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Aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o 2max ). The relative contributions of the specific V̇o 2 components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A - V)O 2 , remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. V̇o 2peak , a surrogate of V̇o 2max , was used to assess aerobic capacity during upright cycle ergometry. Peak exercise left ventricular volumes, heart rate, and CO were estimated using repeated gated cardiac blood pool scans. The Fick equation was used to calculate (A - V)O 2 diff,peak from CO peak and V̇o 2peak . In unadjusted models, V̇o 2peak , (A - V)O 2 diff,peak , and CO peak declined longitudinally over time at steady rates with advancing age. In multiple linear regression models adjusting for baseline values and peak workload, however, steeper declines in V̇o 2peak and (A - V)O 2 diff,peak were observed with advanced entry age but not in CO peak . The association between the declines in V̇o 2peak and (A - V)O 2 diff,peak was stronger among those ≥50 yr old compared with their younger counterparts, but the difference between the two age groups did not reach statistical significance. These findings suggest that age-associated impairment of peripheral oxygen utilization during maximal exercise poses a stronger limitation on peak V̇o 2 than that of CO. Future studies examining interventions targeting the structure and function of peripheral muscles and their vasculature to mitigate age-associated declines in (A - V)O 2 diff are warranted. NEW & NOTEWORTHY The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age.

Aims: High glucose levels and Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) have both tissue inflammatory effects. Here we determined whether G6PDd accelerates arterial aging (information linked stiffening) in diabetes., Methods: Plasma glucose, interleukin 6 (IL6), and arterial stiffness (indexed as carotid-femoral Pulse Wave Velocity, PWV) and red blood cell G6PD activity were assessed in a large (4448) Sardinian population., Results: Although high plasma glucose in diabetics, did not differ by G6DP status (178.2 ± 55.1 vs 169.0 ± 50.1 mg/dl) in G6DPd versus non-G6PDd subjects, respectively, IL6, and PWV (adjusted for age and glucose) were significantly increased in G6PDd vs non-G6PDd subjects (PWV, 8.0 ± 0.4 vs 7.2 ± 0.2 m/sec) and (IL6, 6.9 ± 5.0 vs 4.2 ± 3.0 pg/ml). In non-diabetics, neither fasting plasma glucose, nor IL6, nor PWV were impacted by G6PDd., Conclusion: G6PDd in diabetics is associated with increased inflammatory markers and accelerated arterial aging., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023.)

Hypertrophic carotid geometric phenotypes (h-CGP) are predictors of incident cardiovascular disease (CVD). While arterial aging is hypothesized as a contributor to this associated risk, the association of CGPs with chronological age is not clear. In this manuscript we examine whether hypertrophic CGPs represent accelerated biological, rather than chronological, aging by examining their association with carotid-femoral pulse wave velocity (PWV), the hallmark of arterial aging. We analyzed data from 5516 participants of the SardiNIA study with a wide range of age at baseline (20-101 years), and a median follow-up time of 13 years (mean 11.5 years; maximum 17.9 years). Baseline CGPs were defined based on the common carotid lumen diameter, wall thickness, and their ratio. Subject-specific rates of change of PWV, blood pressure parameters, body mass index, glucose, and lipids were estimated using linear mixed effects models. Compared to those with typical(t-) CGP, those with dilated hypertrophy (dh-) CGP had a greater longitudinal increase in PWV; this increase was significantly greater among older individuals and men. The greater PWV longitudinal increase in dh-CGP remained significant after adjusting for baseline values and rates of change of covariates. Dilated hypertrophic CGP is independently associated with accelerated increase in age-associated arterial stiffening over time, with a strong association in men than in women. Future studies are needed to examine if this association mediates the increased risk for CVD observed in individuals with hypertrophic cardiac remodelling and the role of retarding it to reduce this risk. HIGHLIGHTS: • Individuals with dilated hypertrophic geometric phenotypes of the common carotid artery (increased age- and sex-specific wall thickness and lumen diameter) have greater future central arterial stiffening, independently of other determinants of arterial stiffening. • The dilated hypertrophic phenotype group has a greater age-specific arterial dilation, wall thickening, and stiffness (the arterial aging triad). This suggests that this phenotype is a form of accelerated aging that might explain the worse clinic outcomes observed in this group. • Understanding the natural history of the carotid geometric phenotype across the lifespan and the determinants of the deleterious progression towards the dilated hypertrophic phenotype are needed to develop interventions that reduce the adverse clinical outcomes associated with it., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Peace-through-health has emerged as a promising concept but with variable evidence of success. Cooptation of health initiatives in conflict is believed to be a major challenge undermining peacebuilding potential. We examine the role that existing power structures and health initiative characteristics play at various levels of a conflict in peacebuilding outcomes. Using the Syrian conflict as a case study, we assess healthcare initiatives' characteristics and their peacebuilding tendencies accounting for power dynamics at the (1) state citizen, (2) interbelligerents and (3) intercommunity conflict levels, drawing on the WHO's framework for health and peace initiatives. Healthcare interventions at state citizen and interbelligerent levels generally addressed combat-related and material-dependent health needs, relied on large-scale international funding and centralised governance structures, and bestowed credit to specific agencies with political implications. These characteristics made such initiatives prone to cooptation in conflict with limited peacebuilding capacity. Healthcare initiatives at the community level addressed more basic, service-dependent needs, had smaller budgets, relied on local organisations and distributed credit across stakeholders, making them less amenable to cooptation in the conflict with more propeace potential. A pilot peacebuilding health initiative designed to leverage these propeace attributes navigated the political environment, minimised cooptation and fostered community collaboration, resulting in peacebuilding potential. In summary, peacebuilding health initiatives are more likely to materialise at the community as compared with higher political levels. Further studies, accounting for conflict power structures, are needed to examine the effectiveness of such initiatives and identify methods that maximise their peacebuilding outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To define metrics of phenotypic aging, it is essential to identify biological and environmental factors that influence the pace of aging. Previous attempts to develop aging metrics were hampered by cross-sectional designs and/or focused on younger populations. In the Baltimore Longitudinal Study of Aging (BLSA), we collected longitudinally across the adult age range a comprehensive list of phenotypes within four domains (body composition, energetics, homeostatic mechanisms and neurodegeneration/neuroplasticity) and functional outcomes. We integrated individual deviations from population trajectories into a global longitudinal phenotypic metric of aging and demonstrate that accelerated longitudinal phenotypic aging is associated with faster physical and cognitive decline, faster accumulation of multimorbidity and shorter survival. These associations are more robust compared with the use of phenotypic and epigenetic measurements at a single time point. Estimation of these metrics required repeated measures of multiple phenotypes over time but may uniquely facilitate the identification of mechanisms driving phenotypic aging and subsequent age-related functional decline., Competing Interests: Competing interests M.E.L. holds licenses for epigenetic clocks that she has developed. All other authors declare no conflict of interest.

Background Lower ankle-brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross-sectional analyses. Whether ABI decline is associated with greater declines in thigh muscle oxidative capacity with aging is unknown. Method and Results We analyzed data from 228 participants (100 men) of the BLSA (Baltimore Longitudinal Study of Aging), aged 39 to 97 years, with an ABI between 0.9 and 1.40 at baseline and at follow-up (mean follow-up period of 2.8 years). We examined mitochondrial oxidative capacity of the left thigh muscle, by measuring the postexercise phosphocreatine recovery rate constant ( k PCr) from phosphorus-31 magnetic resonance spectroscopy. Greater k PCr indicated higher mitochondrial oxidative capacity. Although k PCr was available on the left leg only, ABI was measured in both legs. Longitudinal rates of change ( Change ) of left and right ABI and k PCr of the left thigh muscle were estimated using linear mixed effects models, and their association was analyzed by standardized multiple linear regressions. In multivariate analysis including sex, age, baseline k PCr, both left and right baseline ABI, and ABI change in both legs, ( k PCr) Change was directly associated with ipsilateral (left) (ABI) Change (standardized [STD]-β=0.14; P =0.0168) but not with contralateral (right) (ABI) Change ( P =0.22). Adjusting for traditional cardiovascular risk factors, this association remained significant (STD-β=0.18; P =0.0051). ( k PCr) Change was steeper in White race participants (STD-β=0.16; P =0.0122) and body mass index (STD-β=0.13; P =0.0479). There was no significant association with current smoking status ( P =0.63), fasting glucose ( P =0.28), heart rate ( P =0.67), mean blood pressure ( P =0.78), and low-density lipoprotein ( P =0.75), high-density lipoprotein ( P =0.82), or triglycerides ( P =0.15). Conclusions In people without peripheral arterial disease, greater decline in ABI over time, but not baseline ABI, was associated with faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics.

Background: To mitigate the effect of the COVID-19 pandemic, health care systems worldwide have implemented telemedicine technologies to respond to the growing need for health care services during these unprecedented times. In the United Arab Emirates, video and audio consultations have been implemented to deliver health services during the pandemic., Objective: This study aimed to evaluate whether differences exist in physicians' attitudes and perceptions of video and audio consultations when delivering telemedicine services during the COVID-19 pandemic., Methods: This survey was conducted on a cohort of 880 physicians from outpatient facilities in Abu Dhabi, which delivered telemedicine services during the COVID-19 pandemic between November and December 2020. In total, 623 physicians responded (response rate=70.8%). The survey included a 5-point Likert scale to measure physician's attitudes and perceptions of video and audio consultations with reference to the quality of the clinical consultation and the professional productivity. Descriptive statistics were used to describe physicians' sociodemographic characteristics (age, sex, designation, clinical specialty, duration of practice, and previous experience with telemedicine) and telemedicine modality (video vs audio consultations). Regression models were used to assess the association between telemedicine modality and physicians' characteristics with the perceived outcomes of the web-based consultation., Results: Compared to audio consultations, video consultations were significantly associated with physicians' confidence toward managing acute consultations (odds ratio [OR] 1.62, 95% CI 1.2-2.21; P=.002) and an increased ability to provide patient education during the web-based consultation (OR 2.21, 95% CI 1.04-4.33; P=.04). There was no significant difference in physicians' confidence toward managing long-term and follow-up consultations through video or audio consultations (OR 1.35, 95% CI 0.88-2.08; P=.17). Video consultations were less likely to be associated with a reduced overall consultation time (OR 0.69, 95% CI 0.51-0.93; P=.02) and reduced time for patient note-taking compared to face-to-face visits (OR 0.48, 95% CI 0.36-0.65; P<.001). Previous experience with telemedicine was significantly associated with a lower perceived risk of misdiagnosis (OR 0.46, 95% CI 0.3-0.71; P<.001) and an enhanced physician-patient rapport (OR 2.49, 95% CI 1.26-4.9; P=.008)., Conclusions: These results indicate that video consultations should be adopted frequently in the new remote clinical consultations. Previous experience with telemedicine was associated with a 2-fold confidence in treating acute conditions, less than a half of the perceived risk of misdiagnosis, and an increased ability to provide patients with health education and enhance the physician-patient rapport. Additionally, these results show that audio consultations are equivalent to video consultations in providing remote follow-up care to patients with chronic conditions. These findings may be beneficial to policymakers of e-health programs in low- and middle-income countries, where audio consultations may significantly increase access to geographically remote health services., (©Noora Alhajri, Mecit Can Emre Simsekler, Buthaina Alfalasi, Mohamed Alhashmi, Majd AlGhatrif, Nahed Balalaa, Maryam Al Ali, Raghda Almaashari, Shammah Al Memari, Farida Al Hosani, Yousif Al Zaabi, Shereena Almazroui, Hamed Alhashemi, Ovidiu C Baltatu. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 01.06.2021.)

Although mechanical energy transfer between the heart and arterial system, referred to as arterial-ventricular (AV) coupling, is an important determinant of cardiovascular performance, how AV coupling changes over time within and among individuals as they age has not been fully explored. We studied 129 participants (baseline age 21-96) of the Baltimore Longitudinal Study of Aging, free of clinical CVD. Participants underwent repeated multigated cardiac blood pool scans to estimate left ventricular (LV) volumes (SV, EDV, and ESV). Total systemic vascular resistance (TSVR), total arterial compliance (TAC), effective arterial elastance (Ea), and end-systolic LV elastance (Elv) were calculated using LV volumes and brachial BP measurements; calculated Ea/Elv was the measure of AV coupling. Linear mixed-effects models were used to estimate person-specific rates of change (Change) for each variable. The rate at which Ea increased over time was faster than the rate at which Elv increased, resulting in AV uncoupling (increased Ea/Elv) over time that was significantly greater in women than in men. Loss of arterial compliance was the main determinant of (Ea/Elv) Change , which was negatively associated with changes in SV and EDV but positively with changes in ESV. Progressive AV uncoupling occurred with aging and was more pronounced in women than men. While Ea change did not differ by sex, Elv increased at a slower rate in women than in men. AV uncoupling was inversely associated with EDV and SV rates of change and a directly associated with an increase in ESV rate of change. Additional studies are needed to explore the functional consequences of AV uncoupling in healthy individuals with respect to the emergence of age-associated clinical cardiovascular diseases, such as heart failure with preserved ejection fraction.

Levels of angiotensin-converting enzyme 2 (ACE2), the gateway for COVID-19 virus into the cells, have been implicated in worse COVID-19 outcomes associated with aging and cardiovascular disease (CVD). Data on age-associated differences in circulating ACE2 levels in humans and the role of CVD and medications is limited. We analyzed data from 967 participants of the InCHIANTI study, a community-dwelling cohort in the Chianti region, Italy. Relative abundance of ACE2 in plasma was assessed using a proteomics platform. CVD diagnoses, use of renin-angiotensin-aldosterone system (RAAS) antagonists: ACEi, ARBs, and aldosterone antagonists, were ascertained. Multiple linear analyses were performed to examine the independent association of ACE2 with age, CVD, and RAAS antagonist use. Age was independently associated with lower log (ACE2) in persons aged ≥ 55 years (STD β = - 0.12, p = 0.0002). ACEi treatment was also independently associated with significantly lower ACE2 levels, and ACE2 was inversely associated with weight, and positively associated with peripheral artery disease (PAD) status. There was a trend toward higher circulating ACE2 levels in hypertensive individuals, but it did not reach statistical significance. In a stratified analysis, the association between log (ACE2) and log (IL-6) was more evidenced in participants with PAD. Circulating ACE2 levels demonstrate curvilinear association with age, with older individuals beyond the sixth decade age having lower levels. ACEi was associated with greater circulating ACE2 levels. Interestingly, ACE2 was elevated in PAD and positively associated with inflammatory markers, suggesting compensatory upregulation in the setting of chronic inflammation. Further studies are needed to comprehensively characterize RAAS components with aging and disease, and assess its prognostic role in predicting COVID-19 outcomes.

Coronavirus disease 2019 (COVID-19) is a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is frequently characterized by a marked inflammatory response with severe pneumonia and respiratory failure associated with multiorgan involvement. Some risk factors predispose patients to develop a more severe infection and to an increased mortality; among them, advanced age and male gender have been identified as major and independent risk factors for COVID-19 poor outcome. The renin-angiotensin-aldosterone system (RAAS) is strictly involved in COVID-19 because angiotensin converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 and also converts pro-inflammatory angiotensin (Ang) II into anti-inflammatory Ang(1-7). In this review, we have addressed the effect of aging and gender on RAAS with emphasis on ACE2, pro-inflammatory Ang II/Ang II receptor 1 axis and anti-inflammatory Ang(1-7)/Mas receptor axis., (© 2021 The authors.)

Background Common carotid intima medial thickness (IMT) increases with aging. However, the longitudinal association between IMT and other age-associated hemodynamic alterations in men and in women are not fully explored. Methods and Results We analyzed repeated measures of IMT, blood pressure, and carotid-femoral pulse wave velocity over a 20-year period in 1067 men and women of the Baltimore Longitudinal Study on Aging; participants were ages 20 to 92 years at entry and free of overt cardiovascular disease. Linear mixed-effects models were used to calculate the individual rates of change ( Change ) of IMT, pulse pressure, mean arterial pressure, and pulse wave velocity, among other covariates. Multivariate regression analysis was used to examine the association of IMT Change with baseline and rates of change of hemodynamic parameters and cardiovascular risk factors. IMT increased at accelerating rates from 0.02 mm/decade at age 50 years to 0.05 mm/decade at age 80 years greater rates in men than in women. IMT Change was positively associated with baseline low-density lipoprotein, low-density lipoprotein Change , and baseline systolic blood pressure and systolic blood pressure Change , but inversely with baseline diastolic blood pressure and diastolic blood pressure Change . When blood pressure was expressed as pulse pressure and MAP, IMT Change was positively associated with baseline pulse pressure and pulse pressure Change and inversely with baseline mean arterial pressure and mean arterial pressure Change . In sex-specific analysis, these associations were observed in women, but not in men. Conclusions In summary, our analyses showed that IMT increases at accelerating rates with aging. Age-associated changes in IMT were modulated by concurrent changes of low-density lipoprotein in both sexes, and of pulsatile and mean blood pressure in women but not men.

Resting metabolic rate (RMR) declines with aging and is related to changes in health status, but how specific health impairments impact basal metabolism over time has been largely unexplored. We analyzed the association of RMR with 15 common age-related chronic diseases for up to 13 years of follow-up in a population of 997 participants to the Baltimore Longitudinal Study of Aging. At each visit, participants underwent measurements of RMR by indirect calorimetry and body composition by DEXA. Linear regression models and linear mixed effect models were used to test cross-sectional and longitudinal associations of RMR and changes in disease status. Several diseases were associated with higher RMR at baseline. Independent of covariates, prevalent COPD and cancer, as well as incident diabetes, heart failure, and CKD were associated with a steeper decline in RMR over time. Chronic diseases seem to have a two-phase association with RMR. Initially, RMR may increase because of the high cost of resiliency homeostatic mechanisms. However, as the reserve capacity becomes exhausted, a catabolic cascade becomes unavoidable, resulting in loss of total and metabolically active mass and consequent RMR decline.

Background Aging is associated with a modest decline in ankle-brachial index (ABI); however, the underpinnings of this decline are not fully understood. The greater systolic ankle than brachial blood pressure, a normal ABI implies, is partially attributed to lower central than peripheral arterial stiffness. Hence, we examined the hypothesis that the age-associated decline in ABI is associated with central arterial stiffening with aging, assessed by pulse wave velocity. Methods and Results We analyzed longitudinal data from 974 participants aged 27 to 95 years from the Baltimore Longitudinal Study of Aging who were free of clinically significant cardiovascular disease. Participants had an average of 4 visits with a 6.8-year average follow-up time. Linear mixed-effects models showed that the average ABI decline beyond the age of 70 years was 0.03 per decade. In multiple regression analysis, the ABI rate of change was inversely associated with initial age (standardized β=-0.0711, P=0.0282), independent of peripheral disease factors and baseline ABI. After adjustment, the pulse wave velocity rate of change was inversely associated with ABI rate of change (standardized β=-0.0993, P=0.0040), rendering the association of the latter with initial age nonsignificant (standardized β=-0.0265, P=0.5418). Conclusions A modest longitudinal decline in ABI beyond the age of 70 years was shown to be independent of traditional risk factors for peripheral arterial disease but was accounted for by an increase in pulse wave velocity. A modest decline in ABI with aging might be a manifestation of changes in central hemodynamics and not necessarily attributable to peripheral flow-limiting factors.

Purpose: Blood vessels of the retina provide an easily-accessible, representative window into the condition of microvasculature. We investigated how retinal vessel structure captured in fundus photographs changes with age, and how this may reflect features related to patient health, including blood pressure., Results: We used two approaches. In the first approach, we segmented the retinal vasculature from fundus photographs and then we correlated 25 parameterized aspects ("traits")-comprising 15 measures of tortuosity, 7 fractal ranges of self-similarity, and 3 measures of junction numbers-with participant age and blood pressure. In the second approach, we examined entire fundus photographs with a set of algorithmic CHARM features. We studied 2,280 Sardinians, ages 20-28, and an U.S. based population from the AREDS study in 1,178 participants, ages 59-84. Three traits (relating to tortuosity, vessel bifurcation number, and vessel endpoint number) showed significant changes with age in both cohorts, and one additional trait (relating to fractal number) showed a correlation in the Sardinian cohort only. When using second approach, we found significant correlations of particular CHARM features with age and blood pressure, which were stronger than those detected when using parameterized traits, reflecting a greater signal from the entire photographs than was captured in the segmented microvasculature., Conclusions: These findings demonstrate that automated quantitative image analysis of fundus images can reveal general measures of patient health status., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Ilya G. Goldberg is employed by Mindshare Medical, Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Background: Lower muscle mitochondrial energy production may contribute to impaired walking endurance in patients with peripheral arterial disease. A borderline ankle-brachial index (ABI) of 0.91 to 1.10 is associated with poorer walking endurance compared with higher ABI. We hypothesized that in the absence of peripheral arterial disease, lower ABI is associated with lower mitochondrial energy production., Methods and Results: We examined 363 men and women participating in the Baltimore Longitudinal Study of Aging with an ABI between 0.90 and 1.40. Muscle mitochondrial energy production was assessed by post-exercise phosphocreatine recovery rate constant ( k PCr) measured by phosphorus magnetic resonance spectroscopy of the left thigh. A lower post-exercise phosphocreatine recovery rate constant reflects decreased mitochondria energy production.The mean age of the participants was 71±12 years. A total of 18.4% had diabetes mellitus and 4% were current and 40% were former smokers. Compared with participants with an ABI of 1.11 to 1.40, those with an ABI of 0.90 to 1.10 had significantly lower post-exercise phosphocreatine recovery rate constant (19.3 versus 20.8 ms -1 , P =0.015). This difference remained significant after adjusting for age, sex, race, smoking status, diabetes mellitus, body mass index, and cholesterol levels ( P =0.028). Similarly, post-exercise phosphocreatine recovery rate constant was linearly associated with ABI as a continuous variable, both in the ABI ranges of 0.90 to 1.40 (standardized coefficient=0.15, P =0.003) and 1.1 to 1.4 (standardized coefficient=0.12, P =0.0405)., Conclusions: An ABI of 0.90 to 1.10 is associated with lower mitochondrial energy production compared with an ABI of 1.11 to 1.40. These data demonstrate adverse associations of lower ABI values with impaired mitochondrial activity even within the range of a clinically accepted definition of a normal ABI. Further study is needed to determine whether interventions in persons with ABIs of 0.90 to 1.10 can prevent subsequent functional decline., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Serum uric acid (SUA) has long been associated with increased cardiovascular risk, with arterial stiffness proposed as a mediator. However, evidence on the association between SUA and arterial stiffness is limited to contradicting cross-sectional studies. In this analysis, we examined the longitudinal relationship between SUA and pulse wave velocity, a measure of arterial stiffness, in a community-dwelling population. We studied 446 women and 427 men participating in the BLSA (Baltimore Longitudinal Study of Aging), with 1409 and 1434 observations, respectively, over an average period of 6 years. At baseline, mean ages of women and men were 65±13 and 68±13 years; mean SUA, 4.6±1.1 and 5.7±1.3 mg/dL; mean pulse wave velocity, 8.1±1.7 and 8.6±1.9 m/s, respectively (P<0.0001). In gender-stratified models accounting for age, blood pressure, renal function, metabolic measures, and medications, there was a significant interaction between SUA and follow-up time in men (β=0.69; P=0.0002) but not in women. Men, but not women, in the highest gender-specific SUA tertile at baseline (SUA≥6.2 mg/dL in men and SUA≥4.9 mg/dL in women) had a greater rate of pulse wave velocity increase over time than those in the lowest tertiles (β=0.997; P=0.012). This gender difference was lost when the distribution of SUA in men and women was made comparable by excluding hyperuricemic men (SUA≥6.2 mg/dL). In conclusion, higher SUA was associated with greater increase in pulse wave velocity in men but not women; this association was lost when men with SUA≥6.2 mg/dL were not included, suggesting a threshold for SUA association with arterial stiffness, which is more frequently reached in men., (© 2016 American Heart Association, Inc.)

Significant hemodynamic changes ensue with aging, leading to an ever-growing epidemic of hypertension. Alterations in central arterial properties play a major role in these hemodynamic changes. These alterations are characterized by an initial decline in aortic distensibility and an increase of diastolic blood pressure, followed by a sharp increase in pulse wave velocity (PWV), and an increase in pulse pressure (PP) beyond the sixth decade. However, the trajectories of PWV and PP diverge with advancing age. There is an increased prevalence of salt-sensitive hypertension with advancing age that is, in part, mediated by marinobufagenin, an endogenous sodium pump ligand., (Published by Elsevier Inc.)

Competing Interests: No author has any conflict of interest to disclose.

Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naïve. The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of the hemodynamic changes with aging makes the "one-size-fits-all" approach suboptimal and urges for therapies that address the vascular profile that underlies a given blood pressure, rather than the blood pressure values themselves.

The age-associated increase in arterial stiffness has long been considered to parallel or to cause the age-associated increase in blood pressure (BP). Yet, the rates at which pulse wave velocity (PWV), a measure of arterial stiffness, and BP trajectories change over time within individuals who differ by age and sex have not been assessed and compared. This study determined the evolution of BP and aortic PWV trajectories during a 9.4-year follow-up in >4000 community-dwelling men and women of 20 to 100 years of age at entry into the SardiNIA Study. Linear mixed effects model analyses revealed that PWV accelerates with time during the observation period, at about the same rate over the entire age range in both men and women. In men, the longitudinal rate at which BP changed over time, however, did not generally parallel that of PWV acceleration: at ages>40 years the rates of change in systolic BP (SBP) and pulse pressure (PP) increase plateaued and then declined so that SBP, itself, also declined at older ages, whereas PP plateaued. In women, SBP, diastolic BP, and mean BP increased at constant rates across all ages, producing an increasing rate of increase in PP. Therefore, increased aortic stiffness is implicated in the age-associated increase in SBP and PP. These findings indicate that PWV is not a surrogate for BP and that arterial properties other than arterial wall stiffness that vary by age and sex also modulate the BP trajectories during aging and lead to the dissociation of PWV, PP, and SBP trajectories in men., (© 2014 American Heart Association, Inc.)

Objective: Experimental evidence indicates that circulating insulin-like growth factor-1 (IGF-1) counteracts vascular aging and atherosclerosis, for which increased carotid artery intima-media thickness (IMT) is a marker. Yet, IGF-1 concentrations have been inconsistently associated with carotid IMT in epidemiological studies. Since vitamin D is also implicated in vascular protection and affects IGF-1 biology, we hypothesized that it would influence the effect of IGF-1 on IMT., Methods: The relationship between carotid IMT and fasting serum IGF-1 was examined across strata of 25-hydroxyvitamin D [25(OH)D] in 472 participants in the Baltimore Longitudinal Study of Aging (BLSA) with well-controlled blood pressure and in 165 treatment-naive patients with essential hypertension from the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) study. Moreover, the interplay between vitamin D and IGF-1 was preliminarily explored in EA.hy926 endothelial cells., Results: After adjusting for age, sex, BMI, renal function, smoking, systolic blood pressure, LDL-cholesterol, glycemia, antihypertensive or lipid-lowering therapy, season, parathyroid hormone, and vitamin D supplementation, IGF-1 was significantly and negatively associated with carotid IMT only within the lowest 25(OH)D quartile (range 6.8-26 ng/mL) of the BLSA (β -0.095, p = 0.03). Similarly, a significant negative correlation between IGF-1 and carotid IMT was found after full adjustment only in MAGIC patients with 25(OH)D concentrations below either the deficiency cut-off of 20 ng/mL (β -0.214, p = 0.02) or 26 ng/mL (β -0.174, p = 0.03). Vitamin D dose-dependently decreased hydrogen peroxide-induced endothelial cell oxidative stress and apoptosis, which were further inhibited by IGF in the presence of low, but not high vitamin D concentration., Conclusions: Circulating IGF-1 is vasoprotective primarily when vitamin D levels are low. Future studies should address the mechanisms of vitamin D/IGF-1 interaction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A localized hypertrophy of the subaortic segment of the ventricular septum-ventricular septal bulge (VSB)-has been frequently described in series of elderly population, but its prevalence with age, clinical correlates, and impact on cardiac function and exercise capacity remain uncertain. We explored these associations in a cross-sectional sample without known cardiac disease from the Baltimore Longitudinal Study of Aging. We randomly selected 700 participants (50% men, mean age 64 ± 15, range 26 to 95 years) and reviewed their echocardiograms. We identified 28 men and 21 women with VSB (7% overall prevalence). The prevalence of VSB significantly increased with age in both genders (p <0.0001). In multivariate logistic regression including hypertension and other cardiovascular risk factors, only age displayed a significant independent association with VSB (OR 1.06 per year, 95% confidence interval 1.03 to 1.10, p = 0.0001). After multiple adjustments, participants with VSB compared with those without had enhanced global left ventricular contractility (fractional shortening 41 ± 1.3 vs 38 ± 0.3%, p = 0.04; ejection fraction 71 ± 1.6 vs 67 ± 0.4%, p = 0.06; systolic velocity of the mitral annulus 8.4 ± 0.1 vs 8.9 ± 0.3, p = 0.06), and larger aortic root diameters (3.3 ± 0.06 vs 3.1 ± 0.02 cm, p = 0.02). In subgroup of participants who completed a maximal treadmill test (177 women and 196 men), those with VSB (19, 5.1%) had significantly lower peak oxygen consumption than their counterparts (19.6 ± 3.8 vs 22.9 ± 6.6 ml/kg/min, p = 0.03). However, this association was no longer significant after multiple adjustments. In conclusion, the presence of VSB is independently associated with older age and determines enhanced left ventricular contractility, without any evident impact on exercise capacity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: There is a J-shaped relationship between body mass index (BMI) and cardiovascular outcomes in elderly patients (obesity paradox). Whether low BMI correlates with aortic calcification (AC) and whether this association is accounted for by bone demineralization is uncertain., Methods: Presence of AC was evaluated in 687 community-dwelling individuals (49% male, mean age 67 ± 13 years) using CT images of the thoracic, upper and lower abdominal aorta, and scored from 0 to 3 according to number of sites that showed any calcification. Whole-body bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry. Predictors of AC were assessed by logistic regression, and the role of BMD using mediation analysis., Results: Age and cardiovascular risk factors were positively associated while both BMI (r = -0.11, p < 0.01) and BMD (r = -0.17, p < 0.0001) were negatively associated with AC severity. In multivariate models, lower BMI (OR 0.96, 95%CI 0.92-0.99, p = 0.01), older age, higher systolic blood pressure, use of lipid-lowering drugs and smoking were independent predictors of AC. A nonlinear relationship between BMI and AC was noticed (p = 0.03), with decreased AC severity among overweight participants. After adjusting for BMD, the coefficient relating BMI to AC was reduced by 14% and was no longer significant, whereas BMD remained negatively associated with AC (OR 0.82, 95%CI 0.069-0.96, p = 0.01), with a trend for a stronger relationship in older participants., Conclusion: Low BMI is associated with increased AC, possibly through calcium mobilization from bone, resulting in low BMD. Prevention of weight loss and bone demineralization with aging may help reducing AC., (Published by Elsevier Ireland Ltd.)

Carotid-femoral pulse wave velocity is considered the gold standard for measurements of central arterial stiffness obtained through noninvasive methods(1). Subjects are placed in the supine position and allowed to rest quietly for at least 10 min prior to the start of the exam. The proper cuff size is selected and a blood pressure is obtained using an oscillometric device. Once a resting blood pressure has been obtained, pressure waveforms are acquired from the right femoral and right common carotid arteries. The system then automatically calculates the pulse transit time between these two sites (using the carotid artery as a surrogate for the descending aorta). Body surface measurements are used to determine the distance traveled by the pulse wave between the two sampling sites. This distance is then divided by the pulse transit time resulting in the pulse wave velocity. The measurements are performed in triplicate and the average is used for analysis.

A significant inter-arm difference in systolic blood pressure (IADSBP) has recently been associated with worse cardiovascular outcomes. The authors hypothesized that part of this association is mediated by arterial stiffness, and examined the relationship between significant IADSBP and carotid-femoral pulse wave velocity (CF-PWV) in a sample from the Baltimore Longitudinal Study of Aging. Of 1045 participants, 50 (4.8%) had an IADSBP ≥10 mm Hg at baseline, and 629 had completed data from ≥2 visits (for a total of 1704 visits during 8 years). CF-PWV was significantly higher in patients with an IADSBP ≥10 mm Hg (7.3±1.9 vs 8.2±2, P=.002). Compared with others, patients with IADSBP ≥10 mm Hg also had higher body mass index, waist circumference, and triglycerides; higher prevalence of diabetes; and lower high-density lipoprotein (HDL) cholesterol (P<.001 for all). A significant association with IADSBP ≥10 mm Hg was observed for CF-PWV in both cross-sectional (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.87; P=.01) and longitudinal (OR, 1.15; 95% CI, 1.03-1.29; P=.01) multivariate analyses. Female sex, Caucasian race, high body mass index (plus diabetes and low HDL cholesterol only cross-sectionally) were other independent correlates of IADSBP ≥10 mm Hg. Significant IADSBP is associated with increased arterial stiffness in community-dwelling older adults., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)

Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is an established independent cardiovascular risk factor. Little information is available on the pattern and determinants of the longitudinal change in PWV with aging. Such information is crucial to elucidating mechanisms underlying arterial stiffness and the design of interventions to retard it. Between 1988 and 2013, we collected 2 to 9 serial measures of PWV in 354 men and 423 women of the Baltimore Longitudinal Study of Aging, who were 21 to 94 years of age and free of clinically significant cardiovascular disease. Rates of PWV increase accelerated with advancing age in men more than women, leading to sex differences in PWV after the age of 50 years. In both sexes, not only systolic blood pressure (SBP) ≥140 mm Hg but also SBP of 120 to 139 mm Hg was associated with steeper rates of PWV increase compared with SBP<120 mm Hg. Furthermore, there was a dose-dependent effect of SBP in men with marked acceleration in PWV rate of increase with age at SBP ≥140 mm Hg compared with SBP of 120 to 139 mm Hg. Except for waist circumference in women, no other traditional cardiovascular risk factors predicted longitudinal PWV increase. In conclusion, the steeper longitudinal increase of PWV in men than women led to the sex difference that expanded with advancing age. Age and SBP are the main longitudinal determinants of PWV, and the effect of SBP on PWV trajectories exists even in the prehypertensive range.

Obesity is associated with increased diastolic stiffness and myocardial steatosis and dysfunction. The impact of aging on the protective effects of caloric restriction (CR) is not clear. We studied 2-month (younger) and 6-7-month (older)-old ob/ob mice and age-matched C57BL/6J controls (WT). Ob/ob mice were assigned to diet ad libitum or CR for 4 weeks. We performed echocardiograms, myocardial triglyceride assays, Oil Red O staining, and measured free fatty acids, superoxide, NOS activity, ceramide levels, and Western blots. In younger mice, CR restored diastolic function, reversed myocardial steatosis, and upregulated Akt phosphorylation. None of these changes was observed in the older mice; however, CR decreased oxidative stress and normalized NOS activity in these animals. Interestingly, myocardial steatosis was not associated with increased ceramide, but CR altered the composition of ceramides. In this model of obesity, aging attenuates the benefits of CR on myocardial structure and function.

Purpose: To examine the association between alcohol consumption and mortality among older Mexican American men, with and without pre-existing cardiovascular conditions., Methods: We conducted survival analysis among 908 men aged 65-80 years from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE), a longitudinal population-based study of older Mexican Americans who reside in the southwestern United States. Men were categorized into four alcohol-consumption groups: lifetime abstainers, former drinkers, low risk drinkers (< or =30 drinks/month and < or =3 drinks/occasion) and at-risk drinkers (>30 drinks/month or >3 drinks/occasion) and stratified into two groups: those with and those without pre-existing cardiovascular conditions. Mortality was ascertained from 1993-1994 to 2007., Results: Among participants without pre-existing cardiovascular conditions, former, low risk, and at-risk drinkers had a lower risk for all-cause mortality compared to lifetime abstainers [HR: .70, 95% CI (.50-.99), .64 (.42-.97) and .60 (.40-.92), respectively]. There was no statistically significant association between mortality and any of the alcohol consumption groups among those with cardiovascular conditions., Conclusions: Among older Mexican-American men without cardiovascular conditions, former and current drinkers had lower mortality compared to abstainers. No such associations were observed between alcohol use and mortality among those with cardiovascular conditions.

Objective: This study examines the prevalence and correlates of poor glycemic control in Mexican Americans aged 75 years and older with diabetes., Methods: Data are from the 5(th) wave (2004-05) of the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). A total of 2,069 Mexican Americans aged 75 and over were interviewed. Six hundred eighty nine subjects (33.5%) reported having been diagnosed with diabetes and 209 (30.3%) subjects agreed to a blood test of their HbA(1)c level., Results: Of the 209 diabetic subjects with an HbA(1)c test, 73 (34.9%) had good glycemic control (HbA(1)c <7%) and 136 (65.1%) had poor glycemic control (HbA(1)c >7%). Bivariate analysis revealed that subjects with poor control had longer disease duration, had lower education, used the glucometer more frequently, and had more diabetes-complications when compared to those in the good glycemic control group. Multivariable logistic regression analysis found the following factors associated with poor glycemic control: <8 years of education, foreign-born, smoking, obesity, longer disease duration, daily glucometer use, and having macro-complications., Discussion: Prevalence of poor glycemic control is very high in this population with very high and rising prevalence of diabetes. Further studies are needed to explore the effect of these and other characteristics on glycemic control among older Mexican Americans and to develop appropriate interventions to improve diabetes outcomes and increase life-expectancy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The last decade of the 19th century witnessed the rise of a new era in which physicians used technology along with classical history taking and physical examination for the diagnosis of heart disease. The introduction of chest x-rays and the electrocardiograph (electrocardiogram) provided objective information about the structure and function of the heart. In the first half of the 20th century, a number of innovative individuals set in motion a fascinating sequence of discoveries and inventions that led to the 12-lead electrocardiogram, as we know it now. Electrocardiography, nowadays, is an essential part of the initial evaluation for patients presenting with cardiac complaints. As a first line diagnostic tool, health care providers at different levels of training and expertise frequently find it imperative to interpret electrocardiograms. It is likely that an understanding of the electrical basis of electrocardiograms would reduce the likelihood of error. An understanding of the disorders behind electrocardiographic phenomena could reduce the need for memorizing what may seem to be an endless list of patterns. In this article, we will review the important steps in the evolution of electrocardiogram. As is the case in most human endeavors, an understanding of history enables one to deal effectively with the present.

We examined the relations of central adiposity with left ventricular (LV) diastolic dysfunction in men and women who participated in the Baltimore Longitudinal Study of Aging, a prospective community-based study of older persons. The sample for this cross-sectional analysis included 399 women and 370 men. Central adiposity was estimated using the waist circumference (WC) and global adiposity using the body mass index (BMI). Using data from a comprehensive echocardiographic study that included tissue Doppler imaging, diastolic function was graded according to 3 parameters (E/A ratio, E/Em ratio, and left atrial volume index). In the logistic regression models adjusted for age, gender, cardiovascular risk factors, and hemodynamic parameters, WC and BMI were both independently associated with LV diastolic dysfunction. However, when both WC and BMI were in the same model, only WC remained significantly associated with LV diastolic dysfunction (odds ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.02). In the gender-stratified analyses, WC was significantly associated with LV diastolic dysfunction-independently of BMI-in women (odds ratio 1.08, 95% confidence interval 1.04 to 1.14, p <0.001) but not in men (odds ratio 1.00, 95% confidence interval 0.95 to 1.05, p = 0.91). Additional adjustment for LV mass index failed to modify these relations. In conclusion, the adverse effect of central adiposity on LV diastolic function was independent of general adiposity and more pronounced among women. The effect of visceral adiposity on LV diastolic dysfunction would benefit from confirmation in longitudinal studies., (Published by Elsevier Inc.)

Purpose: To describe trends in hypertension prevalence, awareness, treatment, and control among older Mexican Americans living in the Southwestern United States from 1993-1994 to 2004-2005., Methods: This study is a comparison between two separate cross-sectional cohorts of non-institutionalized Mexican Americans 75 years of age or older from the Hispanic Established Population for the Epidemiological Study of the Elderly (919 subjects from the 1993-1994 cohort and 738 from the 2004-2005 cohort). Data were collected on self-reported hypertension, measured blood pressure, medications, as well as sociodemographic and other health-related factors., Results: Hypertension prevalence increased from 73.0% in the period 1993-1994 to 78.4% in 2004-2005. Cross-cohort multivariate analyses showed that the higher odds of hypertension in the 2004-2005 cohort was attenuated by adding diabetes and obesity to the model. There was a significant increase in hypertension awareness among hypertensives (63.0% to 82.6%) and in control among treated hypertensives (42.5% to 55.4%). Cross-cohort multivariate analyses showed that the higher odds of control in 2004-2005 cohorts were accentuated by adding diabetes to the model. There were no significant changes in treatment rates (62.2% to 65.6%), Conclusion: Hypertension prevalence in very old Mexican Americans residing in the Southwestern United States was higher in 2004-2005 than in 1993-1994 and was accompanied by a significant increase in awareness and control rates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Evidence has shown that Mexican Americans have a higher prevalence of diabetes and a greater risk for diabetes-related complications than non-Hispanic whites. However, no studies have described the changes in prevalence among older Mexican Americans. The purpose of this study was to expand on the current literature by examining the trends in diabetes prevalence and diabetes-related complications in Mexican Americans aged >or=75 years from 1993-1994 to 2004-2005., Research Design and Methods: The prevalences of self-reported diabetes and diabetes-related complications were estimated in the original cohort (1993-1994) and the new cohort (2004-2005) of the Hispanic Established Population for the Epidemiologic Study of the Elderly (Hispanic EPESE) and were compared across the two surveys., Results: The prevalence of diabetes among Mexican Americans aged >or=75 years has nearly doubled between 1993-1994 and 2004-2005 from 20.3 to 37.2%, respectively (P < 0.001). The increase in the prevalence of diabetes was similar across all sociodemographic factors. Diabetes complications did not change significantly between the two cohorts. However, the prevalence of having any lower-extremity function disability did increase between the two cohorts., Conclusions: The prevalence of diabetes in older Mexican Americans has increased dramatically. At the same time, there has been no improvement in diabetes-related complications as has been found in the general older population. These findings heighten the urgency for more effective public health interventions targeted to this population. As diabetes and obesity become more prevalent in older adults, physicians should encourage appropriate management in older patients, including early detection and glycemic control.