylglycerol (TAG) did not change. Finally, office SBP and DBP decreased by 4 mmHg (95% CI: 0–8 mmHg; P = 0.034) and 2 mmHg (95% CI: 1–4 mmHg; P = 0.005), respectively. Conclusions A longer-term daily intake of soy nuts improved endothelial function, office blood pressure, and serum LDL-cholesterol concentrations, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Funding Sources This study was supported by a grant from the Alpro Foundation.

Abstract 073: Physical Function And Subsequent Risk Of Cardiovascular Events In Older Adults: The Atherosclerosis Risk In Communities (ARIC) Study

Background: Reduced physical function, an exemplary phenotype of aging, has been associated with cardiovascular disease (CVD). However, few studies have comprehensively investigated the association of physical function with risk of incident and recurrent CVD in community-dwelling older adults. Methods: Physical function, evaluated with the Short Performance Physical Battery (SPPB), was assessed in the ARIC study at visit 5 (2011-2013) among 5548 participants (mean age 75±5 years, female 58%, black 22%). The SPPB score was categorized into low (0-6), intermediate (7-9), and high (10-12) physical function. We assessed the associations of SPPB categories with composite and individual outcomes of coronary heart disease (CHD), stroke, or heart failure (HF) using Cox proportional hazards models adjusting for potential confounders. We also evaluated improvement in c-statistics by adding SPPB to covariates. Results: During a median follow-up of 6.2 years, there were 821 composite events (329 CHD, 226 stroke, and 467 HF cases). Compared to high SPPB score, low and intermediate SPPB score were robustly associated with higher risk of the composite CVD outcome (hazard ratio [HR] 1.59 [95% CI 1.29-1.95] and 1.32 [1.12-1.56], respectively) (Table). These associations were largely consistent between participants with and without a history of CVD at baseline. Among individual outcomes, low SPPB score showed the highest HR for stroke, whereas intermediate SPPB score was only significantly associated with HF. The addition of SPPB significantly improved c-statistic for composite outcome (Δc-statistic 0.006 [95% CI 0.002-0.009]), and the improvement was especially evident in participants without history of CVD (Δc-statistic 0.013 [0.003-0.023]). Conclusions: Lower physical function was robustly associated with the risk of CVD and improved its prediction beyond established predictors in older adults. Clinicians should pay attention to physical function when managing CVD risk in older adults.

Lipopolysaccharide binding protein is associated with CVD risk in older adults.

Intestinal (i.e., "gut") permeability may be related to cardiovascular disease (CVD) risk, but biomarkers for gut permeability are limited and associations with CVD risk are unknown-particularly among older adults. This cross-sectional study aimed to determine if serum biomarkers related to gut permeability [intestinal fatty acid-binding protein (iFABP)] and bacterial toxin clearing [cluster of differentiation 14 (CD14), lipopolysaccharide binding protein (LBP)] are associated with CVD risk among older adults. Older adults (n = 74, 69.6 ± 6.5-years-old) were stratified by CVD risk category. One-way ANOVAs determined differences in each biomarker by risk category, and associations with risk score were evaluated with Pearson correlations. LBP (p = 0.007), but not iFABP and CD14, was significantly different between CVD risk categories. Post-hoc tests indicated LBP was higher in moderate risk and high-moderate risk compared to the high risk category (p < 0.005). Evaluation of LBP and individual components in the risk score demonstrated a moderate, negative correlation of LBP with age and systolic blood pressure (r = -0.335 and r = -0.297) and a small positive correlation between LBP and total cholesterol and LDL cholesterol (r = 0.204 and r = 0.220). Lower risk for CVD was associated with higher circulating concentrations of LBP, lower iFABP, and lower systemic inflammation in older adults. Further, there were small positive relationships between total and LDL cholesterol and circulating levels of LBP. These data suggest LBP may be a key component in reducing CVD risk in older adults.

Acute Systemic Rho‐kinase Inhibition Reduces Blood Pressure and Influences Peripheral Vascular Tone in Healthy Older Adults

Aging is the primary risk factor for cardiovascular disease (CVD), and Rho‐kinase has emerged as an important contributor to the pathogenesis of CVD in preclinical and clinical studies. Therefore, we tested the hypothesis that acute, systemic Rho‐kinase inhibition would improve measures of CVD risk in older adults. We studied healthy young (YA; 25 ± 1 yrs; 6M/6F) and older adults (OA; 65 ± 1 yrs; 6M/7F) under control conditions (CON, intravenous saline) and during inhibition of Rho‐kinase via intravenous fasudil administration (60 mg) in a double‐blind, randomized, crossover design. In separate visits to the laboratory, saline and fasudil were infused over the course of 1 h, after which we measured blood pressure, carotid‐femoral pulse wave velocity (cfPWV; index of arterial stiffness), and central augmentation index (AIx; SphygmoCor XCEL). In a subset of participants (YA: 5M/5F; OA: 6M/3F), we assessed reactive hyperemia (RH) and flow‐mediated dilation (FMD) to evaluate microvascular function and conduit artery endothelial function, respectively. We measured brachial artery diameter and mean blood velocity (MBV; Doppler ultrasound) to calculate forearm vascular conductance (FVC; forearm blood flow/mean arterial pressure · 100). FMD was quantified as the percent change in brachial artery diameter following 5 min of forearm ischemia. Shear rate (8 · MBV/diameter) was expressed as area under the curve (SRAUC) from cuff release to peak diameter to quantify the stimulus for FMD. In OA, fasudil reduced systolic (SBP, 127 ± 4 vs. CON: 134 ± 4 mmHg, P &lt; 0.05), diastolic (DBP, 76 ± 2 vs. CON: 79 ± 1 mmHg, P &lt; 0.05), and mean arterial pressure (MAP, 93 ± 2 vs. CON: 97 ± 2 mmHg, P &lt; 0.05), and BP remained lower 1 and 2 h postinfusion. Although fasudil initially reduced SBP (114 ± 2 vs. CON: 119 ± 2 mmHg, P &lt; 0.05), DBP (68 ± 2 vs. CON: 72 ± 2 mmHg, P &lt; 0.05), and MAP (84 ± 2 vs. CON: 88 ± 2 mmHg, P &lt; 0.05) in YA, BP returned to control levels and was not different from CON at 1 or 2 h post‐infusion. Fasudil lowered cfPWV in OA (7.6 ± 0.4 vs. CON: 7.8 ± 0.4 m/s, P &lt; 0.05) and tended to lower cfPWV in YA (5.2 ± 0.2 vs. CON: 5.4 ± 0.2 m/s, P = 0.07). However, AIx was unchanged by the fasudil treatment in both OA (27 ± 2 vs. CON: 31 ± 2%, P = NS) and YA (−2 ± 2 vs. CON: −5 ± 5%, P = NS). Baseline brachial diameter increased with fasudil in OA (3.29 ± 0.23 vs. CON: 3.16 ± 0.20 mm, P &lt; 0.05), whereas fasudil had no effect on baseline diameter in YA (3.19 ± 0.19 vs. CON: 3.16 ± 0.17 mm, P = NS). Similarly, resting FVC was elevated under fasudil conditions in OA (36 ± 4 vs. CON: 25 ± 3 ml/min/100 mmHg, P &lt; 0.05), while FVC was unchanged with fasudil in YA (36 ± 9 vs. CON: 32 ± 5 ml/min/100 mmHg, P = NS). Following forearm ischemia, there was no effect of fasudil on peak blood flow (OA, 288 ± 30 vs. CON: 286 ± 31 ml/min, P = NS; YA, 346 ± 65 vs. CON: 346 ± 45 ml/min, P = NS) or on FMD (OA, 6.2 ± 1.1 vs. CON: 7.0 ± 1.1%, P = NS; YA, 6.5 ± 1.1 vs. CON: 7.9 ± 1.4%, P = NS). Fasudil did not affect SRAUC (OA, 29 ± 5 vs. CON: 29 ± 4 s−1 · 103, P = NS; YA, 32 ± 5 vs. CON: 36 ± 5 s−1 · 103) in either group. Collectively, these data suggest Rho‐kinase contributes to the age‐related elevation in blood pressure potentially via greater peripheral vasoconstrictor tone in healthy older adults.Support or Funding InformationHL119337

LIPOPOLYSACCHARIDE BINDING PROTEIN IS ASSOCIATED WITH LOWER CVD RISK IN OLDER ADULTS

Intestinal (i.e. “gut”) permeability may be related to cardiovascular disease (CVD) risk, but biomarkers for gut permeability are limited and associations with CVD risk are unknown – particularly among older adults. This cross-sectional study aimed to determine if serum biomarkers related to gut permeability [intestinal fatty acid-binding protein (iFABP)] and bacterial toxin clearing [cluster of differentiation 14 (CD14), lipopolysaccharide binding protein (LBP)] are associated with CVD risk among older adults. Older adults (n = 38, 72.0 ± 7.1 years old) were stratified by CVD risk category (Adult Treatment Panel: moderate, high-moderate, high). One-way ANOVAs determined differences in each biomarker by risk category, and associations with risk score were evaluated via linear regression and/or Pearson correlations. LBP (p < 0.001), but not iFABP and CD14 (p’s > 0.05), was significantly different between CVD risk categories. Post-hoc tests indicated LBP was higher in the moderate risk compared to both higher risk categories (p < 0.005). LBP was a significant predictor of 10-year CVD risk (β = -0.629; p = 0.001) and evaluation of individual components in the risk score demonstrated a moderate, positive correlation of LBP with total cholesterol (r = 0.326, p = 0.046). Higher circulating concentrations of LBP were associated with lower CVD risk among older adults. Further, total cholesterol was positively associated with circulating levels of LBP. Importantly, cholesterol assists LBP in clearing bacterial toxins from circulation by transporting toxins for removal. These data suggest LBP may be a key component in reducing CVD risk in older adults.

Wearable Technology To Reduce Sedentary Behavior And CVD Risk In Older Adults: A Pilot Randomized Clinical Trial.

BackgroundPhysical exercise is associated with decreased cardiovascular disease (CVD) risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk older adults.PurposeThis pilot randomized clinical trial aimed to collect critical data on feasibility, safety, and protocol integrity necessary to design a fully powered randomized controlled trial (RCT) and evaluate the impact of combining structured exercise with an intervention designed to enhance non-exercise physical activity (EX+NEPA) compared to EX alone.MethodsForty participants aged ≥60 years with moderate-to-high risk of coronary heart disease events were randomly assigned to either the EX+NEPA or EX groups and followed for 20 weeks. Both groups underwent a twice-weekly, 8-week center-based exercise intervention with aerobic and resistance exercises. EX+NEPA group also received a wearable activity tracking device along with behavioral monitoring and feedback throughout the study. Study outcomes were evaluated at 8 and 20 weeks.ResultsData are presented as adjusted mean change of the differences over time with 95% confidence intervals at 20 weeks. Relative to EX, the change in steps/day at 20 weeks was 1994 (−40.27, 4028) higher for EX+NEPA. For sedentary time at close-out, the EX+NEPA group was −6.8 (−45.2, 31.6) min/day relative to EX. The between-group differences for systolic and diastolic blood pressure were −9.9 (−19.6, −0.3) and −1.8 (−6.9, 3.3) mmHg, respectively.ConclusionThe addition of wearable technology intervention appeared to positively influence daily activity patterns and changes in blood pressure – potentially improving risk factors for CVD. A fully powered randomized trial is needed to ultimately test this hypothesis.

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC)

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk.Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status.Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms.Results: Neither low plasma phylloquinone (<0.2 nmol/L) nor elevated (dp)ucMGP (≥574 pmol/L) was significantly associated with incident CVD [respective HRs (95% CIs): 1.27 (0.75, 2.13) and 1.02 (0.72, 1.45)]. In participants treated for hypertension (n = 489; 135 events), low plasma phylloquinone was associated with higher CVD risk overall (HR: 2.94; 95% CI: 1.41, 6.13). In those with untreated hypertension (n = 153; 48 events) and without hypertension (n = 418; 92 events), low plasma phylloquinone was not associated with incident CVD. The association between high (dp)ucMGP did not differ by hypertension treatment status (P-interaction = 0.72).Conclusions: Vitamin K status was not significantly associated with CVD risk overall, but low plasma phylloquinone was associated with a higher CVD risk in older adults treated for hypertension. Additional evidence from larger clinical studies is needed to clarify the importance of vitamin K to CVD in persons treated for hypertension, a segment of the population at high risk of clinical CVD events.

Wearable technology to reduce sedentary behavior and CVD risk in older adults: design of a randomized controlled trial.

Persons aged over 65 years account for over the vast majority of healthcare expenditures and deaths attributable to cardiovascular disease (CVD). Accordingly, reducing CVD risk among older adults is an important public health priority. Structured physical activity (i.e. exercise) is a well-documented method of decreasing CVD risk, but recent large-scale trials suggest that exercise alone is insufficient to reduce CVD events in high-risk populations of older adults. Thus adjuvant strategies appear necessary to reduce CVD risk. Accumulating evidence indicates that prolonged sedentary behavior (e.g. sitting) has detrimental health effects that are independent of engagement in recommended levels of moderate-intensity exercise. Yet clinical trials in this area are lacking. We hypothesize that exercise, when combined with a novel technology based intervention specifically designed to reduce sedentary behavior will reduce CVD risk among sedentary older adults. The purpose of this study is to evaluate the feasibility and efficacy of combining a traditional, structured exercise intervention with an innovative intervention designed to decrease sedentary behavior and increase non-exercise physical activity (NEPA). This study will provide us with critical data necessary to design and implement a full-scale trial to test our central hypothesis. Participants aged ≥60 years with moderate to high risk of coronary heart disease (CHD) events are randomly assigned to either the exercise and technology intervention (EX + NEPA) or exercise alone (EX) groups. Study dependent outcomes include changes in 1) daily activity patterns, 2) blood pressure, 3) exercise capacity, 4) waist circumference, and 5) circulating indices of cardiovascular function. This study will provide critical information for designing a fully-powered clinical trial, which could have health implications for the ever increasing population of older adults.

Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study

Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk. We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort. We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis. Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05). PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD.