Background This study aims to describe associations of obesity and CKD in a Swedish urban population. The impact of fat mass, from bioimpedance analysis, on eGFR based on cystatin C and/or creatinine ...is studied. Methods 5049 participants from Malmö Diet and Cancer Study the cardiovascular arm (MDCS-CV) with available body mass composition (single frequency bioimpedance analysis) and cystatin C measured at baseline were selected. Body mass index (kg/m.sup.2) was used to define overweight/obesity. eGFR was calculated using cystatin C (eGFR.sub.CYS) and creatinine (eGFR.sub.CR) equations: Chronic Kidney Disease Epidemiology Collaboration 2012 (CKD-EPI.sub.CR, CKD-EPI.sub.CYS, CKD-EPI.sub.CR-CYS).sub., eGFR.sub.CYS based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised equation (LMrev), and Modified Full Age Spectrum creatinine-based equation (EKFC.sub.CR). Two different fat mass index (FMI) z-scores were calculated: FMI z-score.sub.Larsson and FMI z-score.sub.Lee. Results Lower eGFR.sub.CYS and eGFR.sub.CR-CYS following multiple adjustments were prevalent in overweight/obese subjects. Increase in FMI z-score.sub.Larsson or FMI z-score.sub.Lee was related to decrease in predicted CAPA, CKD-EPI.sub.CYS, CKD-EPI.sub.CR-CYS and CAPA-LMrev equation. Conclusion eGFR.sub.CYS, in contrast to combined eGFR.sub.CR-CYS and eGFR.sub.CR, demonstrate the strongest association between FMI and kidney function.
In a middle-aged population, it was recently shown that the stable vasopressin marker plasma copeptin (copeptin) predicts development of diabetes mellitus, diabetic heart disease and death. Here, it ...was hypothesised whether copeptin predicts a risk of coronary artery disease (CAD), and cardiovascular mortality in an older population.
Between 2002 and 2006, fasting plasma copeptin was examined and measured in 5386 participants of a population-based longitudinal study (mean age 69.4±6.2 years, 69.8% males) and related copeptin to risk of CAD (first myocardial infarction or coronary revascularisation), cardiovascular and total mortality during a mean follow-up time of 6.5 years using multivariate adjusted (age, gender, systolic blood pressure, antihypertensive therapy, smoking, diabetes, low-density lipoprotein and high-density lipoprotein cholesterol) Cox proportional hazards models.
Among subjects free from CAD at baseline, the multivariate adjusted HR (95% CI) per 1 SD increment of log-transformed copeptin for risk of CAD development was 1.20 (1.08 to 1.33) (p=0.001). There was a borderline significant interaction between diabetes and copeptin on CAD risk (p=0.08) with higher copeptin-associated risk in subjects with diabetes (1.49 (1.14 to 1.95); p=0.004) than in non-diabetic subjects (1.15 (1.02 to 1.50); p=0.02). Moreover, each SD increment of copeptin independently predicted total mortality (1.31 (1.21 to 1.41); p<0.001), an effect driven by the copeptin association with cardiovascular mortality (1.36 (1.21 to 1.53); p<0.001). The absolute risks for CAD were 4.9%, 9.3% and 2.9%, total and CV mortality were 4.9%, 9.3% and 2.9% in quartile 1, 7.1%, 9.4% and 3.5% in quartile 2, 8.3%, 14.2% and 5.6% in quartile 3, and 10.3%, 23.3% and 9.1% in quartile 4, respectively.
Copeptin predicts development of CAD and cardiovascular mortality both in diabetics and non-diabetics.
Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the ...largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly (
<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 95% CI, 0.41-0.85), whereas early vascular aging had higher risk (hazard ratio, 2.70 95% CI, 1.55-4.70) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.
With increasing age, the cardiovascular risk increases, as does frailty, with negative health consequences such as coronary disease, stroke, and vascular dementia. However, this aging process seems ...to take a more rapid course in some individuals, as reflected in the Early Vascular Aging (EVA) syndrome that over the recent 10 years has attracted increased attention. The core of the EVA syndrome is arterial stiffness in the media layer of large elastic arteries, a process that can be measured by pulse wave velocity, for example, along the aorta. Hypertension is a well-known cardiovascular risk factor in its own right, but also linked to the EVA process. However, several studies have shown that non-hemodynamic factors also contribute to arterial stiffness and EVA, such as impaired glucose metabolism, chronic inflammation, and oxidative stress. New perspectives have been introduced for linking early life programming affecting new-born babies and birth weight, with a later risk of hypertension, arterial stiffness and EVA. New drugs are being developed to treat EVA when lifestyle intervention and conventional risk factor controlling drugs are not enough. Finally, the opposite phenotype of EVA is Healthy Vascular Aging (HVA) or even Super Normal Vascular Aging (SUPERNOVA). If protective mechanisms can be found and mapped in these fortunate subjects with a slower than expected aging process, there could exist a potential to find new drug targets for preventive therapy.
The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the ...elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.
Loss of cognitive function and hypertension are two common conditions in the elderly and both significantly contribute to loss of personal independency. Microvascular brain damage - the result of ...age-associated alteration in large arteries and the progressive mismatch of their cross-talk with small cerebral arteries - represents a potent risk factor for cognitive decline and for the onset of dementia in older individuals. The present review discusses the complexity of factors linking large artery to microvascular brain disease and to cognitive decline and the evidence for possible clinical markers useful for prevention of this phenomenon. The possibility of dementia prevention by cardiovascular risk factors control has not been demonstrated. In the absence of research clinical trials specifically and primarily designed to demonstrate the antihypertensive treatment efficacy for reducing the risk of dementia, further evidence demonstrating that it is possible to limit the progression of microvascular brain damage is needed.
The Montreal Cognitive Assessment (MoCA) has a high sensitivity for detecting cognitive dysfunction. Swedish normative data does not exist and international norms are often derived from populations ...where cognitive impairment has not been screened for and not been thoroughly assessed to exclude subjects with dementia or mild cognitive impairment.
To establish norms for MoCA and develop a regression-based norm calculator based on a large, well-examined cohort.
MoCA was administered on 860 randomly selected elderly people from a population-based cohort from the EPIC study. Cognitive dysfunction was screened for and further assessed at a memory clinic. After excluding cognitively impaired participants, normative data was derived from 758 people, aged 65-85.
MoCA cut-offs (-1 to -2 standard deviations) for cognitive impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the highest educated, depending on age group. Significant predictors for MoCA score were age, sex and level of education.
We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex, and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject's MoCA score.
As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet ...the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimer's pathology and disease progression.
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