Age-related Changes In Function Research Articles

Healthy Ageing Is Associated with Preserved or Enhanced Nutrient and Mineral Apparent Digestibility in Dogs and Cats Fed Commercially Relevant Extruded Diets.

Simple SummaryPreventative healthcare and provision of optimal nutrition from early ages is increasing the life expectancy of companion animals today. However, as part of the normal ageing process, changes in the capacity to digest and use dietary nutrients may occur, which could contribute to deficiency in energy and/or essential nutrients. Based on previous studies, an effect of ageing on nutrient digestibility has primarily been observed when feeding low-fat or high-fibre diets. In this study, we evaluated the effect of age on nutrient digestibility using healthy dogs and cats up to 14 years old by feeding diets differing in fat and fibre contents. Older dogs and cats had a preserved nutrient digestibility, in some cases showed an enhanced digestibility of fibre and calcium. Interestingly, older cats had a lower nutrient digestibility with one of the diets, which was unrelated to fat and fibre levels, but was possibly associated with other ingredients in the formulation. Our findings support the use of a wide range of fat and fibre levels in healthy older dogs and cats within the studied ages. However, ingredient sources should be considered in the formulation of senior diets.Age-related changes in gastrointestinal function have been reported in companion animals, but the impact on digestive efficiency remains uncertain. Healthy dogs (n = 37; 2.6–14.2 years) received four diets varying in total dietary fibre (TDF; 6–29%, as fed). Healthy cats (n = 28; 1–13 years) received four diets with two fat (10–12%; 17–18%) and TDF (9 and 12%) levels. In a crossover design, diets were provided over four consecutive 10-day cycles, including a 4-day faecal collection. Apparent crude protein (CP), ether extract (EE), TDF, calcium (Ca), and phosphorus (P) digestibilities were determined. The effect of age was analysed as a continuous variable in dogs and as differences between adult (1–5 years) and senior (7–13 years) cats. In dogs, EE digestibility was unaffected by age (p > 0.10). Dogs of 6–12 years had higher digestibility of CP (p = 0.032), TDF (p = 0.019), Ca (p = 0.019), and P (p = 0.024) when fed the 6% TDF diet. Senior cats had greater digestibility of TDF (p < 0.01) and Ca (p = 0.024) but had lower EE and CP digestibility with one diet (17% fat; 9%TDF) (age, p > 0.10; diet × age, p < 0.001). Healthy ageing was associated with preserved nutrient digestibility in dogs and cats within the age ranges studied. The effect of ingredient sources in senior cats warrants further investigation.

Dedifferentiation of Functional Brain Activation Associated With Greater Visual Discrimination Accuracy in Middle-Aged and Older Adults.

Neural dedifferentiation refers to an age-related phenomenon whereby brain functions that are localized to specific, distinct, and differentiated brain areas in young adults become less so as people reach more advanced age. Older adults tend to exhibit greater spread of cortical activation on fMRI during cognitive processing compared to younger adults, with evidence that this occurs during visuoperceptual processing. Some age-related functional changes are considered compensatory, but whether dedifferentiation is compensatory is not clearly understood. The current study assessed dedifferentiation and visual discrimination performance during simultaneous match-to-sample tasks from the Visual Assessment Battery (VAB) among 40 healthy middle-aged and older adults using fMRI. Task-relevant regions of interest (ROIs) were created in the dorsal stream for discrimination of spatial location, the ventral stream for shape, and an area encompassing V5 for velocity. Dedifferentiation, or less specificity in functional activation, was associated with greater discrimination accuracy and more years of education. Secondary analyses showed that reduced functional activation in task-relevant ROIs was associated with faster discrimination speed. Age was unassociated with functional activation. Results suggest that dedifferentiation is compensatory. Lack of age effects suggest that other factors beyond age, such as cognitive or brain reserve, may better predict performance when considering cognitive skills that are relatively stable as adults age, such as visual discrimination.

Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?

Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in the developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily of its “dry” type which is by far the most common (90% of all AMD cases). In the recent years, AMD has become “younger”: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review was to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.

Lifetime depression and age-related changes in body composition, cardiovascular function, grip strength and lung function: sex-specific analyses in the UK Biobank.

Individuals with depression, on average, die prematurely, have high levels of physical comorbidities and may experience accelerated biological ageing. A greater understanding of age-related changes in physiology could provide novel biological insights that may help inform strategies to mitigate excess mortality in depression. We used generalised additive models to examine age-related changes in 15 cardiovascular, body composition, grip strength and lung function measures, comparing males and females with a lifetime history of depression to healthy controls. The main dataset included 342,393 adults (mean age = 55.87 years, SD = 8.09; 52.61% females). We found statistically significant case-control differences for most physiological measures. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in depression. These differences did not uniformly narrow or widen with age and differed by sex. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in depression cases at age 45 and this difference widened to 2.5 mmHg at age 65. These findings suggest that targeted screening for physiological function in middle-aged and older adults with depression is warranted to potentially mitigate excess mortality.

Role of MT1A Polymorphism and Environmental Mercury Exposure on the Montreal Cognitive Assessment (MoCA).

PurposeMany age-related structural and functional changes in the brain have important consequences. Long-term exposure to mercury and the impact of functional polymorphisms of metal-regulating proteins such as metallothioneins (MTs) can result in neurological-neurobehavioral effects in elderly individuals. Therefore, the aims of this study are to examine the associations between biomarkers of mercury exposure and cognitive impairment and to investigate the effect of the rs8052394 single nucleotide polymorphism (SNP) of the potential modifier gene MT1A on different domains of the Montreal Cognitive Assessment (MoCA).Materials and MethodsWe studied 436 participants aged ≥55 years from the Electricity Generating Authority of Thailand study. They underwent a physical examination, an extensive cognitive assessment with the MoCA (cutoff <26 points), and a biochemical analysis related to diabetes and dyslipidemia. The blood mercury level was determined by inductively coupled plasma mass spectrometry. Genotyping of the MT1A rs8052394 SNP was performed by the restriction fragmentation length polymorphism method.ResultsThe mean age of the study population was 58.8±3.01 years, and most had ≥12 years of education (75.7%). The primary study finding was that the prevalence of mild cognitive impairment (MCI) in older Thai adults was 39.7%. The frequency distributions of the G allele of the rs8052394 SNP of the MT1A gene were significantly associated with the total and sub-domain MoCA scores. The prevalence of MCI was significantly associated with increased age, hypertriglyceridemia, hyperhomocysteinemia, the third tertile of blood mercury concentration, and the rs8052394 variant genotype of MT1A (P values for all odds ratios <0.05).ConclusionThese findings suggested that neurocognitive effects associate with mercury exposure and genetic susceptibility in toxicokinetics. Public health strategies can be used to implement as a comprehensive action plan to educate vulnerable populations on how to reduce mercury exposure. Concurrently, impact of such genetic predisposition requires replication for identifying and protecting susceptible individuals from mercury toxicity.

Postępowanie w nietrzymaniu moczu u kobiet z pęcherzem nadaktywnym w codziennej praktyce urologa

Urinary incontinence urinary incontinence is common among women and contributes to decreased quality of life. Several effective treatment options are available for the most common types of urinary incontinence (stress, urge, and mixed), including lifestyle modification and behavioral technique, drug therapy, and minimally invasive procedures. Most women improve with treatment, and urinary incontinence is not an inevitable part of aging. To maximize the opportunity for successful treatment, it is essential to align the therapeutic approach with patient goals and expectations for care, including an assessment of patient-driven priorities regarding potential adverse effects, costs, and expected benefit of different treatment approaches. There are many unique challenges in treating an overactive bladder in older women, such as functional and cognitive impairment, multimorbidity, polypharmacy, and estrogen deficiency, all of which contribute to treating symptoms in older women. This review highlights the current understanding of age-related changes in bladder function and proposes specific clinical considerations for overactive bladder management specific to older women.

Effects of a Tea Cultivar "MK5601" on Behaviors and Hippocampal Neurotrophin-3 Levels in Middle-Aged Mice.

Dietary factors are thought to play an important role in the prevention of cognition diseases and depression in late life. In the present study, we compared the effects between the theogallin-rich tea cultivar, "MK5601" and a common Japanese tea cultivar, "Yabukita" on behaviors and hippocampal neurotrophin levels in experimental animals. Middle-aged mice (aged 8 mo) were given either of the tea infusions or water ad libitum for 4 mo. In the novel object location test, the middle-aged mice drinking water or "Yabukita" performed worse than young mice (aged 2-3 mo) although the middle-aged mice drinking "MK5601" retained spatial memory at the same level as the young mice. We also found that the middle-aged mice drinking "MK5601" showed high levels of neurotrophin-3 in the hippocampus. In conclusion, the "MK5601" tea infusion appears to be effective in preventing age-related changes in cognitive function, as compared with a common Japanese tea cultivar.

Regeneration, Rejuvenation, and Replacement: Turning Back the Clock on Tissue Aging.

While some animals, such as planaria and hydra, appear to be capable of seemingly endless cycles of regeneration, most animals experience a gradual decline in fitness and ultimately die. The progressive loss of cell and tissue function, leading to senescence and death, is generally referred to as aging. Adult ("tissue") stem cells maintain tissue homeostasis and facilitate repair; however, age-related changes in stem cell function over time are major contributors to loss of organ function or disease in older individuals. Therefore, considerable effort is being invested in restoring stem cell function to counter degenerative diseases and age-related tissue dysfunction. Here, we will review strategies that could be used to restore stem cell function, including the use of environmental interventions, such as diet and exercise, heterochronic approaches, and cellular reprogramming. Maintaining optimal stem cell function and tissue homeostasis into late life will likely extend the amount of time older adults are able to be independent and lead healthy lives.

Dysregulation of Systemic Immunity in Aging and Dementia.

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

The regulatory mechanisms of behavioral and cognitive aging.

With the increase of life expectancy, the world's population is aging rapidly. Previous work in the field of aging greatly increases our understanding of biological mechanisms underlying longevity. Researchers have unraveled a number of longevity pathways conserved from yeast to mammals. However, recent evidence shows that mechanisms regulating the life span and those regulating age-related behavioral decline could be dissociated. The regulatory mechanisms underlying behavioral and cognitive aging is largely unknown. Previous work has described a significant age-related decline in cognitive behaviors including episodic memory, working memory, processing speed, as well as motor function deterioration and circadian dysfunction. With the advance of neuroscience and technology, more and more studies have focused on the age-related changes in structure and function of the brain. In this review, we briefly describe the deterioration of cognitive function and other behaviors in the aging process, and survey the role of age-related changes in brain structure and network, neuron morphology and function, transcriptome in brain and some conserved biological pathways on age-related cognitive and behavioral decline. Further studies on the mechanisms underpinning age-related cognitive and behavioral decline may provide clues not only for improving the quality of life for the ageing population, but also for developing intervention approaches for neurodegenerative diseases.

New Perspectives on Avian Models for Studies of Basic Aging Processes.

Avian models have the potential to elucidate basic cellular and molecular mechanisms underlying the slow aging rates and exceptional longevity typical of this group of vertebrates. To date, most studies of avian aging have focused on relatively few of the phenomena now thought to be intrinsic to the aging process, but primarily on responses to oxidative stress and telomere dynamics. But a variety of whole-animal and cell-based approaches to avian aging and stress resistance have been developed—especially the use of primary cell lines and isolated erythrocytes—which permit other processes to be investigated. In this review, we highlight newer studies using these approaches. We also discuss recent research on age-related changes in neural function in birds in the context of sensory changes relevant to homing and navigation, as well as the maintenance of song. More recently, with the advent of “-omic” methodologies, including whole-genome studies, new approaches have gained momentum for investigating the mechanistic basis of aging in birds. Overall, current research suggests that birds exhibit an enhanced resistance to the detrimental effects of oxidative damage and maintain higher than expected levels of cellular function as they age. There is also evidence that genetic signatures associated with cellular defenses, as well as metabolic and immune function, are enhanced in birds but data are still lacking relative to that available from more conventional model organisms. We are optimistic that continued development of avian models in geroscience, especially under controlled laboratory conditions, will provide novel insights into the exceptional longevity of this animal taxon.

Lifetime depression and age-related changes in body composition, cardiovascular function, grip strength and lung function: sex-specific analyses in the UK Biobank

AimsIndividuals with mental disorders, on average, die prematurely, have higher levels of physical comorbidities and may experience accelerated ageing. In individuals with lifetime depression and healthy controls, we examined associations between age and multiple physiological measures.MethodThe UK Biobank study recruited &gt;500,000 participants, aged 37–73 years, between 2006–2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and bone mineral density. Analyses were conducted separately in males and females with depression compared to healthy controls.ResultAnalytical samples included up to 342,393 adults (mean age = 55.87 years; 52.61% females). We found statistically significant differences between individuals with depression and healthy controls for most physiological measures, with standardised mean differences between -0.145 and 0.156. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in individuals with depression. These differences did not uniformly narrow or widen with age. For example, BMI in female cases was 1.1 kg/m2 higher at age 40 and this difference narrowed to 0.4 kg/m2 at age 70. In males, systolic blood pressure was 1 mmHg lower in cases at age 45 and this difference widened to 2.5 mmHg at age 65.ConclusionIndividuals with depression differed from healthy controls across a broad range of physiological measures. Differences in ageing trajectories differed by sex and were not uniform across physiological measures, with evidence of both age-related narrowing and widening of case-control differences.

Two-Year Follow-Up Study of the Relationship Between Brain Structure and Cognitive Control Function Across the Adult Lifespan.

Age-related decline in cognitive control and general slowing are prominent phenomena in aging research. These declines in cognitive functions have been shown to also involve age-related decline in brain structure. However, most evidence in support of these associations is based on cross-sectional data. Therefore, the aim of this study is to contrast cross-sectional and longitudinal analyses to re-examine if the relationship between age-related brain structure and cognitive function are similar between the two approaches. One hundred and two participants completed two sessions with an average interval of 2 years. All participants were assessed by questionnaires, a series of cognitive tasks, and they all underwent neuroimaging acquisition. The main results of this study show that the majority of the conclusions regarding age effect in cognitive control function and processing speed in the literature can be replicated based on the cross-sectional data. Conversely, when we followed up individuals over an average interval of 2 years, then we found much fewer significant relationships between age-related change in gray matter structure of the cognitive control network and age-related change in cognitive control function. Furthermore, there was no “initial age” effect in the relationships between age-related changes in brain structure and cognitive function. This finding suggests that the “aging” relationship between brain structure and cognitive function over a short period of time are independent of “initial age” difference at time point 1. The result of this study warrants the importance of longitudinal research for aging studies to elucidate actual aging processes on cognitive control function.

Age-related changes in physiology in individuals with lifetime bipolar disorder

AimsIndividuals with bipolar disorder have reduced life expectancy and may experience accelerated biological ageing. In individuals with lifetime bipolar disorder and healthy controls, we examined differences in age-related changes in physiology.MethodThe UK Biobank study recruited &gt;500,000 participants, aged 37–73 years, between 2006–2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and bone mineral density. Analyses were conducted separately in males and females with bipolar disorder compared to healthy controls.ResultAnalytical samples included up to 272,462 adults (mean age = 56.04 years, SD = 8.15; 49.51% females). We found statistically significant differences between bipolar disorder cases and controls for grip strength, blood pressure, pulse rate and body composition, with standardised mean differences of up to -0.238 (95% CI -0.282 to -0.193). There was limited evidence of differences in lung function, heel bone mineral density or arterial stiffness. Case-control differences were most evident for age-related changes in cardiovascular function (in both sexes) and body composition (in females). These differences did not uniformly narrow or widen with age and differed by sex. For example, the difference in systolic blood pressure between male cases and controls was -1.3 mmHg at age 50 and widened to -4.7 mmHg at age 65. Diastolic blood pressure in female cases was 1.2 mmHg higher at age 40 and -1.2 mmHg lower at age 65.ConclusionDifferences in ageing trajectories between bipolar disorder cases and healthy controls were most evident for cardiovascular and body composition measures and differed by sex.

Abstract P150: Association Of Leisure Time Physical Activity (LTPA) With Left Atrial Function In Older Adults: The Atherosclerosis Risk In Communities (ARIC) Study

Introduction: Prior research indicates that higher LTPA is associated with better left ventricular (LV) diastolic function, but not with left atrial volume index (LAVI). Left atrial (LA) strain is a more sensitive marker of LA pathology. Hence, we evaluated association of LTPA with LA strain in the ARIC study, a community-based cohort study. Hypothesis: Higher LTPA is associated with better LA reservoir, conduit and contractile function. Methods: We included 4005 participants (mean age 75 years, 63% female, 21% black) with 2D echocardiographic (2DE) LA % strain data, LTPA data, and without prevalent coronary heart disease, valvular heart disease, heart failure, atrial fibrillation, and stroke at Visit 5 (V5, 2011-13). We estimated LTPA as metabolic equivalent-minutes per week from validated Baecke questionnaire and categorized it as poor, intermediate, or ideal as per AHA recommendation. We categorized change in LTPA from V3 (1993-95) to V5 as persistently poor (referent), decreasing, increasing, or persistently active. LA reservoir, conduit, and contractile % strain were measured from speckle-tracking 2DE. Linear regression was used to evaluate association of LTPA with LA function. We modeled LTPA (1) cross-sectionally at V5 as a continuous variable and (2) change from V3 to V5, as continuous and categorical variables (referent- persistently poor). Results: Higher LTPA at V5 (Table) and persistently high (vs poor) LTPA from V3 to 5 (β estimate -0.89, 95% CI -1.40, -0.38) were significantly associated with better LA conduit function after adjusting for CV risk factors, LV function, and LAVI. The same associations with LA reservoir function were no longer significant after adjusting for CV risk factors. LTPA was not associated with LA contractile function (Table). Conclusions: Consistent with LTPA’s salutary effect on LV diastolic function, higher LTPA is associated with better LA conduit function. Maintaining high LTPA from midlife to late-life may be beneficial in mitigating age-related changes in cardiac function.

Age-related functional changes of intestinal flora in rats.

Intestinal flora structure and function change with age and have been associated with a variety of aging-related diseases. Until now, how age affects the functions of gut bacteria has not been fully understood. We used 16S-rRNA-sequencing technology and PICRUSt2 analysis to predict the functions encoded by intestinal flora in male Wistar rats across lifespan. We found that the abundance of gut microbiota genes encoding the L-tryptophan, L-histidine, L-leucine, inositol and catechol degradation pathways as well as L-arginine, ectoine, flavin and ubiquinol synthesis pathways increased with age. Differential analysis of the associated genera revealed that Rhodococcus spp. were significantly abundant during middle-old aged stage. This genus contributed greatly to the L-tryptophan, catechol and inositol degradation pathways as well as ectoine and L-arginine biosynthesis pathways. We concluded that gut bacteria-encoded functions such as amino acid metabolism, B vitamin metabolism, aromatic compound metabolism and energy metabolism varied in an age-dependent manner, and Rhodococcus spp. were the most associated functional bacteria in middle-old aged rats. These may be closely associated with the physiological phenotype of the aging process, which offers new insights for evaluating the relationship between intestinal flora and aging.

Age-related differences in the role of the prefrontal cortex in sensory-motor training gains: A tDCS study

The ability to process multiple sources of information concurrently is particularly impaired as individuals age and such age-related increases in multitasking costs have been linked to impairments in response selection. Previous neuroimaging studies with young adults have implicated the left hemisphere prefrontal cortex (PFC) as a key neural substrate of response selection. In addition, several transcranial direct current stimulation (tDCS) studies have provided causal evidence implicating this region in response selection and multitasking operations. For example, Filmer et al. (2013b) demonstrated that typically observed response selection learning/training gains in young adults were disrupted via offline tDCS of left, but not right, PFC. Here, considering evidence of age-related structural and functional changes in the brains of older adults, we assessed if this pattern of response selection learning disruption via tDCS to the left PFC is observed in older adults, testing if this region remains a key response selection node as individuals age. In a pre-registered study with 58 older adults, we applied anodal, cathodal, and sham stimulation to left and right PFC, and measured performance as participants trained on low- and high-response selection load tasks. Active stimulation did not disrupt training in older adults as compared to younger adults from our previous study. The results highlight age-related differences in the casual neural substrates that subserve response selection and learning.

Effects of age and locomotor demand on foot mechanics during walking

Older adults exhibit reductions in push-off power that are often attributed to deficits in plantarflexor force-generating capacity. However, growing evidence suggests that the foot may also contribute to push-off power during walking. Thus, age-related changes in foot structure and function may contribute to altered foot mechanics and ultimately reduced push-off power. The purpose of this paper was to quantify age-related differences in foot mechanical work during walking across a range of speeds and at a single fixed speed with varied demands for push-off power. 9 young and 10 older adults walked at 1.0, 1.2, and 1.4 m/s, and at 1.2 m/s with an aiding or impeding horizontal pulling force equal to 5% BW. We calculated foot work in Visual3D using a unified deformable foot model, accounting for contributions of structures distal to the hindfoot’s center-of-mass. Older adults walked while performing less positive foot work and more negative net foot work (p < 0.05). Further, we found that the effect of age on mechanical work performed by the foot and the ankle–foot complex increased with increased locomotor demand (p < 0.05). Our findings suggest that during walking, age-related differences in foot mechanics may contribute to reduced push-off intensity via greater energy loss from distal foot structures, particularly during walking tasks with a greater demand for foot power generation. These findings are the first step in understanding the role of the foot in push-off power deficits in older adults and may serve as a roadmap for developing future low-cost mobility interventions.

Nicotine and Cognition in Cognitively Normal Older Adults.

The cholinergic system has been shown to be the primary neurotransmitter system which is responsible for the cognitive symptoms associated with dementia; its role in healthy non-demented older adults remains a gap in the literature. Understanding the effects of age-related functional changes on the nicotinic system will address this knowledge gap. As the older adult population grows and hence the importance of understanding cognitive changes that impact functional abilities and everyday life. In this article we examine the benefits of using nicotine as a method for improving cognition in non-demented healthy older adults which may have the potential for slowing neurodegeneration in aging. Furthermore, we discuss how nicotine can play a crucial role in maintaining cognitive abilities throughout normal cognitive aging.

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study

BackgroundPhysiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.MethodsThis study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).ResultsThe plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.ConclusionLongitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.