Background and aim: Progression to fibrosis in non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of liver-related events, overall mortality and possibly metabolic ...comorbidities. Our aim was to determine if non-invasive fibrosis scoring systems can predict the future risk of diabetes mellitus, cardiovascular disease (CVD), chronic kidney disease (CKD), liver-related events and overall mortality.
Methods: Patients with biopsy-proven NAFLD 1978 to 2006 were identified from a computerised register in Malmö, Sweden. Medical records were scrutinised in detail to collect data from inclusion to endpoint (death or end of 2016). Non-invasive fibrosis scoring systems (FIB-4-index, NAFLD fibrosis score (NFS), APRI and BARD score) were calculated and the scores classified into three risk categories (low, intermediate and high risk for advanced fibrosis). Chronic kidney disease was evaluated using the CKD-EPI equation.
Results: One hundred and forty-four patients with biopsy-proven NAFLD were included, with a mean age of 53.2 years and a mean follow-up time of 18.8 years. At inclusion, 18% had advanced fibrosis. NFS was the only score that could predict the future risk of all included outcomes with fairly good accuracy (Area-under-ROC curve). Multivariate-adjusted hazard ratios revealed that both the intermediate and high-risk category of FIB-4-index and NFS could significantly predict metabolic outcomes. All four scoring systems significantly predicted overall mortality in the high-risk category.
Conclusions: Non-invasive fibrosis scoring systems, especially NFS and FIB-4-index, can be used to identify patients at risk of future liver-related events, overall mortality, metabolic comorbidities and CKD.
Abstract
Background
The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney ...function has remained less clear.
Methods
At baseline (1991–1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine–cystatin C equation at baseline and follow-up examination (2007–2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.
Results
During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 −1.36 versus quartile 4 −1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio OR 1.45 95% confidence interval (CI) 1.10–1.92} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD OR 1.20 (95% CI 1.08–1.33) per 1 standard deviation (SD) increase in p-KIM-1 was comparable to those of age and systolic blood pressure (SBP) OR 1.55 (95% CI 1.38–1.74) and OR 1.21 (95% CI 1.09–1.35) per 1 SD increase, respectively. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 hazard ratio per 1 SD 1.43; (95% CI 1.18–1.74) during a mean follow-up time of 19.2 years.
Conclusion
Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.
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 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 cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, ...genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called
missing heritability
to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
Associations between birth weight (BW) and adult lung function have been inconsistent and limited to early adulthood. We aimed to study this association in two population-based cohorts and explore if ...BW, adjusted for gestational age, predicts adult lung function. We also tested adult lung function impairment according to the mis-match hypothesis-small babies growing big as adults.
We included 3495 individuals (aged 46.4 ± 5.4 years) from the Malmo Preventive Project (MPP), Sweden, born between 1921 and 1949, and 1401 young to middle-aged individuals (aged 28.6 ± 6.7 years) from the Malmo Offspring Study (MOS) with complete data on BW and gestational age. Adult lung function (forced vital capacity FVC, forced expiratory volume in one second FEV1 and the FEV1/FVC-ratio) were analysed as level of impairment (z-score), using multiple linear and logistic regressions.
BW (z-score) did not predict adult lung function in MPP, whereas BW was a significant (p = 0.003) predictor of FEV1 following full adjustment in MOS. For every additional unit increase in BW, children were 0.77 (95% CI 0.65-0.92) times less likely to have impaired adult lung function (FEV1). Moreover, adults born with lower BW (< 3510 g) showed improved lung function (FEV1 and FEV1/FVC in MOS and MPP, respectively) if they achieved higher adult body weight.
Adults born with lower birth weight, adjusted for gestational age, are more likely to have impaired lung function, seen in a younger birth cohort. Postnatal growth pattern may, however, compensate for low birth weight and contribute to better adult lung function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
