Glucose-6-phosphate dehydrogenase deficiency accelerates arterial aging in diabetes

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.MethodsPlasma 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.ResultsAlthough 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.ConclusionG6PDd in diabetics is associated with increased inflammatory markers and accelerated arterial aging

Lower mitochondrial energy production of the thigh muscles in patients with low-normal ankle-brachial index

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 (kPCr) 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\uc2\ub112 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

Longitudinal Changes in Resting Metabolic Rates with Aging Are Accelerated by Diseases

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. Cancer and diabetes 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

Age-related changes of the retinal microvasculature

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GENDER DIFFERENCES IN EARLY MANIFESTATIONS OF ARTERIAL STIFFNESS: RESULTS FROM THE SARDINIA PROJECT

Background Central arterial distensibility declines early in life, setting the stage for a dramatic increase in pulse pressure. However, the underlying alterations in maximal arterial expansion in systole and recoil in diastole, and gender differences in these alterations are not clear. Methods We analyzed longitudinal data of 3066 women and 2155 men (mean age 43 year, range 14-96) from the SardiNIA project. Brachial systolic (SBP) and diastolic (DBP) blood pressure were measured. B-mode ultrasound was used to measure common carotid systolic (SD) and diastolic (DD) diameters. Carotid strain (CS) was calculated as (SD -DD)/DD. Linear regression was used to assess changes in carotid parameters with aging adjusting for SBP and DBP. Results About 80% of the decline in CS occurred by the age of 50. (Fig1A). In men, this decline was due to a pronounced increase in DD (\u3b2=0.1, p<.0001) with no change in SD (Fig1B). Similarly, the decline in CS among women before the age of 30 was due to an increase in DD (\u3b2=0.03, p<.0001) with no change in SD; however, between the ages of 30 and 50, women had a decrease in SD (\u3b2= 120.03, p<.0001) with no change in DD (Fig1C). The smaller decline in CS after the age of 50 (Fig1A) reflected parallel increases in both SD and DD (Fig1B,C). Conclusion In both genders and adjusting for blood pressure, the early decline in CS was due to increasing DD and not decreasing SD suggesting initial impaired recoil rather than restricted expansion; however, the latter seems to subsequently develop in women

Longitudinal trajectories of arterial stiffness and the role of blood pressure. The Baltimore longitudinal study of aging

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) â¥140 mm Hg but also SBP of 120 to 139 mm Hg was associated with steeper rates of PWV increase compared with SBP&lt;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 â¥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

Dilated hypertrophic phenotype of the carotid artery is associated with accelerated age-associated central arterial stiffening

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

Longitudinal Trajectories of Arterial Stiffness and the Role of Blood Pressure

Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is an established independent cardiovascular (CV) 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 CV disease. Rates of PWV increase accelerated with advancing age in men more than women, leading to gender differences in PWV after the age of 50. In both sexes, not only systolic blood pressure (SBP) ≥140mmHg, but also SBP of 120–139mmHg was associated with steeper rates of PWV increase compared to SBP<120mmHg. Furthermore, there was a dose-dependent effect SBP in men with marked acceleration in PWV rate of increase with age at SBP ≥140mmHg compared to SBP of 120–139mmHg. Except for waist circumference in women, no other traditional CV risk factors predicted longitudinal PWV increase. In conclusion, the steeper longitudinal increase of PWV in men than women led to gender difference that expanded with advancing age. Age and systolic blood pressure are the main longitudinal determinants of pulse wave velocity and the effect of systolic blood pressure on PWV trajectories exists even in the pre-hypertensive range

Longitudinal Association between Serum Uric Acid and Arterial Stiffness: Results from the Baltimore Longitudinal Study of Aging

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\ub113 and 68\ub113 years; mean SUA, 4.6\ub11.1 and 5.7\ub11.3 mg/dL; mean pulse wave velocity, 8.1\ub11.7 and 8.6\ub11.9 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 (\u3b2=0.69; P=0.0002) but not in women. Men, but not women, in the highest gender-specific SUA tertile at baseline (SUA 656.2 mg/dL in men and SUA 654.9 mg/dL in women) had a greater rate of pulse wave velocity increase over time than those in the lowest tertiles (\u3b2=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 656.2 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 656.2 mg/dL were not included, suggesting a threshold for SUA association with arterial stiffness, which is more frequently reached in men