Childhood and adulthood serum fatty acid proportions as risk and preventive factors for cardiometabolic outcomes in adulthood : the Cardiovascular Risk in Young Finns Study

Background: The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate. There is a lack of data, from childhood to adulthood, regarding the links between dietary or serum FA composition and cardiometabolic health. The intake of omega-6 (n-6) polyunsaturated FAs (PUFAs) has been linked to both inflammation and oxidative reactions, which are potentially adverse states with regards to cardiometabolic health. Aims: To study at a population level: 1) how FA intake (% from the total FAs) is associated with the corresponding serum FA proportions (% from the total FAs); whether serum FA proportions or FA intake in childhood are associated with 2) blood pressure or 3) carotid artery intima media thickness (cIMT) in adulthood; 4) how the adulthood FA composition affects certain cardiometabolic outcomes, such as obesity, insulin resistance (HOMA-IR), blood pressure or non-alcoholic fatty liver in adulthood; and 5) whether adulthood serum FA proportions are associated with inflammation and/or LDL oxidation. Methods: Baseline of the Young Finns Study was conducted in 1980 (3–18 years old children, n=3596). Adulthood follow-ups for clinical data and outcomes were conducted in 2001 (n=2284), 2007 (n=2204) and/or 2011 (n=2063). Serum cholesteryl ester (CE) FA proportions were measured in 1980 and serum total FA proportions in 2001. The intake of FAs was characterized by a 48-h recall. Results: In childhood (1980), dietary intake and serum CE proportions of FAs correlated well with each other (r=0.30 for saturated FAs (SFAs), r= -0.19 for monounsaturated FAs (MUFAs) and r=0.57 for PUFAs). Childhood CEFAs were associated with adult blood pressure in both sexes and with cIMT in females 27 years later in adulthood (1980->2007). Serum SFA, MUFA and omega-3 (n-3) PUFA proportions showed direct and omega-6s (linoleic acid, 18:2n- 6, in particular) inverse associations. Dietary data, i.e. the P/S ratio (PUFAs/SFAs) and the intake of SFAs, exhibited links which were in line with these serum-based findings. In adulthood (2001), dietary intake and serum total proportions of FAs correlated only weakly with each other, omega-3 PUFAs being an exception (r=0.40). Serum SFA and MUFA proportions showed direct, and omega-6s (+omega-3s borderline significantly) inverse links with prevalent obesity, high HOMA-IR and/or blood pressure in multivariable models. With regard to individual FAs, γ-linolenic (18:3n-6), dihomo-γ-linolenic (20:3n-6) and eicosatetraenoic acids (20:4n-3) displayed direct associations (especially with obesity), whereas the links with linoleic acid were inverse. Adulthood FA intake data did not support these outcome findings. An association profile for the corresponding incident outcomes including fatty liver (2001->2011) was weaker and in many cases statistically non-significant, but its trends were very similar as compared to the cross-sectional data. In addition, serum SFA and MUFA proportions were directly and PUFAs, including omega-6s, inversely associated with C-reactive protein levels and oxidized LDL lipids or proteins in adults (2001 data). Conclusions: These data suggest that childhood and adulthood serum FA proportions are associated with adulthood cardiometabolic outcomes. Serum SFAs are associated with a higher outcome risk, whereas PUFAs, omega-6s and particularly linoleic acid are associated with a lower risk. The role of omega-3 PUFAs and MUFAs remains unclear. These data support dietary recommendations to replace SFAs partly with unsaturated FAs rich in omega- 6 PUFAs already in childhood to improve an individual’s cardiometabolic health.Lapsuuden ja aikuisuuden seerumin rasvahappokoostumus kardiometabolisten sairauksien riski- ja suojatekijänä aikuisiässä: Lasten Sepelvaltimotaudin Riskitekijät-tutkimus Tausta: Rasvahappojen (RH) terveysvaikutukset ovat jatkuvan keskustelun aihe. Tällä hetkellä ei ole olemassa lapsuudesta aikuisuuteen ulottuvaa tietoa RH:jen kardiometabolisista terveysvaikutuksista. Omega-6 (n-6) monityydyttymättömät RH:t (PUFA) on liitetty tulehdusreaktioihin ja hapetusstressiin, jotka ovat kardiometabolisten sairauksien riskitekijöitä. Tavoite: tutkia väestöaineistossa: 1) Miten RH:jen saanti ravinnosta (% RH:jen kokonaissaannista) heijastuu seerumin RH%-koostumukseen; onko lapsuuden seeruminäytteiden RH-koostumus tai RH:jen saanti ravinnosta yhteydessä 2) verenpaineeseen tai 3) kaulavaltimon intima-median paksuuteen (cIMT) aikuisiässä 4) liittyykö aikuisuuden RHkoostumus kardiometabolisiin riskitekijöihin/sairauksiin kuten lihavuus, insuliini-resistenssi (HOMA-indeksi), verenpaine ja ei-alkoholiperäinen rasvamaksa 5) selittääkö seerumin RHkoostumus aikuisuudessa elimistön tulehdus- ja/tai LDL:n hapettumis-reaktioita. Menetelmät: Lasten Sepelvaltimotaudin Riskitekijät-tutkimus (LASERI) alkoi vuonna 1980 (tutkittavat 3–18-vuotiaita, n=3596). Aikuisiän kliinisen terveydentilan tutkimukset suoritettiin vuosina 2001 (n=2284), 2007 (n=2204) ja/tai 2011 (n=2063). Seerumin kolesteroliesteri (KE)-fraktion RH-koostumus määritettiin vuonna 1980 ja seerumin kokonais-RH-koostumus vuonna 2001 otetuista näytteistä. RH-saanti ravinnosta perustui edeltävän 48-tunnin ruuankäyttöön. Tulokset: Lapsuuden (1980) RH-saanti ravinnosta oli yhteydessä seerumin KE-fraktion RH-koostumuksen kanssa (r=0.30 tyydyttyneille RH:ille (SFA), r= -0.19 kertatyydyttymättömille RH:ille (MUFA) ja r=0.57 PUFA:lle). KE-fraktion RH-osuudet olivat yhteydessä verenpaineeseen (pojat+tytöt) sekä kaulavaltimon intima-median paksuuteen (tytöillä) aikuisiässä 27 vuotta myöhemmin siten, että MUFA, SFA ja omega-3 (n-3)-osuudet olivat yhteydessä lisääntyneeseen ja omega-6 (linolihappo, 18:2n-6) alentuneeseen verenpaine- ja cIMT-riskiin. Ravitsemusdata, P/S-suhde (PUFA/SFA) ja SFA-saanti, tukivat edellä mainittuja seerumilöydöksiä. Aikuisiässä (2001), RH-saanti ravinnosta oli ainoastaan heikosti yhteydessä seerumin kokonais-RH-koostumuksen kanssa, omega-3 RH:illa oli kuitenkin vahva yhteys (r=0.40). Seerumin SFA- ja MUFA-osuudet osoittivat suoria ja omega-6 (+omega-3 lähes tilastollisesti merkitsevästi joissakin malleissa) käänteisiä yhteyksiä lihavuuteen, HOMA-indeksiin, ja/tai verenpaineeseen monimuuttuja-malleissa. Yksittäisistä RH:ista γ-linoleeni (18:3n-6)-, dihomo-γ-linoleeni (20:3n-6)- ja eikosatetraeenihappo (20:4n-3) osoittivat suoria ja linolihapppo käänteisiä yhteyksiä, erityisesti lihavuuden kanssa. RH:jen dieetti-data ei tukenut näitä seerumipohjaisia havaintoja. Vastaavat insidenssi-yhteydet, mukaan lukien rasvamaksa-yhteydet (2001 vs. 2011), olivat ennustavuus-trendiltään samansuuntaisia, mutta useimmista yhteyksistä puuttui tilastollinen merkitsevyys. Lisäksi, seerumin SFA- ja MUFA-osuudet olivat yhteydessä lisääntyneeseen C-reaktiivisen proteiinin ja LDL:n hapettuneiden lipidien ja proteiinien määrään, mutta vastaavat PUFA- ja omega-6 PUFA-yhteydet olivat käänteisiä (2001 data). Johtopäätökset: Tutkimuksen havainnot tukevat sitä, että lapsuuden ja aikuisuuden seerumin RH-koostumus on yhteydessä aikuisiän kardiometabolisiin riskitekijöihin, SFA lisääntyneeseen ja PUFA, omega-6-RH:t ja erityisesti linolihappo alentuneeseen riskiin. Omega-3- ja MUFA-rasvahappojen vaikutukset jäävät epäselviksi. Tulokset tukevat suosituksia tyydyttyneen rasvan osittaiseksi korvaamiseksi runsaasti omega-6-rasvoja sisältävällä tyydyttymättömällä rasvalla jo lapsuusiässä kardiometabolisen terveyden parantamiseksi

Suomalaiset löysivät koronavirustaudin oirearvion verkkopalvelun nopeasti : Koronavirustaudin oirearvioon vastanneet 16.3.-15.5.2020

Useiden maiden, mukaan lukien Suomi, terveydenhuoltojärjestelmät joutuivat ottamaan COVID-19-taudin nopeasti alkaneen epidemian iskun vastaan diagnostiikka- ja hoitojärjestelmiensä olemassa olevan ja lisätyn kapasiteetin muutosjoustavuuden (resilienssi) puitteissa. Ensimmäisiä epidemian vaikutuksia olivat nopeasti kuormittuneet puhelupalvelut, potilaiden käytössä olevien verkkosivujen ja niiden viestien lukumäärien kasvu sekä käyntien kysynnän kasvu tiedon saamiseksi tai COVID-19-infektioon liittyvien huolien takia. Suomen koronavirusepidemian ensimmäinen kotimainen tartunta todettiin 25.2.2020 ja tartuntoja oli todettu tuhat 24.3.2020. COVID-19 lisättiin tartuntatautiasetukseen yleisvaarallisten tartuntatautien luetteloon 14.2.2020 alkaen. Suomen poikkeusolojen alussa 16.3.2020 oli todettu 391 tartuntatapausta. Ensimmäinen koronavirustautipotilas otettiin tehohoitoon 16.3.2020 ja ensimmäinen henkilö kuoli koronavirustautiin 21.3.2020. Suomessa avattiin 16.3.2020 väestön käyttöön valtakunnallinen Omaolon koronavirustaudin oirearvio. Tutkimuksen tavoitteena on kuvailla Omaolon koronavirustaudin oirearvion käyttöä ja käyttäjiä 60 ensimmäisen käyttöpäivän aikana 16.3.-15.5.2020. Aineistoon kertyi 329 695 koronavirustaudin oirearviota. Suomalaiset löysivät uuden oirearvion nopeasti. Suomessa on mahdollista tuottaa nopeasti lääketieteellisiä oirearvioita hoitoonohjauksineen eri käyttökohteisiin jo olemassa olevan infrastruktuurin puitteissa

Low Density Lipoprotein-Containing Circulating Immune Complexes : Role in Atherosclerosis and Diagnostic Value

Peer reviewe

Associations of Serum Fatty Acid Proportions with Obesity, Insulin Resistance, Blood Pressure, and Fatty Liver: The Cardiovascular Risk in Young Finns Study

Background: The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate.Objective: Our aim was to investigate the associations between serum standardized FA percentages and cardiometabolic outcomes.Methods: We used cross-sectional (n = 2187-2200 subjects, age 24-39 y, women 54%) and 10-year prospective data (n = 975-1414 subjects) from the Young Finns Study. Outcomes included prevalent and incident obesity, insulin resistance (HOMA-IR index in the upper quintile), elevated blood pressure (BP; taking medication, or diastolic or systolic BP in the upper quintile), and incident nonalcoholic fatty liver. Logistic regression models were used to calculate ORs per SD increase in fatty acids (FAs). The models were adjusted for age and sex, and additionally for other potential confounders.Results: Several cross-sectional findings were also statistically significant in prospective models (Bonferroni corrected P Conclusions: High serum percentages of total SFAs and MUFAs and low PUFAs, but also several specific FAs, predict future unfavorable cardiometabolic outcomes in Finnish adults.</p

Metabolic profiling of fatty liver in young and middle-aged adults : Cross-sectional and prospective analyses of the Young Finns Study

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P <0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P <0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).Peer reviewe

The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study

ObjectiveOxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDLlipids) and oxidized LDL lipids (oxLDLlipids) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24–39 years.MethodsThe analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions.ResultsOxHDLlipids were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDLlipids were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDLlipids. Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDLlipids.ConclusionWe conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDLlipids were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis.</p

Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events

Background: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. Methods: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Results: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively). Conclusions: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.Peer reviewe

Changes in LDL Fatty Acid Composition as a Response to Olive Oil Treatment Are Inversely Related to Lipid Oxidative Damage: The EUROLIVE Study

Objective: The aim of our study was to assess the changes in the fatty acid composition of low density lipoproteins (LDL) after sustained consumption of olive oil at real-life doses (25 mL/day) and their relationship with lipid oxidative damage. Methods: A multi-center randomized, cross-over, clinical trial with 3 similar types of olive oils, but with differences in the phenolic content, was conducted on 200 healthy European subjects. Intervention periods were of 3 weeks separated by 2-week washout periods. The LDL fatty acid content was measured in samples drawn at baseline and after the last intervention period. Results: After olive oil ingestion oleic acid concentration in LDL increased (1.9%; p Ͻ 0.001) and those of linoleic (1.1%; p Ͻ 0.002) and arachidonic acid (0.5%; p Ͻ 0.001) decreased. Monounsaturated/polyunsaturated fatty acid and oleic/linoleic acid ratios in LDL increased after olive oil consumption. An inverse relationship between the oleic/linoleic acid ratio and biomarkers of oxidative stress was observed. One unit increase in the oleic/linoleic acid ratio was associated with a decrease of 4.2 g/L in plasma isoprostanes. Conclusion: Consumption of olive oil at real-life doses improved the fatty acid profile in LDL, the changes being associated with a reduction of the oxidative damage to lipids