Publications by authors named "Jaana Leiviskä"

27 Publications

  • Page 1 of 1

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes.

Sci Rep 2019 06 20;9(1):8887. Epub 2019 Jun 20.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development of T2D.
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http://dx.doi.org/10.1038/s41598-019-43793-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586838PMC
June 2019

Risk Factors for Early-Onset Ischemic Stroke: A Case-Control Study.

J Am Heart Assoc 2018 11;7(21):e009774

1 Clinical Neurosciences University of Helsinki and Department of Neurology, Helsinki University Hospital Helsinki Finland.

Background Recent studies have shown an increasing prevalence of vascular risk factors in young adults with ischemic stroke ( IS ). However, the strength of the association between all vascular risk factors and early-onset IS has not been fully established. Methods and Results We compared 961 patients with a first-ever IS at 25 to 49 years to 1403 frequency-matched stroke-free controls from a population-based cohort study ( FINRISK ). Assessed risk factors included an active malignancy, atrial fibrillation, cardiovascular disease, current smoking status, a family history of stroke, high low-density lipoprotein cholesterol, high triglycerides, low high-density lipoprotein cholesterol, hypertension, and type 1 and type 2 diabetes mellitus. We performed subgroup analyses based on age, sex, and IS etiology. In a fully adjusted multivariable logistic regression analysis, significant risk factors for IS consisted of atrial fibrillation (odds ratio [OR], 10.43; 95% confidence interval [ CI ], 2.33-46.77], cardiovascular disease (OR, 8.01; 95% CI , 3.09-20.78), type 1 diabetes mellitus (OR, 6.72; 95% CI , 3.15-14.33), type 2 diabetes mellitus (OR, 2.31; 95% CI , 1.35-3.95), low high-density lipoprotein cholesterol (OR, 1.81; 95% CI , 1.37-2.40), current smoking status (OR, 1.81; 95% CI , 1.50-2.17), hypertension (OR, 1.43; 95% CI , 1.17-1.75), and a family history of stroke (OR, 1.37; 95% CI , 1.04-1.82). High low-density lipoprotein cholesterol exhibited an inverse association with IS . In the subgroup analyses, the most consistent associations appeared for current smoking status and type 1 diabetes mellitus. Conclusions Our study establishes the associations between 11 vascular risk factors and early-onset IS , among which atrial fibrillation, cardiovascular disease, and both type 1 and 2 diabetes mellitus in particular showed strong associations.
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http://dx.doi.org/10.1161/JAHA.118.009774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404210PMC
November 2018

Serum Insulin and Cognitive Performance in Older Adults: A Longitudinal Study.

Am J Med 2019 03 29;132(3):367-373. Epub 2018 Nov 29.

Aging Research Center, Karolinska Institute, Stockholm, Sweden; Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden.

Purpose: The aim of this study was to examine the association of serum glucose, insulin, and insulin resistance with cognitive functioning 7 years later in a longitudinal population-based study of Finnish older adults.

Methods: Serum glucose and insulin were measured at baseline in 269 dementia-free individuals aged 65-79 years, from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). Participants were reexamined 7 years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed, both at baseline and at follow-up. Multiple linear regression was used to investigate the associations with cognitive performance at follow-up, after adjusting for several potential confounders, including common vascular risk factors.

Results: In the multivariable-adjusted linear regression models, no associations of insulin resistance with cognitive functioning were observed. After excluding 19 incident dementia cases, higher baseline HOMA-IR values were related to worse performance in global cognition (β [standard error (SE)] -.050 [0.02]; P = .043) and psychomotor speed (β [SE] -.064 [.03]; P = [.043]) 7 years later. Raised serum insulin levels were associated with lower scores on global cognition (β [SE] -.054 [.03]; P = .045) and tended to relate to poorer performance in psychomotor speed (β [SE] -.061 [.03]; P = .070).

Conclusions: Serum insulin and insulin resistance may be independent predictors of cognitive performance 7 years later in elderly individuals without dementia. Randomized controlled trials are needed to determine this issue.
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http://dx.doi.org/10.1016/j.amjmed.2018.11.013DOI Listing
March 2019

Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

Sci Rep 2016 12 5;6:38262. Epub 2016 Dec 5.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.

MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10 and FC = 1.25, p = 4.86 * 10, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = -0.143, p = 1.00 * 10) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.
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http://dx.doi.org/10.1038/srep38262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137183PMC
December 2016

Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer's disease: the National Finnish population study (FINRISK).

Age (Dordr) 2016 Dec 23;38(5-6):465-473. Epub 2016 Sep 23.

National Institute for Health and Welfare, PL 30, 00271, Helsinki, Finland.

Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD.
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http://dx.doi.org/10.1007/s11357-016-9950-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266227PMC
December 2016

Cardiovascular risk factors among Russian, Somali and Kurdish migrants in comparison with the general Finnish population.

Eur J Public Health 2016 08 9;26(4):667-73. Epub 2016 Apr 9.

2 Department of Health, National Institute for Health and Welfare, Helsinki, Finland.

Background: There is limited information on cardiovascular risk among migrants. We compared cardiovascular risk factors among three major migrant groups in Finland with the general population.

Methods: Cross-sectional data from 30- to 64-year-old health examination participants (n = 921) of the Migrant Health and Wellbeing Study (2010-12) were used. Data for comparison with the general Finnish population were obtained from the Health 2011 Study (n = 892).

Results: Russian men had a similar risk profile to that of the reference group. Kurdish men had lower prevalence of hypertension [prevalence ratio (PR) 0.55, 95% confidence interval (CI) 0.39-0.79] but higher prevalence of dyslipidaemia (PR: 1.12, 95% CI: 1.02-1.24) and hyperglycaemia (PR: 2.61, 95% CI: 1.88-3.64) compared with the reference group. Somali men had lower prevalence of smoking (PR: 0.18, 95% CI: 0.08-0.44), hypertension (PR: 0.55, 95% CI: 0.32-0.97)) and obesity (PR: 0.35, 95% CI: 0.17-0.71) but higher prevalence of hyperglycaemia (PR: 2.59, 95% CI: 1.73-3.86) compared with the reference group. Similar patterns were observed for women, except for higher prevalence of hyperglycaemia among Russian women (PR: 1.95, 95% CI: 1.26-3.01) and obesity among Kurdish and Somali women (PR: 1.41, 95% CI: 1.15-1.72 and PR: 1.68, 95% CI: 1.40-2.03, respectively) compared with the reference group. All migrant women had significantly lower prevalence of smoking than the reference group.

Conclusions: There were significant variations in cardiovascular risk profiles of Kurdish and Somali migrants compared with the general population. Differences in cardiovascular risk factors by migrant group need to be taken into account in planning and implementing health promotion strategies.
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http://dx.doi.org/10.1093/eurpub/ckw041DOI Listing
August 2016

Altered activation of innate immunity associates with white matter volume and diffusion in first-episode psychosis.

PLoS One 2015 13;10(5):e0125112. Epub 2015 May 13.

Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125112PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430522PMC
February 2016

[Apolipoprotein A-I and B in laboratory diagnostics of dyslipidemia--what benefits do we gain compared with cholesterol measurements?].

Duodecim 2014 ;130(22-23):2331-7

THL, Kansantautien ehkäisyn osato, tautiriskiyksikkö.

Laboratory diagnostics of dyslipidemia has been based on serum total cholesterol, HDL- cholesterol, triglycerides, and calculated or direct LDL-cholesterol measurements. Apolipoprotein A-I (apoA-I) is the main protein in HDL particles, and apoB is the main protein in all other atherogenic lipoprotein particles. An increased number of apoB-containing lipoproteins with normal total and LDL-cholesterol is a common feature associated with obesity, metabolic syndrome, or type 2 diabetes. If the risk assessment of cardiovascular disease in these cardiometabolic disturbances is primarily based on LDL-cholesterol levels, the actual risk may be underestimated. Instead of cholesterol measurements, ApoA-Iand apoB measurements could produce more specific information on dyslipidemia.
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January 2015

Prevention of diabetes and cardiovascular diseases in occupational health care: feasibility and effectiveness.

Prim Care Diabetes 2015 Apr 13;9(2):96-104. Epub 2014 Aug 13.

National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland. Electronic address:

Aims: To evaluate feasibility and effectiveness of lifestyle counseling in occupational setting on decreasing risk for diabetes and cardiovascular disease.

Methods: A health check-up including physical examination, blood tests, questionnaires and health advice was completed on 2312 employees of an airline company. Participants with elevated risk for type 2 diabetes based on FINDRISC score and/or blood glucose measurement (n=657) were offered 1-3 additional lifestyle counseling sessions and 53% of them agreed to participate. After 2.5 years, 1347 employees of 2199 invited participated in a follow-up study.

Results: Among women and men with low baseline diabetes risk, cardiovascular risk factors increased slightly during follow-up. Larger proportion of the men who attended interventions lost weight at least 5% compared with the non-attendees (18.4% vs. 8.4%, p=0.031) and their FINDRISC score increased less (0.6 vs. 1.5, p=0.037). Older age associated with participation in follow-up and higher baseline FINDRISC score and presence of clinical and lifestyle risk factors and problems in sleep and mood increased attendance in interventions.

Conclusions: Identification of employees with cardiovascular and diabetes risk, and the low intensity lifestyle intervention were feasible in occupational health-care setting. However, the health benefits were modest and observed only for men with increased risk.
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http://dx.doi.org/10.1016/j.pcd.2014.07.008DOI Listing
April 2015

Association of serum 25-hydroxyvitamin D with lifestyle factors and metabolic and cardiovascular disease markers: population-based cross-sectional study (FIN-D2D).

PLoS One 2014 7;9(7):e100235. Epub 2014 Jul 7.

Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

Objectives: Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.

Design: In total, 2868 Finnish men and women aged 45-74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n = 2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.

Results: The mean 25OHD level was 58.2 nmol/l in men (n = 1348) and 57.1 nmol/l in women (n = 1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p<0.0001 both in men and women). This study confirmed that low physical activity (p<0.0001 both in men and women), smoking (p = 0.0002 in men and p = 0.03 in women) and high BMI (p<0.0001 in women) are factors that independently associate with low 25OHD level. Of the metabolic and cardiovascular disease markers high triglyceride concentration (p = 0.02 in men and p = 0.001 in women) and high apolipoprotein B/apolipoprotein A1 ratio (p = 0.04 in men and p = 0.03 in women) were independently associated with low 25OHD level.

Conclusions: Higher age did not predict lower 25OHD level in this study population of aged 45-74 years which may derive from a healthy life-style of "active pensioners". Low physical activity and smoking came up as independent lifestyle factors associated with low 25OHD level. Defining the molecular mechanisms behind the associations of 25OHD with low physical activity and smoking are important objective in future studies. The association of 25OHD with BMI, high triglyceride concentration and apolipoprotein B/apolipoprotein A1 ratio may be related to the role of vitamin D in inflammation, but more detailed studies are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100235PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085035PMC
February 2015

Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort.

Am J Psychiatry 2014 Sep;171(9):960-8

Objective: The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank.

Method: A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens.

Results: Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status.

Conclusions: This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.
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http://dx.doi.org/10.1176/appi.ajp.2014.13121579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159178PMC
September 2014

Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study.

Mol Cell Endocrinol 2014 Jun 28;391(1-2):41-9. Epub 2014 Apr 28.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.

Since metabolic syndrome (MetS) is a collection of cardiovascular risk factors involving multiple signaling systems, we related the metabolic abnormalities associated with MetS with circulating microRNA profiles to pinpoint the affected signaling pathways. The blood microRNA profile, genome wide gene expression and serum NMR metabolomics were analyzed from 71 participants of the Young Finns Study. We found nine microRNAs that associated significantly with metabolites connected to MetS. MicroRNA-144-5p concentration correlated with glucose levels, hsa-1207-5p with glycosylated hemoglobin and hsa-miR-484 with metabolites related to insulin resistance. Hsa-miR-625-3p correlated with cholesterol levels, hsa-miR-1237-3p and hsa-miR-331-3p expression with certain fatty acids levels and hsa-miR-129-1-3p, -129-2-3p, and -1288-3p with glycerol levels. The down-regulated targets of miR-1207-5p and -129-2-3p were enriched in PI3K and MAPK pathways and 8 out of the 12 enriched pathways were down-regulated in individuals with MetS. In conclusion microRNAs associated with several aspects of MetS, possibly regulating glucose and lipid metabolism.
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http://dx.doi.org/10.1016/j.mce.2014.04.013DOI Listing
June 2014

Associations of the Baltic Sea diet with obesity-related markers of inflammation.

Ann Med 2014 Mar 22;46(2):90-6. Epub 2014 Jan 22.

Department of Chronic Disease Prevention, National Institute for Health and Welfare , Helsinki and Turku , Finland.

Introduction: Inflammation is an important contributor to the development of chronic diseases. We examined whether a healthy Nordic diet, also called the Baltic Sea diet, associates with lower concentrations of inflammatory markers.

Methods: We used two independent cross-sectional studies: the DILGOM study including Finnish participants aged 25-74 years (n = 4579), and the Helsinki Birth Cohort Study including individuals born at Helsinki University Central Hospital between 1934 and 1944 and who participated in a clinical examination in 2001-2004 (n = 1911). Both studies measured anthropometrics, drew blood, and assessed concentrations of leptin, high-molecular-weight adiponectin, tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein (hs-CRP). A food frequency questionnaire was used to measure dietary intake over the past year and calculate the Baltic Sea Diet Score (BSDS).

Results: In both studies, linear regression adjusting for age, sex, energy intake, lifestyle factors, obesity, statin medication, and upstream inflammatory markers revealed an inverse association between the BSDS and hs-CRP concentrations (P < 0.01). Especially, high intake of Nordic fruits and cereals, low intake of red and processed meat, and moderate intake of alcohol contributed to the emerged association (P < 0.05). The BSDS did not associate with other inflammatory markers.

Conclusion: The Baltic Sea diet is associated with lower hs-CRP concentrations.
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http://dx.doi.org/10.3109/07853890.2013.870020DOI Listing
March 2014

Association between vitamin b12 levels and melancholic depressive symptoms: a Finnish population-based study.

BMC Psychiatry 2013 May 24;13:145. Epub 2013 May 24.

Background: An association between vitamin B12 levels and depressive symptoms (DS) has been reported in several epidemiological studies. The purpose of this study was to evaluate vitamin B12 levels in population-based samples with melancholic or non-melancholic DS as the relationship between vitamin B12 levels and different subtypes of DS has not been evaluated in previous studies.

Methods: Subjects without previously known type 2 diabetes, aged 45-74 years were randomly selected from the National Population Register as a part of the Finnish diabetes prevention programme (FIN-D2D). The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out between October and December 2007 according to the WHO MONICA protocol. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off ≥10 points). A DSM-IV- criteria based summary score of melancholic items in the BDI was used in dividing the participants with DS (N = 429) into melancholic (N = 138) and non-melancholic DS (N = 291) subgroups. In the statistical analysis we used chi-squared test, t-test, permutation test, analysis of covariance, multivariate logistic regression analysis and multinomial regression model.

Results: The mean vitamin B12 level was 331±176 pmol/L in those without DS while the subjects with non-melancholic DS had a mean vitamin B12 level of 324 ± 135 pmol/L, and those with melancholic DS had the lowest mean vitamin B12 level of 292±112 pmol/L (p < 0.001 after adjusted for age, sex, use of antidepressive medication and chronic diseases sum index). The adjusted difference of vitamin B12 levels between the non-melancholic and the melancholic group was 33 pmol/L (95%CI 8 to 57, p = 0.008). Melancholic DS and vitamin B12 levels showed an independent linearly inverse association. The relative risk ratio (RRR) for melancholic DS was 2.75 (95%CI 1.66 to 4.56) in the lowest vitamin B12 level tertile versus the highest (p for linearity <0.001) when those without DS formed the reference group. The RRR in the non-melancholic subgroup was nonsignificant.

Conclusions: The vitamin B12 level was associated with melancholic DS but not with non-melancholic DS.
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http://dx.doi.org/10.1186/1471-244X-13-145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674945PMC
May 2013

Early growth and postprandial appetite regulatory hormone responses.

Br J Nutr 2013 Nov 19;110(9):1591-600. Epub 2013 Apr 19.

Department of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland.

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34-69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.
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http://dx.doi.org/10.1017/S0007114513000950DOI Listing
November 2013

Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk.

Atherosclerosis 2013 Jan 2;226(1):245-51. Epub 2012 Nov 2.

Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

Objective: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values.

Methods: ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT).

Results: Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96 for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk.

Conclusions: Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.10.049DOI Listing
January 2013

What have we learnt about high-density lipoprotein cholesterol measurements during 32 years? Experiences in Finland 1980-2012.

Clin Chim Acta 2013 Jan 18;415:118-23. Epub 2012 Oct 18.

Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

Background: High-density lipoprotein cholesterol (HDL-C) is important in risk assessment for cardiovascular disease or metabolic syndrome; however, different direct HDL-C assays may lead to erroneous risk estimates and potentially misclassify people.

Methods: Data for 30-year HDL-C trends in Finland were obtained from the national FINRISK surveys during 1982-2012 (n=45766) taking into account biases from three external quality assessment programs (EQA). We also compared two different direct HDL-C and turbidimetric apolipoprotein A-I methods using 413 fresh serum samples.

Results: HDL-C concentrations in the Finnish population were on average 1.33 (±0.04) mmol/l for men and 1.62 (±0.05) mmol/l for women after bias-correction. Positive HDL-C trends were observed for both sexes with original data, but trends disappeared after bias-correction. Comparison of two direct HDL-C methods demonstrated concentration-dependent difference. When HDL-C concentrations were <1.0 mmol/l, the mean bias was -12.0% (95% CI -13.5 to -10.0) whereas HDL-C concentrations >1.55 mmol/l showed mean bias of 9.0% (95% CI 7.0-10.5).

Conclusions: Accurate reporting of HDL-C concentrations at the population level requires proper and regular attendance to reliable EQA programs. We found evidence for a concentration-dependent difference between some direct HDL-C methods, which may cause misclassification of people in cardiovascular risk assessment.
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http://dx.doi.org/10.1016/j.cca.2012.10.027DOI Listing
January 2013

Serum lipids modify periodontal infection - C-reactive protein association.

J Clin Periodontol 2012 Sep 11;39(9):817-23. Epub 2012 Jul 11.

Institute of Dentistry, University of Oulu, Finland.

Aim: To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein.

Material And Methods: This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket ≥4 mm and teeth with periodontal pocket ≥6 mm and systemic inflammation using high sensitive C-reactive protein.

Results: The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C ≥ 1.3 mmol/l or LDL-C ≤ 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent.

Conclusion: This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition.
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http://dx.doi.org/10.1111/j.1600-051X.2012.01920.xDOI Listing
September 2012

Modifying effects of alcohol on the postprandial glucose and insulin responses in healthy subjects.

Am J Clin Nutr 2012 Jul 30;96(1):44-9. Epub 2012 May 30.

Departments of Lifestyle and Participation, National Institute for Health and Welfare, Helsinki, Finland.

Background: Moderate alcohol consumption associates with lower risk of type 2 diabetes, but in postprandial studies, alcohol induced impaired insulin sensitivity. The measurement of the glycemic index (GI) for beer has been considered challenging because of its low carbohydrate content. Therefore, imputed GI values from 36 to 95 on the basis of carbohydrate-rich beverages have been used for beer in epidemiologic studies.

Objectives: We investigated the acute effects of alcohol on glucose and insulin responses and measured GIs and insulinemic indexes (IIs) of nonalcoholic and alcoholic beers.

Design: In a crossover design, 10 healthy volunteers were served beer with 4.5% alcohol by volume, nonalcoholic beer, and a glucose solution with alcohol once and the reference glucose solution twice. Each portion contained 25 g available carbohydrate, and the beer and glucose solution with alcohol contained 21 g alcohol. Capillary blood samples were collected up to 2 h after ingestion, and the incremental AUCs (IAUCs), GIs, and IIs were calculated.

Results: Compared with the reference glucose solution, the glucose solution with alcohol produced an 18% higher postprandial glucose IAUC (P = 0.03) and had no significant effect on the insulin IAUC. Compared with the reference glucose solution, beer had no significant effect on glucose or insulin IAUCs, and nonalcoholic beer tended to reduce the glucose IAUC (P = 0.06) but not the insulin IAUC. GIs of beer and nonalcoholic beer were 119 and 80, and IIs were 130 and 88, respectively.

Conclusions: Alcohol increases the postprandial glucose response, probably through impaired insulin sensitivity. GI values published for alcohol-containing beers have underestimated the true glycemic effects.
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http://dx.doi.org/10.3945/ajcn.111.031682DOI Listing
July 2012

Coffee does not modify postprandial glycaemic and insulinaemic responses induced by carbohydrates.

Eur J Nutr 2012 Oct 25;51(7):801-6. Epub 2011 Oct 25.

Department of Lifestyles and Participation, National Institute for Health and Welfare, Mannerheimintie 166, 00271, Helsinki, Finland.

Background: Strong epidemiological evidence suggests that coffee consumption is associated with lower risk of type 2 diabetes. In postprandial studies, however, caffeine consumption has been associated with impaired glucose regulation.

Aim Of The Study: To study the acute effects of coffee and caffeine-containing soft drinks on glycaemic and insulinaemic responses.

Design: Twelve healthy volunteers were served each test food once and the reference glucose solution twice, containing 50 g of available carbohydrates, after an overnight fast at 1-week intervals in a random order. Capillary blood samples were drawn at 15-30 min intervals for 2 h after each study meal. The incremental areas under the curve (IAUC), glycaemic index (GI) and insulinaemic index (II), were calculated to estimate the glycaemic and insulinaemic responses.

Results: Glucose and insulin responses of coffees with glucose containing 150 or 300 mg of caffeine did not differ from responses of pure glucose solution; the GIs were 104 and 103, and the IIs were 89 and 92, respectively. When a bun or sucrose and milk were consumed together with coffee, lower GI values and insulin responses were observed, reflecting the carbohydrate quality and protein content of the accompaniments. Sucrose-sweetened cola produced a high GI value of 90 and an II of 61.

Conclusions: Coffee does not modify glycaemic and insulinaemic responses when ingested with a carbohydrate source. Therefore, there is no need to avoid coffee as a choice of beverage in GI testing.
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http://dx.doi.org/10.1007/s00394-011-0258-4DOI Listing
October 2012

Impact of early growth on postprandial responses in later life.

PLoS One 2011 31;6(8):e24070. Epub 2011 Aug 31.

Department of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland.

Background: Low birth weight and slow growth during infancy are associated with increased rates of chronic diseases in adulthood. Associations with risk factors such as fasting glucose and lipids concentrations are weaker than expected based on associations with disease. This could be explained by differences in postprandial responses, which, however, have been little studied. Our aim was to examine the impact of growth during infancy on postprandial responses to a fast-food meal (FF-meal) and a meal, which followed the macro-nutrient composition of the dietary guidelines (REC-meal).

Methodology/principal Findings: We recruited 24 overweight 65-75 year-old subjects, 12 with slow growth during infancy (SGI-group) and 12 with normal early growth. All the subjects were born at term. The study meals were isocaloric and both meals were consumed once. Plasma glucose, insulin, triglycerides (TG) and free fatty acids (FFA) were measured in fasting state and over a 4-h period after both meals. Subjects who grew slowly during infancy were also smaller at birth. Fasting glucose, insulin or lipid concentrations did not differ significantly between the groups. The TG responses were higher for the SGI-group both during the FF-meal (P = 0.047) and the REC-meal (P = 0.058). The insulin responses were significantly higher for the SGI-group after the FF-meal (P = 0.036). Glucose and FFA responses did not differ significantly between the groups.

Conclusions: Small birth size and slow early growth predict postprandial TG and insulin responses. Elevated responses might be one explanation why subjects who were small at birth and experiencing slow growth in infancy are at an increased risk of developing cardiovascular diseases in later life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024070PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164134PMC
April 2012

The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys.

BMC Med Res Methodol 2011 May 10;11:63. Epub 2011 May 10.

National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland.

Background: For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome.

Methods: Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines.

Results: The median (25th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (P < 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ≥ 3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons).

Conclusions: Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%.
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http://dx.doi.org/10.1186/1471-2288-11-63DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112195PMC
May 2011

Apolipoprotein A-I, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I ratio: reference intervals compared with values in different pathophysiological conditions from the FINRISK 2007 study.

Clin Chim Acta 2011 May 17;412(11-12):1146-50. Epub 2011 Mar 17.

National Institute for Health and Welfare, Department of Chronic Disease Prevention, Disease Risk Unit, Helsinki, Finland.

Background: In addition to traditional measurements of serum lipid levels, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and apoB/apoA-I ratio may add more value to risk assessment guidelines for cardiovascular disease.

Methods: We calculated reference intervals for apoA-I, apoB, and apoB/apoA-I ratio using a reference sample (n=2828) from the FINRISK 2007 study.

Results: The reference intervals for apoA-I were 1.1-2.0 g/l for men and 1.2-2.3 g/l for women. The corresponding reference intervals for apoB were 0.6-1.5 g/l and 0.6-1.3 g/l. The reference intervals for apoB/apoA-I ratio were 0.3-1.0 for men and 0.3-0.8 for women. Compared with the healthy reference group, obese men had the lowest ApoA-I, the highest apoB, and the highest apoB/apoA-I ratio. Men with CVD and cholesterol-lowering medication, or diabetes had lower apoB levels and apoB/apoA-1 ratio than the reference group but the opposite was true for women. The therapeutic goal for low-risk individuals for apoB was 0.9 g/l coinciding with LDL-C concentration of 3.0 mmol/l.

Conclusions: Reference intervals for apoA-I, apoB, and the apoB/apoA-I ratio and their cutoff values may be useful for the risk evaluation and follow-up of treatment among individuals having CVD or other metabolic disorders.
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http://dx.doi.org/10.1016/j.cca.2011.03.015DOI Listing
May 2011

Metabonomic, transcriptomic, and genomic variation of a population cohort.

Mol Syst Biol 2010 Dec;6:441

Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

Comprehensive characterization of human tissues promises novel insights into the biological architecture of human diseases and traits. We assessed metabonomic, transcriptomic, and genomic variation for a large population-based cohort from the capital region of Finland. Network analyses identified a set of highly correlated genes, the lipid-leukocyte (LL) module, as having a prominent role in over 80 serum metabolites (of 134 measures quantified), including lipoprotein subclasses, lipids, and amino acids. Concurrent association with immune response markers suggested the LL module as a possible link between inflammation, metabolism, and adiposity. Further, genomic variation was used to generate a directed network and infer LL module's largely reactive nature to metabolites. Finally, gene co-expression in circulating leukocytes was shown to be dependent on serum metabolite concentrations, providing evidence for the hypothesis that the coherence of molecular networks themselves is conditional on environmental factors. These findings show the importance and opportunity of systematic molecular investigation of human population samples. To facilitate and encourage this investigation, the metabonomic, transcriptomic, and genomic data used in this study have been made available as a resource for the research community.
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http://dx.doi.org/10.1038/msb.2010.93DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018170PMC
December 2010

Role of serum cytokines tumour necrosis factor-alpha and interleukin-6 in the association between body weight and periodontal infection.

J Clin Periodontol 2009 Feb;36(2):100-5

Institute of Dentistry, University of Oulu, Oulu, Finland.

Aim: To study the role of serum cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) as potential mediators in the association between body weight and periodontal infection among an adult population.

Material And Methods: This study was based on a subpopulation of the Health 2000 Health Examination Survey, which included dentate non-diabetic, non-rheumatic subjects, aged between 45 and 64 years, who had never smoked and whose serum levels of TNF-alpha and IL-6 were analysed and whose periodontal status was clinically determined (effective n=425). The number of teeth with periodontal pockets of 4 mm or more and the number of teeth with periodontal pockets of 6 mm or more were used as outcome variables. Relative risks and 95% confidence intervals were estimated using Poisson regression models.

Results: Serum IL-6, but not TNF-alpha associated with teeth with deepened periodontal pockets. Multivariate models showed that IL-6, but not TNF-alpha, could mediate the effect of body weight on periodontium.

Conclusion: In this population of non-diabetic and non-rheumatic subjects, who had never smoked, serum IL-6 was associated with periodontal infection. The results suggest that serum IL-6 could be one mediating factor that connects body weight and periodontal infection.
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http://dx.doi.org/10.1111/j.1600-051X.2008.01350.xDOI Listing
February 2009

Systematic error of serum triglyceride measurements during three decades and the effect of fasting on serum triglycerides in population studies.

Clin Chim Acta 2008 Nov 18;397(1-2):55-9. Epub 2008 Jul 18.

Department of Health and Functional Capacity, National Public Health Institute, KTL, Helsinki, Finland.

Background: An uncontrolled systematic error in serum biomarkers may be a serious problem when comparing their trends both within and between populations. The aim of the study was to assess which factors are responsible for systematic errors in the measurement of serum triglycerides (Tg) and the effect of fasting on serum triglycerides in Finnish population surveys.

Methods: Data on precision and accuracy during 30 years for serum triglycerides were documented from participation in 492 rounds of five different external quality assessment (EQA) programs. Data on fasting and health status from questionnaires were combined from three population surveys comprising 27,131 participants.

Results: The mean annual accuracy (bias) of the Tg methods from all EQAs during 1978-2007 was -1.54% (95% CI -2.25, -0.83). The mean relative change in triglyceride concentration per fasting hour was -3.7% (95% CI -4.2, -3.1) in all subjects. A minimum serum Tg concentration was seen in men and women who had fasted for at least 8 and 7 h, respectively.

Conclusions: The mean bias in serum Tg analyses has been very small throughout the 30-year period. Fasting has a considerable effect on triglyceride levels, but they can be converted either to fasting or non-fasting levels using specific factors.
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http://dx.doi.org/10.1016/j.cca.2008.07.015DOI Listing
November 2008

Serum cholesterol during 27 years: assessment of systematic error and affecting factors and their role in interpreting population trends.

Clin Chim Acta 2007 Mar 12;378(1-2):93-8. Epub 2006 Dec 12.

Department of Health and Functional Capacity, National Public Health Institute Mannerheimintie 166, FI-00300 Helsinki, Finland.

Background: The aim was to assess which factors cause a systematic error in serum total cholesterol measurements and how bias can influence the interpretation of serum cholesterol changes of the Finnish population.

Methods: Data on precision and accuracy during 27 years for serum total cholesterol were documented from participation in 438 rounds of five different external quality assessment (EQA) programs.

Results: The mean annual accuracy (bias) of the cholesterol assay using the results from all EQAs during 1978-2004 was -0.74% (95%CI -0.88 to -0.60). An exceptionally large deviation in bias coincided with the introduction of a new serum calibrator lot. New methods or instrumentation had only a minor impact on serum cholesterol bias. The mean serum cholesterol bias during the latest five population studies in 1982-2002 was -0.10% (95%CI -0.60 to 0.40) but comparison of the bias between the last study (CDC EQA in 2002) and the four previous ones (WHO EQA) showed a net difference of 3.32% (p<0.001). Correcting the mean serum cholesterol of men with respect to WHO and CDC EQA bias changed the interpretation for the last two survey years from an increase of 1.8% to no change.

Conclusions: It is necessary to participate in EQA programs, which include target values measured by the CDC cholesterol reference method and then to perform bias corrections on the mean cholesterol values of the populations.
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http://dx.doi.org/10.1016/j.cca.2006.10.021DOI Listing
March 2007